The ocular surface is facing various unspecific stress factors resulting in irritation and inflammation of the epithelia, causing discomfort to the patients. Ectoine is a bacteria-derived extremolyte with the ability to protect proteins and biological membranes from damage caused by extreme environmental conditions like heat, UV-light, high osmolarity, or dryness. Evidence from preclinical and clinical studies attest its effectiveness in treating several epithelium-associated inflammatory diseases, including the eye surface. In this review, we analysed 16 recent clinical trials investigating ectoine eye drops in patients with allergic conjunctivitis or with other unspecific ocular inflammations caused by e.g. ophthalmic surgery. Findings from these studies were reviewed in context with other published work on ectoine. In summary, patients with irritations and unspecific inflammations of the ocular surface have been treated successfully with ectoine-containing eye drops. In these patients, significant improvement was observed in ocular symptoms of allergic rhinoconjunctivitis, postoperative secondary dry eye syndrome, or ocular reepithelisation after surgery. Using ectoine as an add-on therapy to antihistamines, in allergy patients accelerated symptom relief by days, and its use as an add-on to antibiotics resulted in faster wound closure. Ectoine is a natural substance with an excellent tolerability and safety profile thus representing a helpful alternative for patients with inflammatory irritation of the ocular surface, who wish to avoid local reactions and side effects associated with pharmacological therapies or wish to increase the efficacy of standard treatment regimen.

Moringa stenopetala is a medicinal plant that has been used in Ethiopian traditional medicine as a remedy for the treatment of hypertension, diabetes, and stomach pain. The study is aimed at assessing the toxicity of the methanol extracts of the seeds of Moringa stenopetala on the developing embryo and fetuses of rats. The seeds of Moringa were extracted by maceration using 80% methanol. The extract (250-1000 mg/kg) was orally administered to pregnant Swiss albino rats from days 6 to12 of gestation. Embryos and fetuses were recovered by laparotomy on gestational day 12 and day 20, respectively, and were assessed for developmental anomalies. On day 20, significant prenatal growth retardation such as reduced litter weight and crown-rump length were observed in near term fetuses of 1000 mg/kg treated rats. Litter weight in 1000 mg/kg and pair-fed control groups was 2.41 g ± 0.108 and 3.08 g ± 0.093, respectively. Delay in the development of an otic, optic, and olfactory system, as well as a reduction in a number of branchial bars, occurred on day 12 embryos of 1000 mg/kg treated rats. The rate of fetal resorption in 1000 mg/kg and pair-fed control groups was 1.6 ± 0.55 and 0.42 ± 0.52, respectively. There was also a high incidence of fetal death in the 1000 mg/kg treated group but it was not statistically significant. The offspring's of Moringa-treated rats did not show gross external malformations at all doses. These findings suggest that the methanol seed extract of Moringa stenopetala is not safe to rat embryos and fetuses. Its toxic effects were evidenced by a significant delay in embryonic and fetal development and an increase in fetal resorptions and fetal death.

Erratum for Biomed Res Int. 2020 Jun 30;2020:3575038.

BACKGROUND: The present study is aimed at exploring the specific expression of miR-193a-3p and the mechanism underlying miR-193a-3p-mediated mesenchymal transition (MT), invasion, and migration in glioma. METHODS: The gene expression profile datasets of GSE39486 and GSE25676 were downloaded from the National Center for Biotechnology (NCBI). Data regarding the expression of miR-193a-3p and survival curves were derived from Chinese Glioma Genome Atlas (CGGA). Online websites including miRWalk, DIANA, and starbase were employed to predict the target genes for miR-193a-3p. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by the Omicsbean online software. Module analysis of the protein-protein interaction (PPI) networks was performed by the plug-in Molecular Complex Detection (MCODE), and the degrees of genes were calculated by CytoHubba plug-in of Cytoscape. Survival curves were based on the Gene Expression Profile Interaction Analysis (GEPIA). Transwell, wound healing, and Western blot experiments were performed to investigate the effects of miR-193a-3p and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) on the invasion, migration, and MT of glioma. RESULTS: miR-193a-3p was highly expressed in glioma tissues and significantly correlated with poor survival in patients with glioma. The target genes for miR-193a-3p were involved in many cancer-related signaling pathways. The PPI showed 11 genes with both high degrees and MCODE scores in the network. Survival analysis demonstrated that the expression of BTRC was significantly correlated with the prognosis of patients with glioma. The results from the transwell, wound healing, and Western blot analyses suggested that miR-193a-3p promoted the invasion, migration, and MT of glioma cells, which could be reversed by BTRC. CONCLUSIONS: miR-193a-3p was upregulated in patients with glioma and could affect the invasion, migration, and MT of glioma by regulating BTRC.

BACKGROUND: Severe dengue (SD), experienced by only a fraction of dengue patients, can be lethal. Due to the lack of early markers that can predict the evolution of SD, all dengue patients have to be monitored under hospital care. We discovered early oxidative stress markers of SD to identify patients who can benefit from early intervention before the symptoms appear. METHODS: The expression of inducible nitric oxide synthase (iNOS) in peripheral blood cells (PBC), nitric oxide (NO), and oxidized low-density lipoprotein (oxLDL) levels in plasma and saliva collected at early stages of dengue infection from 20 nonsevere dengue fever (DF) patients and 20 patients who later developed SD were analyzed in a retrospective nested case-control study. RESULTS: The expression of iNOS is significantly (P < 0.05) lower in patients who developed SD than in DF patients at admission within 4 days from fever onset. Median plasma NO concentration within 4 days from fever onset is also significantly (P < 0.05) lower in patients who developed SD (17.9 ± 1.6 μmol/L) than DF (23.0 ± 2.1 μmol/L). Median oxLDL levels in plasma within 3 days from fever onset is significantly (P < 0.05) lower in patients who developed SD (509.4 ± 224.1 ng/mL) than DF (740.0 ± 300.0 ng/mL). Median salivary oxLDL levels are also significantly (P < 0.05) lower in patients who developed SD (0.8 ± 0.5 ng/mL) than DF (3.6 ± 2.6 ng/mL) within 4 days from fever onset. CONCLUSIONS: These findings suggest that the expression of iNOS (73% sensitivity, 86% specificity) and plasma NO (96% sensitivity, 61% specificity at 22.3 μmol/L; P < 0.05) may serve as early markers of SD within 3 days from fever onset. Salivary oxLDL levels may serve as early noninvasive markers of SD with a sensitivity and specificity, respectively, of 57% and 91% at 0.9 ng/mL; 76% and 55% at 2.3 ng/mL; and 100% and 50% at 4.6 ng/mL (P < 0.05) within 4 days from fever onset.

BACKGROUND: Regulatory T cells (Tregs) and recent thymic emigrants (RTEs) have an essential role in the regulation of allogeneic immune responses. However, their mechanisms of action in chronic antibody-mediated rejection (cAMR) are still unclear. In this study, we aimed to compare Treg and RTE levels between stable graft function (SGF) patients and cAMR subjects after kidney transplantation. METHOD: Mononuclear cells (MNs) were separated from peripheral blood, and flow cytometry analysis was performed for detection of CD4+ and CD25high as Treg markers and CD4+, CD31+, and CD45RA+ as RTE immunophenotyping markers. RESULT: The level of peripheral Treg cells was significantly lower in cAMR subjects in comparison to stable graft function patients. Moreover, SGF patients who had received cyclosporine A had a higher level of Treg in comparison to the tacrolimus recipients. Nevertheless, the RTE level between SGF and cAMR patients did not show any significant differences. CONCLUSION: It seems that Treg cells are significantly associated with transplant outcomes in cAMR patients, and prescribed immunosuppressive drugs can influence the frequency of this crucial subset of T cells. Although these drugs are beneficial and inevitable for allograft maintenance, more investigations are needed to elucidate their complete effects on different immune cell subsets which some of them like Tregs are in favor of transplant tolerance. Besides, the thymic output is seemingly not a beneficial biomarker for predicting cAMR; however, more in vivo and in vitro studies are needed for revealing the precise role of Tregs and RTEs in the transplantation context.

Erratum for Biomed Res Int. 2018 Jan 29;2018:7507314.

BACKGROUND: Intestinal parasitic infections are among the most common infections worldwide. The present study was undertaken to provide baseline information on the status of gastrointestinal nematodes in Melong Subdivision, Moungo Division, Littoral Region, Cameroon. Material and Methods. Seven hundred and eighty-eight stool samples were collected in randomly selected quarters in the community of Melong. These stool samples were brought to the Laboratory of Applied Biology and Ecology in the University of Dschang for analysis using the qualitative (simple flotation) and quantitative (Mc Master count) technique. RESULTS: The nematodes identified were Ascaris lumbricoides, hookworm, Trichuris trichiura, and Capillaria hepatica with respective prevalences and intensities of infection of 2.2% and 3691.12 ± 3898.47, 1.4% and 940.91 ± 1825.90, 1.0% and 193.75 ± 227.47, and 0.4%and 50 ± 00. The data on the prevalence of nematodes with respect to sex and age showed that females (6.0%) were more infected than males (2.76%) with no significant difference (P > 0.05). Furthermore, with respect to age, adults were more infected than children. The percentage of educational level showed a reduction in the number of parasites in the higher educational level. The prevalence of A. lumbricoides between localities showed a significant difference (P < 0.05) with "Quarter 1" harboring most of the nematodes. Cases of double (Ascaris lumbricoides + Trichuris trichiura) and triple (Ascaris lumbricoides + Trichuris trichiura + hookworm) parasitism were encountered with both having a prevalence of 0.3%. According to the fecal concentration of eggs, 63.89% of the infections were light, 5.56% moderate, and 30.56% heavy. CONCLUSION: A relatively low overall prevalence was obtained in our study, showing that the national deworming campaign is proving effective, but more effort is needed to completely eradicate these parasites for a single infected individual can cause havoc.

BACKGROUND: Road traffic accidents (RTAs) remain an important public health issue worldwide. Psychoactive substance use is one of the main contributors to the occurrence of traffic accidents, and its use by truck drivers is a global problem. Also, psychoactive substance use is a commonly observed behavior among truck drivers. To the best of our knowledge, no evidence shows the prevalence and factors associated with psychoactive substance use among truck drivers in Ethiopia. Therefore, this study was aimed at assessing the prevalence and factors associated with psychoactive substance use among truck drivers in Ethiopia. METHODS: A cross-sectional study was conducted among 400 systematically selected truck drivers at Modjo dry port in Ethiopia, from February 1 to March 1, 2018. The data were collected through face-to-face individual interviews using a structured questionnaire. The collected data were entered into EpiData version 4.2.0.0 and analyzed using SPSS version 20. Binary logistic regression analysis was computed to determine the association using crude and adjusted odds ratios at 95% confidence intervals. The level of significance was declared at p value < 0.05 in the multivariable binary logistic regression analysis. RESULTS: Of the 400 truck drivers interviewed, the overall one-month self-reported prevalence of psychoactive substance use was 70% (n = 280). In the multivariable binary logistic regression analysis, aged 38 years and above (AOR = 0.40, 95% CI [0.23-0.69]), Christianity religion (AOR = 0.52, 95% CI [0.28-0.97]), college and university education (AOR = 3.47, 95% CI [1.27-9.47]), having a family size of 3 or more (AOR = 0.34, 95% CI [0.20-0.60]), having 6 or more hours spent sleeping at night (AOR = 0.46, 95% CI [0.28-0.75]), and rest breaks between driving (AOR = 2.13, 95% CI [1.14-3.97]) were significantly associated with psychoactive substance use. CONCLUSION: The one-month prevalence of psychoactive substance use among truck drivers was remarkably high. We can conclude that psychoactive substance use is a public health problem among truck drivers, which is a major threat to themselves and others on the road. The sociodemographic and occupational factors are the factors associated with drivers' psychoactive substance use. Therefore, devising health education and counseling program for drivers to tackle the problem plays paramount importance.

The in vivo characterization of the passive mechanical properties of the human triceps surae musculotendinous unit is important for gaining a deeper understanding of the interactive responses of the tendon and muscle tissues to loading during passive stretching. This study sought to quantify a comprehensive set of passive muscle-tendon properties such as slack length, stiffness, and the stress-strain relationship using a combination of ultrasound imaging and a three-dimensional motion capture system in healthy adults. By measuring tendon length, the cross-section areas of the Achilles tendon subcompartments (i.e., medial gastrocnemius and soleus aspects), and the ankle torque simultaneously, the mechanical properties of each individual compartment can be specifically identified. We found that the medial gastrocnemius (GM) and soleus (SOL) aspects of the Achilles tendon have similar mechanical properties in terms of slack angle (GM: -10.96° ± 3.48°; SOL: -8.50° ± 4.03°), moment arm at 0° of ankle angle (GM: 30.35 ± 6.42 mm; SOL: 31.39 ± 6.42 mm), and stiffness (GM: 23.18 ± 13.46 Nmm-1; SOL: 31.57 ± 13.26 Nmm-1). However, maximal tendon stress in the GM was significantly less than that in SOL (GM: 2.96 ± 1.50 MPa; SOL: 4.90 ± 1.88 MPa, p = 0.024), largely due to the higher passive force observed in the soleus compartment (GM: 99.89 ± 39.50 N; SOL: 174.59 ± 79.54 N, p = 0.020). Moreover, the tendon contributed to more than half of the total muscle-tendon unit lengthening during the passive stretch. This unequal passive stress between the medial gastrocnemius and the soleus tendon might contribute to the asymmetrical loading and deformation of the Achilles tendon during motion reported in the literature. Such information is relevant to understanding the Achilles tendon function and loading profile in pathological populations in the future.

OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder. Its most severe form is referred to as chronic recurrent multifocal osteomyelitis (CRMO). Currently, the exact molecular pathophysiology of CNO/CRMO remains unknown. No uniform diagnostic standard and treatment protocol were available for this disease. The aim of this study was to identify the differentially expressed genes (DEGs) in CRMO tissues compared to normal control tissues to investigate the mechanisms of CRMO. MATERIALS: Microarray data from the GSE133378 (12 CRMO and 148 matched normal tissue samples) data sets were downloaded from the Gene Expression Omnibus (GEO) database. DEGs were identified using the limma package in the R software. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network analysis were performed to further investigate the function of the identified DEGs. RESULTS: This study identified a total of 1299 differentially expressed mRNAs, including1177 upregulated genes and 122 downregulated genes, between CRMO and matched normal tissue samples. GO analyses showed that DEGs were enriched in immune-related terms. KEGG pathway enrichment analyses showed that the DEGs were mainly related to oxidative phosphorylation, ribosome, and Parkinson disease. Eight modules were extracted from the gene expression network, including one module constituted with immune-related genes and one module constituted with ribosomal-related genes. CONCLUSION: Oxidative phosphorylation, ribosome, and Parkinson disease pathways were significantly associated with CRMO. The immune-related genes including IRF5, OAS3, and HLA-A, as well as numerous ribosomal-related genes, might be implicated in the pathogenesis of CRMO. The identification of these genes may contribute to the development of early diagnostic tools, prognostic markers, or therapeutic targets in CRMO.

Erratum in Biomed Res Int. 2021 May 29;2021:9863187.

Protein S-nitrosylation (SNO) is a process of covalent modification of nitric oxide (NO) and its derivatives and cysteine residues. SNO plays an essential role in reversible posttranslational modifications of proteins. The accurate prediction of SNO sites is crucial in revealing a certain biological mechanism of NO regulation and related drug development. Identification of the sites of SNO in proteins is currently a very hot topic. In this review, we briefly summarize recent advances in computationally identifying SNO sites. The challenges and future perspectives for identifying SNO sites are also discussed. We anticipate that this review will provide insights into research on SNO site prediction.

Vision loss caused by inherited retinal degeneration affects millions of people worldwide, and clinical trials involving gene supplementation strategies are ongoing for select forms of the disease. When early therapeutic intervention is not possible and patients suffer complete loss of their photoreceptor cells, there is an opportunity for vision restoration techniques, including optogenetic therapy. This therapy provides expression of light-sensitive molecules to surviving cell types of the retina, enabling light perception through residual neuronal pathways. To this end, the bipolar cells make an obvious optogenetic target to enable upstream processing of visual signal in the retina. However, while AAV transduction of the bipolar cells has been described, the expression of human opsins in these cell types within a model of retinal degeneration (rd1) has been less successful. In this study, we have expanded the optogenetic toolkit and shown successful expression of human rhodopsin driven by an ON-bipolar cell promoter (Grm6) in the rd1 mouse model using modified AAV capsids (AAV2.4YF, AAV8.BP2, and AAV2.7m8) delivered via intraocular injection. We also show the first presentation of ectopic expression of human cone opsin in the bipolar cells of rd1 mice. These data provide evidence of an expansion of the optogenetic toolkit with the potential to restore useful visual function, setting the stage for future trials in human patients.

To analyze the outcomes and adverse events of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiation with modified radiotherapy volume and increased radiation dose. This was a retrospective analysis of patients with ESCC treated with definitive chemoradiotherapy at the Sun Yat-sen University Cancer Center (02/2015 to 02/2017). The dose to the planning gross tumor volume (PGTV) and planning clinical tumor volume (PTV1) was 66-68 Gy (2.0-2.2 Gy/fraction). The dose to the planning regional lymph node drainage area volume (PTV2) was 46 Gy (2.0 Gy/fraction). Treatment response, adverse events, progression-free survival (PFS), overall survival (OS), and locoregional failure-free survival (LRFFS) were analyzed. Twenty-six patients were included. The median follow-up was 31 (range, 4.3-51.3) months. Sixteen (61.5%) patients had a complete response, and four (15.4%) achieved a partial response. The objective response rate was 76.9%, and the disease control rate was 80.8%. The median PFS and OS were not achieved. The 4-year PFS was 63.9%, and the 4-year OS was 71.0%. Grade 1-2 and 3-4 radiation-related esophagitis was observed in 15 (57.7%) and one (4.5%) patients, respectively. Grade 1-2 and 3-4 radiation-related pneumonitis was observed in 12 (46.2%) and one (4.5%) patients, respectively. No patients developed radiation-related heart or skin damage. The modified target volume definition and increased dose of definitive radiotherapy combined with chemotherapy in patients with ESCC had low toxicity and might improve survival, but additional trials are necessary to prove the superiority of this strategy.

Due to the instability of unstable intertrochanteric fractures, the selection of a suitable internal fixation has always been a challenge for orthopedic surgeons. This study is aimed at comparing the clinical efficacy of PFNA combined with cerclage cable and without cerclage cable and finally recommend a stable internal fixation method to provide the basis for clinical therapy. From January 2014 to January 2018, we retrospectively analyzed all cases of unstable intertrochanteric fractures who received treatment in the Orthopedics Department of our hospital and finally screened 120 cases, 51 of whom were treated with cerclage cable, 69 without cerclage cable. The follow-up period was one year. HHS, BI, and RUSH scores were given within the specified time. We divided the patients into the PFNA+cable (PFNA combined with cerclage cable) group and the PFNA group. The time of fracture healing and weight-bearing in the PFNA+cable group was shorter than that in the PFNA group. With regard to HHS, BI, and RUSH, the PFNA+cable group was higher than the PFNA group at 1 month, 3 months, 6 months, and 12 months after operation. For HHS rating, the PFNA+cable group has a higher excellent rate than the PFNA group, which was 96.1% and 84.1%, respectively. All the results mentioned above were statistically significant. Compared with the group without cerclage cable, the application of cerclage cable can reduce the incidence of complications. From the comparison between the two groups, it can be seen that the surgical method of PFNA combined with cerclage cable can not only help to improve the stability of fracture reduction, shorten the time of fracture healing and postoperative weight-bearing, and significantly improve patients' self-care ability but also reduce the incidence of postoperative complications. Therefore, we think PFNA combined with cerclage cable is a good choice.

Platelet aggregates, such as PRP, PRF, and CGF, have been used alone or in combination with other grafting materials to enhance restoration outcomes. The process for preparing these autografting materials requires two-step centrifugation or specific centrifuges. In this study, we obtained an injectable fibrin scaffold (IFS) rich in growth factors by one-step centrifugation of whole blood from rabbits. The purpose of this study is to introduce some characteristics of IFS. This scaffold was characterized using various techniques, including Masson's trichrome staining, scanning electron microscopy, porosity measurements, and cell counting. The sustained release of growth factors, including PDGF, VEGF, TGF-β1, IGF, FGF, and EGF, was quantified using ELISA assay. The obtained IFS was tested for its effects on cell proliferation, extracellular matrix deposition, and full-thickness skin defect repair. The prepared IFS is characterized by a loose fibrin network structure with white blood cells and platelets that slowly release growth factors and can promote the healing of skin defects via the promotion of cell proliferation, collagen deposition, and tissue revascularization. In addition, its liquid properties and porous structure are conducive to its application as a therapeutic component in tissue engineering.

METHODS: We enrolled pediatric subjects with developmental dyslexia and, as a control group, healthy age- and sex-matched subjects without developmental dyslexia. Thyroid function was evaluated in subjects with developmental dyslexia measuring serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4). Thyroid autoimmunity was evaluated in all subjects measuring antithyroid peroxidase (TPO-Ab) and antithyroglobulin (TG-Ab) antibodies. In subjects with developmental dyslexia, thyroid ultrasonography (US) was also performed. RESULTS: We enrolled 51 subjects with developmental dyslexia (M : F = 39 : 12, mean age 12.4 ± 9 years) and 34 controls (M : F = 24 : 10, mean age 10.8 ± 4 years). TPO-Ab positivity was significantly higher in subjects with developmental dyslexia compared to controls (60.8% vs. 2.9%, p < 0.001), while no significant difference was found in TG-Ab positivity (16% vs. 5.8%). Thyroid US performed in 49 subjects with developmental dyslexia revealed a thyroiditis pattern in 60%. CONCLUSIONS: We found an extremely high prevalence of thyroid autoimmunity in children with developmental dyslexia. Further studies are needed to confirm our observations, but our findings may change the approach to this disorder and eventually lead to a systematic determination of thyroid autoimmunity in children with developmental dyslexia.

Erratum in Biomed Res Int. 2021 May 31;2021:9792626.

The capability of regeneration for skeletal muscle after injury depends on the differentiation and proliferation ability of the resident stem cells called satellite cells. It has been reported that electrical stimulation was widely used in clinical conditions to facilitate muscle regeneration after injury, but the characterization of satellite cell responses to the context of low-frequency electrical stimulation in early-phase muscle strain conditions has not been fully clarified. In this study, we aim to investigate the effects of low-frequency electrical stimulation (frequency: 20 Hz; duration: 30 minutes, twice daily) on satellite cell activities in a rat model for the early phase of muscle strain. Firstly, we adopted our previously developed rat model to mimic the early phase of muscle strain in human. After then, we examined the effects of low-frequency electrical stimulation on histopathological changes of the muscle fiber by hematoxylin and eosin (H&E) staining. Finally, we investigated the effects of low-frequency electrical stimulation on satellite cell proliferation and differentiation by quantification of the expression level of the specific proteins using western blot analyses. The muscle strain in biceps femoris muscles of rats can be induced by high-speed rotation from knee flexion 50° to full knee extension at 960°·s-1 angular velocity during its tetany by activating the sciatic nerve, as evidenced by a widening of the interstitial space between fibers, and more edema or necrosis fibers were detected in the model rats without treatment than in control rats. After treatment with low-frequency electrical stimulation (frequency: 20 Hz; duration: 30 minutes, twice daily), the acute strained biceps femoris muscles of rats showed obvious improvement of histomorphology as indicated by more mature muscle fibers with well-ordered formation with clear boundaries. Consistently, the expression levels of the MyoD and myogenin were marked higher than those in the rats in the animal model group, indicating increased satellite cell proliferating and differentiating activities by low-frequency electrical stimulation. This study shows that low-frequency electrical stimulation provides an effective stimulus to upregulate the protein expression of MyoD/myogenin and accelerate the restoration of structure during the early phase of muscle strain. This may have significance for clinical practice. Optimization of low-frequency electrical stimulation parameters may enhance the therapeutic outcome in patients.

The off-label use of antiviral and antimalarial drugs has been considered by many researchers as a fast and relatively safe alternative to provide therapeutic options to treat COVID-19, but the assessment of such drug-specific effectiveness in this regard is far from complete. Especially, the current body of knowledge about COVID-19 therapeutics needs more data regarding drug effectiveness and safety in the severely ill patients with comorbidities. In the present article, we retrospectively analyze data from 61 patients that received treatment with chloroquine, lopinavir/ritonavir, both drugs administered together, or a standard treatment with no antiviral drugs, and the study was carried in severely ill patients. We found that either drug is ineffective at treating COVID-19, as they are not able to reduce hospitalization length, mortality, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-Dimer, or ferritin, or to enhance gasometric parameters, lymphocytes, total leukocytes, and neutrophil levels, whereas both drugs administered together decrease circulating lymphocytes, increase LDH and ferritin levels, and more importantly, enhance mortality. In this way, our results show that both drugs are ineffective and even potentially harmful alternatives against SARS-CoV-2.

The digital workflow and the application of Computer-Aided Manufacturing (CAM) to prosthodontics present the clinician with the possibility of adopting new materials that confer several advantages. Especially in the case of zirconia, these innovations have profoundly changed daily practice. This paper compares the satisfaction and perception of patients who received implant-supported single crowns (SC) and fixed partial dentures (FPD) made from zirconia, either monolithic or partially veneered, after 3 years of follow-up; the success and survival rate of these restorations were also measured. Forty patients, who had been previously treated with implant-supported SC or FPD, either monolithic or partially veneered, and submitted to a yearly maintenance program, were recalled 3 years after their treatment and requested to complete an 8-question questionnaire regarding their perceptions of the treatment. Any mechanical or biological complication that had occurred from the time of delivery was also recorded. Patients that experienced ≥1 complication were less likely to be prone to repeat the treatment. The 3-year success rate was 92.6% for monolithic restoration and 92.3% for partially veneered restoration, while the survival rate was 100% for both restorations. The 3-year follow-up found that monolithic and partially veneered zirconia restorations are both well-accepted treatment options, and patients preferred the veneered restorations (0.76, p < 0.05) from an aesthetic point of view. According to our results, monolithic and veneered zirconia restorations are both reliable treatment options and are both equally accepted by patients.

N6-Methyladenosine (m6A), the most common form of mRNA modification, is dynamically regulated by the m6A RNA methylation regulators, which play an important role in regulating the gene expression and phenotype in both health and disease. However, the role of m6A in papillary renal cell carcinoma (pRCC) is unknown. The purpose of this work is to investigate the prognostic value of m6A RNA methylation regulators in pRCC; thus, we can build a risk score model based on m6A RNA methylation regulators as a risk signature for predicting the prognosis of pRCC. Here, we investigated the expression and corresponding clinical data by bioinformatic analysis based on 289 pRCC tissues and 32 normal kidney tissues obtained from TCGA database. As a result, we identified the landscape of m6A RNA methylation regulators in pRCC. We grouped all pRCC patients into two clusters by consensus clustering to m6A RNA methylation regulators, but we found that the clusters were not correlated to the prognosis and clinicopathological features of pRCC. Therefore, we additionally built a two-m6A RNA methylation regulator risk score model as a risk signature by the univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. The risk signature was constructed as follows: 0.031HNRNPC + 0.199KIAA1429. It revealed that the risk score was associated with the clinicopathological features such as pT status and pN status of pRCC. More importantly, the risk score was an independent prognostic marker for pRCC patients. Thus, m6A RNA methylation regulators contributed to the malignant progression of pRCC influencing its prognosis.

OBJECTIVES: This study examined the validity and reliability of the Family Health Climate Scale (FHC-Scale) among Iranian families. Second, can it be attributed to other family members by measuring the health climate in one person? METHOD: In total, 261 female students and 196 mothers completed the FHC-Scale. The study instrument was a Persian version of the FHC-Scale prepared through a translation and back-translation process. RESULTS: The results showed that the Persian version of the FHC-Scale is acceptable. Cronbach's alpha coefficient for FHC-PA in female students and their mothers, respectively, was 0.88 and 0.86 for the whole scale. Cronbach's alpha coefficient for FHC-NU in female students and their mothers, respectively, was 0.83 and 0.92 for the whole scale. The CVI values for all the items were equal to or above 0.8, and the CVR value for the total scale was 0.90. CONCLUSION: The Persian version of the FHC-Scale is therefore an effective tool for evaluating the different dimensions of family health climate in the Iranian population.

BACKGROUND: A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested. METHODS: The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140. RESULTS: QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues (P < 0.0001). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion (P < 0.05), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion (P < 0.05). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan-Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004) and overall survival (OS) times (P = 0.010) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS (P = 0.004) and OS times (P = 0.014) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC.

Nasopharyngeal carcinoma (NPC) is a kind of malignancy generated from the nasopharyngeal epithelium. Recently, long noncoding RNA (lncRNA) has been shown to be involved in the regulation of many signaling pathways and is closely associated with carcinogenesis and tumor progression. However, the precise role of lncRNA Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in NPC is not well understood. Here, we find that OIP5-AS1 is overexpressed in NPC patient specimens and NPC cell lines. Further investigations reveal that knockdown of OIP5-AS1 significantly inhibits the proliferation, migration, and invasion and accelerates the apoptosis of NPC cells in vitro. Consistent with these findings, NPC progression is significantly slowed in mice when OIP5-AS1 is knocked down. Interestingly, there is a functional link between OIP5-AS1 and microRNA-203 (miR-203), a tumor suppressor, in NPC cells. In conclusion, our data demonstrate that OIP5-AS1 plays an important role in the development and progression of NPC by targeting miR-203 and therefore provide a promising target for the treatment of NPC.

OBJECTIVE: To identify the shared genetic and epigenetic mechanisms between the osteogenic differentiation of dental pulp stem cells (DPSC) and bone marrow stem cells (BMSC). MATERIALS AND METHODS: The profiling datasets of miRNA expression in the osteogenic differentiation of mesenchymal stem cells from the dental pulp (DPSC) and bone marrow (BMSC) were searched in the Gene Expression Omnibus (GEO) database. The differential expression analysis was performed to identify differentially expressed miRNAs (DEmiRNAs) dysregulated in DPSC and BMSC osteodifferentiation. The target genes of the DEmiRNAs that were dysregulated in DPSC and BMSC osteodifferentiation were identified, followed by the identification of the signaling pathways and biological processes (BPs) of these target genes. Accordingly, the DEmiRNA-transcription factor (TFs) network and the DEmiRNAs-small molecular drug network involved in the DPSC and BMSC osteodifferentiation were constructed. RESULTS: 16 dysregulated DEmiRNAs were found to be overlapped in the DPSC and BMSC osteodifferentiation, including 8 DEmiRNAs with a common expression pattern (8 upregulated DEmiRNAs (miR-101-3p, miR-143-3p, miR-145-3p/5p, miR-19a-3p, miR-34c-5p, miR-3607-3p, miR-378e, miR-671-3p, and miR-671-5p) and 1 downregulated DEmiRNA (miR-671-3p/5p)), as well as 8 DEmiRNAs with a different expression pattern (i.e., miR-1273g-3p, miR-146a-5p, miR-146b-5p, miR-337-3p, miR-382-3p, miR-4508, miR-4516, and miR-6087). Several signaling pathways (TNF, mTOR, Hippo, neutrophin, and pathways regulating pluripotency of stem cells), transcription factors (RUNX1, FOXA1, HIF1A, and MYC), and small molecule drugs (curcumin, docosahexaenoic acid (DHA), vitamin D3, arsenic trioxide, 5-fluorouracil (5-FU), and naringin) were identified as common regulators of both the DPSC and BMSC osteodifferentiation. CONCLUSION: Common genetic and epigenetic mechanisms are involved in the osteodifferentiation of DPSCs and BMSCs.

Interleukin-37 (IL-37) inhibits the pathogenesis of rheumatoid arthritis (RA) via downregulating proinflammatory cytokines. Accordingly, we performed an analysis to accurately assess the relationship between serum IL-37 cytokine levels and disease activity of RA. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Correlation coefficient (r) was utilized to evaluate the relationship between IL-37 and disease activity of RA patients. Ten studies were included into the research. Functional analysis revealed elevated serum IL-37 concentrations in RA patients (SMD = 1.61, P < 0.00001). The relationship between serum IL-37 levels and disease activity was statistically significant (C-reactive protein: r = 1.47, P = 0.0002; erythrocyte sedimentation rate: r = 1.55, P < 0.00001; rheumatoid factor: r = 1.40, P = 0.004; tumor necrosis factor⁃α: r = 1.64, P = 0.0003; Disease Activity Score for 28 joints: r = 1.63, P < 0.00001; tender joint count: r = 1.48, P < 0.00001; and swollen joint count: r = 1.52, P = 0.0003), but anti-CCP was not significant (anti-CCP: r = 0.98, P = 0.72). In summary, these data are suggesting that the elevated serum level of IL-37 in RA is positively correlated with the disease activity of RA, suggesting a role for IL-37in the pathogenesis of RA.

Children in schools are facing many academic challenges. Moreover, there is constant pressure on children and parents to maximize academic achievement. We aimed to determine the relationship between motor competence, physical fitness, and academic achievement in young school-aged children. Participants were 130 elementary school children (mean ± SD8.60 ± 0.61 years; 51 boys and 79 girls) from Serbia. The KTK (Körperkoordinations Test für Kinder) battery of tests was used to assess the motor competence in children; children' physical fitness was assessed using the EUROFIT battery of tests, while academic achievement was assessed based on the children's GPA (grade point average) scores at the end of the school year. Pearson's r showed the weak to moderate relationships between the GPA and motor competence and physical fitness measures. The GPA correlates positively and significantly with almost all motor competence and physical fitness measures, but negatively with BMI (p ≤ 0.05). However, the hierarchical linear regression indicated only the plate tapping and sit and reach as the significant predictors of the GPA. Although both tests positively affect the GPA, the plate tapping (B = -0.22, p = 0.02) tends to influence the GPA more than the sit and reach test (B = 0.18, p = 0.04) after adjusting for effects of motor competence (B = 0.19, p = 0.03), age (B = -0.01, p = 0.89), and BMI (B = -0.19, p = 0.03). This study provides evidence demonstrating that academic achievement is generally associated with physical fitness and motor competence in children. However, plate taping and sit and reach were accounted as the most important predictors for academic achievement.

BACKGROUND: Platelet-rich fibrin (PRF) is a kind of autologous platelet concentrate which is easy to obtain and cheap. In recent years, it has been studied to improve the effect of periodontal regeneration. However, few studies have systematically evaluated the complementary effect of PRF in the treatment of intrabony defects. The present review is aimed at systematically assessing the effects of PRF on clinical and radiological outcomes of the surgical treatment of periodontal intrabony defects. METHODS: The protocol was registered at PROSPERO (International Prospective Register of Systematic Reviews) as CRD42020206056. An electronic search was conducted in MEDLINE, Cochrane, and EMBASE databases. Only randomized clinical trials were selected. Systematically healthy patients with two or three walls of intrabony defects were considered. Intrabony defect (IBD) depth reduction and bone fill (BF) % were set as primary outcomes while probing depth (PD) reduction, clinical attachment level (CAL) gain, and gingival margin level (GML) gain were considered as the secondary outcome. When possible, a meta-analysis was performed. RESULTS: Eighteen articles fulfilled the inclusion criteria, and seventeen studies were quantitatively analyzed. Of 17 studies, four were rated as high risk of bias and thirteen as the moderate risk of bias. Two comparisons were set: (1) open flap debridement (OFD) combined with PRF and OFD alone and (2) bone grafting (BG) combined with PRF and BG alone. Compared to OFD alone, OFD+PRF showed significantly greater in all primary and secondary outcomes. Compared to BG alone, BG+PRF showed significantly greater in IBD depth reduction, PD reduction, CAL gain, and GML gain. CONCLUSIONS: The use of PRF was significantly effective in the treatment of periodontal intrabony defects. The benefit of OFD+PRF may be greater than BG+PRF. PRF can promote early wound healing in periodontal surgery. As all included studies were not at low risk of bias, well-designed RCTs having a high methodological quality are needed to clarify the additional effectiveness of PRF in the treatment of intrabony defects in the future.

Among orbital lymphoproliferative disorders, about 55% of diagnosed cancerous tumors are orbital lymphomas, and nearly 50% of benign cases are immunoglobulin G4-related ophthalmic disease (IgG4-ROD). However, due to nonspecific characteristics, the differentiation of the two diseases is challenging. In this study, conventional magnetic resonance imaging-based radiomics approaches were explored for clinical recognition of orbital lymphomas and IgG4-ROD. We investigated the value of radiomics features of axial T1- (T1WI-) and T2-weighted (T2WI), contrast-enhanced T1WI in axial (CE-T1WI) and coronal (CE-T1WI-cor) planes, and 78 patients (orbital lymphoma, 36; IgG4-ROD, 42) were retrospectively reviewed. The mass lesions were manually annotated and represented with 99 features. The performance of elastic net-based radiomics models using single or multiple modalities with or without feature selection was compared. The demographic features showed orbital lymphoma patients were significantly older than IgG4-ROD patients (p < 0.01), and most of the patients were male (72% in the orbital lymphoma group vs. 23% in the IgG4-ROD group; p = 0.03). The MR imaging findings revealed orbital lymphomas were mostly unilateral (81%, p = 0.02) and wrapped eyeballs or optic nerves frequently (78%, p = 0.02). In addition, orbital lymphomas showed isointense in T1WI (100%, p < 0.01), and IgG4-ROD was isointense (60%, p < 0.01) or hyperintense (40%, p < 0.01) in T1WI with well-defined shape (64%, p < 0.01). The experimental comparison indicated that using CE-T1WI radiomics features achieved superior results, and the features in combination with CE-T1WI-cor features and the feature preselection method could further improve the classification performance. In conclusion, this study comparatively analyzed orbital lymphoma and IgG4-ROD from demographic features, MR imaging findings, and radiomics features. It might deepen our understanding and benefit disease management.

Dry weight is the normal weight of hemodialysis patients after hemodialysis. If the amount of water in diabetes is too much (during hemodialysis), the patient will experience hypotension and shock symptoms. Therefore, the correct assessment of the patient's dry weight is clinically important. These methods all rely on professional instruments and technicians, which are time-consuming and labor-intensive. To avoid this limitation, we hope to use machine learning methods on patients. This study collected demographic and anthropometric data of 476 hemodialysis patients, including age, gender, blood pressure (BP), body mass index (BMI), years of dialysis (YD), and heart rate (HR). We propose a Sparse Laplacian regularized Random Vector Functional Link (SLapRVFL) neural network model on the basis of predecessors. When we evaluate the prediction performance of the model, we fully compare SLapRVFL with the Body Composition Monitor (BCM) instrument and other models. The Root Mean Square Error (RMSE) of SLapRVFL is 1.3136, which is better than other methods. The SLapRVFL neural network model could be a viable alternative of dry weight assessment.

OBJECTIVE: To develop and externally validate a CT-based radiomics nomogram for pretreatment prediction of relapse in osteosarcoma patients within one year. MATERIALS AND METHODS: In this multicenter retrospective study, a total of 80 patients (training cohort: 63 patients from three hospitals; validation cohort: 17 patients from three other hospitals) with osteosarcoma, undergoing pretreatment CT between August 2010 and December 2018, were identified from multicenter databases. Radiomics features were extracted and selected from tumor regions on CT image, and then, the radiomics signature was constructed. The radiomics nomogram that incorporated the radiomics signature and clinical-based risk factors was developed to predict relapse risk with a multivariate Cox regression model using the training cohort and validated using the external validation cohort. The performance of the nomogram was assessed concerning discrimination, calibration, reclassification, and clinical usefulness. RESULTS: Kaplan-Meier curves based on the radiomics signature showed a significant difference between the high-risk and the low-risk groups in both training and validation cohorts (P < 0.001 and P = 0.015, respectively). The radiomics nomogram achieved good discriminant results in the training cohort (C-index: 0.779) and the validation cohort (C-index: 0.710) as well as good calibration. Decision curve analysis revealed that the proposed model significantly improved the clinical benefit compared with the clinical-based nomogram (P < 0.001). CONCLUSIONS: This multicenter study demonstrates that a radiomics nomogram incorporated the radiomics signature and clinical-based risk factors can increase the predictive value of the osteosarcoma relapse risk, which supports the clinical application in different institutions.

Echis carinatus is one of the highly venomous snakes of Pakistan that is responsible for numerous cases of envenomation and deaths. In Pakistan, medicinal plants are commonly used traditionally for snakebite treatment because of their low cost and easy availability in comparison with antivenom. The current research is aimed at evaluating the inhibitory activity of Pakistani medicinal plants against acetylcholinesterase and 5'-nucleotidases present in Echis carinatus venom. Acetylcholinesterase and 5'-nucleotidase enzymatic assays were performed at different venom concentrations to check the activity of these enzymes. Methanolic extracts from different parts of plants were used for in vitro determination of their inhibitory activity against 5'-nucleotidases in snake venom. Active methanolic extracts were subsequently fractioned using different solvents, and these fractions were also assessed for their anti-5'-nucleotidase activity. Results of this study exhibited that Eugenia jambolana Willd. ex O. Berg, Rubia cordifolia L., Trichodesma indicum (L.) R. Br., Calotropis procera (Wild.) R. Br., Curcuma longa L., and Fagonia arabica L. were able to significantly (p > 0.5) neutralize the 5'-nucleotidase activity by 88%, 86%, 86%, 85%, 83.7%, and 83%, respectively, compared with a standard antidote (snake venom antiserum). Thus, this study indicates that these plants possess the potential to neutralize one of the toxic enzymatic components of Echis carinatus venom and hence can help to augment the future efforts of developing alternative therapy for the management of snakebites.

Living kidney donors represent a unique population of patients. Potential donors are selected based on the belief that their preoperative fitness is likely to mitigate the risks of long- and short-term harm following uninephrectomy. Studies performed on postdonation outcomes have largely focused on mortality and the risk of end-stage renal failure, but have also investigated secondary outcomes such as cardiovascular morbidity and hypertension. It has been postulated that hypertension is a possible outcome of living kidney donation. A variety of studies have been conducted to investigate the prevalence, epidemiology, mechanisms, treatment strategies, and long-term ramifications of hypertension postdonation. These studies are heterogeneous in their population, design, methodology, and outcome measures and have presented contradicting outcomes. Additionally, the absence of a well-matched control group has made it challenging to interpret and generalise the reported findings. As such, it is not possible to definitively conclude that hypertension occurs at a higher rate among donors than the general population. This article will review the evidence of postdonation hypertension prevalence, mechanisms, treatment, and complications.

Copper has demonstrated utility in multiple industrial applications for its high conductivity and antibacterial/antiviral properties. However, numerous findings have suggested potential hazards regarding pathogenesis. This study was conducted to demonstrate the application of zebrafish (Danio rerio) as a cost-effective biological assay to detect environmental pollution, i.e., heavy metal of coins. We demonstrated that zebrafish larvae exposed to copper-plated coins or copper (II) ion solution elicited a consistent phenotype of early mortality without signs of morphological defects in surviving individuals. Copper ion solution served as a standard to (1) corroborate copper exposure from coins and (2) demonstrate proportional increase in early mortality phenotype according to concentration. We found that 5 μM CuSO4·5H2O was the minimal concentration to elicit the observed phenotypes from copper toxicity. This study aimed to demonstrate how a simple protocol involving wild-type zebrafish larvae could provide an economical solution to water monitoring in areas of rapid technological advancement and increasing environmental concerns, especially in communities without access to expensive analytical methods.

OBJECTIVE: To identify and evaluate characteristics of the most influential articles in achalasia research during the period 1995-2020. METHODS: Articles in Scopus, Web of Science Core Collection (WoSCC), and PubMed were scanned from 1995 to 2020 with achalasia as the keyword. We retrieved the articles that met all criteria by descending order after using EndNote to remove the duplicated references. Our bibliometric analysis highlighted publication year, country, journals, and networks of keywords. RESULTS: Fifteen percent of the top 100 most-cited articles were published in Annals of Surgery. They were performed in 15 countries, and most (n = 55) were from the USA. The number of citations of the 482 articles ranged from 30 to 953, 38 of which had been published in American Journal of Gastroenterology. Those articles were from 31 countries, and most of the studies (n = 217) had been performed in the USA. Most of articles (n = 335) were clinical research. Treatments were hotspots in the field of achalasia in the past years. The most influential title words were "achalasia," "esophagomyotomy," "pneumatic dilation," and "lower esophageal sphincter." CONCLUSION: Our study offers a historical perspective on the progress of achalasia research and identified the most significant evolution in this field. Results showed treatment was the most influence aspect in achalasia.

Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL) represent 15% and 20%, respectively, of all lymphoma types. The aim of this study was to identify and compare circulating serum miRNA (c-miRNA) and peripheral whole blood miRNA (wb-miRNA) profiles in patients with these lymphomas. Serum samples (20 HL, 21 DLBCL, and 30 healthy controls) and whole blood samples (21 HL, 17 DLBCL patients, and 30 healthy controls) were collected at the time of diagnosis. Serum and whole blood were also collected from 18 HL/17 DLBCL and eight HL/nine DLBCL patients, respectively, after treatment. Pairwise comparisons identified 125 c-miRNAs (adjusted P value < 0.05) showing significant dysregulation between 30 healthy controls and patients; of these, 47 and 55 differentiated controls from pretherapeutic HL and DLBCL patients, respectively. In addition, 60 and 16 c-miRNAs differentiated controls from posttherapeutic HL and DLBCL, respectively. Pairwise comparisons identified 292 wb-miRNAs (adjusted P value < 0.05) showing significant dysregulation between 30 controls and patients; of these, 103 and 169 differentiated controls from pretherapeutic HL and DLBCL, respectively, and 142 and 151 wb-miRNAs differentiated controls from posttherapeutic HL and DLBCL, respectively. Thus, lymphoma-associated miRNAs may be a better source of noninvasive candidate biomarkers than miRNAs in serum. It is unclear whether miRNA alterations in lymphoma cells are similar to those observed in white blood cells.

INTRODUCTION: It has been shown that miR-192 is abnormally expressed in a variety of cancer types and participates in different kinds of signaling pathways. The role of miR-192 in the diagnosis and prognosis of cancer has not been verified. This article is aimed at exploring the diagnostic and prognostic value of miR-192 through a systematic review and meta-analysis. METHODS: A systematic search was performed through PubMed, Embase, Web of Science, and Cochrane Library databases up to June 16, 2020. A total of 16 studies were enrolled in the meta-analyses, of which 11 articles were used for diagnostic meta-analysis and 5 articles were used for prognostic meta-analysis. The values of sensitivity and specificity using miR-192 expression as a diagnostic tool were pooled in the diagnostic meta-analysis. The hazard ratios (HRs) of overall survival (OS) with 95 confidence intervals (CIs) were extracted from the studies, and pooled HRs were evaluated in the prognostic meta-analysis. Eleven studies including 667 cancer patients and 514 controls met the eligibility criteria for the diagnostic meta-analysis. Five studies including 166 patients with high miR-192 expression and 236 patients with low miR-192 expression met the eligibility criteria for the prognostic meta-analysis. RESULTS: The overall diagnostic accuracy was as follows: sensitivity 0.79 (95%CI = 0.75-0.82), specificity 0.74 (95%CI = 0.64-0.82), positive likelihood ratio 3.03 (95%CI = 2.11-4.34), negative likelihood ratio 0.29 (95%CI = 0.23-0.37), diagnostic odds ratio 10.50 (95%CI = 5.89-18.73), and area under the curve ratio (AUC) 0.82 (95%CI = 0.78-0.85). The overall prognostic analysis showed that high expression of miR-192 in patients was associated with positive survival (HR = 0.62, 95%CI : 0.41-0.93, p = 0.020). CONCLUSION: Our results revealed that miR-192 was a potential biomarker with good sensitivity and specificity in cancers. Moreover, highly expressed miR-192 predicted a good prognosis for patients.

Active ageing" has become the leading scientific and policy conceptualization of a later life over the past two decades in the European Union (EU). It has been used as a key strategy for responding to demographic ageing. In the United States, in contrast, discourses around successful ageing have been more prevalent. This review article charts the development of active ageing responses to demographic change, showing how the concept compares with the notion of successful ageing and other terms associated with "ageing well." It identifies how, in practice, active ageing has been dominated by a narrow economic or productivist interpretation that prioritizes the extension of working life (to reduce the "burden" of population ageing). Such interpretations of active ageing undermine its value and emphasize the need for a more comprehensive approach which is set out. The development of the Active Ageing Index in 2012 provided a new analytical tool to promote evidence-based strategies towards population ageing. However, in practice, we show how it has not yet engaged fully with a comprehensive approach to active ageing or with the critical role of the life course in shaping the experience of old age. Nonetheless, this review article shows that the concept of active ageing still has an important role to play in our understanding of and responses to population ageing.

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is an accurate and convenient method for mRNA quantification. Selection of optimal reference gene(s) is an important step in RT-qPCR experiments. However, the stability of housekeeping genes in spinach (Spinacia oleracea) under various abiotic stresses is unclear. Evaluating the stability of candidate genes and determining the optimal gene(s) for normalization of gene expression in spinach are necessary to investigate the gene expression patterns during development and stress response. In this study, ten housekeeping genes, 18S ribosomal RNA (18S rRNA), actin, ADP ribosylation factor (ARF), cytochrome c oxidase subunit 5C (COX), cyclophilin (CYP), elongation factor 1-alpha (EF1α), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), histone H3 (H3), 50S ribosomal protein L2 (RPL2), and tubulin alpha chain (TUBα) from spinach, were selected as candidates in roots, stems, leaves, flowers, and seedlings in response to high temperature, CdCl2, NaCl, NaHCO3, and Na2CO3 stresses. The expression of these genes was quantified by RT-qPCR and evaluated by NormFinder, BestKeeper, and geNorm. 18S rRNA, actin, ARF, COX, CYP, EF1α, GAPDH, H3, and RPL2 were detected as optimal reference genes for gene expression analysis of different organs and stress responses. The results were further confirmed by the expression pattern normalized with different reference genes of two heat-responsive genes. Here, we optimized the detection method of the gene expression pattern in spinach. Our results provide the optimal candidate reference genes which were crucial for RT-qPCR analysis.

INTRODUCTION: Bloodstream infections (BSI) among patients with hematological malignancies (HM) could predispose them to higher morbidity and mortality for various underlying conditions. Several microorganisms, either pathogenic or opportunistic normal human flora, could cause severe bacteremia and septicemia. While conventional methods have their own limitations, molecular methods such as next-generation sequencing (NGS) can detect these blood infections with more reliability, specificity, and sensitivity, in addition to information on microbial population landscape. Methodology. Blood samples from HM patients (n = 50) and volunteer blood donor control individuals with no HM (n = 50) were subjected to 16S rRNA gene amplification using standard PCR protocols. A metagenomic library was prepared, and NGS was run on a MiSeq (Illumina) sequencer. Sequence reads were analyzed using MiSeq Reporter, and microbial taxa were aligned using the Green Genes library. RESULTS: 82% of the patients showed BSI with Gram-negative bacteria as the most predominant group. E. coli comprised a major chunk of the bacterial population (19.51%), followed by K. pneumoniae (17.07%). The CoNS and Viridans Streptococci groups are 17.07% and 14.63%, respectively. Other major species were S. aureus (9.75%), P. aeruginosa (7.31%), A. baumannii (4.87%), E. cloacae (4.87%), and P. mirabilis (4.87%). 34.14% of the cases among patients showed a Gram-positive infection, while 14.63% showed polymicrobial infections. CONCLUSION: Most of the BSI in patients were characterized by polymicrobial infections, unlike the control samples. Molecular methods like NGS showed robust, fast, and specific identification of infectious agents in BSI in HM, indicating the possibility of its application in routine follow-up of such patients for infections.

Active immunotherapy against cancer is based on immune system stimulation, triggering efficient and long-lasting antigen-specific immune responses. Immunization strategies using whole dead cells from tumor tissue, containing specific antigens inside, have become a promising approach, providing efficient lymphocyte activation through dendritic cells (DCs). In this work, we generate whole dead tumor cells from CT26, E.G7, and EL4 live tumor cells as antigen sources, which termed immunogenic cell bodies (ICBs), generated by a simple and cost-efficient starvation-protocol, in order to determine whether are capable of inducing a transversal anticancer response regardless of the tumor type, in a similar way to what we describe previously with B16 melanoma. We evaluated the anticancer effects of immunization with doses of ICBs in syngeneic murine tumor models. Our results showed that mice's immunization with ICBs-E.G7 and ICBs-CT26 generate 18% and 25% of tumor-free animals, respectively. On the other hand, all carrying tumor-animals and immunized with ICBs, including ICBs-EL4, showed a significant delay in their growth compared to not immunized animals. These effects relate to DCs maturation, cytokine production, increase in CD4+T-bet+ and CD4+ROR-γt+ population, and decrease of T regulatory lymphocytes in the spleen. Altogether, our data suggest that whole dead tumor cell-based cancer immunotherapy generated by a simple starvation protocol is a promising way to develop complementary, innovative, and affordable antitumor therapies in a broad spectrum of tumors.

PURPOSE: To investigate the hyperreflective foci (HRF) as an inflammatory biomarker using optical coherence tomography angiography (OCTA) in neovascular age-related macular degeneration (AMD) patients after antivascular endothelial growth factor (anti-VEGF) treatment and its association with the retinal microcapillary density. METHODS: Twenty-five eyes from 25 patients with neovascular AMD were included in the study. All eyes were imaged with OCTA at baseline (M0) and after 3 consecutive injections (M3; injection performed each month) of anti-VEGF. The number of HRF in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and outer retina was counted. The vascular density of the fovea, parafovea, and the whole macula, as well as the area of the foveal avascular zone (FAZ), was measured. RESULTS: The mean interval between baseline and follow-up with OCTA was 93.08 ± 5.00 (range, 85-101) days. Compared with the baseline, the number of HRF significantly decreased in DCP (7.52 ± 3.06 vs. 3.76 ± 1.48, P < 0.01) and outer retina (12.04 ± 4.91 vs. 5.88 ± 3.32, P < 0.01) after treatment. There was no significant difference for HRF number in the SCP, the vascular density (containing foveal, parafoveal, and whole macular), and FAZ area before and after treatments. CONCLUSION: The number of HRF in DCP and outer retina might serve as an inflammatory biomarker in patients with neovascular AMD. The reduced HRF possibly represents the alleviation of inflammation after anti-VEGF treatment in patients with AMD.

BACKGROUND: Pericoronitis is a painful inflammatory condition commonly associated with third molar teeth. The purpose of this study was to investigate the relationship between oral hygiene and periodontal health status and the presence of pericoronitis in semi-impacted third molar teeth. METHODS: A cross-sectional study was conducted, and 54 patients having at least one mandibular vertically semi-impacted third molar tooth with or without pericoronitis were consecutively enrolled. Subjects with pericoronitis and subjects with healthy third molars were selected according to symptoms in the gingiva overlying semi-impacted third molar teeth. Periodontal health status and oral hygiene were evaluated with the measures of plaque index (PI), gingival index (GI), and total number of sites with a probing depth (PD) ≥ 4 mm. The clinical data collected in this study was analyzed with Mann-Whitney U test using SPSS 20.0 package program. RESULTS: The PI scores were found to be significantly higher in patients with pericoronitis (p < 0.05). Although the GI scores and PD scores were higher in patients with pericoronitis, the difference did not reach statistical significance when compared with those in healthy subjects (p > 0.05). CONCLUSION: The findings obtained in this study suggest that the amount of dental plaque was positively associated with third molar pericoronitis. Gingival and periodontal health conditions were similar between patients with and without pericoronitis. Improving oral hygiene and controlling dental plaque may help prevent third molar pericoronitis.

AIM: We aimed to perform a meta-analysis to determine whether antibiotic prophylaxis reduces the incidence of urinary tract infections (UTIs) after urodynamic studies (UDS). METHODS: We conducted a systematic search of PubMed, Web of Science, Ovid, Elsevier, ClinicalKey, Embase, Cochrane Library, Medline, and Wiley Online Library. Randomized controlled trials (RCTs) comparing the effectiveness of prophylactic antibiotics with placebo or no treatment in preventing UTI after UDS were included. Two reviewers extracted data independently, and RevMan 5.3 software was used to analyze relative risk (RR) with 95% confidence intervals (CI). Heterogeneity was assessed by the Q test and I 2 test. RESULTS: The final meta-analysis included 1829 patients in 13 RCTs. Compared with the placebo or no treatment group, prophylactic antibiotics could significantly reduce the risk of bacteriuria (RR = 0.42, 95% CI: 0.30-0.60) and the risk of symptomatic UTI (RR = 0.65, 95% CI: 0.48-0.88). In addition, there was no statistically significant difference in the risk of adverse events (RR = 4.93, 95% CI: 0.61-40.05). No significant heterogeneity or publication bias was found in this study. CONCLUSIONS: Current evidence showed that prophylactic antibiotics could reduce the risk of asymptomatic bacteriuria and symptomatic UTI after UDS without increasing the incidence of adverse events.

Based on the better generalization ability and the feature learning ability of the deep convolutional neural network, it is very significant to use the DCNN on the computer-aided diagnosis of a lung tumor. Firstly, a deep convolutional neural network was constructed according to the fuzzy characteristics and the complexity of lung CT images. Secondly, the relation between model parameters (iterations, different resolution) and recognition rate is discussed. Thirdly, the effects of different model structures for the identification of a lung tumor were analyzed by changing convolution kernel size, feature dimension, and depth of the network. Fourthly, the different optimization methods on how to influence the DCNN performance were discussed from three aspects containing pooling methods (maximum pooling and mean pooling), activation function (sigmoid and ReLU), and training algorithm (batch gradient descent and gradient descent with momentum). Finally, the experimental results verified the feasibility of DCNN used on computer-aided diagnosis of lung tumors, and it can achieve a good recognition rate when selecting the appropriate model parameters and model structure and using the method of gradient descent with momentum.

Long noncoding RNAs (lncRNAs) are a class of important regulators participating in various pathological processes. Until now, the role of lncRNAs in the occurrence and development of intrahepatic cholestasis of pregnancy (ICP) has rarely been investigated. The data from microarray screening revealed 58 upregulated and 85 downregulated lncRNAs and 47 upregulated and 71 downregulated mRNAs in ICP patients compared to healthy controls. Bioinformatics analysis revealed biological processes focused on lipid metabolism, apoptosis, cell cycle, cell differentiation, and oxidative stress. Furthermore, the expressions of three lncRNAs (ENST00000505175.1, ASO3480, and ENST00000449605.1) chosen for verification were significantly decreased and showed the diagnostic and prognostic value for ICP based on ROC analysis. This is the first study to report the specific role of lncRNAs in ICP, which may be helpful for the diagnosis and prognosis of ICP clinically.

Immunotherapy, a treatment based on host immune system activation, has been shown to provide a substitute for marginally effective conventional chemotherapy in controlling visceral leishmaniasis (VL), the deadliest form of leishmaniasis. As the majority of endemic inhabitants exhibit either subclinical or asymptomatic infection which often develops into the active disease state, therapeutic intervention seems to be an important avenue for combating infections by stimulating the natural defense system of infected individuals. With this perspective, the present study focuses on two immunodominant Leishmania (L.) donovani antigens (triosephosphate isomerase and enolase) previously proved to be potent prophylactic VL vaccine candidates, for generating a recombinant chimeric antigen. This is based on the premise that in a heterogeneous population, a multivalent antigen vaccine would be required for an effective response against leishmaniasis (a complex parasitic disease). The resulting molecule rLdT-E chimeric protein was evaluated for its immunogenicity and immunotherapeutic efficacy. A Th1 stimulating adjuvant BCG was employed with the protein which showed a remarkable 70% inhibition of splenic parasitic multiplication positively correlated with boosted Th1 dominant immune response against lethal L. donovani challenge in hamsters as evidenced by high IFN-γ and TNF-α and low IL-10. In addition, immunological analysis of antibody subclass presented IgG2-based humoral response besides considerable delayed-type hypersensitivity and lymphocyte proliferative responses in rLdT-E/BCG-treated animals. Our observations indicate the potential of the chimera towards its candidature for an effective vaccine against Leishmania donovani infection.

Several theories on the origin of adenomyosis (ADS) have been proposed, of which the most widely accepted is the fundamental pathogenic role of uterine eutopic endometrium. Emerging evidence suggests that circular RNAs participate in the multiple tumorgenesis. The vital importance of circular RNA PVT1 (circPVT1) in the pathological progress like malignancies has been well documented. Nevertheless, its underlying correlation with ADS remains elusive yet. The purpose of this study was to investigate the expression pattern, regulatory effect, and internal mechanism of circPVT1 in ADS. qRT-PCR was performed to detect the relative mRNA expression of circPVT1, miR-145, and Talin1 in ADS endometrial tissue and cells. The protein level of Talin1 was measured by Western blot and immunochemistry. Immunofluorescence was used to identify the primary endometrial epithelial and stromal cells. circPVT1 knockdown in vitro was achieved by transfecting with specific lentivirus vector CCK-8, and colony formation assays were utilized to assess cell proliferation; meanwhile, the transwell assay was employed for evaluating cell invasion ability. By conducting bioinformatics, dual-luciferase reporter assay, or RNA immunoprecipitation (RIP) experiment, the interaction between miR-145 and circPVT1 or Talin1 was verified. Rescue experiments further determined the regulatory effect of circPVT1/miR-145/Talin1 axis. We found both circPVT1 and Talin1 were markedly upregulated in ADS endometrial tissue and cells, whereas miR-145 was decreased. Elevated expression of circPVT1 was closely related to the severity of dysmenorrhea, menorrhagia, and uterine enlargement of patients with ADS. Knockdown of circPVT1 inhibited adenomyotic epithelial and stromal cell proliferation and invasion. Further mechanistic experiments revealed that circPVT1 negatively regulated miR-145 through serving as a molecular sponge. And the facilitating effect of circPVT1 was partially reversed by miR-145. Talin1 was demonstrated to be a down target of miR-145 and indirectly affected by circPVT1. Our findings unveiled that enhanced circPVT1 may be involved in the pathogenesis of ADS via stimulating endometrial cell proliferation and invasion. The establishment of circPVT1/miR-145/Talin1 pathway might present a novel therapeutic insight for ADS.

BACKGROUND: The application of biomolecular interventions in the early stage of intervertebral disc degeneration (IVDD) is considered an ideal method for the treatment of IVDD. However, the precise definition of the "early stage" of IVDD is unclear. Silent information regulation 2 homologue-1 (SIRT1) can protect human degenerative nucleus pulposus (NP) cells from apoptosis by activating autophagy. However, the mechanism of this effect is still unclear. This study tried to confirm the "early stage" of IVDD and the role of NP cell autophagy during IVDD as well as to determine the mechanism by which SIRT1 protects NP cells. METHODS: The characteristics of the NP in various stages of degeneration were assessed to confirm the "early stage" of IVDD. Then, autophagy and apoptosis were detected in NP cells after SIRT1 upregulation/downregulation. Finally, LY294002 and PD98059 were used to inhibit the AKT/ERK pathway to determine the mechanism by which SIRT1 regulates autophagy in NP cells. RESULTS: Our data showed that mildly degenerative (Pfirrmann grade III with normal height of intervertebral disc) NP cells may be the key target for biomolecular interventions in IVDD and that SIRT1 protects human mildly degenerative NP cells from apoptosis by activating autophagy via the ERK signalling pathway. CONCLUSION: Our data showed that SIRT1 inhibits apoptosis by promoting the autophagic flux in NP cells via the ERK signalling pathway during the key stage of degeneration. These findings will assist in the development of novel therapeutic approaches for IVDD treatment.

PURPOSE: To investigate the levels of transforming growth factor-β (TGF-β) in human aqueous humor (AH) and plasma (PL) of patients with myopia, and verify whether there is an association between these levels and their association with axial length (AL). METHODS: Thirty-eight myopic patients who received intraocular collamer lens (ICL) implantation were enrolled in this cross-sectional study. Patients were divided into three groups based on AL with cut-off points of 26 and 28 mm. AH and PL samples were obtained during ICL implantation surgery. The levels of TGF-β1, TGF-β2, and TGF-β3 in the AH and PL samples were measured using Luminex xMAP Technology kits (Milliplex xMAP kits). The protein levels of TGF-βs in both AH and PL samples and their relationships with AL were analyzed. RESULTS: In all, 38 patients (59 eyes) were enrolled and divided into the three groups: group A contained 7 people (10 eyes), group B contained 22 people (37 eyes), and group C contained 9 people (12 eyes). In the AH group, we detected TGF-β1 (P 50: 19.97 pg/mL), TGF-β2 (2446.00 pg/mL), and TGF-β3 (26.33 pg/mL); in PL, these concentrations were 8984.00, 523.44, and 210.47 pg/mL, respectively. The levels of TGF-β1 and TGF-β3 in AH were positively associated with AL. None of the three isoforms in PL were related to those in AH or to AL. CONCLUSIONS: The levels of TGF-β1 and TGF-β3 in AH were more strongly associated with the severity of myopia than the types of TGF-β in PL.

BACKGROUND: The outbreak of coronavirus disease (COVID-19) has become a global public health emergency. OBJECTIVE: To evaluate the characteristics and outcomes of patients with COVID-19 in Anhui and to identify predictors of viral clearance. METHODS: We retrospectively analyzed the data collected from discharged patients with laboratory-confirmed SARS-CoV-2 infections. We compared clinical features between viral clearance and viral persistence, and evaluated factors associated with SARS-CoV-2 shedding using multiple linear regression. RESULTS: Among the 83 patients involved in the study, the median age was 43 years, while 60.2% were male, 35.4% had comorbidities, and the mortality was zero. The median time from illness onset to admission was 5 days (interquartile range (IQR), 2-7 days), and the median time from the illness onset to SARS-CoV-2 RNA detection was 16 days (IQR, 13-18 days). The factors influencing viral clearance were as follows: (1) delayed admission (beta 1.057, 95% CI 0.810-1.304; p ≤ 0.001) and (2) underlying comorbidities (beta 1.907, 95% CI 0.198-3.616; p = 0.029). No significant differences were observed in the length of stay (p = 0.246) and pneumonia between asymptomatic and symptomatic patients based on computed tomography (CT) (p = 0.124). CONCLUSIONS: Delayed admission and underlying comorbidities may effectively predict SARS-CoV-2 RNA clearance. For those infected with SARS-CoV-2, even asymptomatic patients without any clinical symptoms should be traced and isolated. This practice may reduce the spread of SARS-CoV-2 and slow the COVID-19 pandemic caused by the virus. Clinical Trial Registration Number: This trial is registered with 2020-051.

BACKGROUND: Coronaviruses (CoVs) are enveloped positive-strand RNA viruses which have club-like spikes at the surface with a unique replication process. Coronaviruses are categorized as major pathogenic viruses causing a variety of diseases in birds and mammals including humans (lethal respiratory dysfunctions). Nowadays, a new strain of coronaviruses is identified and named as SARS-CoV-2. Multiple cases of SARS-CoV-2 attacks are being reported all over the world. SARS-CoV-2 showed high death rate; however, no specific treatment is available against SARS-CoV-2. METHODS: In the current study, immunoinformatics approaches were employed to predict the antigenic epitopes against SARS-CoV-2 for the development of the coronavirus vaccine. Cytotoxic T-lymphocyte and B-cell epitopes were predicted for SARS-CoV-2 coronavirus protein. Multiple sequence alignment of three genomes (SARS-CoV, MERS-CoV, and SARS-CoV-2) was used to conserved binding domain analysis. RESULTS: The docking complexes of 4 CTL epitopes with antigenic sites were analyzed followed by binding affinity and binding interaction analyses of top-ranked predicted peptides with MHC-I HLA molecule. The molecular docking (Food and Drug Regulatory Authority library) was performed, and four compounds exhibiting least binding energy were identified. The designed epitopes lead to the molecular docking against MHC-I, and interactional analyses of the selected docked complexes were investigated. In conclusion, four CTL epitopes (GTDLEGNFY, TVNVLAWLY, GSVGFNIDY, and QTFSVLACY) and four FDA-scrutinized compounds exhibited potential targets as peptide vaccines and potential biomolecules against deadly SARS-CoV-2, respectively. A multiepitope vaccine was also designed from different epitopes of coronavirus proteins joined by linkers and led by an adjuvant. CONCLUSION: Our investigations predicted epitopes and the reported molecules that may have the potential to inhibit the SARS-CoV-2 virus. These findings can be a step towards the development of a peptide-based vaccine or natural compound drug target against SARS-CoV-2.

The aim of this study was to evaluate the effects of a 6-month combined aerobic and strength exercise training program on functional and psychological aspects and health-related quality of life in patients with PH and to evaluate its longer-term impact. In total, 22 stable patients (mean age 53.9 ± 13.8, 13 female) with pulmonary hypertension of World Health Organization (WHO) class I-III participated in a nine-month study. They were randomly assigned into two groups: Group A participated in a 6-month combined aerobic and strength exercise training program, whereas Group B remained untrained. All patients underwent physical and psychological assessment at baseline and at month 6 (after completing the exercise program) and physical assessment after 9 months (3 months posttraining). After the 6-month exercise training program, patients of Group A significantly improved their physical (6MWD, STS 10 rep, STS 20 rep, TUG, lower limb strength, cardiopulmonary exercise time, METs, peak VO2, VCO2, and VE/VCO2 slope) and psychological aspects (SF-36, STAI, and BDI). Between the two groups, differences were observed at the 6MWD (95% CI: 36.2-64.6, η 2 = 0.72), STS 10 rep (95% CI: 6.6-2.2, η 2 = 0.4), STS 20 rep (95% CI: 10.8-2.4, η 2 = 0.34), lower limb strength (95% CI: 7.2-3.6, η 2 = 0.38), cardiopulmonary exercise time (95% CI: 0.1-3.3, η 2 = 0.2), and VCO2 (95% CI: 0.1-0.5, η 2 = 0.2). Additionally, psychological changes were noted at SF-36, PCS (95% CI: 3.6-14.8, η 2 = 0.35), MCS (95% CI: 1.3-16.1, η 2 = 0.22), TCS (95% CI: 1.3-16.1, η 2 = 0.22), and STAI (95% CI: 1.8-28.2, η 2 = 0.18). The favorable results of exercise were maintained at the 3-month posttraining follow-up assessment. No exercise-induced complications were observed throughout the study. In conclusion, a long-term exercise training program is a safe and effective intervention to improve functional status, psychological aspects, and health-related quality of life in patients with PH.

BACKGROUND: Diabetes mellitus (DM) aggravates symptoms and prognosis of acute ischemic stroke (AIS), and inflammation plays an important role therein. Resolvin D2 (RvD2) is one of the specialized pro-resolving mediators (SPMs), while leukotriene B4 (LTB4) is a classic proinflammatory mediator. The ratio of RvD2 to LTB4 is an index of pro-resolving/proinflammatory balance. We aim to explore the role of RvD2/LTB4 ratio in ischemic stroke complicated with DM. METHODS: The plasma levels of RvD2 and LTB4 were analyzed by enzyme immunoassay in stroke patients with DM (DM + AIS group) or without DM (nonDM+AIS group). Patients were followed up at 90 days after stroke onset, and modified Rankin Score (mRS) was assessed. The association of RvD2/LTB4 ratio with stroke severity and prognosis was also analyzed. RESULTS: The plasma levels of RvD2 were positively correlated to LTB4. The RvD2/LTB4 ratio in DM + AIS group was lower than that in the nonDM+AIS group. No correlation was found between the RvD2/LTB4 ratio and infarct size or NIHSS score. The RvD2/LTB4 ratio at baseline was significantly lower in the poor prognosis group (mRS ≥ 3) than that in the good prognosis group (mRS ≤ 2). CONCLUSIONS: Our study indicated that the balance between pro-resolving and proinflammatory mediators was impaired by diabetes in ischemic stroke. The RvD2/LTB4 ratio may serve as a biomarker of prognosis for ischemic stroke.

Neurodevelopmental disorder caused by malformations of cortical development is a rare neurological disease. Heterozygous missense variants in the TUBG1 gene lead to malformations of human cortical development, which further result in intellectual disability, developmental retardation, and epilepsy. To the best of our knowledge, only thirteen patients and a total of nine pathogenic TUBG1 variants have been described in the published literature. This study reports the case details and genetic data analysis of a girl (aged 8 years, 9 months) with developmental delay, psychomotor regression, epilepsy, and left external ear deformity. A novel TUBG1 mutation was identified by whole-exome sequencing and Sanger sequencing, confirming that this mutation may be the cause of the neurodevelopmental disorders. This case report characterizes the phenotypic spectrum, molecular genetic findings, and functional consequences of novel pathogenic TUBG1 variants in neurodevelopmental disorders caused by cortical development malformations.

Scientists have continuously searched for novel bioactive compounds to overcome the inherent problems associated with drug resistance, the evolution of unknown diseases, and the toxicity of currently used compounds. The ocean has been considered a rich source of compounds that possess unique chemical structures and novel biological capabilities. Biologically active molecules isolated from marine flora and fauna have shown significant advancement over the past century in the pharmaceutical industry. Marine natural products (MNPs) have been used as nanomedicine, cosmetics, wound healing, antimicrobial agents, anticancer agents, and anti-inflammatory agents. The physicochemical parameters of the collection site were also recorded. This study's marine sponge species were collected from Phillip's Reef, South Africa, at 12 m during the spring season. Ethyl acetate (EA) and dichloromethane : methanol (DCM : ME, 1 : 1) were used as extraction solvents. Crude extracts of the marine sponges were tested against MRSA, P. aeruginosa, C. difficile, A. fumigatus, and C. albicans. Phytochemical screening was conducted to identify seven critical phytochemical groups. A pH reading of 8.01 and a temperature of 15.45°C were recorded at the sampling site. Clathria sp. 1 and Tedania (Tedania) stylonychaeta EA crude extracts showed bioactivity against all five test pathogens. The DCM : ME crude extract of Clathria sp. 1 was the only bioactive crude extract from DCM : ME extracts. This crude extract was only bioactive against C. albicans as no activity was observed against the other four pathogens. EA crude extracts of Clathria sp. 1 yielded more significant inhibition zones against both fungal pathogens. These EA crude extracts performed better than fluconazole as inhibition zones of 35 ± 0 mm at 24 mg/ml, 31 ± 0 mm at 19 mg/ml, 31 ± 0 mm at 14.4 mg/ml, 30 ± 0 mm at 9.6 mg/ml, and 25 ± 0 mm at 7.2 mg/ml were recorded. Clathria sp. 1 crude extracts exhibited higher inhibition zones compared to Tedania (Tedania) stylonychaeta. The antibiotic imipenem (26 ± 0.7 mm at 10 μg) and ciprofloxacin (30 ± 0.3 mm at 5 μg) exhibited higher zones of inhibition than EA crude extracts of Tedania (Tedania) stylonychaeta at all test concentrations. In this study, Clathria sp. 1 was observed to have broad-spectrum bioactivity as EA crude extracts were bioactive against MRSA, P. aeruginosa, C. difficile, A. fumigatus, and C. albicans. In addition to this, the EA crude extract of Clathria sp. 1 was bacteriostatic (9.6 mg/ml). Clathria sp. 1 DCM : ME crude extract only tested positive for the presence of terpenoids. In contrast, EA crude extracts did not test positive for the existence of any of the seven phytochemicals. Our study has revealed that Tedania (Tedania) stylonychaeta and Clathria sp. 1 sponge species collected from Phillip's Reef in South Africa can produce bioactive compounds useful against bacterial and fungal species.

OBJECTIVE: The study is aimed at investigating the regulatory relationship between miR-145-5p and ABRACL, and has tried at clarifying the mechanisms underlying the proliferation, migration, and invasion of esophageal carcinoma (EC) cells. METHODS: Gene expression data related to EC were accessed from TCGA database, and the "edgeR" package was used to screen differentially expressed genes. TargetScan, miRDB, and miRTarBase databases were used to predict potential targets for the target miRNA miR-145-5p. qRT-PCR and Western blot were performed to assess the expression of miR-145-5p and ABRACL in EC cells. Dual-luciferase reporter assay was performed to validate the targeting relationship between miR-145-5p and ABRACL. Functional experiments including CCK-8 assay, Transwell migration, and invasion assays were used to detect the proliferation, migration, and invasion of EC cells. RESULTS: The expression of miR-145-5p was significantly decreased in EC, while ABRACL was remarkably increased. In addition, there was a negative correlation identified between miR-145-5p and ABRACL mRNA. Overexpressing miR-145-5p was able to suppress cell proliferation, migration, and invasion, whereas silencing miR-145-5p posed an opposite effect. In the meantime, ABRACL was identified as a direct target of miR-145-5p by dual-luciferase reporter assay. Furthermore, miR-145-5p could inhibit the expression of ABRACL, in turn inhibiting the proliferation, migration, and invasion of EC cells. CONCLUSION: miR-145-5p functions on the proliferation, migration, and invasion of EC cells via targeting ABRACL, and it may be a novel therapeutic target in EC treatment.

Congenital heart defects (CHD) are structural imperfections of the heart or large blood vessels that are detected around birth and their symptoms vary wildly, with mild case patients having no obvious symptoms and serious cases being potentially life-threatening. Using cardiovascular magnetic resonance imaging (CMRI) technology to create a patient-specific 3D heart model is an important prerequisite for surgical planning in children with CHD. Manually segmenting 3D images using existing tools is time-consuming and laborious, which greatly hinders the routine clinical application of 3D heart models. Therefore, automatic myocardial segmentation algorithms and related computer-aided diagnosis systems have emerged. Currently, the conventional methods for automatic myocardium segmentation are based on deep learning, rather than on the traditional machine learning method. Better results have been achieved, however, difficulties still exist such as CMRI often has, inconsistent signal strength, low contrast, and indistinguishable thin-walled structures near the atrium, valves, and large blood vessels, leading to challenges in automatic myocardium segmentation. Additionally, the labeling of 3D CMR images is time-consuming and laborious, causing problems in obtaining enough accurately labeled data. To solve the above problems, we proposed to apply the idea of adversarial learning to the problem of myocardial segmentation. Through a discriminant model, some additional supervision information is provided as a guide to further improve the performance of the segmentation model. Experiment results on real-world datasets show that our proposed adversarial learning-based method had improved performance compared with the baseline segmentation model and achieved better results on the automatic myocardium segmentation problem.

Lung cancer has a higher incidence rate and mortality rate than all other cancers. Early diagnosis and treatment of lung cancer remain a major challenge, and the 5-year survival rate of its patients is only 15%. Basic and clinical research, especially the discovery of biomarkers, is crucial for improving the diagnosis and treatment of lung cancer patients. To identify novel biomarkers for lung cancer, we used the iTRAQ8-plex labeling technology combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the serum and urine of patients with different stages of lung adenocarcinoma and healthy individuals. A total of 441 proteins were identified in the serum, and 1,161 proteins were identified in the urine. The levels of elongation factor 1-alpha 2, proteasome subunit alpha type, and spermatogenesis-associated protein increased significantly in the serum of patients with lung cancer compared with those in healthy controls. The levels of transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 decreased significantly in the serum of patients with metastases compared with those of nonmetastatic lung cancer patients. In the urine of stage III and IV lung cancer patients, the prostate-specific antigen and prostatic acid phosphatase decreased significantly, whereas neutrophil defensin 1 increased significantly. The results of LC-MS/MS were confirmed by enzyme-linked immunosorbent assay (ELISA) for transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 in the serum. These proteins may be a potential early diagnosis and metastasis biomarkers for lung adenocarcinoma. Furthermore, the relative content of these markers in the serum and urine could be used to determine the progression of lung adenocarcinoma and achieve accurate staging and diagnosis.

[This retracts the article DOI: 10.1155/2013/372646.].

The short tandem repeat (STR) loci are polymorphic markers in the combined DNA index system (CODIS) and non-CODIS STR loci. Due to the highly polymorphic characteristic of STR loci, they are popular and widely used in forensic DNA typing laboratories. In this study, 22 STR loci (1 CODIS, 21 non-CODIS STR loci) and an Amelogenin locus were genotyped and analyzed in 590 unrelated individuals of the Guanzhong Han population. None of the 22 STR loci deviated from the Hardy-Weinberg equilibrium, and all the loci were in the linkage equilibrium state. We observed 247 alleles, and the corresponding allelic frequencies ranged from 0.0008 to 0.3695 in the Guanzhong Han population. The combined power of discrimination and the cumulative exclusion probability was 0.999 999 999 999 999 999 999 999 999 346 36 and 0.999 999 999 709 74, respectively. The results including Nei's D A genetic distance, multidimensional scaling analysis, and principal component analysis showed that the Guanzhong Han population has closer genetic affinities with Northern Han, Chengdu Han, and Xinjiang Hui groups from China based on allelic frequencies of 15 overlapped STR loci from Guanzhong Han and 13 reference groups. The present results indicated that Microreader™ 23sp ID kit included highly polymorphic loci, and it could be well used for individual identification, paternity testing, and population genetics in the Guanzhong Han population.

BACKGROUND: Mutations in insulin receptor genes can cause severe insulin resistance syndrome. Compared with Rabson-Mendenhall Syndrome and Donohue's Syndrome, type A insulin resistance syndrome is generally not serious. The main manifestations in woman with type A insulin resistance syndrome are hyperinsulinemia, insulin resistance, acanthosis nigricans, hyperandrogenism, and polycystic ovary. Case Presentation. A 13-year-old girl (Han nationality) visited the hospital due to hairiness and acanthosis nigricans. Further examination revealed severe hyperinsulinemia, insulin resistance, elevated blood glucose, hyperandrogenism, and polycystic ovary. Analysis of the insulin receptor gene by sequencing showed the presence of a nucleotide change in intron 7 (c. 1610+1G > A). The mutation was a splicing mutation, which can obviously affect the mRNA splicing of the insulin receptor and cause its function loss. The patient was finally diagnosed with type A insulin resistance syndrome. After 2 months of metformin treatment, the patient had spontaneous menstrual cramps and significantly improved acanthosis nigricans and sex hormones. CONCLUSION: We report for the first time a new splicing mutation on the insulin receptor gene at the 7th intron (c.1610+1G > A), which leads to type A insulin resistance syndrome. In clinically suspected patients with polycystic ovary syndrome, if there are extremely high blood levels of insulin in the blood, genetic testing should be performed to detect insulin receptor gene mutation of type A insulin resistance syndrome.

Alzheimer's disease (AD) is the most common neurodegenerative disease, which is associated with extracellular deposition of amyloid-β proteins (Aβ). It has been reported that triptolide (TP), an immunosuppressive and anti-inflammatory agent extracted from a Chinese herb Tripterygium wilfordii, shows potential neuroprotective effects pertinent to AD. However, the clinical use of TP for AD could be hampered due to its high toxicity, instability, poor water solubility, and nonspecific biodistribution after administration. In this paper, we reported a kind of multiple-coated PLGA nanoparticle with the entrapment of TP and surface coated by chitosan hydrochloride, Tween-80, PEG20000, and borneol/mentholum eutectic mixture (MC-PLGA-TP-NP) as a novel nasal brain targeting preparation for the first time. The obtained MC-PLGA-TP-NP was 147.5 ± 20.7 nm with PDI of 0.263 ± 0.075, zeta potential of 14.62 ± 2.47 mV, and the entrapment efficiency and loading efficiency of 93.14% ± 4.75% and 1.17 ± 0.08%, respectively. In comparison of TP, MC-PLGA-TP-NP showed sustained-release profile and better transcellular permeability to Caco-2 cells in vitro. In addition, our data showed that MC-PLGA-TP-NP remarkably reduced the cytotoxicity, attenuated the oxidative stress, and inhibited the increase of the intracellular Ca2+ influx in differentiated PC12 cells induced by Aβ 1-42. Therefore, it can be concluded that MC-PLGA-TP-NP is a promising preparation of TP, which exerts a better neuroprotective activity in the AD cellular model.

Mesenchymal stem cells (MSCs) were shown to have potential therapeutic effects for treatment of liver fibrosis, and dysregulated expression of microRNAs (miRNAs) played a pivotal role in the pathogenesis of liver fibrosis by regulating their downstream target genes. However, the mechanism by which MSCs affect the progression of liver fibrosis by regulating miRNA expression remains unclear. Here, we investigated whether human umbilical cord MSCs (HUC-MSCs) attenuated hepatic fibrosis by regulating miR-455-3p and its target gene. Significantly upregulated miRNA (miR-455-3p) was screened out by GEO datasets analysis and coculture HUC-MSCs with hepatic stellate cell (HSC) LX-2 cells. p21-activated kinase-2 (PAK2) was forecasted to be the target gene of miR-455-3p by bioinformatics analyses and confirmed by luciferase reporter assay. HUC-MSCs were transplanted into mice with carbon tetrachloride- (CCl4-) induced liver fibrosis, the result showed that HUC-MSC transplantation significantly ameliorated the severity of CCl4-induced liver fibrosis, attenuated collagen deposition, improved liver function by reducing the expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, upregulated miR-455-3p, and suppressed PAK2 expression of liver tissue in mice. Taken together, our study suggests that HUC-MSCs inhibit the activation of HSCs and mouse CCl4-induced liver fibrosis by upregulation of miR-455-3p through targeting PAK2.

This study investigated potential imaging biomarkers for predicting the efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). A total of 59 PD patients and 50 healthy control subjects underwent high-resolution 3-dimensional T1-weighted brain magnetic resonance imaging. Bilateral STN volumes were compared between the 2 groups, and a correlation analysis was performed to assess the relationship between bilateral STN volumes or intracranial volume (ICV) and pre- or postoperative clinical scale scores. The results showed that the left STN volume differed significantly between PD patients and controls. In patients, the left STN volume was negatively correlated with pre- and postoperative quality of life scores and positively correlated with Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment scores; ICV was also positively correlated with the MMSE score. These findings indicate that changes in the left STN volume are a useful biomarker for evaluating the clinical outcome of PD patients following DBS.

The aim of this study was to investigate the therapeutic efficacy and safety of transplanting human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the treatment of cartilage injury. First, the articular cartilage defect model in rabbits was constructed. Then, the identified hUCB-MSCs and rabbit bone marrow stem cells (rBM-MSCs) were transplanted into the bone defect, respectively, and the cartilage repair effect was observed by hematoxylin-eosin (HE) staining and immunohistochemistry. Besides, the glycosaminoglycan (GAG) content and biomechanics of the restoration area were also evaluated. In our study, hUCB-MSCs and rBM-MSCs exhibited typical MSC characteristics, with positive expressions of CD73, CD105, and CD90 and negative for CD45, CD34, CD14, and HLA-DR. After the transplantation of hUCB-MSCs and rBM-MSCs, the overall quality of cartilage tissue was significantly improved, and the recipients did not show significant side effects in general. However, the expression of matrix metalloproteinase-13 (MMP-13) in the de novo tissues of the hUCB-MSCs and rBM-MSCs groups was both increased, indicating that the novel tissues may have some potential osteoarthritic changes. In conclusion, our results suggest the therapeutic effect of hUCB-MSCs transplantation in cartilage regeneration, providing a promising future in the clinical treatment of cartilage injury.

T cell exhaustion has been recognized to play an immunosuppressive role in malignant diseases. Persistent tumor antigen stimulation, the presence of inhibitory immune cells and cytokines in tumor microenvironment (TME), upregulated expression of inhibitory receptors, changes in T cell-related transcription factors, and metabolic factors can all result in T cell exhaustion. Strategies dedicated to preventing or reversing T cell exhaustion are required to reduce the morbidity from cancer and enhance the effectiveness of adoptive cellular immunotherapy. Here, we summarize the current findings of T cell exhaustion in hematological malignancies and chimeric antigen receptor T (CAR-T) immunotherapy, as well as the value of novel technologies, to inverse such dysfunction. Our emerging understanding of T cell exhaustion may be utilized to develop personalized strategies to restore antitumor immunity.

OBJECTIVES: We conducted the present study to identify novel hub candidate genes in the pathogenesis of type 2 diabetes mellitus (T2DM) and provide potential biomarkers or therapeutic targets for dealing with the disease. METHODS: We conducted weighted gene coexpression network analysis on a series of the expression profiles of the pancreas islet of T2DM patients obtained from the Gene Expression Omnibus database to construct a weighted coexpression network. After dividing genes into separated coexpression modules, we identified a T2DM-related module using Pearson's correlation analysis. Then, hub genes were identified from the T2DM-related module using the Maximal Clique Centrality method and validated by correlation analysis with clinical traits, differentially expressed gene analysis, validation in other datasets, and single-gene gene set enrichment analysis (GSEA). RESULTS: Genes were divided into 16 coexpression modules, and one module was identified as a T2DM-related module. Four hub candidate genes were identified, and MEDAG was a novel hub candidate gene. The expression level of MEDAG was positively correlated with hemoglobin A1c (HbA1c) and was evidently overexpressed in the pancreas islet tissue of T2DM patients compared with normal control. Analyses on two other datasets supported the results. GSEA verified that MEDAG plays essential roles in T2DM. CONCLUSIONS: MEDAG is a novel hub candidate of T2DM, and its irregular expression in the pancreas islet plays vital roles in the pathogenesis of T2DM. MEDAG is a potential target of intervention in the future for the treatment of T2DM.

Antiseptic wound ointments are widely used to treat dermal wounds that are microbially contaminated. Polygalacturonic acid (PG)+caprylic acid (CAP) is a novel combination that has been shown to eradicate biofilms. We developed a novel PG+CAP ointment and compared the biofilm eradication capability and cytotoxicity of PG+CAP with that of commercially available antiseptic wound ointments. We used a well-established biofilm model to quantitatively assess the eradication of organisms following exposure to the wound ointments for 2 hours. PG+CAP ointment completely eradicated Candida albicans, multidrug-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus biofilms, whereas MediHoney, polyhexamethylene biguanide (PHMB), and benzalkonium chloride (BZK) ointments failed to eradicate all biofilms within 2 hours. We assessed cytotoxicity by exposing L-929 fibroblasts to extracts of each ointment; Trypan blue exclusion was used to assess cell viability, and Alamar blue conversion was used to assess metabolic function. After exposure to PG+CAP and MediHoney, fibroblast viability was 96.23% and 95.23%, respectively (Trypan blue), and was comparable to untreated cells (98.77%). PHMB and BZK showed reduced viability (83.25% and 77.83%, respectively, p < 0.05). Metabolic activity results followed a similar pattern. Cytotoxicity of PG+CAP ointment towards erythrocytes was comparable to saline. PG+CAP ointment seems to be safe and can rapidly eradicate microbial biofilm; thus, PG+CAP ointment merits further in vivo testing as a potential antimicrobial wound ointment.

Drug- and herb-induced liver injury (DILI and HILI) is an increasingly common and serious condition. Here, data for DILI and HILI patients from two large tertiary hospitals were retrospectively analyzed. Patient characteristics, causes and severity of DILI and HILI, the correlation between expression of p62 and the severity of DILI and HILI, treatment of DILI and HILI, and the prognostic factors of DILI and HILI were studied. A total of 82 patients with DILI and HILI were recruited for the study. Most patients presented with hepatocellular injury, followed by cholestatic injury and mixed injury. Our results indicate that traditional Chinese medicine or herbal and dietary supplements were the prevalent causal agents of HILI, which was characterized by higher frequencies of hepatocellular injury. Expression of p62 in the liver correlated with the severity of DILI and HILI. Improvements in the results of the liver enzymatic tests correlated with alanine transaminase (ALT) levels upon the first diagnosis of DILI and HILI and with the hepatocellular type of DILI and HILI. In conclusion, we provide an epidemiological assessment of DILI and HILI based on causality using the updated RUCAM on patients from two hospitals in China. ALT levels at first diagnosis and the hepatocellular type of injury may be prognostic factors of DILI and HILI.

BACKGROUND: Giant congenital melanocytic nevi (GCMN) treatment remains controversial. While surgical resection is the best option for complete removal, skin shortage to reconstruct the skin defect remains an issue. We report a novel treatment using a high hydrostatic pressurization (HHP) technique and a cryopreservation procedure. However, cryopreservation may inhibit revascularization of implanted nevus tissue and cultured epidermal autograft (CEA) take. We aimed to investigate the influence of the cryopreservation procedure on the HHP-treated dermis specimen and CEA take on cryopreserved tissue. METHODS: Nevus tissue harvested from a patient with GCMN was inactivated with HHP of 200 MPa and then cryopreserved at -30°C for 28 days. The cryopreserved specimen was compared with fresh (HHP-treated without cryopreservation) tissue and with untreated (without HHP treatment) tissue to evaluate the extracellular matrix, basal membranes, and capillaries. Cultured epidermis (CE) take on the cryopreserved tissue was evaluated following implantation of the cryopreserved nevus tissue with CE into the subcutis of nude mice. RESULTS: No difference was observed between cryopreserved and fresh tissue in terms of collagen or elastic fibers, dermal capillaries, or basement membranes at the epidermal-dermal junction. In 4 of 6 samples (67%), applied CE took on the nevus tissues and regenerated the epidermis in the cryopreserved group compared with 5 of 6 samples (83%) in the fresh group. CONCLUSION: Cryopreservation at -30°C for 28 days did not result in significant damage to inactivated nevus tissue, and applied CE on the cryopreserved nevus tissues took and regenerated the epidermis. Inactivated nevus tissue with HHP can be used as a dermal substitute after 28-day cryopreservation.

Automated heart sound signal quality assessment is a necessary step for reliable analysis of heart sound signal. An unavoidable processing step for this objective is the heart sound segmentation, which is still a challenging task from a technical viewpoint. In this study, ten features are defined to evaluate the quality of heart sound signal without segmentation. The ten features come from kurtosis, energy ratio, frequency-smoothed envelope, and degree of sound periodicity, where five of them are novel in signal quality assessment. We have collected a total of 7893 recordings from open public heart sound databases and performed manual annotation for each recording as gold standard quality label. The signal quality is classified based on two schemes: binary classification ("unacceptable" and "acceptable") and triple classification ("unacceptable", "good," and "excellent"). Sequential forward feature selection shows that the feature "the degree of periodicity" gives an accuracy rate of 73.1% in binary SVM classification. The top five features dominate the classification performance and give an accuracy rate of 92%. The binary classifier has excellent generalization ability since the accuracy rate reaches to (90.4 ± 0.5) % even if 10% of the data is used to train the classifier. The rate increases to (94.3 ± 0.7) % in 10-fold validation. The triple classification has an accuracy rate of (85.7 ± 0.6) % in 10-fold validation. The results verify the effectiveness of the signal quality assessment, which could serve as a potential candidate as a preprocessing in future automatic heart sound analysis in clinical application.

BACKGROUND: In the United States, functional stress testing is the primary imaging modality for patients with stable symptoms suspected to represent coronary artery disease (CAD). Coronary computed tomography angiography (CTA) is excellent at identifying anatomic coronary artery disease (CAD). The application of computational fluid dynamics to coronary CTA allows fractional flow reserve (FFR) to be calculated noninvasively (FFRCT). The relationship of noninvasive stress testing to coronary CTA and FFRCT in real-world clinical practice has not been studied. METHODS: We evaluated 206 consecutive patients at Loyola University Chicago with suspected CAD who underwent noninvasive stress testing followed by coronary CTA and FFRCT when indicated. Patients were categorized by stress test results (positive, negative, indeterminate, and equivocal). Duke treadmill score (DTS), METS, exercise duration, and chest pain with exercise were analyzed. Lesions ≥ 50%stenosis were considered positive by coronary CTA. FFRCT < 0.80 was considered diagnostic of ischemia. RESULTS: Two hundred and six patients had paired noninvasive stress test and coronary CTA/FFRCT results. The median time from stress test to coronary CTA was 49 days. Average patient age was 60.3 years, and 42% were male. Of the 206 stress tests, 75% were exercise (70% echocardiographic, 26% nuclear, and 4% EKG). There were no associations of stress test results with CAD > 50% or FFRCT < 0.80 (p = 0.927 and p = 0.910, respectively). Of those with a positive stress test, only 30% (3/10) had CAD > 50% and only 50% (5/10) had FFRCT < 0.80. Chest pain with exercise did not correlate with CAD > 50% or FFRCT < 0.80 (p = 0.66 and p = 0.12, respectively). There were no significant correlations between METS, DTS, or exercise duration and FFRCT (r = 0.093, p = 0.274; r = 0.012, p = 0.883; and r = 0.034, p = 0.680; respectively). CONCLUSION: Noninvasive stress testing, functional capacity, chest pain with exercise, and DTS are not associated with anatomic or functional CAD using a diagnostic strategy of coronary CTA and FFRCT.

Type 2 diabetes (T2DM) epidemic is rising in Vietnam. Identifying associated factors with glycaemic control in patients with T2DM is vital to improve treatment outcomes. This study is aimed at examining the uncontrolled glycaemic level of patients with type 2 diabetes (T2DM) at an urban hospital in Hanoi, Vietnam, and determining associated factors. An observational longitudinal cohort survey was performed among T2DM patients. Glycaemic control was evaluated by using the HbA1c level ≥ 6.5% or fasting blood glucose level ≥ 7.5 g/mmol. Information about sociodemographic, clinical, and behavioral characteristics was collected. Multivariate mixed-effects logistic regression was employed to identify associated factors with control glycaemic level conditions. Among 189 T2DM patients, 70.4% had an uncontrolled glycaemic level. A higher number of comorbidities were associated with a lower likelihood of having uncontrolled glycaemic levels (OR = 0.71, p < 0.001, 95%CI = 0.52 - 0.98). Meanwhile, a higher body mass index (OR = 1.15, p < 0.05, 95%CI = 1.02 - 1.29), higher initial HbA1C (OR = 3.75, p < 0.01, 95%CI = 2.59 - 5.44), and higher initial fasting blood glucose levels (OR = 1.57, p < 0.01, 95%CI = 1.29 - 1.90) were positively associated with a higher risk of uncontrolled glycaemic levels. This study reveals that poor glycaemic control was common among T2DM patients in the urban hospital in Vietnam. Findings underlined the need for appropriate management strategies to control glycaemic levels and weight in this population.

INTRODUCTION: Oral lichen planus (OLP) is a chronic mucocutaneous disease. It is mainly an immune system-related disorder. Vitamins can modulate immune system functions, and thus, vitamin deficiency might have roles in exacerbating OLP. We aim to determine the serum levels of vitamins A, B12, C, D3, and E in OLP patients. METHODS AND MATERIALS: 34 OLP patients referred to Shiraz Dental School entered the study. Blood samples were collected and levels of A, B12, C, D3, and E vitamins were measured in serum. 43 healthy people were also included as the control group. Serum levels of vitamins were measured by HPLC (A, B12, D3, and E) and Kiazist analyzing kit (vitamin C). RESULTS: Most of the patients were female (62.3%), and the mean age of patients was 48.03 ± 11.57. Serum levels of vitamins A, C, and E were lower in OLP patients in comparison with the healthy group; however, the difference was not significant. Vitamins B12 and D3 were higher in the OLP group but the difference was not significant. CONCLUSION: Serum levels of vitamins A, B12, C, D3, and E do not have a significant difference in OLP patients and healthy groups. These vitamins may not have a considerable role in OLP pathogenesis in the southwest of Iran.

BACKGROUND: Active aging is aimed at promoting quality of life in older adults. Nevertheless, the relationship between physical role and the practice of physical activity (PA) can be influenced by bodily pain feeling and by a low level of health-related quality of life (HRQoL). Passive and active strategies are susceptible to being modified and constitute an important psychological predictor of adaptation to pain. This cross-sectional study (1) analyzed the differences between inactive/active older adult women in terms of clinical and sociodemographic characteristics, pain coping strategies, and HRQoL; (2) studied the associations between pain coping strategies, the dimensions of the HRQoL questionnaire, and physical role; and (3) determined if passive strategies, bodily pain, physical function, and general health were significant mediators in the link between being inactive/active and physical role. METHODS: Participants of the present cross-sectional study completed measures of clinical and sociodemographic characteristics, HRQoL using the Short-Form Health Survey-36, and active and passive strategies using the Vanderbilt Pain Management Inventory (VPMI). RESULTS: A total of 157 inactive (69.9 ± 7.1 years) and 183 active (68.8 ± 5.3 years) women from rural areas were included in the study. Both groups significantly differed in the majority of the clinical and sociodemographic characteristics measured, pain coping strategies, and HRQoL. Bodily pain, physical function, and general health predicted physical role. Moreover, passive strategies, bodily pain, physical function, and general health mediated the link between inactive/active participants and physical role. CONCLUSIONS: Being physically active or inactive contributes to a better understanding of the link between PA, pain coping strategies, and physical role in older women.

BACKGROUND: The optimal body mass index (BMI) and fat mass index (FMI) values for a positive change or the lowest risk of no positive change after high-intensity interval training (HIIT) using the Tabata protocol remain unclear. This study is aimed at establishing these optimal BMI and FMI values for the lowest risk of failure of aerobic performance in adolescents. METHODS: A 10-week HIIT programme was introduced into the physical education of 73 students. BMI was calculated using height and weight. Bioelectrical impedance analysis measured body fat, and the InBody apparatus generated the FMI. Based on BMI and FMI, the participants were divided into four groups. Pre- and post-HIIT intervention analyses were carried out using the Harvard step test, which was used to determine the physical efficiency index (PEI). RESULTS: The Youden index confirmed that the risk of no positive effects in PEI was the lowest for the second BMI interval (19.01-22.00 kg/m2) and FMI Q 2-3 (7.96-8.91 kg/m2). The optimal BMI value for the lowest risk of no change in PEI was 20.60 kg/m2, and the optimal FMI value was 8.84 kg/m2. CONCLUSION: A comparison of the two indices shows that FMI had stronger effects on PEI than BMI. In addition, the model obtained for FMI had higher accuracy. Identifying at-risk individuals, those in need of improving health-related fitness (H-RF), and those with a low risk of poor H-RF allows for efficient planning of individual intervention services and training programmes.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and has poor outcomes. However, the potential molecular biological process underpinning the occurrence and development of HCC is still largely unknown. The purpose of this study was to identify the core genes related to HCC and explore their potential molecular events using bioinformatics methods. HCC-related expression profiles GSE25097 and GSE84005 were selected from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) between 306 HCC tissues and 281 corresponding noncancerous tissues were identified using GEO2R online tools. The protein-protein interaction network (PPIN) was constructed and visualized using the STRING database. Gene Ontology (GO) and KEGG pathway enrichment analyses of the DEGs were carried out using DAVID 6.8 and KOBAS 3.0. Additionally, module analysis and centrality parameter analysis were performed by Cytoscape. The expression differences of key genes in normal hepatocyte cells and HCC cells were verified by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). Additionally, survival analysis of key genes was performed by GEPIA. Our results showed that a total of 291 DEGs were identified including 99 upregulated genes and 192 downregulated genes. Our results showed that the PPIN of HCC was made up of 287 nodes and 2527 edges. GO analysis showed that these genes were mainly enriched in the molecular function of protein binding. Additionally, KEGG pathway analysis also revealed that DEGs were mainly involved in the metabolic, cell cycle, and chemical carcinogenesis pathways. Interestingly, a significant module with high centrality features including 10 key genes was found. Among these, CDK1, NDC80, HMMR, CDKN3, and PTTG1, which were only upregulated in HCC patients, have attracted much attention. Furthermore, qRT-PCR also confirmed the upregulation of these five key genes in the normal human hepatocyte cell line (HL-7702) and HCC cell lines (SMMC-7721, MHCC-97L, and MHCC-97H); patients with upregulated expression of these five key genes had significantly poorer survival and prognosis. CDK1, NDC80, HMMR, CDKN3, and PTTG1 can be used as molecular markers for HCC. This finding provides potential strategies for clinical diagnosis, accurate treatment, and prognosis analysis of liver cancer.

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic with millions of infected patients. Alteration in humans' microbiota was also reported in COVID-19 patients. The alteration in human microbiota may contribute to bacterial or viral infections and affect the immune system. Moreover, human's microbiota can be altered due to SARS-CoV-2 infection, and these microbiota changes can indicate the progression of COVID-19. While current studies focus on the gut microbiota, it seems necessary to pay attention to the lung microbiota in COVID-19. This study is aimed at reviewing respiratory microbiota dysbiosis among COVID-19 patients to encourage further studies on the field for assessment of SARS-CoV-2 and respiratory microbiota interaction.

The existing studies have shown that miRNAs are related to human diseases by regulating gene expression. Identifying miRNA association with diseases will contribute to diagnosis, treatment, and prognosis of diseases. The experimental identification of miRNA-disease associations is time-consuming, tremendously expensive, and of high-failure rate. In recent years, many researchers predicted potential associations between miRNAs and diseases by computational approaches. In this paper, we proposed a novel method using deep collaborative filtering called DCFMDA to predict miRNA-disease potential associations. To improve prediction performance, we integrated neural network matrix factorization (NNMF) and multilayer perceptron (MLP) in a deep collaborative filtering framework. We utilized known miRNA-disease associations to capture miRNA-disease interaction features by NNMF and utilized miRNA similarity and disease similarity to extract miRNA feature vector and disease feature vector, respectively, by MLP. At last, we merged outputs of the NNMF and MLP to obtain the prediction matrix. The experimental results indicate that compared with other existing computational methods, our method can achieve the AUC of 0.9466 based on 10-fold cross-validation. In addition, case studies show that the DCFMDA can effectively predict candidate miRNAs for breast neoplasms, colon neoplasms, kidney neoplasms, leukemia, and lymphoma.

OBJECTIVE: Apoptotic events mediated by mitochondrial injury play an important role on the onset of Pemphigus vulgaris (PV). The thioredoxin-2 (Trx2)/apoptosis signal-regulating kinase 1 (ASK1) signaling pathway is considered a key cascade involved on the regulation of mitochondrial injury. Hence, we have investigated the regulatory mechanism of the Trx2/ASK1 signaling in PV-induced mitochondrial injury. METHODS: Serum and tissue samples were collected from clinical PV patients to detect the oxidative stress factors, cell apoptosis, and expression of members from Trx2/ASK1 signaling. HaCaT cells were cultured with the serum of PV patients and transfected with Trx2 overexpression or silencing vector. Changes in the levels of reactive oxygen species (ROS), mitochondrial membrane potential (△ψm), and apoptosis were further evaluated. A PV mouse model was established and administered with Trx2-overexpressing plasmid. The effect of ectopic Trx2 expression towards acantholysis in PV mice was observed. RESULTS: A series of cellular and molecular effects, including (i) increased levels of oxidative stress products, (ii) destruction of epithelial cells in the skin tissues, (iii) induction of apoptosis in keratinocytes, (iv) reduction of Trx2 protein levels, and (v) enhanced phosphorylation of ASK1, were detected in PV patients. In vitro experiments confirmed that Trx2 can inhibit ASK1 phosphorylation, alleviate ROS release, decrease △ψm, and lower the apoptotic rate. Injection of Trx2-overexpressing vectors in vivo could also relieve acantholysis and blister formation in PV mice. CONCLUSION: The Trx2/ASK1 signaling pathway regulates the incidence of PV mediated by mitochondrial injury.

OBJECTIVE: To develop and validate a sensitive and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of enasidenib in rat plasma and to investigate the effect of Xiao-ai-ping injection (XAPI) on the pharmacokinetics of enasidenib in rats. METHODS: The rat plasma was precipitated with acetonitrile, enasidenib and internal standard (IS) were separated on an Acquity UPLC BEH C18 column, and acetonitrile and 0.1% formic acid were used as the mobile phase in gradient mode. Enasidenib and IS were monitored and detected by multiple reaction monitoring (MRM) using tandem mass spectrometry in positive ion mode. 12 Sprague-Dawley (SD) rats were randomly divided into control group (group A) and experimental group (group B), 6 rats in each group. Group B was intramuscularly injected with XAPI (0.3 mL/kg) every morning, 7 days in a row. Group A was intramuscularly injected with normal saline, 7 days in a row. On the seventh day, enasidenib (10 mg/kg) was given to both groups 30 min after injection of normal saline (group A) or XAPI (group B), and the blood was collected at different time points such as 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 h. The concentration of enasidenib was detected by UPLC-MS/MS, and the main parameters of pharmacokinetic of enasidenib were calculated using the DAS 2.0 software. RESULTS: Under the current experimental conditions, this UPLC method showed good linearity in the detection of enasidenib. Interday and intraday precision did not exceed 10%, the range of accuracy values were from -1.43% to 2.76%. The results of matrix effect, extraction recovery, and stability met the requirements of FDA approval guidelines of bioanalytical method validation. The C max of enasidenib in the group A and the group B was (458.87 ± 136.02) ng/mL and (661.47 ± 107.32) ng/mL, t 1/2 was (7.74 ± 0.91) h and (8.64 ± 0.42) h, AUC(0 - t) was (4067.24 ± 1214.36) ng·h/mL and (5645.40 ± 1046.30) ng·h/mL, AUC(0 - ∞) was (4125.79 ± 1235.91) ng·h/mL and (5759.61 ± 1078.59) ng·h/mL, respectively. The C max of enasidenib in group B was 44.15% higher than that in group A, and the AUC(0 - t) and AUC(0 - ∞) of enasidenib in group B were 38.80% and 39.60% higher than that in group A, respectively, and the t 1/2 was prolonged from 7.74 h to 8.64 h. CONCLUSION: An UPLC-MS/MS method for the determination of enasidenib in rat plasma was established. XAPI can inhibit the metabolism of enasidenib and increase the concentration of enasidenib in rats. It is suggested that when XAPI was combined with enasidenib, the herb-drug interaction and adverse reactions should be paid attention to, and the dosage should be adjusted if necessary.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. METHODS: The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. RESULTS: WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in-silico softwares. CONCLUSION: Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.

Psoriasis is an inflammatory skin disease with substantial morbidity. Numerous patients with psoriasis experience recurrence after therapy. The underlying mechanism about psoriasis is still not fully understood. Some evidences suggest that innate immunity may play an unexpected and important role in active severe psoriasis. In this work, the deconvolution algorithm CIBERSORT was conducted to identify the infiltration of innate immune cells and related core genes in psoriatic plaque. Datasets from the Gene Expression Omnibus, including skin samples from 405 psoriasis patients and 91 healthy donors, were downloaded for analysis. Considerable differences of the innate immune cell composition were uncovered between psoriatic plaque and control skin. Results revealed that γδ T cells, resting NK cells, M0 macrophages, M1 macrophages, activated dendritic cells, and neutrophils were significantly increased in psoriatic skin, while resting mast cells and active NK cells were significantly decreased. Moreover, the proportion of M0 macrophages or resting mast cells was found to be associated with disease severity. Spearman correlation analysis suggests that RORC and S100A12 genes were related to disease severity, while genes including S100A12, CLEC4C, IL-19, AIM2, IL-17F, and PPARGC1A were correlated with biologic treatment response. In conclusion, this work displays innate immune status in psoriatic skin and provides novel clues for clinical decisions and mechanism study.

Acrylamide (AA) formation in starch-based processed foods at elevated temperatures is a serious health issue as it is a toxic and carcinogenic substance. However, the formation of more AA entangles with modern-day fast food industries, and a considerable amount of this ingredient is being consumed by fast food eaters inadvertently throughout the world. This article reviews the factors responsible for AA formation pathways, investigation techniques of AA, toxicity, and health-related issues followed by mitigation methods that have been studied in the past few decades comprehensively. Predominantly, AA and hydroxymethylfurfural (HMF) are produced via the Maillard reaction and can be highlighted as the major heat-induced toxins formulated in bread and bakery products. Epidemiological studies have shown that there is a strong relationship between AA accumulation in the body and the increased risk of cancers. The scientific community is still in a dearth of technology in producing AA-free starch-protein-fat-based thermally processed food products. Therefore, this paper may facilitate the food scientists to their endeavor in developing mitigation techniques pertaining to the formation of AA and HMF in baked foods in the future.

BACKGROUND: Clausena excavata Burum. f. has long been applied in ethnomedicine for the treatment of various disorders like rhinitis, headache, cough, wound healing, fever, and detoxification. This study is aimed at investigating the antibacterial activity against Enterococcus faecalis ATCC 49532 using AlamarBlue assay and atomic force microscopy (AFM) as well as the cytotoxicity, anticancer, and phytotoxicity of C. excavata. METHOD: Bacterial cell viability was performed by using microplate AlamarBlue assay. Atomic force microscopy was used to determine morphological changes in the surface of bacterial cells. Cytotoxicity and phytotoxicity were determined by brine shrimp lethality and Lemna minor bioassay. Caco-2 (colorectal adenocarcinoma) cell line was used for the evaluation of the anticancer effects. RESULT: Among the fractions tested, ethyl acetate (EA) fraction was found to be active with minimum inhibitory concentration (MIC) of 750 μg/mL against E. faecalis, but other fractions were found to be insensitive to bacterial growth. Microscopically, the EA fraction-treated bacteria showed highly damaged cells with their cytoplasmic content scattered all over. The LC50 value of the EA fraction against brine shrimp was more than 1000 μg/mL showing the nontoxic nature of this fraction. Chloroform (CH), EA, and methanol (MOH) fractions of C. excavata were highly herbicidal at the concentration of 1000 μg/mL. EA inhibited Caco-2 cell line with an IC50 of 20 μg/mL. CONCLUSIONS: This study is the first to reveal anti-E. faecalis property of EA fraction of C. excavata leaves, natural herbicidal, and anticancer agents thus highlight the potential compound present in its leaf which needs to be isolated and tested against multidrug-resistant E. faecalis.

Preoperative evaluation of hepatic functional reserve in patients with hilar cholangiocarcinoma (hCCA) has vital clinical significance for prevention of posthepatectomy liver failure (PHLF) and mortality. The aim of the present study was to evaluate the clinical significance of the indocyanine green retention rate at 15 minutes (ICG R15) and related factors of postoperative outcomes in patients with hCCA. 147 patients who scheduled for hCCA resection underwent a preoperative ICG test between May 2015 and May 2020 and were prospectively analyzed. Single-factor analysis was used to evaluate the risk factors for PHLF and postoperative outcomes in hCCA. After univariate analysis, significant differences in ICG R15 were found between the PHLF group and the liver function recovered well (LFRW) group (P ≤ 0.05). In terms of postoperative complications, ICG R15 was also a risk factor for moderate-to-severe postoperative complications. Preoperative ICG R15 was significantly associated with PHLF and moderate-to-severe postoperative complications. ICG R15 may become an ideal clinical indicator for the evaluation of liver function reserve before hCCA and can better predict the postoperative complications.

An increase of steroid hormones in controlled ovarian hyperstimulation (COH) procedures is reducing the success rate in assisted reproductive technology (ART), and this includes the pregnancy rate and/or implantation rate. Research has found that the decrease in the success rate occurred due to the decreased expression of the protein that is needed to prepare the endometrium so that the embryo could attach. The aim of the study was to analyse the changes in E-chaderin expression due to COH and its relations with increased level of steroid hormones as one of the proteins in the endometrium. There were 13 samples of stored biological tissue from Macaca nemestrina endometrial tissue; came from one group of natural cycles as the control group (n = 4) and three groups of stimulated cycles. The first stimulated cycle group was injected by a 30 IU dose of rFSH (n = 2). The second stimulated cycle group was injected by a 50 IU dose of rFSH (n = 4). The third stimulated cycle group was injected by a 70 IU dose of rFSH (n = 3). The expression of E-cadherin was measured by the immunohistochemistry (IHC) technique. Estradiol (E2) and progesterone (P4) levels were assessed using ELISA and have already been done. The IHC staining expression of E-cadherin was found in the cytoplasm of glandular epithelium. Immunostaining measurement used the H_SCORE. We found that the expression of E-cadherin within the group was not significantly different (p value: 0.178). Similarly, both the correlation between the estradiol level with E-cadherin and the correlation between the progesterone level with E-cadherin were not significantly different (p value: 0.872 and p value: 0.836). The conclusion is that the level of E-Cadherin expression in the endometrium that were taken in themiddle secretion phase not affected by the dose regimen that given. In addition, the level of expression is not influenced by the increase of serum E2 and P4 levels.

BACKGROUND: Hepatocellular carcinoma (HCC), one of the most common primary malignancies, is theoretically an epitope candidate for immune checkpoint inhibitors, and therefore, the identification of HCC biomarkers is important. Structure-specific recognition protein 1 (SSRP1) is involved in almost all chromatin-related processes, including DNA replication, repair, and transcription. However, its role in HCC remains to be elucidated. METHODS: This study investigated the expression of SSRP1 in HCCDB, Oncomine, HPA, and other databases. The prognostic value of SSRP1 in HCC and its relationship with clinical characteristics were then explored using Kaplan-Meier plotter. At the same time, SSRP1 coexpression genes were explored and functionally annotated in the LinkedOmics database. Finally, the correlation between the SSRP1 expression and HCC immune cell infiltration was explored in TIMER and online single-cell sequencing database. RESULTS: Significantly elevated transcriptional and proteomic SSRP1 expressions were found in HCC. Increased SSRP1 mRNA expression was significantly correlated with relevant clinicopathological parameters such as immune cells. Notably, the SSRP1 expression was positively correlated with the infiltration levels of Treg and CD8+ T cells, especially exhausted CD8+ T cells. Interestingly, the SSRP1 expression was higher in both tumor Treg and exhausted CD8+ T cells than in adjacent tissues. CONCLUSION: SSRP1, as a new prognostic marker for HCC, promotes HCC development by influencing the infiltration of depleted CD8+ T cells and may influence the effect of immunotherapy.

Barley landraces is among the major cereal crops grown in Ethiopian highlands including Bale highlands. However, in recent days, the crop is highly declining to the extents of total loss. This study was, therefore, aimed at assessing the extents of its on-farm diversity and genetic erosion from Bale highlands, Ethiopia. Data were generated from twelve administrative districts and analyzed considering important ecological and genetic erosion models. A total of 25 distinct (at least in naming) barley landraces with varying distribution patterns have been identified in the areas. Landrace richness (R) revealed higher magnitude among all the study districts, the smallest being 2.02 (D Mg) and 1.41 (D Mn) and considerable range of variations (D Mg = 2.02 to 5.02, D Mn = 1.41 to 3.17). Among the study districts, Dinsho consisted the highest on-farm diversity estimate (D Mg = 5.02, D Mn = 3.17) followed by Goba and Sinana (D Mg = 4.50 and 3.97; D Mn = 2.87 and 2.57 in that order). Estimate of the landrace evenness (E) also showed the highest magnitude (>0.95) except in Agarfa district (0.77). The result suggests potentiality of the areas and wide cultivation of majority of the landraces in the villages. However, nowadays, only 14 landraces are under cultivation and the remaining 11 are totally eroded from the district(s) constituting the highest (56.0%) combined genetic erosion suggesting loss of important agronomic traits and, thus, a major bottleneck for further improvement and conservation plans. Thus, attention should be payed to conserving the landraces for better further use.

Ischemia-reperfusion- (IR-) induced kidney injury is difficult to avoid during renal transplantation and robot-assisted partial nephrectomy. Renal IR injury is characterized by tubular damage, microcirculation failure, and inflammation, which coordinately augment renal injury; however, no specific treatment is available for these conditions. Protease-activated receptor-1 (PAR-1) and its ligand, thrombin, are involved in coagulation and were shown to be associated with epithelial cell injury. Here, we hypothesized that PAR-1 exaggerated renal IR-induced tubular cell damage and microcirculation failure and that pharmacological inhibition of PAR-1 by Q94 could prevent these injuries. Renal warm IR increased the expression of PAR-1 in the renal tubules. Q94 attenuated renal IR-induced changes and histopathological damage. Microcirculation failure analyzed by congestion in the histopathology and blood cell flow examined by intravital multiphoton microscopy were suppressed by Q94 treatment. Q94 also dramatically increased tubular cell proliferation despite the lower renal damage. Thrombin suppressed cell proliferation and induced apoptosis in the tubules; these effects were prevented by Q94 treatment. Taken together, PAR-1 was associated with renal IR injury. Inhibition of PAR-1 ameliorated injury possibly by improving renal microcirculation and tubular cell survival/proliferation.

Nutraceuticals have taken on considerable significance due to their supposed safety and possible nutritional and medicinal effects. Pharmaceutical and dietary companies are conscious of monetary success, which benefits healthier consumers and the altering trends that result in these heart-oriented value-added products being proliferated. Numerous nutraceuticals are claimed to have multiple therapeutic benefits despite advantages, and unwanted effects encompass a lack of substantial evidence. Several common nutraceuticals involve glucosamine, omega-3, Echinacea, cod liver oil, folic acid, ginseng, orange juice supplemented with calcium, and green tea. This review is dedicated to improving the understanding of nutrients based on specific illness indications. It was reported that functional foods contain physiologically active components that confer various health benefits. Studies have shown that some foods and dietary patterns play a major role in the primary prevention of many ailment conditions that lead to putative functional foods being identified. Research and studies are needed to support the possible health benefits of different functional foods that have not yet been clinically validated for the relationships between diet and health. The term "functional foods" may additionally involve health/functional health foods, foods enriched with vitamins/minerals, nutritional improvements, or even conventional medicines.

INTRODUCTION: Cancer is the second leading cause of death worldwide. Breast cancer is the second most common cause of cancer-related mortality, accounting for 11.6% of the total number of deaths. The main treatments for this disease are surgical removal of the tumor, radiotherapy, and chemotherapy. Recently, different minimally invasive technologies have been applied (e.g., emission of electromagnetic waves, thermal and chemical means) to overcome the important side effects of these treatment modalities. The objective of this study was to develop and evaluate a predictive computational model of microwave ablation. MATERIALS AND METHODS: The predictive computational model of microwave ablation was constructed by means of a dual-slot coaxial antenna. The model was compared with an experiment performed using a breast phantom, which emulates the dielectric properties of breast tissue with segmental microcalcifications. The standing wave ratio (SWR) was obtained for both methods to make a comparison and determine the feasibility of applying electromagnetic ablation to premalignant lesions in breasts. Specifically, for the analysis of segmental microcalcifications, a breast phantom with segmental microcalcifications was developed and two computational models were performed under the same conditions (except for blood perfusion, which was excluded in one of the models). RESULTS: The SWR was obtained by triplicate experiments in the phantom, and the measurements had a difference of 0.191 between the minimum and maximum SWR values, implying a change of power reflection of 0.8%. The average of the three measurements was compared with the simulation that did not consider blood perfusion. The comparison yielded a change of 0.104, representing a 0.2% change in power reflection. Discussion. Both experimentation in phantom and simulations demonstrated that ablation therapy can be performed using this antenna. However, an additional optimization procedure is warranted to increase the efficiency of the antenna.

Hypertension develops in the recipient rats that are transferred with the activated T helper (Th) 17 cells of the donor rats exposed to high-fructose or high-salt intake. This result suggests that a pathologic Th17 cell plays a role in the development and maintenance of hypertension. Here, we tested the hypothesis that the transfer of Th17 cells from adult spontaneous hypertensive rats (SHR) accelerates the development of hypertension in juvenile SHR. The tail-cuff method was used to measure systolic blood pressure. T cell (Th17 and regulatory T (Treg)) profiling was analyzed by flow cytometry. The expressions of Th17-related interleukin- (IL-) 17A and Treg-related IL-10 were measured by ELISA. Th17 cells isolated from adult SHR were intraperitoneally injected into juvenile recipient SHR and Wistar-Kyoto rats (WKY). SHR exhibited prominent development of hypertension at 15 weeks. The proportion of CD4+IL-17A+ (Th17) cells among Th cells increased whereas the proportion of CD4+FoxP3+ (Treg) cells decreased in SHR, as compared to WKY. The serum levels of IL-17A increased gradually with aging in SHR, but the serum levels of IL-10 did not. The serum levels of IL-17A and IL-10 seemed to be well related to the proportion of Th17 cells and Treg cells, respectively. Injection of Th17 cells isolated from adult SHR accelerates the development of hypertension in juvenile SHR but not in juvenile WKY though it increased the proportion of Th17 cells in juvenile recipient WKY and SHR. The transfer of Th17 cells from adult SHR accelerates the development of hypertension in juvenile SHR. These results implicate that the hypertension in SHR is ascribed to activation of Th17 cells.

A recent population cohort study reported that benign paroxysmal positional vertigo (BPPV) was a risk factor for ischemic stroke. This study investigated the risk of ischemic and hemorrhagic strokes in patients with BPPV. A nested case-control study used the data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013. We used data of patients aged ≥50 years obtained from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013. A total of 15,610 patients with ischemic stroke and 4,923 patients with hemorrhagic stroke were matched for age, sex, income, residential location, hypertension, diabetes, and dyslipidemia with 62,440 and 19,692 controls, respectively. History of BPPV was evaluated in the stroke and control groups. Crude and adjusted odds ratios (ORs) for stroke in patients with BPPV were analyzed using stratified logistic regression analysis. Subgroup analyses were performed for age and sex. Notably, 3.7% (572/15,610) of patients with ischemic stroke and 2.7% (1,702/62,440) of the control subjects reported a history of BPPV (P < 0.001). The adjusted OR for BPPV in patients with ischemic stroke was 1.35 (95% confidence interval (CI) 1.22-1.49, P < 0.001). Patients with ischemic stroke showed higher ORs for BPPV in the subgroup of women. Patients with hemorrhagic stroke did not show a high OR for BPPV. Ischemic stroke patients demonstrated the increased OR for BPPV in subjects aged ≥50 years old.

INTRODUCTION: Valproic acid is a medication most commonly used in the treatment of emotional and neurological depression, psychological imbalances, epilepsy, and bipolar disorder. Dark honey, like thyme honey, contains more antioxidant compounds than other samples. The purpose of this study was to evaluate the effect of thyme honey on the potential hepatic effects of valproic acid. METHODS: In this study, 48 male rats were randomly divided into 8 groups (n = 6): G1 (control): healthy rats (normal saline 0.9%), G2: thyme honey (1 g/kg), G3: thyme honey (2 g/kg dose), G4: thyme honey (3 g/kg dose), G5: VPA (500 mg/kg), G6: VPA (500 mg/kg) and thyme honey (1 g/kg), G7: VPA (500 mg/kg) and thyme honey (2 g/kg dose), and G8: VPA (500 mg/kg) and thyme honey (3 g/kg dose). Groups G1 to G5 received the drug for 28 days. On day 14, administration of thyme honey for G6 to G8 groups was carried out using gavage until day 28. VPA was administered one hour after honey. To carry out the biochemical evaluation, blood samples were collected from all the groups and their serums were used for MDA, TAC, and liver enzymes (AST, ALT, and GGT). Tissue samples of each rat were also removed for histological studies with hematoxylin-eosin and Masson's trichrome staining. RESULTS: The use of thyme honey significantly improved the histopathological parameters of the liver tissue, including hypertrophic degeneration and nucleus alteration, expansion of sinusoids, fibrosis and hepatic necrosis, and inflammation as well as hypertrophy of Kupffer cells. In the groups receiving VPA, the rate of lipid peroxidation increased, which indicates the destruction of the liver cell membrane due to drug consumption. TAC levels also increased following increase in thyme honey dosage (p ≤ 0.05). The results of liver enzyme analysis showed a decrease in AST and ALT levels in the G6 group and a decrease in GGT level in the G8 group (p ≤ 0.05). CONCLUSION: Based on the results of this study, it seems that high percentage of antioxidants in thyme honey enabled it to improve hepatic complications and reduce the rate of hepatocellular destruction.

BACKGROUND: A prediction model can be developed to predict the risk of cancer-related cognitive impairment in colorectal cancer patients after chemotherapy. METHODS: A regression analysis was performed on 386 colorectal cancer patients who had undergone chemotherapy. Three prediction models (random forest, logistic regression, and support vector machine models) were constructed using collected clinical and pathological data of the patients. Calibration and ROC curves and C-indexes were used to evaluate the selected models. A decision curve analysis (DCA) was used to determine the clinical utility of the line graph. RESULTS: Three prediction models including a random forest, a logistic regression, and a support vector machine were constructed. The logistic regression model had the strongest predictive power with an area under the curve (AUC) of 0.799. Age, BMI, colostomy, complications, CRA, depression, diabetes, QLQ-C30 score, exercise, hypercholesterolemia, diet, marital status, education level, and pathological stage were included in the nomogram. The C-index (0.826) and calibration curve showed that the nomogram had good predictive ability and the DCA curves indicated that the model had strong clinical utility. CONCLUSIONS: A prediction model with good predictive ability and practical clinical value can be developed for predicting the risk of cognitive impairment in colorectal cancer after chemotherapy.

Echocardiography represents a first level technique for the evaluation of coronary artery disease (CAD) which supports clinicians in the diagnostic and prognostic workup of these syndromes. However, visual estimation of wall motion abnormalities sometimes fails in detecting less clear or transient myocardial ischemia and in providing accurate differential diagnosis. Speckle tracking echocardiography (STE) is a widely available noninvasive tool that could easily and quickly provide additive information over basic echocardiography, since it is able to identify subtle myocardial damage and to localize ischemic territories in accordance to the coronary lesions, obtaining a clear visualization with a "polar map" useful for differential diagnosis and management. Therefore, it has increasingly been applied in acute and chronic coronary syndromes using rest and stress echocardiography, showing good results in terms of prediction of CAD, clinical outcome, left ventricular remodeling, presence, and quantification of new/residual ischemia. The aim of this review is to illustrate the current available evidence on STE usefulness for the assessment and follow-up of CAD, discussing the main findings on bidimensional and tridimensional strain parameters and their potential application in clinical practice.

INTRODUCTION: Hemorrhagic transformation (HT) is one of the most common complications of ischemic stroke which is exacerbated by hyperglycemia. Oxidative stress, inflammatory response, and matrix metalloproteinases (MMPs) have been evidenced to play a vital role in the pathophysiology of HT. Our previous study has reported that 17-DMAG, an Hsp90 inhibitor, protects the brain against ischemic injury via inhibiting inflammation and reducing MMP-9 after ischemia. However, whether 17-DMAG would attenuate HT in hyperglycemic middle cerebral artery occlusion (MCAO) rats is still unknown. METHODS: Acute hyperglycemia was induced by an injection of 50% dextrose. Rats were pretreated with 17-DMAG before MCAO. Infarction volume, hemorrhagic volume neurological scores, expressions of inflammatory molecules and tight junction proteins, and activity of MMP-2 and MMP-9 were assessed 24 h after MCAO. RESULTS: 17-DMAG was found to reduce HT, improve neurological function, and inhibit expressions of inflammatory molecules and the activation of MMPs at 24 h after MCAO. CONCLUSION: These results implicated that Hsp90 could be a novel therapeutic target in HT following ischemic stroke.

OBJECTIVE: Enterococcus faecalis and Streptococcus salivarius are the most important species in dental decay and producing biofilm. Treatment with chlorhexidine 2% mouthwash for 7 days is the best way to eliminate these bacteria. However, due to the ability of these bacteria to survive in harsh environments, increasing emergence of bacterial resistance against available antibiotics, and favorable properties of nanoparticles including broad spectrum antimicrobial activity and lower toxicity, we decided to evaluate reducing biofilm forming bacteria in oral cavity by bismuth nanoparticles. MATERIALS AND METHODS: This was a cross-sectional study of 40 samples isolated from the patients visiting dental clinics in Shiraz in 2019. Samples, which showed growth, were cultured on blood agar plates and incubated for the PCR procedure. Nanoparticle powder was dissolved in high-purity water, and the final concentration of bismuth nanoparticles (BiNPs) was measured with a spectrophotometer. Minimum inhibitory concentration (MIC) of BiNPs against E. faecalis and S. salivarius was determined by the microbroth dilution method according to methods for antimicrobial susceptibility tests. Also, bactericidal assays were conducted in a Mueller-Hinton broth medium and reported as the concentration of BiNPs that reduced the viable bacterial count by 99.9%. Statistical analysis was carried out using SPSS 21 and one-way analysis of variance, and P values less than 0.05 were considered significant. RESULTS: MICs of BiNP suspension against Streptococcus salivarius and Enterococcus faecalis were 2.5 and 5 μg/ml, respectively. Minimum bactericidal concentrations (MBC) of BiNP suspension against Streptococcus salivarius and Enterococcus faecalis were 5 and 10 μg/ml, respectively. Antibacterial activity of BiNPs was compared with chlorhexidine 2%. MICs of BiNPs against Streptococcus salivarius and Enterococcus faecalis were one-twentieth less than those of chlorhexidine. MBC of BiNPs against both pathogens was one-tenth less than those of chlorhexidine. CONCLUSION: BiNPs were more effective than chlorhexidine, and MIC and MBC of bismuth nanoparticles are lower than those of chlorhexidine.

OBJECTIVE: Osteoarthritis (OA) is the most common degenerative joint disease, causing joint pain, stiffness, and even disability. Guidelines recommend intra-articular injections as an alternative treatment to relieve OA symptoms for patients who demonstrate poor tolerability or compliance to oral administration of drugs. Mesenchymal stem cells (MSCs) are a potential treatment for of OA. We conducted this network meta-analysis to comprehensively compare the efficacy and safety between hyaluronic acid (HA), corticosteroids (GCs), platelet-rich plasma (PRP), and MSCs. DESIGN: Systematic review and Bayesian network meta-analysis. Data Sources. Relevant studies, published from January 2000 to January 2020, in the PubMed, Cochrane library, EMBASE, and CKNI databases. METHODS: Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement, improvement in joint stiffness, and risk of adverse effects (AEs) were assessed. RESULTS: Twenty-five articles with 4642 patients were included. Overall, MSC therapy was the most effective treatment for pain relief (standardized mean difference compared with placebo = 3.61, 95% CI [1.87 to 5.35]). Both MSC and PRP therapies improved every symptom of OA effectively and have an advantage over HA and GCs which are recommended by guidelines. MSCs, PRP, HA, and GCs are tolerated well for patients in long-term treatment of OA compared with placebo. CONCLUSIONS: The results show that MSCs relieve pain, stiffness, and dysfunction due to OA better than PRP, HA, and GCs and are not statistically correlated with greater safety concerns. More high-quality trials are needed to reconfirm the findings of this study, however, standardization of preparation of MSCs and PRP should be investigated in the future.

OBJECTIVE: To evaluate the efficiency of a radiomics model in predicting the prognosis of patients with acute paraquat poisoning (APP). MATERIALS AND METHODS: Chest computed tomography images and clinical data of 80 patients with APP were obtained from November 2014 to October 2017, which were randomly assigned to a primary group and a validation group by a ratio of 7 : 3, and then the radiomics features were extracted from the whole lung. Principal component analysis (PCA) and least absolute shrinkage and selection operator (LASSO) regression were used to select the features and establish the radiomics signature (Rad-score). Multivariate logistic regression analysis was used to establish a radiomics prediction model incorporating the Rad-score and clinical risk factors; the model was represented by nomogram. The performance of the nomogram was confirmed by its discrimination and calibration. RESULT: The area under the ROC curve of operation was 0.942 and 0.865, respectively, in the primary and validation datasets. The sensitivity and specificity were 0.864 and 0.914 and 0.778 and 0.929, and the prediction accuracy rates were 89.5% and 87%, respectively. Predictors included in the individualized predictive nomograms include the Rad-score, blood paraquat concentration, creatine kinase, and serum creatinine. The AUC of the nomogram was 0.973 and 0.944 in the primary and validation datasets, and the sensitivity and specificity were 0.943 and 0.955, respectively, in the primary dataset and 0.889 and 0.929 in the validation dataset, and the prediction accuracy was 94.7% and 91.3%, respectively. CONCLUSION: The radiomics nomogram incorporates the radiomics signature and hematological laboratory data, which can be conveniently used to facilitate the individualized prediction of the prognosis of APP patients.

[This retracts the article DOI: 10.1155/2015/134027.].

Gastric cancer is one of the most prevalent human cancers with poor prognosis. Trastuzumab is a well-used targeted drug for gastric cancer with HER2 amplification. Trastuzumab resistance restrains the clinical use of trastuzumab. In this study, we reported human Gse1 coiled-coil protein (GSE1) promoted trastuzumab resistance in HER2-positive gastric cancer cells. Acquired trastuzumab-resistant gastric cancer cells overexpressed GSE1, and depletion of GSE1 decreased the trastuzumab resistance of trastuzumab-resistant gastric cancer cells. BCL-2 was a downstream gene positively regulated by GSE1 and also performed promoting the role of trastuzumab resistance in HER2-positive gastric cancer cells. A high level of GSE1 was associated with a high risk of tumor lymph node metastasis and higher clinical stage in HER2-positive gastric cancer patients. GSE1 was a potential target that could be used for HER2-positive gastric cancer therapy.

Circular RNAs are a class of RNAs with a covalently closed configuration, and several members of them have been reported to be capable of regulating various biological processes and predicting the outcome of disease. Among them, circular RNA circ-ITCH has been identified to be aberrantly expressed and associated with disease progression in diverse cancers. However, the correlation of circ-ITCH expression with clinicopathological features, as well as the prognosis of cancers, remains inconclusive. Therefore, a meta-analysis was performed to investigate the clinical significance of circ-ITCH in cancers by systematically summarizing all eligible literatures. Up to August 31, 2020, relevant articles were searched in PubMed, Web of Science, Cochrane library, Embase, CNKI, and Wanfang databases. Pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. A total of 1604 patients from 14 studies were included in this meta-analysis. The results showed that cancer patients with low circ-ITCH expression were more susceptible to develop lymph node metastasis (OR = 2.25, 95% CI: 1.67-3.02, p ≤ 0.01), larger tumor size (OR = 3.01, 95% CI: 2.01-4.52, p ≤ 0.01), advanced TNM stage (OR = 2.82, 95% CI: 1.92-4.14, p ≤ 0.01), and poor overall survival (OS) (HR = 2.45, 95% CI: 2.07-2.90, p ≤ 0.01, univariate analysis; HR = 2.69, 95% CI: 1.82-3.96, p ≤ 0.01, multivariate analysis). Thus, low circ-ITCH expression was significantly associated with aggressive clinicopathological features and unfavorable outcome in various cancers. Therefore, circ-ITCH may serve as a molecular therapy target and a prognostic marker in human cancers.

OBJECTIVE: This work analyzes the role of versican (VCAN) on bladder cancer (BLCA). Versican (VCAN) is a chondroitin sulfate proteoglycan which is important for tumorigenesis and the development of cancer. However, the expression of VCAN on human bladder cancer (BLCA) has been rarely reported. METHODS: The clinical significance of VCAN in BLCA has been determined by our bioinformatics tools. Then, we performed immunohistochemical staining (IHC) and analyzed the correlation between VCAN expression and clinicopathological features. RESULTS: The bioinformatics results reveal that a high VCAN mRNA level was significantly associated with stage, histological subtype, molecular subtype, and metastasis in BLCA. Furthermore, IHC reveals that expression of VCAN was significantly correlated with the number of tumors, invasion depth, lymph node metastasis, distant metastasis, and histological grade. Kaplan-Meier survival analysis reveals that patients with a high expression of VCAN have poor prognosis than those patients with a low expression of VCAN. According to our result from the bioinformatics database, the mechanism of VCAN in BLCA revealed that VCAN was related to FBN1 and genes of the ECM remodeling pathway (MMP1, MMP2). CONCLUSION: VCAN expression might be included in the process of carcinogenesis and prognosis. Hence, VCAN could be a reliable biomarker of the clinical prognosis on BLCA.

Age-related macular degeneration (AMD) is an eye disease that impairs the sharp and central vision need for daily activities. Recent advances in molecular biology research not only lead to a better understanding of the genetics and pathophysiology of AMD but also to the development of applications based on targeted gene expressions to treat the disease. Clarification of molecular pathways that causing to development and progression in dry and wet types of AMD needs comprehensive and comparative investigations in particular precious biopsies involving peripheral blood samples from the patients. Therefore, in this investigation, dry and wet types of AMD patients and healthy individuals were aimed at investigating in regard to targeted gene candidates by using gene expression analysis for the first time. 13 most potent candidate genes involved in neurodegeneration were selected via in silico approach and investigated through gene expression analysis to suggest new targets for disease therapy. For the analyses, 30 individuals (10 dry and 10 wet types AMD patients and 10 healthy people) were involved in the study. SYBR-Green based Real-Time PCR analysis was performed on isolated peripheral blood mononuclear cells (PBMCs) to analyze differentially expressed genes related to these cases. According to the investigations, only the CRP gene was found to be upregulated for both dry and wet disease types. When the downregulated genes were analyzed, it was found that 11 genes were commonly decreased for both dry and wet types in the aspect of expression pattern. From these genes, CFH, CX3CR1, FLT1, and TIMP3 were found to have the most downregulated gene expression properties for both diseases. From these results, it might be concluded that these common upregulated and downregulated genes could be used as targets for early diagnosis and treatment for AMD.

Orthotic bracing and minimally invasive surgery are currently the treatment methods for pectus carinatum. We present our experience with the advantages, method selection criteria, and precautions for both treatment methods. A total of 767 pediatric patients (596 boys and 171 girls) with pectus carinatum were retrospectively analyzed. All of them received orthotic bracing, and 108 pediatric patients received minimally invasive surgery, achieving good outcomes. Among the 767 pediatric patients, 644 obtained satisfactory chest appearance through orthotic bracing, with a success rate of 84.0%. Younger pediatric patients had better orthotic outcomes. Among the 123 failure cases, 108 pediatric patients underwent minimally invasive surgery as the treatment. Seventy-six pediatric patients with simple chondrogladiolar prominence underwent a minimally invasive sternal depression procedure, whereas 32 pediatric patients with complex chondromanubrial prominence underwent surgery. All 108 pediatric patients successfully completed the surgery. The operation time was 112.8 ± 23.5 min, and the average length of hospital stay after the surgery was 7 days. A follow-up was conducted for at least 3 months and up to 3 years. The orthotic effect was satisfactory. For younger pediatric patients with pectus carinatum, noninvasive orthotic bracing treatment should be considered first. For older pediatric patients, the failure rate of the bracing was higher, and the outcomes were often unsatisfactory. Especially for patients over 15 years old, minimally invasive sternal depression may be the preferred treatment for pectus carinatum.

The spread of drug-resistant bacteria via food has contributed to the dissemination of resistant bacteria among humans. However, the status of food contamination with resistant bacteria, particularly the quantitative level of resistant bacteria in food, has not yet been well elucidated. In this study, the abundance of colistin-resistant Escherichia coli in meat samples was quantified to understand the origin of the contamination of meat available in local Vietnamese markets. Fifteen samples each of chicken and pork meat purchased from local Vietnamese markets were assessed for the presence of colistin-resistant E. coli with the mobile colistin resistance gene, mcr. The results showed that 40% (6/15) and 66% (10/15) of the pork and chicken meat samples, respectively, were contaminated with colistin-resistant E. coli. The median quantitative levels of colistin-resistant E. coli in the contaminated pork and chicken samples were 1.8 × 104 and 4.2 × 103 CFU/g, respectively. The results of phylogenetic analysis of isolates from a chicken meat sample showed that the contaminated colistin-resistant E. coli was a mix of multiple phylogenetical clones of bacteria that may have multiplied during sale. This is the first study to quantify the abundance of colistin-resistant E. coli in meat samples.

BACKGROUND: Assessing knee joint orientation changes after SMO may help clinical advancement in managing patients with ipsilateral ankle and knee joint arthritis. However, knee joint changes after supramalleolar osteotomy (SMO) have not been reported. We investigated changes in coronal alignment of the knee joint after SMO. METHODS: In this multicentre study, from January 2014 to December 2018, 47 ankles with varus osteoarthritis treated with SMO were retrospectively identified. Ankle joint changes were assessed using the tibiotalar angle, talar tilt angle, and lateral distal tibial angle (LDTA); knee joint changes using the medial proximal tibial angle (MPTA), medial and lateral joint space widths (mJSW and lJSW, respectively), and medial and lateral joint line convergence angles (JLCA); and lower limb alignment changes using mechanical axis deviation angle (MADA) and the hip-knee-ankle (HKA) angle measured on full-length anteroposterior radiographs of the lower extremity. Correlation analysis and binary logistic regression analysis were performed. RESULTS: Postoperatively, LDTA (p < 0.001) and tibiotalar angle (p < 0.001) significantly changed, indicating meaningful improvement in the ankle joint varus deformity. Regarding the knee joint changes, JLCA significantly changed into valgus direction (p = 0.044). As for lower limb alignment changes, MADA significantly decreased (p < 0.001), whereas the HKA angle significantly increased (p < 0.001). In univariate and multivariate logistic regression analyses, changes in the MADA (p < 0.001) and the HKA angle (p < 0.001) were significantly correlated with the correction angle. CONCLUSIONS: SMO remarkably improves ankle joint varus deformity, followed by significant lower limb alignment changes. Despite meaningful changes in JLCA, the relationship between the amount of osteotomy near the ankle joint and improvement in knee joint radiographic parameters was not significant. Radiographic parameters of the knee joint would less likely be changed following SMO.

OBJECTIVE: To investigate if 3D printed guides and preoperative planning can accurately control femoral stem anteversion. METHODS: A prospective comparative study was carried out from 2018 to 2020, including 53 patients who underwent hip arthroplasty for femoral neck fracture. The target rotation center of the femoral head is determined by three-dimensional planning. In group A, planning was made by 2D templates. In group B, preoperative 3D planning and 3D printed osteotomy/positioning guides were performed. After the operation, 3D model registration was performed to calculate the accuracy of anteversion restoration. RESULTS: We screened 60 patients and randomized a total of 53 to 2 parallel study arms: 30 patients to the group A (traditional operation) and 23 patients to the group B (3D preoperative planning and 3D printed guide). There were no significant differences in demographic or perioperative data between study groups. The restoration accuracy of group A was 5.42° ± 3.65° and of group B was 2.32° ± 1.89°. The number and rate of abnormal cases was 15 (50%) and 2 (8.7%), respectively. Significant statistical differences were found in angle change, restoration accuracy, and number of abnormal cases. CONCLUSION: Three-dimensional preoperative planning and 3D printed guides can improve the accuracy of the restoration of femoral anteversion during hip arthroplasty.

[This retracts the article DOI: 10.1155/2020/9424725.].

[This retracts the article DOI: 10.1155/2014/486407.].

circRNAs are a class of endogenous noncoding RNA molecules with closed loop structures. They are mainly responsible for regulating gene expression in eukaryotic cells. With the emergence of high-throughput RNA sequencing (RNA-Seq) and new types of bioinformatics tools, thousands of circRNAs have been discovered, making circRNA one of the research hotspots. Recent studies have shown that circRNAs play an important regulatory role in the growth, reproduction, and formation of livestock products. They can not only regulate mammalian fetal growth and development but also have important regulatory effects on livestock muscle development and lactation. In this review, we briefly introduce the putative biogenic pathways and regulatory functions of circRNA and highlight our understanding of circRNA and its latest advances in fetal development, muscle development, and lactation biogenesis as well as expression in livestock. This review will provide a theoretical basis for the research and development of related industries.

Erratum for Biomed Res Int. 2017;2017:5718968.

The effectiveness of additional usage of adjuvants for bowel preparation is still unclear. This study compared 1L polyethylene glycol plus ascorbic acid with adjuvant drug regimens (1L PEG-AA, lower volume) with 2L polyethylene glycol plus ascorbic acid (2L PEG-A, low volume) to evaluate whether the adjuvants can be used to reduce the standard dosage of purgative further. The PubMed/MEDLINE, EMBASE, Cochrane Library, and Web of Science database were searched for randomized controlled trials (RCTs). The primary outcome was the efficacy of bowel preparation, and the secondary outcomes were patients' tolerability and complication rate. The overall quality of evidence was assessed using the GRADEpro guideline development tool. Five RCTs with a total of 1013 patients from Korea were included. The majority of patients were outpatients from different hospitals. The pooled data showed no significant difference in the adequate bowel preparation rate (89.3% versus 89.4%, RR 1, 95% CI 0.95-1.05, I 2 = 47%) as well as in the complication rate (RR for nausea 1.22, 95% CI 0.89-1.65, I 2 = 49%; RR for bloating 0.96, 95% CI 0.73-1.28, I 2 = 0%; RR for vomiting 0.69, 95% CI 0.32-1.50, I 2 = 33%; RR for abdominal pain 1.01, 95% CI 0.61-1.69, I 2 = 0%). But a significantly higher willingness rate was observed in the lower volume (85.1% versus 67.9%, RR 1.25, 95% CI 1.14-1.38, I 2 = 46%). The quality of primary outcome evidence was moderate. The findings of this meta-analysis revealed that 1L PEG-AA may be a viable alternative to 2L PEG-A, with comparable effectiveness, better patient preference, and no statistically significant adverse event occurrence.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of preoperative planning of the femurofibular angle (FFA) in medial open-wedge high tibial osteotomy (OWHTO) for mild medial knee osteoarthritis. METHODS: Thirty-two patients (32 knees) with mild medial knee OA were retrospectively reviewed. The patients underwent preoperative planning of the FFA for OWHTO. For preoperative planning, a full-length weight-bearing X-ray photograph of the lower limb was opened within Adobe Photoshop Software, and a targeted corrective mechanical axis line of the lower limb and its intersecting point at the lateral tibial plateau surface was drawn using rectangle selection and filling tools. A frame, which encircled the tibia and fibula, was created around the predicted osteotomy plane and then rotated until the ankle center was on the targeted mechanical axis line. Subsequently, a distal femoral condyle line and a proximal fibula axis line were drawn, and the angle between the two lines was measured and defined as the femurofibular angle (FFA). During biplane OWHTO, the preoperatively determined FFA was used to complete the correction of the mechanical axis. During follow-up, the postoperative mechanical weight-bearing line (WBL) of the lower limb, the mechanical femorotibial angle (mFTA), and the FFA were measured and compared with the preoperatively determined values. RESULTS: The mechanical WBL shifted from a preoperative value of 25.36 ± 5.02% to a postoperative value of 56.19 ± 0.10% from the medial border along the mediolateral width of the tibial plateau, and it was 56.57 ± 0.08% at the final follow-up (P < 0.01). The preoperatively determined value was 56.25%, and no significant difference was found compared with postoperative week-one and final follow-up values (P > 0.05). The mFTA was corrected from a preoperative varus of 4.02 ± 0.63° to a postoperative week-one valgus of 2.37 ± 0.28°, and it had a valgus of 2.48 ± 0.39° at the final follow-up (P < 0.01). No significant difference in the valgus was found compared with the postoperative week-one, final follow-up and preoperatively determined valgus of 2.34 ± 0.26° (P > 0.05). The postoperative week-one and final follow-up FFAs were 90.34 ± 1.53° and 90.33 ± 1.52°, respectively, and no significant difference was found compared with the preoperatively determined value of 90.12 ± 1.72° and the intraoperative setting value of 90.25 ± 1.67° (P > 0.05). All corrected values were within the acceptable range of preoperative planning. CONCLUSION: Preoperative planning of the FFA may be useful in OWHTO for patients with mild medial knee OA. Satisfactory correction of the postoperative targeted mechanical axis line of the lower limb can be obtained.

BACKGROUND: Increasing evidences have reported gut microbiota dysbiosis in many diseases, including chronic kidney disease and pediatric idiopathic nephrotic syndrome (INS). There is lack evidence of intestinal microbiota dysbiosis in adults with INS, however. Here, we to address the association between the gut microbiome and INS. METHODS: Stool samples of 35 adult INS patients and 35 healthy volunteers were collected. Total bacterial DNA was extracted, and the V4 regions of the bacterial 16S ribosomal RNA gene were sequenced. The fecal microbiome was analyzed using bioinformatics. The correlation analysis between altered taxa and clinical parameters was also included. RESULTS: We found that microbial diversity in the gut was reduced in adult patients with INS. Acidobacteria, Negativicutes, Selenomonadales, Veillonellaceae, Clostridiaceae, Dialister, Rombousia, Ruminiclostridium, Lachnospira, Alloprevotella, Clostridium sensu stricto, Megamonas, and Phascolarctobacterium were significantly reduced, while Pasteurellales, Parabacteroides, Bilophila, Enterococcus, Eubacterium ventriosum, and Lachnoclostridium were markedly increased in patients with INS. In addition, Burkholderiales, Alcaligenaceae, and Barnesiella were negatively correlated with serum creatinine. Blood urea nitrogen levels were positively correlated with Christensenellaceae, Bacteroidales_S24.7, Ruminococcaceae, Ruminococcus, and Lachnospiraceae_NK4A136, but were negatively correlated with Flavonifractor_plautii and Erysipelatoclostridium_ramosum. Enterobacteriales, Enterobacteriaceae, Porphyromonadaceae, Escherichia/Shigella, Parabacteroides, and Escherichia_coli were positively correlated with albumin. Proteinuria was positively correlated with Verrucomicrobia, Coriobacteriia, Thermoleophilia, Ignavibacteria, Coriobacteriales, Nitrosomonadales, Coriobacteriaceae, and Blautia, but was negatively correlated with Betaproteobacteria, Burkholderiales, and Alcaligenaceae. CONCLUSION: Our findings show compositional alterations of intestinal microbiota in adult patients with INS and correlations between significantly altered taxa and clinical parameters, which points out the direction for the development of new diagnostics and therapeutic approaches targeted intestinal microbiota.

PURPOSE: To present applications of anterior segment optical coherent tomography (AS OCT) for anomalies of the eye in a Polish paediatric cohort. MATERIALS AND METHODS: Seventy-four eyes of infants and older children were examined. The majority of them underwent general anaesthesia to allow OCT to be performed in the operating room, but a few were examined in a routine way. We focused on corneal, anterior chamber, iris, and lens disorders. Measurements included corneal morphology, anatomy of the anterior chamber, and general involvement of surrounding tissues in pathologic lesions. RESULTS: We divided the paediatric patients into several groups by considering the type of disease and involvement of particular tissues. The groups were selected based on OCT usefulness in describing their ocular disorders. CONCLUSION: The collected anterior segment disorders showed huge usefulness for paediatric diagnosis and treatment planning.

Oxidative stress is a crucial factor and key promoter of a variety of cardiovascular diseases associated with cardiomyocyte injury. Emerging literatures suggest that pyroptosis plays a key role in cardiac damages. However, whether pyroptosis contributes to cardiomyocyte injury under oxidative stress and the underlying molecular mechanisms are totally unclear. This study was designed to investigate the potential role of pyroptosis in H2O2-induced cardiomyocyte injury and to elucidate the potential mechanisms. Primary cardiomyocytes from neonatal Wistar rats were utilized. These myocytes were treated with different concentrations of H2O2 (25, 50, and 100 μM) for 24 h to induce oxidative injury. Our results indicated that mRNA and protein levels of ASC were remarkably upregulated and caspase-1 was activated. Moreover, the expressions of inflammatory factors IL-1β and IL-18 were also increased. Luciferase assay showed that miR-599 inhibited ASC expression through complementary binding with its 3'UTR. MiR-599 expression was substantially reduced in H2O2-treated cardiomyocytes. Upregulation of miR-599 inhibited cardiomyocyte pyroptosis under oxidative stress, and opposite results were found by decreasing the expression of miR-599. Consistently, miR-599 overexpression ameliorated cardiomyocyte injury caused by H2O2. Therefore, miR-599 could be a promising therapeutic approach for the management of cardiac injury under oxidative condition.

[This retracts the article DOI: 10.1155/2018/8481243.].

BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent chronic disease that increases the risk of cardiovascular disease and metabolic and neuropsychiatric disorders, resulting in a considerable socioeconomic burden. The present study was aimed at identifying potential key genes influencing the mechanisms and consequences of OSA. METHODS: Gene expression profiles associated with OSA were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in subcutaneous adipose tissues from patients with OSA and normal tissues were screened using R software, followed by gene ontology and pathway enrichment analyses. Subsequently, a protein-protein interaction (PPI) network was constructed and hub genes were extracted using Cytoscape plugins. The intersected core genes derived from different topological algorithms were considered hub genes, and the potential candidate gene was selected from them for further analyses of expression variations using another GEO dataset and targeted capture sequencing in 100 subjects (50 with severe OSA and 50 without OSA). RESULTS: A total of 373 DEGs were identified in OSA samples relative to normal controls, which were primarily associated with olfactory transduction and neuroactive ligand-receptor interaction. Upon analyses of nine topological algorithms and available literature, we finally focused on glial cell-derived neurotrophic factor (GDNF) as the candidate gene and validated its low expression in OSA samples. Two rare nonsynonymous variants (p.D56N and p.R93Q) were identified among the 100 cases through targeted sequencing of GDNF, which could be potentially deleterious based on pathogenicity prediction programs; however, no significant association was detected in single nucleotide polymorphisms. CONCLUSION: The present study identified GDNF as a promising candidate gene for OSA and its two rare and potentially deleterious mutations through a combination of bioinformatics and targeted capture sequencing analyses.

In this study, the ultrasound-assisted extraction (UAE) of flavonoid from Paeonia lactiflora seed peel was optimized by response surface methodology (RSM). Single-factor experiments and a three-factor three-level Box-Behnken design (BBD) were performed to explore the effects of the following parameters on flavonoid extraction: ethanol concentration (X 1), liquid-solid ratio (X 2), and ultrasonic time (X 3). The results showed that the optimal flavonoid yield (10.9045 mg RE/g) was as follows: ethanol concentration 62.93%, ultrasonic time 64.56 min, and liquid-solid ratio 24.86 mL/g. The optimized extract of P. lactiflora seed shell was further analyzed by UPLC-ESI-MS/MS, and 20 main flavonoids were identified and quantified, among which protocatechuic acid, vanillic acid, 4-hydroxybenzoic acid, and 3,4-dihydroxybenzaldehyde had the highest content. Furthermore, the results of the antioxidant test showed that the P. lactiflora seed peel extract obtained under optimized UAE conditions exhibited good antioxidant activity. The experimental results showed that ultrasound-assisted extraction was a fast, efficient, and simple method for extracting active ingredients from P. lactiflora seed peel, thereby making this byproduct a promising source of compounds in food and healthcare sectors.

BACKGROUND: The prevalence of coronary artery anomalies (CAAs) is rare and varies among different countries or areas. More importantly, the symptoms exhibited by some CAAs make the diagnosis of coronary artery disease (CAD) difficult and hamper the physician from making the right intervention for CAD patients. OBJECTIVE: To investigate the prevalence of CAAs in 11,267 patients from three hospitals in Southwest China. METHODS: 11,267 patients who have undergone coronary angiography from three Southwest China hospitals were investigated retrospectively. Dominance patterns, prevalence, and the location of each CAA were recorded and analyzed. RESULTS: The presence of a dominant right coronary artery (RCA) was found in 60.58% of patients. CAAs were found in 11.12% (1258) patients, and 87.66% anomalies were located in the left anterior descending (LAD) artery and its branches. Most of CAAs were found to be myocardial bridges (MBs, 1060 cases, 9.41%). Other CAAs included anomalous coronary origin (43 cases, 0.38%), coronary artery fistulas (CAFs, 36 cases, 0.32%), and coronary artery aneurysm or ectasia (119 cases, 1.06%). It also noted that most anomalies were found with RCA originating from the left coronary sinus (79.07%), most CAFs were located in the LAD and its branches (58.33%), and most coronary artery ectasias were located in the RCA (43.25%). CONCLUSIONS: CAAs in patients from Southwest China were unique compared to other studies. Recognition of these CAAs is important for accurate diagnosis and treatment choice of patients with chest pain.

The aims of this study were to analyze the autonomic stress response of nurse degree students during a hospital clinical simulation and to analyze differences in the autonomic stress response of nurse degree students during a hospital clinical simulation depending on their psychological profile. We analyzed in 45 nurse students their psychological profile (purpose in life, coping flexibility, perceived stress, Framingham Type A Behavior, and personality) and the autonomic modulation by the heart rate variability in a hospital clinical simulation. Students presented decreased heart rate variability and different autonomic stress responses depending on the different psychological parameters evaluated. We concluded that a hospital clinical simulation produced a large sympathetic modulation of nurse students that was maintained during the entire clinical simulation. The autonomic response was modulated by the psychological profile of students, showing higher purpose in life, perceived stress, and neuroticism, presenting higher parasympathetic modulation.

Like other populations of developing countries, most of the populations of Ethiopia depend greatly on the use of traditional herbal medicines as the primary source of health care. However, these resources have been degraded throughout the country. Therefore, recording and documenting medicinal plants are essential for the future conservation of the species. Thus, the current study is related to this issue. Three hundred ninety-five informants participated in this study. The main data collection tools were semistructured interviews, discussions, and observation. The data were analyzed using both qualitative and quantitative methods. The quantitative methods (informant consensus factor, fidelity level) were used to analyze the level of homogeneity of the data, the agreements of informants, and the healing potential of medicinal plants. The ranking exercises (preference and direct matrix ranking) were used to quantify the most preferred and multipurpose medicinal plants. A statistical test was conducted using SPSS version 20 to test knowledge differences among the people. Following the analysis, 112 species of medicinal plants with 62 families were recorded. Most of the species were herbs, of which Fabaceae was the dominant family. Blood pressure and asthma were the most commonly reported human health problems. Most of the remedies were prepared from leaves, and most of them were prepared by pounding and were applied orally. Gastrointestinal diseases had the highest informant consensus. Five medicinal plants were recorded with the highest healing potential value for malaria, asthma, tapeworm, cough, and stomach ulcer. Verbascum sinaiticum Benth. was the most preferred medicinal plant in treating blood pressure. Trigonella foenum-graecum L. had the highest use value. The analysis results showed that local people showed significant knowledge differences (p < 0.05). In conclusion, the indigenous people have a wealth of indigenous herbal knowledge. Therefore, to sustain the wealth of indigenous knowledge of the districts, immediate and well-designed conservation practices of medicinal plants should be conducted.

BACKGROUND: Cancer of unknown primary (CUP) is a type of malignant tumor, which is histologically diagnosed as a metastatic carcinoma while the tissue-of-origin cannot be identified. CUP accounts for roughly 5% of all cancers. Traditional treatment for CUP is primarily broad-spectrum chemotherapy; however, the prognosis is relatively poor. Thus, it is of clinical importance to accurately infer the tissue-of-origin of CUP. METHODS: We developed a gradient boosting framework to trace tissue-of-origin of 20 types of solid tumors. Specifically, we downloaded the expression profiles of 20,501 genes for 7713 samples from The Cancer Genome Atlas (TCGA), which were used as the training data set. The RNA-seq data of 79 tumor samples from 6 cancer types with known origins were also downloaded from the Gene Expression Omnibus (GEO) for an independent data set. RESULTS: 400 genes were selected to train a gradient boosting model for identification of the primary site of the tumor. The overall 10-fold cross-validation accuracy of our method was 96.1% across 20 types of cancer, while the accuracy for the independent data set reached 83.5%. CONCLUSION: Our gradient boosting framework was proven to be accurate in identifying tumor tissue-of-origin on both training data and independent testing data, which might be of practical usage.

OBJECTIVE: To investigate the initial hemodialysis vascular access in Hangzhou and provide evidence for improving the use of autologous arteriovenous fistula by identifying factors associated with the choice of initial vascular access. METHODS: We retrospectively studied the initial hemodialysis vascular access of 257 patients in five hemodialysis units in Hangzhou of China during a 21-month period (January 2018 to September 2019). A logistic regression was used to identify the risk factors of failing to use an arteriovenous fistula at the initiation of hemodialysis. RESULTS: (1) 257 participants with mean age 67.65 ± 13.43 years old were reviewed, including 165 males (64.2%) and 92 females (35.8%). The etiologies of end-stage renal disease included diabetic nephropathy (37.35%), chronic glomerulonephritis (31.13%), hypertensive nephropathy (14.01%), and other diseases (17.51%). Only 51 patients (19.84%) received arteriovenous fistula, whereas the remaining 206 patients (80.16%) initiated dialysis with a central venous catheter. (2) Logistic regression analysis revealed that the independent risk factors for central venous catheter at the initial hemodialysis were age >70 years old (OR = 4.827, p < 0.01 versus ≤70 years old), chronic glomerulonephritis as the primary etiology (OR = 2.565, p < 0.05 versus nonchronic glomerulonephritis) and eGFR <8.5 mL/min/1.73m2 (OR = 2.283, p < 0.05 versus eGFR ≥8.5 mL/min/1.73m2). CONCLUSION: The proportion of patients using arteriovenous fistula as the initial hemodialysis vascular access in Hangzhou was still low. The choice of vascular access for the first hemodialysis was related to age, eGFR, and the primary etiology of end-stage renal disease. Increasing the proportion of planned vascular access and arteriovenous fistula at the initiation of hemodialysis is still our current goal.

Comment on Biomed Res Int. 2018 Jun 26;2018:8293594.

Optical coherence tomography (OCT) provides the visualization of macular edema which can assist ophthalmologists in the diagnosis of ocular diseases. Macular edema is a major cause of vision loss in patients with retinal vein occlusion (RVO). However, manual delineation of macular edema is a laborious and time-consuming task. This study proposes a joint model for automatic delineation of macular edema in OCT images. This model consists of two steps: image enhancement using a bioinspired algorithm and macular edema segmentation using a Gaussian-filtering regularized level set (SBGFRLS) algorithm. We then evaluated the delineation efficiency using the following parameters: accuracy, precision, sensitivity, specificity, Dice's similarity coefficient, IOU, and kappa coefficient. Compared with the traditional level set algorithms, including C-V and GAC, the proposed model had higher efficiency in macular edema delineation as shown by reduced processing time and iteration times. Moreover, the accuracy, precision, sensitivity, specificity, Dice's similarity coefficient, IOU, and kappa coefficient for macular edema delineation could reach 99.7%, 97.8%, 96.0%, 99.0%, 96.9%, 94.0%, and 96.8%, respectively. More importantly, the proposed model had comparable precision but shorter processing time compared with manual delineation. Collectively, this study provides a novel model for the delineation of macular edema in OCT images, which can assist the ophthalmologists for the screening and diagnosis of retinal diseases.

OBJECTIVE: This study is set out to determine the relationship between IL-32 and radiosensitivity of esophageal squamous cell carcinoma (ESCC). METHODS: Western blot was adopted for measuring IL-32 expression in Eca-109 and TE-10 cells. Eca-109 and TE-10 cells with interference or overexpression of IL-32 were treated with the presence or absence of X-ray irradiation. Then, the use of CCK8 assay was to detect proliferation ability, and effects of IL-32 expression on radiosensitivity of ESCC were tested by colony formation assay. The cell apoptosis was detected using flow cytometry. STAT3 and p-STAT expression, and apoptotic protein Bax were detected by western blot. RESULTS: Colony formation assay and CCK8 assay showed that compared with the NC group without treatment, the growth of the ESCC cells, that is Eca-109 and TE-10, was significantly inhibited in the OE+IR group with highly expressed IL-32 and irradiation. In flow cytometry analysis, in Eca-109 and TE-10 cells, highly expressed IL-32 combined with irradiation significantly increased apoptosis compared with the control group. Highly expressed IL-32 has a synergistic effect with irradiation, inhibiting STAT3 and p-STAT3 expression and increasing apoptotic protein Bax expression. CONCLUSION: IL-32 can improve the radiosensitivity of ESCC cells by inhibiting the STAT3 pathway. Therefore, IL-32 can be used as a new therapeutic target to provide a new attempt for radiotherapy of ESCC.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a known long noncoding RNA, was reported to play a crucial role in follicular growth and ovarian disease. However, the physiological function of MALAT1 in mouse granulosa cells (mGCs) remains largely unclear. The aims of this study were to determine the biological function and molecular mechanism of MALAT1 in mGCs. We knocked down MALAT1 in mGCs by using siRNA against MALAT1. We found that knockdown of MALAT1 promoted apoptosis and caspase-3/9 activities in mGCs. Enzyme-linked immunosorbent assay demonstrated that knockdown of MALAT1 significantly decreased the production of estradiol (E2) and progesterone (P4) in mGCs. Mechanistically, MALAT1 serves as a competing endogenous RNA (ceRNA) to sponge microRNA-205 (miR-205), thereby facilitating its downstream target of cyclic AMP response element- (CRE-) binding protein 1 (CREB1). Furthermore, CREB1 overexpression or miR-205 downregulation partially recovered the effect of MALAT1 depletion in mGCs. In summary, these findings suggested that MALAT1 regulated apoptosis and estradiol synthesis of mGCs through the miR-205/CREB1 axis.

Biomechanical models based on the finite element method have already shown their potential in the simulation of the mechanical behaviour of cells. For instance, development of atherosclerosis is accelerated by damage of the endothelium, a monolayer of endothelial cells on the inner surface of arteries. Finite element models enable us to investigate mechanical factors not only at the level of the arterial wall but also at the level of individual cells. To achieve this, several finite element models of endothelial cells with different shapes are presented in this paper. Implementing the recently proposed bendotensegrity concept, these models consider the flexural behaviour of microtubules and incorporate also waviness of intermediate filaments. The suspended and adherent cell models are validated by comparison of their simulated force-deformation curves with experiments from the literature. The flat and dome cell models, mimicking natural cell shapes inside the endothelial layer, are then used to simulate their response in compression and shear which represent typical loads in a vascular wall. The models enable us to analyse the role of individual cytoskeletal components in the mechanical responses, as well as to quantify the nucleus deformation which is hypothesized to be the quantity decisive for mechanotransduction.

PURPOSE: Mixed reality (MixR) technology merges the real and virtual worlds to produce new environments and visualizations; it is being tested for numerous minimally invasive surgical procedures. This study is aimed at evaluating the use of MixR technology using optical see-through head-mounted displays (OST-HMDs) during transforaminal percutaneous endoscopic discectomy (TPED). METHODS: Forty-four patients treated with MixR-assisted TPED through OST-HMDs were compared with matched patients treated with conventional TPED (n = 43). In the MixR-assisted TPED group, MixR technology was used to navigate the four procedures of marking, needle insertion, foraminoplasty, and positioning of the working sheath. The clinical outcomes were evaluated based on the numerical rating scale (NRS) scores and Oswestry Disability Index (ODI) on preoperative and postoperative day 1 and at the last follow-up examination. The procedural times, radiation exposure, and eye fatigue were also recorded. All patients were followed up for at least 6 months. RESULTS: The NRS scores and ODI were significantly improved in both groups at the last follow-up visit compared with the preoperative values (P < 0.05); these values were not statistically different between the groups. The operation time and radiation exposure during marking, needle insertion, and total procedure significantly decreased in the MixR-assisted TPED group compared to those in the conventional TPED group (P < 0.05). Unfortunately, the incidence of eye fatigue increased owing to the use of OST-HMDs in the MixR-assisted TPED group. CONCLUSION: This study shows the utility of MixR technology for image guidance in conventional TPED. Radiation exposure is decreased, and this technology serves as a valuable tool during the TPED procedure; however, the assistance of conventional fluoroscopy is still required.

Autologous fat grafting has been widely used for soft tissue filling in plastic surgery. Platelet-rich plasma (PRP) could play a wide role in health and disease because of containing a variety of growth factors and cytokines. Although previous studies have described the positive effect of autologous PRP mixed with fat grafts, only minimal improvements in fat graft survival have been reported. The present study is aimed at comparing the effects of PRP and platelet-poor plasma (PPP) on the survival and quality of fat grafting. We built a 180-day nude mouse model implanted with a fat graft supplemented with PRP, PPP, or saline, respectively. The above reagents (PRP, PPP, or saline) were injected two additional times after the initial engraftment. The survival ratio of the fat grafts and the capillary density in the PRP group were significantly higher than those in the PPP group and the saline group (control group) at 15, 30, 90, and 180 days posttransplantation (P < 0.05). The survival ratio of the PPP group was higher than that of the saline group (P < 0.05), but the capillary density in the PPP group was not significantly different from that in the saline group at any time point (P > 0.05). We hence conclude that the repeated application of PRP or PPP three times can enhance the survival of fat grafts within 180 days. Moreover, the effect of PRP is superior to that of PPP.

Erratum for Biomed Res Int. 2014;2014:895986.

Umbilicaria antarctica (UA) is a member of the family Umbilicariaceae. To the best of our knowledge, no studies on its anti-inflammatory effects have been reported yet. In the present study, we examined its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells and a zebrafish model of inflammation. We investigated the effects of UA on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated RAW 264.7 cells. To explore the anti-inflammatory mechanisms of UA, we measured the mRNA and protein expression of proinflammatory mediators in LPS-stimulated RAW 264.7 cells using quantitative RT-PCR and western blot analyses, respectively. UA significantly inhibited the production of NO, PGE2, interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α in the LPS-stimulated RAW 264.7 cells. It also suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor- (NF-) κB activation in LPS-stimulated RAW 264.7 cells and tail pin-cutting-induced zebrafish model. Collectively, these findings indicate that UA significantly inhibits LPS-stimulated inflammatory responses. These effects were considered to be strongly associated with the suppression of NF-κB activation. Overall, our results demonstrate that UA extract exerts strong anti-inflammatory activities in in vitro and in vivo models and suggest that UA may be an effective novel therapeutic agent for the treatment of inflammatory diseases.

PURPOSE: Bony resection is the primary step during total knee arthroplasty. The accuracy of bony resection was highly addressed because it was deemed to have a good relationship with mechanical line. Patient-specific instruments (PSI) were invented to copy the bony resection references from the preoperative surgical plan during a total knee arthroplasty (TKA); however, the accuracy still remains controversial. This study was aimed at finding out the accuracy of the bony resection during PSI-assisted TKA. METHODS: Forty-two PSI-assisted TKAs (based on full-length leg CT images) were analyzed retrospectively. Resected bones of every patient were given a CT scan, and three-dimensional radiographs were reconstructed. The thickness of each bony resection was measured with the three-dimensional radiographs and recorded. The saw blade thickness (1.27 mm) was added to the measurements, and the results represented intraoperative bone resection thickness. A comparison between intraoperative bone resection thickness and preoperatively planned thickness was conducted. The differences were calculated, and the outliers were defined as >3 mm. RESULTS: The distal femoral condyle had the most accurate bone cuts with the smallest difference (median, 1.0 mm at the distal medial femoral condyle and 0.8 mm at the distal lateral femoral condyle) and the least outliers (none at the distal medial femoral condyle and 1 (2.4%) at the distal lateral femoral condyle). The tibial plateau came in second (median difference, 0.8 mm at the medial tibial plateau and 1.4 mm at the lateral tibial plateau; outliers, none at the medial tibial plateau and 1 (2.6%) at the lateral tibial plateau). Regardless of whether the threshold was set to >2 mm (14 (17.9%) at the tibial plateau vs. 12 (14.6%) at the distal femoral condyle, p > 0.05) or >3 mm (1 (1.3%) at the tibial plateau vs. 1 (1.2%) at the distal femoral condyle, p > 0.05), the accuracy of tibial plateau osteotomy was similar to that of the distal femoral condyle. Osteotomy accuracy at the posterior femoral condyle and the anterior femoral condyle were the worst. Outliers were up to 6 (15.0%) at the posterior medial femoral condyle, 5 (12.2%) at the posterior lateral femoral condyle, and 6 (15.8%) at the anterior femoral condyle. The percentages of overcut and undercut tended to 50% in most parts except the lateral tibial plateau. At the lateral tibial plateau, the undercut percentage was twice that of the overcut. CONCLUSION: The tibial plateau and the distal femoral condyle share a similar accuracy of osteotomy with PSI. PSI have a generally good accuracy during the femur and tibia bone resection in TKA. PSI could be a kind of user-friendly tool which can simplify TKA with good accuracy. Level of Evidence. This is a Level IV case series with no comparison group.

There is a lack of data on drug-related problems (DRPs) among elderly patients from surgical departments. The current study is aimed at identifying and categorizing types of DRPs and assessing the severities of the DRPs. Medication orders for hospitalized patients aged ≥65 years from six surgery departments were reviewed to determine DRPs over 6 months in a tertiary teaching hospital of Chongqing, China. DRPs were classified based on the Pharmaceutical Care Network Europe classification V8.02. The severity ratings of the DRPs were assessed using the National Coordinating Council for Medication Error Reporting and Prevention classification. A total of 53,231 medication orders from 1,707 elderly patients were reviewed, and 1,061 DRPs were identified. Treatment safety (44.9%) was the most common DRP type. Drug selection (43.1%) and dose selection (43.1%) were the major causes of DRPs. A total of 75.1% of the DRPs were classified into severity categories B to D (causing no or potential harm), and 24.9% were classified as categories E to H (causing actual harm). DRPs are common in hospitalized elderly surgical patients. Pharmacists should provide medication order reviews in this vulnerable patient population.

OBJECTIVE: This study was aimed at investigating the relationship between serum amyloid A (SAA) levels and cognitive dysfunction in patients with vascular dementia (VAD). METHODS: Using cross-sectional research methods, 146 patients with VAD were selected as the VAD group and 70 normal people were selected as the NC group. Upon admission, the clinical and biochemical characteristics of the two groups of study subjects were collected, and the MMSE scale was used to assess cognitive function. A sandwich enzyme-linked immunosorbent assay was used to detect SAA levels. RESULTS: There was no significant difference in clinical data and biochemical characteristics in the VAD group (p > 0.05). Compared with the VAD group, the NC group has a higher level of education (p < 0.05). The SAA level of the VAD group was higher than that of the NC group, and there was a significant difference (p < 0.05). Spearman correlation analysis showed that SAA and MMSE in the VAD group were negatively correlated. Further multiple regression analysis showed that the serum amyloid A level is an independent risk factor for cognitive dysfunction in VAD patients. CONCLUSION: The level of SAA in VAD patients is significantly increased, which can be used as a potential peripheral blood marker to predict cognitive impairment in VAD patients.

Platelet (PLT) indices have been proposed as potential markers in the assessment of liver fibrosis and exacerbation of liver failure. The aim of our study was to verify mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) in alcohol-related liver cirrhosis (ALC) and nonalcoholic fatty liver disease (NAFLD) patients. One hundred forty-two patients with ALC, 92 with NAFLD, and 68 in control group were enrolled in this study. Hematological indices (MPV, PCT, and PDW) and serological (indirect and direct) markers of liver fibrosis (AAR, APRI, FIB-4, GPR, PICP, PIIINP, TGF-α, PDGF-AB, laminin) were measured in each participant. MELD score in ALC patients and NAFLD fibrosis score (NFS) together with BARD score in the NAFLD group were also obtained. Results were compared between research and control groups. Then, a correlation between evaluated indices was performed in study groups. Receiver operating characteristic curves (ROCs) and area under the curve (AUC) values were applied to assess the diagnostic accuracy of measured indices. Significant increase in PDW and decrease in PCT in comparison to controls were noted in examined ALC (60.4% vs. 51.2% and 0.1% vs. 0.21%, respectively, p < 0.0001) and NAFLD (54.75% vs. 51.2% and 0.19 vs. 0.21%, respectively, p < 0.01) patients. Decreased level of MPV was observed in NAFLD group (7.85 fl vs. 8.90 fl, p < 0.0001). Additionally, PCT correlated with NFS (p < 0.0001). Evaluated PLT indices correlated with MELD score (MPV and PDW, p < 0.001; PCT, p < 0.05). They correlated with indirect and direct markers of liver fibrosis in the whole research group, too. PCT was the parameter with the greatest diagnostic accuracy in ALC patients (AUC = 0,839 for cutoff < 0.17%); in NAFLD group, it was MPV (AUC = 0,808 for cutoff < 7.9 fl). PCT in ALC and MPV in NAFLD can be perceived as potential diagnostic markers.

Dendrimers are nanosized, symmetrical molecules in which a small atom or group of atoms is surrounded by the symmetric branches known as dendrons. The structure of dendrimers possesses the greatest impact on their physical and chemical properties. They grow outwards from the core-shell which further reacts with monomers having one reactive or two dormant molecules. Dendrimers' unique characteristics such as hyperbranching, well-defined spherical structure, and high compatibility with the biological systems are responsible for their wide range of applications including medical and biomedical areas. Particularly, the dendrimers' three-dimensional structure can incorporate a wide variety of drugs to form biologically active drug conjugates. In this review, we focus on the synthesis, mechanism of drug encapsulations in dendrimers, and their wide applications in drug delivery.

The current results for extremely-low-frequency magnetic fields (ELF-MF) on DNA damage are still debated. A sensitive indicator and systematic research are needed to assess the effects of ELF-MF. In this study, we used γH2AX as an early and sensitive molecular marker to evaluate the DNA damage effects of ELF-MF in vitro. Human amnion epithelial cells (FLs), human skin fibroblast cells (HSFs), and human umbilical vein endothelial cells (HUVECs) were exposed to 50 Hz ELF-MF at 0.4, 1, and 2 mT for 15 min, 1 h, and 24 h, respectively. After exposure, cells were subjected to γH2AX immunofluorescence and western blot. The results showed no significant difference in the average number of foci per cell, the percentage of γH2AX foci-positive cells, or the expression of γH2AX between the sham and 50 Hz ELF-MF exposure groups (P > 0.05). In conclusion, 50 Hz ELF-MF did not induce DNA damage in FLs, HSFs, or HUVECs, which was independent of the intensity or duration of the exposure.

OBJECTIVE: Assessing excess adrenal hormones is important in patients with adrenal mass. Current screening tests for excess cortisol hormones are complex, so it cannot be done sometimes due to the limited medical resources. The aim of the study was to evaluate whether the neutrophil-lymphocyte ratio (NLR) can be used as an initial screening biomarker for Cushing's syndrome (CS) in patients with an adrenal mass. METHODS: This retrospective study included a total of 185 patients with CS and 185 patients with nonfunctional adrenal adenoma (matched 1 : 1 by sex, body mass index, and discharge date). The NLR was compared between the two groups. The association between NLR and serum and urinary cortisol concentrations was analyzed, and an NLR cut-off value for CS screening was calculated. RESULTS: NLR (3.38 (2.33, 5.45) vs. 2.13 (1.74, 3.00), P < 0.001) was significantly higher in the CS group than in the nonfunctional adenoma group. In CS patients, the NLR was positively associated with serum cortisol concentrations at 8 am, with 24-hour urine free cortisol and with serum cortisol after a 1 mg dexamethasone suppression test (P < 0.001 each). An NLR cut-off of 2.2 had a sensitivity of 80.0% and a specificity of 54.05%. The weighted Youden index for the NLR was similar to that of the 24-hour urine free cortisol and late-night serum cortisol tests, which are recommended initial tests for CS diagnosis. CONCLUSION: The NLR may be useful for initial screening for CS among patients with an adrenal mass as an easy and convenient marker.

OBJECTIVES: A high urine albumin/creatinine ratio (UACR) is associated with microvascular disease in hypertensive patients. However, hypertensive patients frequently have other comorbidities. Thus, it is difficult to distinguish the role of UACR from that of comorbidities in microvascular disease. The aim of this study was to evaluate the association between UACR and microvascular disease in elderly hypertension patients without comorbidities. METHODS: A cross-sectional cohort study of 2252 essential hypertension patients aged 65-94 years without comorbidities between January 1, 2016, and December 31, 2017, was conducted. Microvascular disease was evaluated by hypertension retinopathy (HR). Multivariable adjusted odds of HR by UACR quartiles were determined using logistic regression. RESULTS: The HR prevalence was 22.1% (n = 472) among the cohort study and was significantly different among UACR quartiles (19.7%, 20.3%, 22.0%, and 26.4% in quartiles 1, 2, 3, and 4, respectively, P = 0.036). After adjustment for covariates, higher UACR (odds ratio (OR) = 1.42, 95% confidence interval (CI) 1.05-1.92, quartile 4 versus 1) were significantly associated with HR. Among male patients, higher UACR (OR = 1.65, 95% CI 1.07-2.55, quartile 4 versus 1) were significantly associated with HR after adjustment for covariates. Among female patients, however, 64% and 40% increased odds of HR were noted in the highest and lowest UACR (quartiles 4 and 1, respectively) compared to UACR quartile 2. CONCLUSIONS: Microvascular disease was associated with higher UACR in elderly male essential hypertension patients without comorbidities but was associated with lower and higher UACR in female patients without comorbidities.

BACKGROUND: Standardization of clinical practices is an essential part of continuing education of newly registered nurses in the intensive care unit (ICU). The development of educational standards based on evidence can help improve the quality of educational programs and ultimately clinical skills and practices. OBJECTIVES: The objectives of the study were to develop a standardized learning curve of arterial blood gas (ABG) sampling competency, to design a checklist for the assessment of competency, to assess the relative importance of predictors and learning patterns of competency, and to determine how many times it is essential to reach a specific level of ABG sampling competency according to the learning curve. DESIGN: A quasi-experimental, nonrandomized, single-group trial with time series design. Participants. All newly registered nurses in the ICU of a teaching hospital of Tehran University of Medical Sciences were selected from July 2016 to April 2018. Altogether, 65 nurses participated in the study; however, at the end, only nine nurses had dropped out due to shift displacement. METHODS: At first, the primary checklist was prepared to assess the nurses' ABG sampling practices and it was finalized after three sessions of the expert panel. The checklist had three domains, including presampling, during sampling, and postsampling of ABG competency. Then, 56 nurses practiced ABG sampling step by step under the supervision of three observers who controlled the processes and they filled the checklists. The endpoint was considered reaching a 95 score on the learning curve. The Poisson regression model was used in order to verify the effective factors of ABG sampling competency. The importance of variables in the prediction of practice scores had been calculated in a linear regression of R software by using the relaimpo package. RESULTS: According to the results, in order to reach a skill level of 55, 65, 75, 85, and 95, nurses, respectively, would need average ABG practice times of 6, 6, 7, 7, and 7. In the linear regression model, demographic variables predict 47.65 percent of changes related to scores in practices but the extent of prediction of these variables totally decreased till 7 practice times, and in each practice, nurses who had the higher primary skill levels gained 1 to 2 skill scores more than those with low primary skills. CONCLUSIONS: Utilization of the learning curve could be helpful in the standardization of clinical practices in nursing training and optimization of the frequency of skills training, thus improving the training quality in this field. This trial is registered with NCT02830971.

PURPOSE: The study is aimed at assessing the role of preoperative computerised tomography (CT) examination in the quality of reduction and outcomes in elderly patients with intertrochanteric fracture. METHODS: The elderly patients with an intertrochanteric fracture who were treated with proximal femoral nail antirotation were included. The patients were divided into the CT group and the no-CT group according to the presence of preoperative CT examination. Patients' baseline characteristics, quality of reduction, and function were recorded at follow-up. Functional outcomes were evaluated using the Harris hip scores (HHS). RESULTS: Totally, the study included 182 patients with intertrochanteric fractures, with 85 in the CT group and 97 in the no-CT group, admitted between January 2018 and June 2019. There was no difference in the quality of reduction, HHS, the fracture healing, or postoperative complications between the CT group and the no-CT group. However, the CT group experienced the shorter mean operative time and blood transfusion, compared to the no-CT group. CONCLUSIONS: The preoperative CT examination seems to be excessive for elderly patients with an intertrochanteric fracture.

In order to explore the specific mechanism of YiqiChutan formula (YQCTF) in inhibiting the angiogenesis of lung cancer and its relationship with delta-like ligand 4- (DLL4-) Notch signaling, 30 healthy BALB/c-nu/nu rats were selected and divided into three groups: A549 group (implanted with lung adenocarcinoma cell line A549), NCI-H460 group (implanted with human lung large-cell carcinoma cell line NCI-H460), and NCI-H446 group (implanted with human lung small cell carcinoma cell line NCI-H446) for constructing lung cancer transplanted tumor models. After modeling, the group treated with normal saline was taken as control group, 200 mg/kg of YQCTF was adopted for intervention, and the tumor volume and growth inhibition rate were compared with the vascular targeted inhibitor Sorafenib. HE staining, CD31 fluorescent antibody staining, and microelectron microscopy were adopted to observe the neovascular endothelial cells of the transplanted tumor. The expression of VEGF, HIF-1α, DLL4, and Notch-1 in the transplanted tumors in each group was detected by Western blot and RT-PCR at the protein level or mRNA level. Compared with the control group, the YQCTF-treated group had obvious inhibitory effect on lung cancer transplanted tumor and lung cancer angiogenesis. In the YQCTF-treated group, the density of angiogenesis decreased significantly and the vascular lumen structure also decreased, and the expression levels of VEGF, HIF-1α, DLL4, and Notch-1 in the YQCTF-treated group were all lower than those in the control group. YQCTF could inhibit the growth of lung cancer transplanted tumor through antiangiogenesis, and it could also reduce the amount of angiogenesis in lung cancer transplanted tumor. In addition, the generation of lumen structure was also hindered, which was realized through the VEGF signaling pathway and DLL4-Notch signaling pathway.

This study is to investigate the effect of bisphosphonates on the osseointegration of dental implants in a rabbit model. Twenty female New Zealand White rabbits were equally assigned into control and experiment groups which received saline or zoledronic acid treatment 4 weeks prior to surgery. Titanium dental implant was placed on the calvarial bone. Zoledronic acid or saline treatment continued after surgery for 4 weeks (short-term subgroup) or 8 weeks (long-term subgroup) until sacrifice. Three different fluorochrome labeling solutions were administrated for assessing bone growth rates. Samples of the calvarial bone and mandible were subjected to microcomputed tomography (micro-CT), confocal microscope, and histology analysis. Zoledronic acid treatment significantly reduced bone growth rates in the calvarial bone, but had no significant influence in bone mineral density and trabecular microarchitecture. Significantly lower bone-to-implant contact ratios were found in zoledronic acid-treated animals compared to controls at week 4 but not at week 8. Oncologic dose zoledronic acid suppresses the bone growth rates of the calvarial bone; ZA may have an adverse effect on osseointegration of dental implant in short term, but this effect tends to diminish in long term.

OBJECTIVES: To evaluate the in vitro effectiveness of desensitizing agents in reducing dentine permeability. METHODS: The efficacy of desensitizing agents in reducing dentine permeability by occluding dentine tubules was evaluated using a fluid filtration device that conducts at 100 cmH2O (1.4 psi) pressure, and SEM/EDX analyses were evaluated and compared. Forty-two dentine discs (n = 42) of 1 ± 0.2 mm width were obtained from caries-free permanent human molars. Thirty dentine discs (n = 30) were randomly divided into 3 groups (n = 10): Group 1: 2.7% wt. monopotassium-monohydrogen oxalate (Mp-Mh oxalate), Group 2: RMGI XT VAR, and Group 3: LIQ SiO2. Dentine permeability was measured following treatment application after 10 minutes, storage in artificial saliva after 10 minutes and 7 days, and citric acid challenge for 3 minutes. Data were analysed with a repeated measures ANOVA test. Dentine discs (n = 12) were used for SEM/EDX analyses to acquire data on morphological changes on dentine surface and its mineral content after different stages of treatment. RESULTS: Desensitizing agents' application on the demineralized dentine discs exhibited significant reduction of permeability compared to its maximum acid permeability values. Mp-Mh oxalate showed a significant reduction in dentine permeability (p < 0.05) when compared to RMGI XT VAR and LIQ SiO2. On SEM/EDX analysis, all the agents formed mineral precipitates that occluded the dentine tubules. CONCLUSIONS: 2.7% wt. monopotassium-monohydrogen oxalate was significantly effective in reducing dentine permeability compared to RMGI XT VAR and LIQ SiO2.

Erratum in Biomed Res Int. 2021 Apr 24;2021:9796816.

[This retracts the article DOI: 10.1155/2014/364207.].

AIM: The aim of this study was to investigate the possible therapeutic impacts of two pineal hormones, melatonin and 5-methoxytryptophol (5-MTX), in a rat model of acute pulpitis by analyzing biochemical and histopathological parameters. METHODS: This research was done using 32 male and female Wistar albino rats with weight between 200 and 250 g. The rats were randomly divided into four groups: a control group (rats without any treatment), acute pulpitis (AP) group, AP+melatonin group, and AP+5-MTX group. In the AP-induced groups, the crowns of the upper left incisors were removed horizontally. Lipopolysaccharide solution was applied to the exposed pulp tissue before the canal orifices were sealed with a temporary filling material. Melatonin (10 mg/kg) and 5-MTX (5 mg/kg) were administered intraperitoneally. The rats were sacrificed 24 hours after pulp injury, and trunk blood and pulp samples were collected. The concentrations of TNF-α, IL-1β, MMP-1, and MMP-2 in sera and pulp samples were determined using ELISA assay kits. RESULTS: TNF-α, IL-1β, MMP-1, and MMP-2 levels in the serum and pulp tissues were considerably higher in the AP group than the control group (p < 0.01-0.001). In the AP+melatonin and AP+5-MTX groups, TNF-α, IL-1β, MMP-1, and MMP-2 levels in the serum and pulp tissues were significantly lower than in the AP group (p < 0.05-0.001). CONCLUSIONS: Both melatonin and 5-MTX provided protective effects on acute pulpitis, which indicates they may be promising as a therapeutic strategy for oral disease.

OBJECTIVE: To evaluate the influence of manual therapy of the chest and diaphragm on the spirometry parameters in patients with cerebral palsy (CP). METHOD: The study was carried out on 20 youths with CP. All participated in 6 sessions (3 sham and 3 actual), with measurements of spirometry at baseline, postsham therapies 1 and 3, before actual therapy, and postactual therapy sessions 1 and 3. Two manual techniques were included: soft tissue mobilization of the chest and the diaphragm. RESULTS: After the first actual therapy, there was a significant (p < 0.01) improvement in forced vital capacity (FVC) by 0.23 L (8% of the average predicted value) and forced expiratory volume in one second (FEV1) by 0.18 L (7% of the average predicted value) as compared to results before the therapy. Change in FVC parameter was clinically significant, whereas change in FEV1 was not clinically significant. After sham therapy, there was no improvement in spirometry parameters as compared to baseline results. CONCLUSION: Single-time manual therapy of the chest and diaphragm has a positive effect on FVC and FEV1.

PPP2R5D-related neurodevelopmental disorder, which is mainly caused by de novo missense variants in the PPP2R5D gene, is a rare autosomal dominant genetic disorder with about 100 patients and a total of thirteen pathogenic variants known to exist globally so far. Here, we present a 24-month-old Chinese boy with developmental delay and other common clinical characteristics of PPP2R5D-related neurodevelopmental disorder including hypotonia, macrocephaly, intellectual disability, speech impairment, and behavioral abnormality. Trio-whole exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variant. The pathogenicity of the variant was evaluated using bioinformatics tools. We identified a novel pathogenic variant in the PPP2R5D gene (c.620G>T, p.Trp207Leu). The variant is located in the variant hotspot region of this gene and is predicted to cause PPP2R5D protein dysfunction due to an increase in local hydrophobicity and unstable three-dimensional structure. We report a novel pathogenic variant of PPP2R5D associated with PPP2R5D-related neurodevelopmental disorder from a Chinese family. Our findings expanded the phenotypic and mutational spectrum of PPP2R5D-related neurodevelopmental disorder.

Hepatic fibrosis is a consequence of chronic liver diseases. Metalloproteinase and its inhibitor have crucial roles in the resolution of liver fibrosis. The current relevant study is aimed to evaluate the therapeutic effect of Haematococcus pluvialis (H. pluvialis) extract, astaxanthin-rich fraction, astaxanthin ester-rich fraction, and β-carotene-rich fraction as well as their mechanisms of action in curing hepatic fibrosis induced by thioacetamide (TAA). Liver fibrosis was induced using TAA (intraperitoneal injection, two times a week for 6 weeks), in a rat model and H. pluvialis extract (200 mg/kg), and other fractions (30 mg/kg) were orally administered daily for 4 weeks after the last TAA injection. Based on HPLC analysis, H. pluvialis extract contains β-carotene (12.95 mg/g, extract) and free astaxanthin (10.85 mg/g, extract), while HPLC/ESI-MS analysis revealed that H. pluvialis extract contains 28 carotenoid compounds including three isomers of free astaxanthin, α or β-carotene, lutein, 14 astaxanthin mono-esters, 5 astaxanthin di-esters, and other carotenoids. H. pluvialis and its fractions reduced liver enzymes, nitric oxide, collagen 1, alpha-smooth muscle actin, and transforming growth factor-beta as well as elevated catalase antioxidant activity compared to the TAA group. Also, H. pluvialis extract and its fractions exceedingly controlled the balance between metalloproteinase and its inhibitor, activated Kupffer cells proliferation, and suppressed liver apoptosis, necrobiosis, and fibrosis. These findings conclude that H. pluvialis extract and its fractions have an antifibrotic effect against TAA-induced liver fibrosis by regulating the oxidative stress and proinflammatory mediators, suppressing multiple profibrogenic factors, and modulating the metalloproteinase and its inhibitor pathway, recommending H. pluvialis extract and its fractions for the development of new effective medicine for treating hepatic fibrosis disorders.

Increasing evidence has shown that noncoding RNAs play significant roles in the initiation, progression, and metastasis of tumours via participating in competing endogenous RNA (ceRNA) networks. However, the survival-associated ceRNA in lung adenocarcinoma (LUAD) remains poorly understood. In this study, we aimed to investigate the regulatory mechanisms underlying ceRNA in LUAD to identify novel prognostic factors. mRNA, lncRNA, and miRNA sequencing data obtained from the GDC data portal were utilized to identify differentially expressed (DE) RNAs. Survival-related RNAs were recognized using univariate Kaplan-Meier survival analysis. We performed functional enrichment analysis of survival-related mRNAs using the clusterProfiler package of R and STRING. lncRNA-miRNA and miRNA-mRNA interactions were predicted based on miRcode, Starbase, and miRanda. Subsequently, the survival-associated ceRNA network was constructed for LUAD. Multivariate Cox regression analysis was used to identify prognostic factors. Finally, we acquired 15 DE miRNAs, 49 DE lncRNAs, and 843 DE mRNAs associated with significant overall survival. Functional enrichment analysis indicated that survival-related DE mRNAs were enriched in cell cycle. The survival-associated lncRNA-miRNA-mRNA ceRNA network was constructed using five miRNAs, 49 mRNAs, and 21 lncRNAs. Furthermore, seven hub RNAs (LINC01936, miR-20a-5p, miR-31-5p, TNS1, TGFBR2, SMAD7, and NEDD4L) were identified based on the ceRNA network. LINC01936 and miR-31-5p were found to be significant using the multifactorial Cox regression model. In conclusion, we successfully constructed a survival-related lncRNA-miRNA-mRNA ceRNA regulatory network in LUAD and identified seven hub RNAs, which provide novel insights into the regulatory molecular mechanisms associated with survival of LUAD, and identified two independent prognostic predictors for LUAD.

Exercise-induced benefits are being increasingly recognized in promoting health and preventing diseases. However, initial adaption to exercise response can have different effects on cells, including an increase in the formation of oxidants and inflammatory mediators that ultimately leads to oxidative stress, but this scenario depends on the exercise type and intensity and training status of the individual. Therefore, we aimed to understand the effect of different types of exercise on oxidative stress. Indeed, exercise-induced minimum oxidative stress is required for regulating signaling pathways. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a search for relevant articles was carried out on PubMed/Medline, ISI Web of Science, and Google Scholar using a broad range of synonyms such as oxidants, reactive oxygen species (ROS), oxidative stress, exercise, physical training, aerobic exercise, and strength exercise until 2019. This study selected a total of 18 articles for assessing the oxidative damage using various parameters such as malondialdehyde (MDA), protein carbonyl (PCO), and F1-isoprostanes and enzymatic antioxidants. We observed that any type of exercise can increase the oxidative damage in an exercise type and intensity manner. Further, the training status of the individual and specific oxidative damage marker plays a crucial role in predicting earlier oxidative damage in the exercise condition. However, some of the studies that we included for review did not perform follow-up evaluations. Therefore, follow-up programs using larger numbers need to be performed to confirm our findings.

Accurate segmentation of abdominal organs has always been a difficult problem, especially for organs with cavities. And MRI-guided radiotherapy is particularly attractive for abdominal targets compared with low CT contrast. But in the limit of radiotherapy environment, only low field MRI segmentation can be used for stomach location, tracking, and treatment planning. In clinical applications, the existing 3D segmentation network model is trained by the low field MRI, and the segmentation result cannot be used in radiotherapy plan since the bad segmentation performance. Another way is that historical high field intensity MR images are directly used for data expansion to network learning; there will be a domain shift problem. How to use different domain images to improve the segmentation accuracy of deep neural network? A 3D low field MRI stomach segmentation method based on transfer learning image enhancement is proposed in this paper. In this method, Cycle Generative Adversarial Network (CycleGAN) is used to construct and learn the mapping relationship between high and low field intensity MRI and to overcome domain shift. Then, the image generated by the high field intensity MRI through the CycleGAN network is with transferred information as the extended data. The low field MRI combines these extended datasets to form the training data for training the 3D Res-Unet segmentation network. Furthermore, the convolution layer, batch normalization layer, and Relu layer together were replaced with a residual module to relieve the gradient disappearance of the neural network. The experimental results show that the Dice coefficient is 2.5 percent better than the baseline method. The over segmentation and under segmentation are reduced by 0.7 and 5.5 percent, respectively. And the sensitivity is improved by 6.4 percent.

Major depressive disorder (MDD) is a prevalent, chronic, and relapse-prone psychiatric disease. However, the intermediate molecules resulting from stress and neurological impairment in different brain regions are still unclear. To clarify the pathological changes in the dentate gyrus (DG) and anterior cingulate cortex (ACC) regions of the MDD brain, which are the most closely related to the disease, we investigated the published microarray profile dataset GSE84183 to identify unpredictable chronic mild stress- (UCMS-) induced differentially expressed genes (DEGs) in the DG and ACC regions. Based on the DEG data, functional annotation, protein-protein interaction, and transcription factor (TF) analyses were performed. In this study, 1071 DEGs (679 upregulated and 392 downregulated) and 410 DEGs (222 upregulated and 188 downregulated) were identified in DG and ACC, respectively. The pathways and GO terms enriched by the DEGs in the DG, such as cell adhesion, proteolysis, ion transport, transmembrane transport, chemical synaptic transmission, immune system processes, response to lipopolysaccharide, and nervous system development, may reveal the molecular mechanism of MDD. However, the DEGs in the ACC involved metabolic processes, proteolysis, visual learning, DNA methylation, innate immune responses, cell migration, and circadian rhythm. Sixteen hub genes in the DG (Fn1, Col1a1, Anxa1, Penk, Ptgs2, Cdh1, Timp1, Vim, Rpl30, Rps21, Dntt, Ptk2b, Jun, Avp, Slit1, and Sema5a) were identified. Eight hub genes in the ACC (Prkcg, Grin1, Syngap1, Rrp9, Grwd1, Pik3r1, Hnrnpc, and Prpf40a) were identified. In addition, eleven TFs (Chd2, Zmiz1, Myb, Etv4, Rela, Tcf4, Tcf12, Chd1, Mef2a, Ubtf, and Mxi1) were predicted to regulate more than two of these hub genes. The expression levels of ten randomly selected hub genes that were specifically differentially expressed in the MDD-like animal model were verified in the corresponding regions in the human brain. These hub genes and TFs may be regarded as potential targets for future MDD treatment strategies, thus aiding in the development of new therapeutic approaches to MDD.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) display high tumor tropism and cause indirect effects through the cytokines they secrete. However, the effects of BM-MSCs on the biological behaviors of glioblastoma multiforme remain unclear. In this study, the conditioned medium from BM-MSCs significantly inhibited the proliferation of C6 cells (P < 0.05) but promoted their migration and invasion (P < 0.05). Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) proteomic analysis revealed 17 proteins differentially expressed in C6 cells exposed to the BM-MSC-conditioned medium including five upregulated proteins and 12 downregulated proteins. Among these, six differentially expressed proteins (Calr, Set, Oat, Npm1, Ddah1, and Tardbp) were closely related to cell proliferation and differentiation, and nine proteins (Pdia6, Sphk1, Anxa4, Vim, Tuba1c, Actr1b, Actn4, Rap2c, and Tpm2) were associated with motility and the cytoskeleton, which may modulate the invasion and migration of tumor cells. Above all, by identifying the differentially expressed proteins using proteomics and bioinformatics analysis, BM-MSCs could be genetically modified to specifically express tumor-suppressive factors when BM-MSCs are to be used as tumor-selective targeting carriers in the future.

The prediction of drug-target interaction (DTI) is a key step in drug repositioning. In recent years, many studies have tried to use matrix factorization to predict DTI, but they only use known DTIs and ignore the features of drug and target expression profiles, resulting in limited prediction performance. In this study, we propose a new DTI prediction model named AdvB-DTI. Within this model, the features of drug and target expression profiles are associated with Adversarial Bayesian Personalized Ranking through matrix factorization. Firstly, according to the known drug-target relationships, a set of ternary partial order relationships is generated. Next, these partial order relationships are used to train the latent factor matrix of drugs and targets using the Adversarial Bayesian Personalized Ranking method, and the matrix factorization is improved by the features of drug and target expression profiles. Finally, the scores of drug-target pairs are achieved by the inner product of latent factors, and the DTI prediction is performed based on the score ranking. The proposed model effectively takes advantage of the idea of learning to rank to overcome the problem of data sparsity, and perturbation factors are introduced to make the model more robust. Experimental results show that our model could achieve a better DTI prediction performance.

OBJECTIVE: To assess the mortality and attrition rates within the first year of antiretroviral therapy (ART) initiation among people living with human immunodeficiency virus (PLHIV) in rural Guangxi, China. DESIGN: Observational cohort study. Setting. The core treatment indicators and data were collected with standard and essential procedures as per the Free ART Manual guidelines across all the rural health care centers of Guangxi. Participants. 58,115 PLHIV who were under ART were included in the study. Interventions. The data collected included sociodemographic characteristics that consist of age, sex, marital status, route of HIV transmission, CD4 cell count before ART, initial ART regimen, level of ART site, and year of ART initiation. Primary and Secondary Outcome Measures. Mortality and attrition rate following ART initiation. RESULTS: The average mortality rate was 5.94 deaths, and 17.52 attritions per 100 person-years within the first year of ART initiation among PLHIV. The mortality rate was higher among intravenous drug users (Adjusted Hazard Ratio (AHR) 1.27, 95% Confidence Interval (CI) 1.14-1.43), prefecture as a level of ART site (AHR 1.14, 95% CI 1.02-1.28), and county as the level of ART site (AHR 2.12, 95% CI 1.90-2.37). Attrition was higher among intravenous drug users (AHR 1.87, 95% CI 1.75-2.00), the first-line ART containing AZT (AHR 1.09, 95% CI 1.03-1.16), and first-line ART containing LVP/r (AHR 1.34, 95% CI 1.23-1.46). CONCLUSION: The mortality and attrition rates were both at the highest level in the first year of post-ART; continued improvement in the quality of HIV treatment and care is needed.

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare low-grade metastatic tumor; however, LAM patients were always found in young age with difficulty for diagnosis. Our study is aimed at observing the clinical characteristics of patients with lymphangiomatosis, including the clinical manifestations, imaging findings, histopathological features, and immunophenotype. METHODS: We did a systematic review on LAM/PLAM cases, especially on male cases, and collected the clinical features and molecular mechanisms of PLAM based on previous findings. RESULTS: Diagnosis criteria were summarized by combining CT scans, MRI, immunohistochemistry results, and gene sequencing results for effectively distinguishing between PLAM and similar diseases. Moreover, our study illustrated the molecular mechanism of PLAM as well as the signaling pathway involved in the disease initials. In addition, a male case was reported with differential diagnosis on the clinical manifestations, microscopic features, immunophenotypes, and genotypes. CONCLUSION: Our review will definitely improve the understanding of diagnosis and treatment in PLAM cases.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is one of the worst-prognosis malignant tumors. This study used bioinformatic analysis of the transcriptome sequencing data of HNSCC and the patients' survival and clinical data to construct a prediction signature of glycolysis-related genes as the prognostic risk markers. METHODS: Gene expression profile data about HNSCC tissues (n = 498) and normal tissues in the head and neck (n = 44) were got from The Cancer Genome Atlas (TCGA), as well as patients' survival and clinical data. Then, we obtained core genes; their expression in head and neck squamous cell carcinoma tissues is significantly different from that in normal head and neck tissues. The predicted glycolysis-related genes are screened through univariate Cox regression analysis, and then, the prognostic risk markers were constructed through further correction of multivariate Cox regression analysis. The Kaplan-Meier curve and receiver operating characteristic curve are used to analyze the potential value of these risk markers in diagnosis and prognosis. We also evaluated that the glycolysis-related prognostic risk markers composed of 6 oncogenes are correlated with clinical features, such as age, gender, grade, and clinical stage of the tumor, by univariate and multivariate Cox regression analyses. RESULTS: Differentially expressed glycolytic genes in HNSCC tissues and normal head and neck tissues were screened from TCGA databases using the bioinformatic method. We confirmed a set of six glycolytic genes that were significantly associated with OS in the test series. According to our analysis, the prognostic risk markers composed of HPRT1, STC2, PLCB3, GPR87, PYGL, and SLC5A12 may be an independent risk factor for the prognosis of HNSCC. CONCLUSIONS: Through this analysis, we constructed new prognostic risk markers related to glycolysis as a prognostic risk marker for patients with HNSCC and provided new ideas and molecular targets for the research and individualized treatment of HNSCC.

OBJECTIVES: Our study will investigate the effect of ultrasound-guided thoracic paravertebral block (UG-TPVB) on postoperative pain, quality of life, and enhanced recovery in patients with non-small-cell lung cancer (NSCLC) undergoing lobectomy surgery. METHODS: Our study included 100 patients aged 52 to 75 years who underwent lobectomy surgery with pathological diagnosis of NSCLC. Patients received ultrasound-guided thoracic paravertebral block or general anesthesia with tracheal intubation. Patients' pain score was recorded on a numeric rating scale (NRS) 24 hours post operation. The total postoperative dosage of tramadol hydrochloride, length of hospitalization, quality of life (QoL), and inflammation levels were recorded. RESULTS: Compared with patients who received general anesthesia with tracheal intubation, patients in the UG-TPVB group had lower postoperative NRS scores at 24 h (1.8 vs. 3.5, P = 0.035); the average 24 h postoperative NRS score of the UG-TPVB group is lower than that of the general anesthesia with tracheal intubation (4.6 vs. 5.3, P = 0.012), thus receiving less dosage of tramadol hydrochloride (221 ± 45 vs. 250 ± 38 mg, P < 0.01). Patients in the UG-TPVB group had better EORTC QLQ-C30 scores compared with patients in the general anesthesia with tracheal intubation group. The difference of length of hospitalization, hs-CRP, and IL-6 between two groups did not reach statistical difference (length of hospitalization 6.2 vs. 6.9 days, P = 0.055; hs-CRP: 7.1 ± 1.9 vs. 10.4 ± 6.6, P = 0.095; and IL-6: 71.3 ± 7.2 vs. 68.9 ± 8.7, P = 0.529). Discussion. NSCLC patients undergoing lobectomy surgery who received UG-TPVB had less postoperative pain, used less dosage of tramadol hydrochloride, and had better QoL.

OBJECTIVE: We aimed to investigate the protective effect of s-nitrosoglutathione (SNG) pretreatment on acute kidney injury (AKI) in septic rats. METHODS: We constructed a rat model of sepsis by cecal ligation and puncture and observed the survival of the rats. We obtained kidney and blood samples from rats, observed the pathological damage to the kidney tissues, and evaluated kidney function and the expression levels of inflammatory factors. We also detected the expression of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the kidneys by immunohistochemistry and evaluated the apoptosis of kidney tubular epithelial cells (KTEC) by TUNEL. RESULTS: Pretreatment with SNG significantly reduced the mortality of septic rats, attenuated kidney pathological damage, and decreased the levels of serum creatinine, plasma neutrophil gelatinase-associated lipocalin, and plasma kidney injury molecule-1. Moreover, SNG pretreatment decreased the levels of TNF-α and IL-1β in serum and kidney and reduced the expressions of NO, iNOS, PGE2, and COX-2 in the kidneys. Furthermore, pretreatment with SNG significantly reduced the apoptotic rate of KTEC and decreased the levels of caspase-3 and Bax mRNA, but increased the level of Bcl-2 mRNA. CONCLUSION: Pretreatment with SNG has a protective effect on AKI in septic rats, and the specific mechanisms are related to inhibition of inflammation, oxidation, and apoptosis.

[This retracts the article DOI: 10.1155/2014/526391.].

PURPOSE: Chronic periodontitis (CP) is a long-lasting inflammatory disease that seriously affects oral health. This study is aimed at investigating the regulatory mechanism of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in CP. METHODS: Primary human periodontal ligament cells (PDLCs) were treated with P. gingivalis lipopolysaccharide (LPS) to establish a CP model. Quantitative real-time PCR (qRT-PCR) was used to measure the expression of MALAT1 and miR-769-5p in gingival tissues of patients with CP and LPS-treated PDLCs. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of inflammatory cytokines. The protein levels of caspase-3, Bax, Bcl-2, and hypoxia-inducible factor (HIF) 3A were determined by western blot assay. Dual-luciferase reporter (DLR) assay was applied to validate the target relationships between miR-769-5p and MALAT1/HIF3A. RESULTS: The expression of MALAT1 and HIF3A was enhanced, and the expression of miR-769-5p was reduced in gingival tissues of patients with CP and LPS-treated PDLCs. MALAT1 knockdown promoted cell viability and inhibited inflammation and cell apoptosis in LPS-treated PDLCs. MALAT1 targeted miR-769-5p and negatively regulated miR-769-5p expression. miR-769-5p overexpression promoted cell viability and inhibited inflammation and cell apoptosis in LPS-treated PDLCs. Besides, miR-769-5p targeted HIF3A and negatively modulated HIF3A expression. Both miR-769-5p inhibition and HIF3A overexpression reversed the inhibitory effects of MALAT1 silencing on LPS-induced PDLC injury in vitro. CONCLUSION: MALAT1 knockdown attenuated LPS-induced PDLC injury via regulating the miR-769-5p/HIF3A axis, which may supply a new target for CP treatment.

Proton pumps are membrane-bound enzymes important in generating gradients that help in maintaining cellular ion homeostasis, cell membrane potential, water, and solute transport across the cell surface. This study investigated the modulatory role of vitamin E on proton pump activity and reproductive parameters in cadmium-induced testicular damage. Twenty (20) male Wistar rats weighing between 180 and 200 g were sorted into 4 groups of five rats each. Group I served as the control and was given normal saline orally, Group II rats were treated with a single dose of 2 mg/kg BW cadmium chloride (CdCl2) intraperitoneally, Group III rats were given 100 mg/kg BW of vitamin E orally, and Group IV rats were given 100 mg/kg BW of vitamin E orally for 30 days prior to intraperitoneal administration of single dose of 2 mg/kg BW of cadmium chloride. The rats were anaesthetized with diethyl ether, and blood samples were obtained for sex hormonal analysis; caudal epididymis was dissected for sperm count, motility, and viability, and the testis were homogenized for lipid peroxidation and proton pump (Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase) activity. Proton pump activity was assayed spectrophotometrically using the Stewart method to determine the inorganic phosphate level. Histopathological changes of the testis were also studied. The group treated with CdCl2 showed a significant (p < 0.05) decrease in proton pump activity, sperm count, and motility and a significant (p < 0.05) increase in malondialdehyde level when compared with the control group. The CdCl2-treated group also showed decrease reproductive organ weights and hormonal levels and cause necrosis of spermatogonia lining the seminiferous tubules. Rats treated with vitamin E orally for 30 days prior to CdCl2 exposure showed improvement in proton pump activity, a significant (p < 0.05) increase in sperm parameters and luteinizing hormonal level, and a decrease in the lipid peroxidation level as compared with the CdCl2 group. This study showed that vitamin E ameliorated the toxic effect of CdCl2 on proton pump activity in the testes, hence improving testicular integrity, structures, and functions.

PURPOSE: To discretely and collectively compare black hole sign (BHS) and satellite sign (SS) with recently introduced gemstone spectral imaging-based iodine sign (IS) for predicting hematoma expansion (HE) in spontaneous intracerebral hemorrhage (SICH). METHODS: This retrospective study includes 90 patients from 2017 to 2019 who underwent both spectral computed tomography angiography (CTA) as well as noncontrast computed tomography (NCCT) within 6 hours of SICH onset along with subsequent follow-up NCCT scanned within 24 hours. We named the presence of any of BHS or SS as any NCCT sign. Two independent reviewers analyzed all the HE predicting signs. Receiver-operator characteristic curve analysis and logistic regression were performed to compare the predictive performance of HE. RESULTS: A total of 61 patients had HE, out of which IS was seen in 78.7% (48/61) while BHS and SS were seen in 47.5% (29/61) and 41% (25/61), respectively. The area under the curve for BHS, SS, and IS was 63.4%, 67%, and 82.4%, respectively, while for any NCCT sign was 71.5%. There was no significant difference between IS and any NCCT sign (P = 0.108). Multivariate analysis showed IS (odds ratio 68.24; 95% CI 11.76-396.00; P < 0.001) and any NCCT sign (odds ratio 19.49; 95% CI 3.99-95.25; P < 0.001) were independent predictors of HE whereas BHS (odds ratio 0.34; 95% CI 0.01-38.50; P = 0.534) and SS (odds ratio 4.54; 95% CI 0.54-38.50; P = 0.165) had no significance. CONCLUSION: The predictive accuracy of any NCCT sign was better than that of sole BHS and SS. Both any NCCT sign and IS were independent predictors of HE. Although IS had higher predictive accuracy, any NCCT sign may still be regarded as a fair predictor of HE when CTA is not available.

The maintenance and sharing of electronic medical records are one of the essential tasks in the medical treatment combination. Traditional cloud-based electronic medical record storage system is difficult to realize data security sharing. The tamper resistance and traceability of blockchain technology provide the possibility for the sharing of highly sensitive medical data. This paper proposes a safe sharing scheme of stroke electronic medical records based on the consortium blockchain. The scheme adopts the storage method of ciphertext of medical records stored in the cloud and index of medical records stored on the blockchain. The privacy protection mechanism proposed in this paper innovatively combines proxy reencryption and searchable encryption which supports patient pseudoidentity search. The mechanism could achieve controllable sharing of medical records and precise search. According to the organizational characteristics of the stroke medical treatment combination, this paper proposes an improved Practical Byzantine Fault Tolerance mechanism to reach a consensus between consensus nodes. Then, the proposed scheme is analyzed and evaluated from three aspects of medical record integrity, user privacy, and data security. The results show that the scheme can not only ensure the privacy of patient identity information and private key data but also resist the tampering and deletion attacks of internal and external malicious nodes on the medical record data. Therefore, the proposed scheme is conducive to the improvement of the timeliness of stroke treatment and the safe sharing of electronic medical records in stroke medical treatment combination.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer that has a high level of morbidity and mortality. Long noncoding RNA (lncRNA) is a novel regulatory factor of tumour proliferation, apoptosis, and metastasis. Our previous studies indicated that lncRNA FOXP4-AS1 is a functional oncogene in HCC; thus, this study is aimed at further evaluating the clinical and biological function of FOXP4-AS1 in HCC. Material and Methods. First, we detected the expression of FOXP4-AS1 in HCC tissues and paracarcinoma normal tissues by qRT-PCR. Second, the prognostic effects of FOXP4-AS1 in patients with HCC were analysed in a training group and a verification group. Subsequently, to investigate the biological effects of FOXP4-AS1 on HCC cells, downexpression tests were further conducted. RESULTS: The expression of FOXP4-AS1 was higher in HCC tissues than adjacent nontumourous tissues, whereas the low expression of FOXP4-AS1 was correlated with optimistic treatment outcomes, which suggested that FOXP4-AS1 may be an independent prognostic biomarker for HCC. Moreover, the downregulation of FOXP4-AS1 significantly reduced the cell proliferation and clonal abilities and inhibited the invasion, migration, and angiogenesis of hepatoma cells (P < 0.05). CONCLUSION: These results revealed the clinical significance and biological function of FOXP4-AS1 in HCC development, which may provide a new direction for finding therapeutic targets and potential prognostic biomarkers of HCC.

OBJECTIVE: The mechanism of peach kernel-safflower in treating diabetic nephropathy (DN) was investigated using network pharmacology. METHODS: Network pharmacology methodology was applied to screen the effective compounds of peach kernel-safflower in the SymMap and TCMSP databases. Potential targets were then screened in the ETCM, SEA, and SymMap databases to construct a compound-target network. This was followed by screening of DN targets in OMIM, Gene, and GeneCards databases. The common targets of drugs and diseases were selected for analysis in the STRING database, and the results were imported into Cytoscape 3.8.0 to construct a protein-protein interaction network. Next, GO and KEGG enrichment analyses were performed. Finally, Schrödinger molecular docking verified the reliability of the results. RESULTS: A total of 23 effective compounds and 794 potential targets resulted from our screening process. Quercetin and luteolin were identified as the main effective ingredients in peach kernel-safflower. Furthermore, five key targets (VEGFA, IL6, TNF, AKT1, and TP53), AGE-RAGE, fluid shear stress and atherosclerosis, IL-17, and HIF-1 signaling pathways may be involved in the treatment of DN using peach kernel-safflower. CONCLUSIONS: This study embodies the complex network relationship of multicomponents, multitargets, and multipathways of peach kernel-safflower to treat DN and provides a basis for further research on its mechanism.

The present study is aimed at assessing the changes in tibial rotation at the osteotomy site after an open-wedge, high-tibial osteotomy (OWHTO) and analysing the factors that affect rotational changes in the distal tibial fragment relative to the proximal tibial fragment at the same site. This study involved 53 patients (60 knees; 16 males and 37 females) with medial osteoarthritis (OA) who underwent OWHTO and preoperative and 3-month postoperative computed tomography (CT) scans. Rotational angles of the distal tibia were measured using Stryker OrthoMap 3D by comparing preoperative and postoperative CTs. The mean rotational angle yielded an external rotation of 2.9° ± 4.8°. There were 17 knees with internal rotations, 37 knees with external rotations, and one knee with no rotation. The rotational angle significantly correlated with the resultant change in the femorotibial angle (correction angle) and the angle between the ascending and transverse osteotomy lines on the anterior osteotomised surface on which a flange was formed with the distal tibial osteotomised surface (flange angle). The flange angle affected the rotation, but it may have been affected by our surgical technique. The rotational angle did not significantly correlate with the change in the angle of the posterior tibial slope or body mass index. There were significant correlations between the rotational angle and correction angle (r = 0.42, p < 0.05). Additionally, the rotational angle correlated with the flange angle (r = -0.41, p < 0.05).

The association between blood urea nitrogen (BUN) and prognosis has been the focus of recent research. Therefore, the objective of this study was to investigate the association between BUN and hospital mortality in critically ill patients with cardiogenic shock (CS). This was a retrospective cohort study, in which data were obtained from the Medical Information Mart for Intensive Care III V1.4 database. Data from 697 patients with CS were analyzed. Logistic regression and subgroup analyses were used to assess the association between BUN and hospital mortality in patients with CS. The average age of the 697 participants was 71.14 years, and approximately 42.18% were men. In the multivariate logistic regression model, after adjusting for age, sex, diabetes, cardiac arrhythmias, urine output, simplified acute physiology score II, sequential organ failure assessment, creatinine, anion gap, and heart rate, high BUN demonstrated strong associations with increased in-hospital mortality (per standard deviation increase: odds ratio [OR] 1.47, 95% confidence interval [CI] 1.13-1.92). A similar result was observed in BUN tertile groups (BUN 23-37 mg/dL versus 6-22 mg/dL: OR [95% CI], 1.42 [0.86-2.34]; BUN 38-165 mg/dL versus 6-22 mg/dL: OR [95% CI], 1.99 [1.10-3.62]; P trend 0.0272). Subgroup analysis did not reveal any significant interactions among various subgroups, and higher BUN was associated with adverse clinical outcomes in patients with CS.

BACKGROUND: Chronic injuries of the distal tibiofibular syndesmosis are common in patients who fail to receive adequate diagnosis and timely treatment. Reconstruction of the distal tibiofibular syndesmosis with an autogenous tendon graft in these patients is effective, although relatively rarely reported. PURPOSE: To investigate clinical outcomes of syndesmosis reconstruction with an autogenous tendon graft for chronic injuries of the distal tibiofibular syndesmosis by reviewing the current literature. METHODS: An English literature search was conducted in the MEDLINE, CENTRAL, and Cochrane databases to identify published studies up to October 2017. Preset inclusion and exclusion criteria were applied to identify all eligible articles. RESULTS: Five studies (all with level IV evidence) that included a total of 51 patients who underwent reconstruction with an autogenous tendon graft were identified. It was reported that the symptoms were relieved postoperatively, including obviously improved functional outcomes and restoration of motions and exercise capacity. The mean American Orthopedic Foot and Ankle Society scale score of 16 patients was 53 preoperatively and 89 postoperatively. The visual analogue scale score of 14 patients decreased from 82.4 preoperatively to 12.6 postoperatively. A total of 5 (9.8%) complication cases were reported. CONCLUSION: Reconstruction of the distal tibiofibular syndesmosis with an autogenous tendon for chronic syndesmosis injury showed a good therapeutic effect in terms of both subjective symptoms and objective evaluation scores. The interosseous ligament could be an appropriate reconstruction target in the treatment of chronic syndesmosis injury.

The human papilloma virus (HPV) is responsible for different pathological manifestations in humans. This agent gives rise to lesions of different types and in different areas of the organism, including the oral cavity. The aim of this study is to show which are the main diseases for which HPV is responsible and to bring to light some of the interceptive and therapeutic strategies. The analysis was conducted by consulting the major scientific databases with the aim of obtaining information on the characteristics of oral HPV and its management; furthermore, the literature was supported by some clinical cases proposed by the authors. The role of dentistry is essential in the early diagnosis of this type of pathologies and above all in knowing how to direct patients towards a path that can lead to patient management, especially in the event that these lesions have a malignant potential. Enhancing the knowledge and role of dentistry can lead to early diagnosis of this type of injury, intercepting a pathology that could have multiorgan implications.