Imaging of CD8 receptors on T-cells by positron emission tomography (PET) has been considered a promising strategy for monitoring the treatment response to immunotherapy. In this study, a trial of imaging CD8 with our newly developed sequential multiple-agent receptor targeting (SMART) technology was conducted. Mice bearing a subcutaneous colorectal CT26 tumor received three times different immunotherapy treatments (PD1 or CTLA4 or combined). On either day 7 or day 14 after the first time treatment, the PET imaging study was performed with sequentially administered TCO-modified anti-CD8 antibody and 64Cu-labeled MeTz-NOTA-RGD. However, no positive response was detected, probably due to (1) inappropriate selection of biomarkers for the SMART strategy, (2) limited TCO modification on the anti-CD8 antibody, and (3) inadequate response of the CT26 tumor to the selected immunotherapies. Therefore, the potential of applying SMART in imaging CD8 was not demonstrated in this study, and further optimization will be necessary before it can be applied in imaging CD8.

INTRODUCTION: The determination of skeletal maturity stages is very important in orthodontic treatment planning, especially skeletal discrepancies in growing individuals. A hand-wrist radiograph is considered the most accurate approach for skeletal maturity detection. Dental calcification stages have been suggested as an alternative diagnostic method to decrease radiation exposure. The recent study is aimed at detecting the efficacy of dental calcification stages in assessing skeletal maturity during the prepubertal and pubertal growth periods. METHODS: Patients' records were collected from the Aleppo Orthodontic Center. Dental maturity stages were assessed from a panoramic radiograph using the Demirjian method, while skeletal maturity stages were determined using the Björk method. Four permanent left mandibular teeth were included (canine, 1st premolar, 2nd premolar, and 2nd molar) for the study. RESULTS: From 517 records, 295 records (145 males and 150 females) were included. The Spearman rank-order correlation coefficients between skeletal maturation and dental maturation were strong and statistically significant (ranging from 0.789 to 0.835). The highest correlation was between skeletal stages and the second molar (r = 0.829 and 0.88 in males and females, respectively). Receiver operating characteristic (ROC ) curve suggested a high validity of the sum of dental stages for the four teeth in identifying MP3= stage (sensitivity was 70%, specificity was 92.77%, and ROC area was 0.81) but not for MP3cap (sensitivity was 50.85%, specificity was 81.36%, and ROC area was 0.66). CONCLUSIONS: The correlation between the skeletal maturity stages and the dental calcification stages was high. The orthodontist can use the dental stages as a definite diagnostic tool for prepubertal growth period.

PURPOSE: Chemoresistance is a challenge of improving chemotherapeutic efficacy and prolonging survival time for patients with colorectal cancer (CRC); it is the major cause of frequent recurrence, rapid metastasis, and poor prognosis for CRC patients. FXYD6 is a regulator of Na+/K+-ATPase which is depressed in chemoresistant CRC patients. However, the biological roles of FXYD6 on regulating chemoresistance in CRC are still unclear. METHODS: GSE3964 and GSE69657 from GEO DataSets were used to analyze the relationship of genes and chemoresistance. The FXYD6 expression level was detected by western blotting and real-time PCR and also analyzed from TCGA DataSet. To investigate the functional role of FXYD6 and ATP-α1, FXYD6 and ATP-α1 functional cell models were constructed. Drug sensitivity and cell proliferation were performed by MTT assay. Autophagy and apoptosis were conducted by autophagy fluorescence analysis and flow cytometric analysis, respectively. Autophagy and apoptosis markers were tested by western blotting. RESULTS: FXYD6 was downregulated in CRC resistant patients and irinotecan- (Iri-) resistant SW620 cells (SW620/Iri). FXYD6 silence inhibited cell apoptosis and enhanced prosurvival autophagy, whereas FXYD6 overexpression produced the opposite effect which alleviated the drug resistance to irinotecan and oxaliplatin of CRC cells. FXYD6 regulates chemosensitivity by mediating the expression of Na+/K+-ATPase α1 and affecting cell autophagy and apoptosis in colorectal cancer. CONCLUSION: FXYD6 functions as a chemosensitivity regulator which may predict the curative effect of chemotherapy in colorectal cancer.

Erratum for Biomed Res Int. 2016;2016:8569684.

The emergence of multidrug resistant (MDR) bacteria which is attributable to extended spectrum β-lactamases (ESBLs) production of CTX-M types is an obvious problem worldwide. This study is aimed at determining the prevalence of CTX-M β-lactamases producing multidrug resistant Escherichia coli and Klebsiella pneumoniae among patients attending Bir Hospital. A cross-sectional study was conducted between April and September 2019 at Bir Hospital, Kathmandu, and Department of Microbiology, National College, Kathmandu, Nepal. A total of 5,690 different clinical specimens were subjected to cultural, microscopic, and biochemical analyses for the identification of the isolates. Antimicrobial susceptibility testing of the isolates was done, and MDR isolates were selected and processed for further ESBL confirmation by the combination disks method. All confirmed ESBL isolates were screened for CTX-M type β-lactamases (bla CTX-M) by PCR. Of the total 345 isolates (227 Escherichia coli and 118 Klebsiella pneumoniae), 232 were MDR. All 232 (67.24%) MDR isolates were suspected as ESBL producers on the screening test. However, on the phenotypic test, 135 (58.18%) of total MDR bacteria were confirmed as ESBL producers with the highest proportion in K. pneumoniae (59.37%). The major source of ESBL producers was urine. ESBL producing isolates were mostly identified from outpatients and patients belonging to age group 41-60. Gentamicin was found to be effective against ESBL producers. The prevalence of bla CTX-M was (89.62%) with the highest frequency for E. coli (93.81%). High prevalence of ESBL of CTX-M types among MDR E. coli and K. pneumoniae was detected from clinical specimens of patients in Bir Hospital. This study warrants the need for the judicious use of antibiotics as well as emphasize the use of modern diagnostic tools for the early detection of MDR and ESBL producers to curb the emergence and spread of MDR and ESBL producing bacteria in the clinical settings of Nepal.

Cirsimarin is a bioactive antilipogenic flavonoid isolated from the cotyledons of Abrus precatorius and represents one of the most abundant flavonoids present in this plant species. Cirsimarin exhibits excellent antioxidant, lipolysis, and other biological properties; it can effectively trigger lipid movement and demonstrates antiobesity effects. In this work, an ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of cirsimarin in rat plasma after intravenous administration. A standard curve of cirsimarin in blank rat plasma was generated over the concentration range of 1-3000 ng/mL. Six rats were administered cirsimarin intravenously (1 mg/kg). The method only required 50 μL of plasma for sample preparation, and the plasma proteins were precipitated with acetonitrile to pretreat the plasma sample. The precisions of cirsimarin in rat plasma were less than 14%, while the accuracies varied between 92.5% and 107.3%. In addition, the matrix effect varied between 103.6% and 107.4%, while the recoveries were greater than 84.2%. This UPLC-MS/MS method was then applied in measuring the pharmacokinetics of cirsimarin in rats. The AUC(0-t) values of cirsimarin from the pharmacokinetic analysis were 1068.2 ± 359.2 ng/mL·h for intravenous administration. The half-life (t 1/2) was 1.1 ± 0.4 h (intravenous), indicating that the metabolism of the compound was quick in the rats. Exploring the pharmacokinetics of cirsimarin in vivo can help better understand its metabolism.

PURPOSE: Neck and shoulder pain (NSP) is very common in the general population. However, scarce information exists on the relationship between NSP and health-related quality of life (HRQOL) outcomes in this population. The present study described NSP prevalence and its impact on the HRQOL of middle-aged and older persons undergoing a routine medical checkup. METHODS: This study recruited 318 subjects (125 males and 193 females; average age, 63.4 years) in good health, collected underwent anthropometric measurements, physical function examinations, and blood testing. This study defined NSP as the presence of muscle tension, stiffness, pressure, or dull pain in areas between the neck and the arch of the scapular. Study subjects were divided into two groups (NSP (+) and NSP (-) groups). The subjects completed questions on the Medical Outcomes Study 36-item short-form health survey (SF-36) and the EuroQol 5-dimension, 5-level version (EQ-5D-5L) tool. RESULTS: Of the patients, 150 and 168 were NSP (+) and NSP (-), respectively. The NSP complaint rate was 47.2%. The NSP (+) group had younger and more female participants than the NSP (-) group. In the multivariate regression analysis, the NSP (+) group had lower physical QOL based on the SF-36 physical component summary (odds ratio (OR), 2.45) and lower mental QOL based on the SF-36 mental component summary (OR, 2.05). Overall, the NSP (+) group had a higher risk of having low QOL scores (EQ-5D-5L index; OR, 1.76). CONCLUSIONS: The NSP (+) rate in healthy middle-aged and older persons was 47.2%. Furthermore, NSP (+) status was directly related poor HRQOL. NSP is a predictor of suboptimal physical and mental QOL. Therefore, NSP prevention or intervention for NSP may improve middle-aged and older adults' QOL.

METHODS: We prospectively included 200 patients with LAA-type AIS and tested their CRP levels on admission. We followed these patients consecutively. The primary outcome was an adverse event, defined as a modified Rankin Scale score of 2-6 at months 3, 6, and 12 after discharge. A logistic regression model was used to analyze the relationship between CRP and the functional outcome of LAA stroke. RESULTS: We divided 200 patients into 3 groups evenly based on CRP level. After adjustment for gender, age, smoking history, drinking history, history of hyperlipidemia, history of diabetes, lipid levels, and blood glucose levels, logistic regression showed that the incidence of LAA-type AIS poor outcome was positively associated with CRP level at admission, whether it was 3 months, 6 months, or 12 months after discharge, respectively (OR: 2.574, 95% CI: 1.213-5.463; OR: 2.806, 95% CI: 1.298-6.065; OR: 2.492, 95% CI: 1.167-5.321. In the highest tertile vs. the lowest tertile as a reference), and both were statistically different. CONCLUSIONS: High CRP level predicts poor functional outcome in LAA-type AIS patients, which provides a strong basis for clinicians to make treatment decisions for these patients.

Wallflower (Erysimum cheiri) is employed as a popular herbal drug in traditional Persian medicine. Topical formulations including cerates, lotions, sitz baths, and poultices for inflammatory disorders such as arthritis, anal fissure, endometriosis, and mastitis are known. However, there is no monograph in current pharmacopoeia for the wallflower drug. The present study is aimed to screen in vitro anti-inflammatory activity of wallflower and perform quality control and characterization tests for different organs of the herb. In this regard, albumin denaturation activity, macroscopic and microscopic, phytochemical, HPTLC, and FT-IR characteristics were investigated. Wallflower showed strong anti-inflammatory activity compared to diclofenac sodium. The root (1.25, 2.5, and 5 mg/mL) and flower (10 mg/mL) extract exhibited higher anti-inflammatory activities than that of other plant organs at the same concentrations. Moreover, total ash was found higher in aerial parts (21.52 ± 0.06%) than flower (11.01 ± 0.03%), root (5.03 ± 0.03%), and seed (6.95 ± 0.06%), while water-soluble ash was higher in seed (34.89 ± 0.26%) than flower (5.00 ± 0.03%), aerial parts (7.16 ± 0.06%), and root (5.04 ± 0.01%). Acid-insoluble ash and sulphated ash were higher in root (9.50 ± 0.04%) and aerial part (28.37 ± 0.57%), respectively. In addition, loss on drying was ranged from 2.20 ± 0.20% in flowers to 6.00 ± 0.10% in aerial parts. On the other hand, HPTLC analysis verified cardenolide compounds in all organs of the herb, and quercetin was detected in the flavonoid fingerprint of acid hydrolysed flowers. According to FT-IR results, the observed spectral region at ~3500 cm-1 attributed to -OH stretching vibration. Also, C-H (~2900-2950 cm-1), isothiocyanate (~2340 cm-1), -C=O (~1740 cm-1), conjugated C=C of the aromatic ring (~1650 cm-1), and structure of the aromatic group (~1200-1000 cm-1) were monitored. This work is the first study to the best of our knowledge, suggesting wallflower as a potential drug candidate with the basis for a monograph in addition to initial in vitro anti-inflammatory data.

MicroRNAs (miRNAs) have been demonstrated to involve in liver fibrogenesis. However, the miRNA-gene regulation in liver fibrosis is still unclear. Herein, the miRNA expression profile GSE40744 was obtained to analyze the dysregulated miRNAs between liver fibrosis and normal samples. Then, we predicted the target genes of screened miRNAs by miRTarBase, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, the protein-protein interaction (PPI) network was constructed to identify the functional miRNA-gene regulatory modules. Furthermore, we verified the hub gene expression using the gene expression profile GSE14323. Finally, 89 DEMs were identified in fibrotic liver samples compared to normal liver samples. The top 3 upregulated DEMs (miR-200b-3p, miR-200a-3p, and miR-182-5p) and downregulated DEMs (miR-20a-5p, miR-194-3p, and miR-148a-3p) were further studied. 516 and 1416 target genes were predicted, respectively. KEGG analysis demonstrated that the predicted genes were enriched in the p53 signaling pathway and hepatitis B, etc. Through constructing a PPI network, the genes with the highest connectivity were identified as hub genes. Of note, most of the hub genes were potentially targeted by miR-20a-5p and miR-200a-3p. Based on the data from GSE14323, the expression of EGFR, STAT3, CTNNB1, and TP53 targeted by miR-200a-3p was significantly downregulated in fibrotic liver samples. Oppositely, the expression of PTEN, MYC, MAPK1, UBC, and CCND1 potentially targeted by miR-20a-5p was significantly upregulated. In conclusion, it is demonstrated that miR-20a-5p and miR-200a-3p were identified as the novel liver fibrosis-associated miRNAs, which may play critical roles in liver fibrogenesis.

Erratum for Biomed Res Int. 2019 Nov 29;2019:3757149.

During the intake of contaminated water, for diarrheal disease to occur, Vibrio cholerae must survive through the bactericidal digestive secretion of gastric fluid during passage through the stomach. Determining the viability of these bacteria is challenging, with the standard cultivation methods for viability being time-consuming and unable to culture cells that may still function accordingly. This study assessed the use of enzyme action and membrane integrity as alternatives for determining vitality and viability, respectively, in gastric acid-stressed pathogenic Vibrio cholerae O1 and O139, using fluorescent probes thiazole orange (TO) for viability based on membrane integrity, carboxyfluorescein diacetate (CFDA) with acetoxymethyl ester (AM) for vitality based on metabolic activity, and propidium iodide (PI) for cell death/damage due to loss of membrane integrity, with flow cytometry. Simulated gastric fluid-treated bacterial cells were labelled with blends of TO+PI and CFDA-AM+PI, and these stained cells were separated into heterologous populations based on their fluorescence signal. The gastric acid exposed cells presented with high green fluorescence signals after staining with the metabolic probe CFDA-AM, which indicated intact (live) cells due to being metabolically active, whereas when the same cells were stained with the DNA probe (TO), these appeared to be in a "stressed state" due to loss of membrane integrity. Damaged cells (dead cells) showed high red fluorescence levels after staining with PI probe. The use of flow cytometry with fluorescent probes is a favorable method for evaluating the vitality and viability of bacteria when cells are labelled with a combination of CFDA-AM+PI.

Increasing evidences have revealed that N6-methyladenosine (m6A) RNA methylation regulators participate in the tumorigenesis and development of multiple tumors. So far, there has been little comprehension about the effects of m6A RNA methylation regulators on lower-grade gliomas (LGG). Here, we systematically investigated the expression profiles and prognostic significance of 36 m6A RNA methylation regulators in LGG patients from the TCGA and CGGA databases. Most of the m6A RNA methylation regulators are differentially expressed in LGG tissues as compared with normal brain tissues and glioblastoma (GBM) tissues. The consensus clustering for these m6A RNA methylation regulators identified three clusters. Patients in cluster 3 exhibited worse prognosis. In addition, we constructed an m6A-related prognostic signature, which exhibited excellent performance in prognostic stratification of LGG patients according to the results of the Kaplan-Meier curves, ROC curves, and univariate and multivariate Cox regression analyses. In addition, a significant correlation was observed between the m6A-related prognostic signature and the immune landscape of the LGG microenvironment. The high-risk group exhibited higher immune scores, stromal scores, and ESTIMATE scores but lower tumor purity and lower abundance of activated NK cells. Moreover, the expression level of immune checkpoints was positively correlated with the risk score. To conclude, the current research systematically demonstrated the prognostic roles of m6A RNA methylation regulators in LGG.

BACKGROUND: Cardiovascular disease (CVD) contributes critically to the mortality, morbidity, and economic problem of illness globally. Exercise is a share of everyone's life. Some evidence-based studies have frequently shown a progressive correlation between physical activity and good health. OBJECTIVE: The effects of daily exercise on cardiomyocyte size, collagen content (fibrosis), and releasing mast cells (MCs') tryptase of the model of myocardial infarction (MI) were assessed. METHODS: 40 rats were coincidentally spread into sham+inertia (control), sham+exercise, infarction+inertia, and infarction+exercise groups. An experimental model of acute MI was induced in infarction groups. One week after surgery, exercising groups were allowed to an aerobic exercise program for six weeks. At the endpoint of the study, all examinations were performed. RESULTS: We found lesser fibrosis in sham+exercise and infarction+exercise groups compared to sham+inertia and infarction+inertia groups, respectively (p = 0.023, p = 0.001). Also, infarction groups were significantly lower than sham groups (p < 0.05) and the infarction+exercise group was significantly lower than the infarction+inertia group (p < 0.05). The effect of exercise on MCs while increased MC density and degranulation occur at the site of fibrosis, we demonstrated that exercise decreases both total MC density and degranulation in both sham and infarction groups (p < 0.05). Immunohistochemistry examinations were significantly higher expression of MCs' tryptase in infarction groups than sham groups (p < 0.05, p < 0.0001). CONCLUSION: Exercise improves fibrosis and cardiac function in both healthy and MI rats by inhibiting released MCs' tryptase.

The study is aimed at establishing the optimal parameters for RNA purification of pooled specimens, in SARS-CoV-2 assay. This research work evaluates the difference of extracted RNA purity of pooled samples with and without treatment with isopropyl alcohol and its effect on real-time RT-PCR. As per the protocol of the Indian Council of Medical Research (ICMR), 5 sample pools were analysed using qRT-PCR. A total of 100 pooled samples were selected for the study by mixing 50 μL of one COVID-19 positive nasopharyngeal/oropharyngeal (NP/OP) specimen and 50 μL each of 4 known negative specimens. Pool RNA was extracted using the column-based method, and 1 set of pooled extracted RNA was tested as such, while RNA of the second set was treated additionally with chilled isopropyl alcohol (modified protocol). Further, the purity of extracted RNA in both the groups was checked using Microvolume Spectrophotometers (Nanodrop) followed by RT-PCR targeting E-gene and RNaseP target. The results showed that the purity index of extracted RNA of untreated pooled specimens was inferior to isopropyl alcohol-treated templates, which was observed to be 85% sensitivity and 100% specificity. The average Cq (E gene) in the unpurified and purified pool RNA group was 34.66 and 31.48, respectively. The nanodrop data suggested that purified RNA concentration was significantly increased with an average value of 24.73 ± 1.49 ng/uL, which might be the reason for high sensitivity and specificity. Thus, this group testing of SARS-CoV-2 cases using pools of 5 individual samples would be the best alternative for saving molecular reagents, personnel time, and can increase the overall testing capacity. However, purity of RNA is one of the important determinants to procure unfailing results, thus, this additional purification step must be included in the protocol after RNA has been extracted using commercially available kit before performing qRT-PCR.

OBJECTIVE: We aimed to evaluate the advantages of preoperative digital design of skin flaps to repair fingertip defects during the COVID-19 pandemic. We combined digital design with a 3D-printed model of the affected finger for preoperative communication with fingertip defect patients under observation in a buffer ward. METHODS: From December 2019 to January 2021, we obtained data from 25 cases of 30 fingertip defects in 15 males and 10 females, aged 20-65 years old (mean 35 ± 5 years). All cases were treated by digitally designing preoperative fingertip defect flaps combined with a 3D-printed model. Preoperative 3D Systems Sense scanning was routinely performed, 3-matic 12.0 was used to measure the fingertip defect area ranging from 1.5 cm × 3.5 cm to 2.0 cm × 5.0 cm, and the skin flap was designed. The flap area was 1.6 cm × 3.6 cm to 2.1 cm × 5.1 cm. CURA 15.02.1 was used to set parameters, and the 3D model of the affected finger was printed prior to the operation. Full-thickness skin grafts were taken from donor areas for repair. RESULTS: No vascular crises occurred in any of the 25 cases, and all flaps survived. The postoperative follow-up occurred over 3-12 months. All patients were evaluated 3 months after operation according to the trial standard of hand function evaluation of the Chinese Hand Surgery Society. The results showed that 20 cases had excellent outcomes (80%), four cases had good outcomes (16%), and one case had a fair outcome (4%). The excellent and good rate was 96%. CONCLUSIONS: During the COVID-19 epidemic, fingertip defects were treated with preoperative digital design of fingertip defect flaps combined with 3D printing. Precision design saves surgery time and improves the success rate of surgery and the survival rates of skin flaps. In addition, 3D model simulations improve preoperative communication efficiency, and the personalized design improves patient satisfaction.

OBJECTIVE: The aim of this study was to monitor the behavior of interfacial gaps formed under different bonded polymeric restorations before and after thermocycling (TC), using swept-source optical coherence tomography (SS-OCT) and confirming the obtained findings with confocal laser scanning microscopy (CLSM). MATERIALS AND METHODS: Cylindrical class I cavities were prepared in twenty noncarious human premolar teeth (1.5 mm depth × 3.5 mm diameter) and divided randomly into two groups: TS and SN, according to the adhesive system (n = 10). In the TS group, one-step self-etch adhesive Clearfil Tri-S Bond Plus (Kuraray Noritake Dental, Japan) was used, followed by composite restoration using Estelite Sigma Quick (Tokuyama Dental, Japan). In the SN group, the cavities were restored with the two-step self-etch/composite silorane-based resin restoration system (3M ESPE, USA). All specimens were restored in bulk filling technique and cured in accordance with the manufacturers' instructions. Both groups were imaged under SS-OCT after 24 h and recorded as controls. Then, each group was subjected to thermal challenge using the TC machine (5-55°C) and B-scans were recorded at different TC intervals (2600, 5200, and 10000). In order to confirm the SS-OCT findings, additional specimens were prepared, scanned, and sectioned for CLSM observation. RESULTS: B-scans demonstrated white clusters at the tooth-resin interface that corresponded to the gap location on CLSM images. The TS group showed significantly less gap formation than the SN group before and after TC (p < 0.001). CONCLUSIONS: An optimal composite adaptation can be achieved when the bonded restoration comprises a combination of an adhesive containing 10-MDP monomer and a considerable highly filled composite.

Virologic failure may occur because of poor treatment adherence and/or viral drug resistance mutations (DRM). In Brazil, the northern region exhibits the worst epidemiological scenarios for the human immunodeficiency virus (HIV). Thus, this study is aimed at investigating the genetic diversity of HIV-1 and DRM in Manaus. The cross-sectional study included people living with HIV on combined antiretroviral therapy and who had experienced virological failure during 2018-2019. Sequencing of the protease/reverse transcriptase (PR/RT) and C2V3 of the viral envelope gp120 (Env) regions was analyzed to determine subtypes/variants of HIV-1, DRMs, and tropism. Ninety-two individuals were analyzed in the study. Approximately 72% of them were male and 74% self-declared as heterosexual. Phylogenetic inference (PR/RT-Env) showed that most sequences were B subtype, followed by BF1 or BC mosaic genomes and few F1 and C sequences. Among the variants of subtype B at PR/RT, 84.3% were pandemic (B PAN), and 15.7% were Caribbean (B CAR). The DRMs most frequent were M184I/V (82.9%) for nucleoside reverse transcriptase inhibitors (NRTI), K103N/S (63.4%) for nonnucleoside reverse transcriptase inhibitor (NNRTI), and V82A/L/M (7.3%) for protease inhibitors (PI). DRM analysis depicted high levels of resistance for lamivudine and efavirenz in over 82.9% of individuals; although, low (7.7%) cross-resistance to etravirine was observed. A low level of resistance to protease inhibitors was found and included patients that take atazanavir/ritonavir (16.6%) and lopinavir (11.1%), which confirms that these antiretrovirals can be used-for most individuals. The thymidine analog mutations-2 (TAM-2) resistance pathway was higher in B CAR than in B PAN. Similar results from other Brazilian studies regarding HIV drug resistance were observed; however, we underscore a need for additional studies regarding subtype B CAR variants. Molecular epidemiology studies are an important tool for monitoring the prevalence of HIV drug resistance and can influence the public health policies.

Among the primary causes of cancer-associated death in the world, liver hepatocellular carcinoma (LIHC) ranks the third. LIHC is defined as the sixth most frequently diagnosed carcinoma. The gene mitochondrial carrier 1 (MTCH1) is a protein-coding gene. Recent research suggests that MTCH1 may be associated with some diseases. Here, our study attempts to explore the role and implication of MTCH1 in LIHC. Kaplan Meier Plotter and GEPIA (Gene Expression Profiling Interactive Analysis) databases were employed to determine the expression of MTCH1 and its correlation with prognostic status in LIHC patients. For the first time, our results suggested that MTCH1 was aberrantly expressed in human pan-cancer and highly expressed in LIHC. Its high expression was closely associated with metastasis of tumor, stage of cancer, and poor survival of patients. Then, through enrichment analysis, MTCH1 was found to be closely related to RNA splicing in LIHC. Subsequently, we conducted a series of functional experiments. PCR data showed that LIHC cell lines and samples are highly expressed MTCH1. CCK-8 (Cell Counting Kit-8) assays and Transwell assays indicated that silencing MTCH1 certainly suppressed cell proliferation, migration, and invasion. These findings shed the clue that MTCH1 could be regarded as the potential prognosis biomarker of LIHC and a promising therapeutic target for LIHC.

Adipose-derived mesenchymal stem cells (ADSCs) are a well-recognized multilineage stem cell with vital clinical feasibility for tissue regeneration. Extensive evidence indicates that oxidative stress and microRNAs (miRNAs/miRs) play an important role in the osteoinduction of adipose-derived mesenchymal stem cells. In this study, we investigated the mechanism of miR-125a-5p in regulating the osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs) under oxidative stress. The expression of miR-125a-5p lessened gradually during the osteogenic differentiation of hADSCs. Relative to the negative group, the expression levels of runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osterix in the miR-125a-5p group were marked lower than those in the miR-125a-5p inhibitor group. The levels of p16, p21, p53, miR-125a-5p, and ROS during osteoinduction of hADSCs were assessed in vitro under oxidative stress and were observed to be upregulated. Further experiments showed that oxidative stress and miR-125a-5p together suppressed the expression of VEGF during osteogenic differentiation of hADSCs and that the inhibition of miR-125a-5p reversed the effect of oxidative stress. In short, our study indicated that miR-125a-5p is induced under oxidative stress and inhibits the expression of VEGF, leading to the reduction of osteogenic differentiation of hADSCs. Our outcomes showed that miR-125a-5p could be a potential clinical target for bone repairing.

PURPOSE: Retrospective analysis of the effect of portable 3D gait analysis as an innovative evaluation method in the treatment with MTT on chronic ankle instability patient. METHODS: From January 1, 2019, to December 31, 2019, 56 cases of chronic ankle instability (CAI) were extracted from the medical record system of Shenzhen Longhua District Central Hospital. All the patients of 56 cases accepted the medical training therapy (MTT). As outcome parameters, the alterations of the Cumberland ankle instability tool (CAIT), foot and ankle ability measure (FAAM), were used before the treatment and after treatment; meanwhile, the portable apparatus 3D gait analysis was used to measure the gait parameters. CONCLUSION: The results showed only ankle angle parameters Y-axis, maximum dorsiflexion during support period (°) had a significant difference, and the p value is 0.039. Meanwhile, the CAIT, FAAM, and most 3D gait analysis data had no significant difference. This particular statistical difference shows that CAI can be measured scientifically and objectively, although most measurement parameters have no change. These results make further reveal that the CAI patients are suffering with dynamic abnormality of ankle motion angle; this also provides us with a measurable and systematic evaluation reference plan for CAI treatment in the future.

BACKGROUND: Erectile dysfunction has remained as one of the major global health issues. Since the discovery of phosphodiesterase type 5 inhibitors, a significant portion of the patients has solved the issue of erectile dysfunction. However, the wide distribution of phosphodiesterase type 5 enzymes at various sites of the body led phosphodiesterase type 5 inhibitors to cause various unnecessary outcomes. Hence, it is vital to look for and find optional agents that could solve these limitations. The people of Ethiopia depend heavily on medicinal plants to ease their ailments, including erectile dysfunction. Aim of the study. The current study was carried out to systematically review the traditional medicinal plants used for the management of erectile dysfunction in Ethiopia. METHOD: A systematic and manual search was conducted to retrieve relevant articles published from 2000 to August 2020. Electronic databases of PubMed (Medline), Google Scholar, and grey literature were employed to access the studies. Accordingly, fifty-four published articles and thesis papers were finally included in this study. RESULT: Seventy plant species have been reported for the management of erectile dysfunction in Ethiopia. The commonly recorded family was Fabaceae, followed by Asteraceae, Malvaceae, Convolvulaceae, and Solanaceae. The plant species that represented the highest number of citations were Asparagus africanus, succeeded by Ricinus communis and Carissa spinarum. The commonest plant part used was roots. Majority of the medicinal plants were administered orally. The growth forms of the reported species were primarily herbs followed by shrubs. CONCLUSION: The present review compiled medicinal plants utilized by the Ethiopian community to manage erectile dysfunction. The findings will serve as a reference for the selection of plants for further pharmacological, toxicological, and phytochemical investigations in developing new plant-based drugs used for the treatment of erectile dysfunction.

Xiaoxuming decoction (XXMD) is a traditional Chinese herbal medicine (CHM) that is used for the treatment of stroke in China. Stroke injury damages the cerebral vasculature and disrupts the autoregulation of vasoconstriction and vasodilatation, which is crucial for maintaining constant cerebral blood flow (CBF). It has been reported that XXMD exerts a positive effect on cerebral circulation in animal models of stroke. However, the mechanisms underlying the regulatory effect of XXMD on vascular tone, and the interactions among the multiple components of XXMD, remain unclear. In this study, XXMD was found to induce relaxation of the basilar artery rings of rats precontracted by 5-hydroxytryptamine (5-HT) in vitro, in a dose-dependent manner. The modulation of vascular tone and the process of cerebral ischemia are mediated via the interactions between G protein-coupled receptors (GPCRs) and their ligands, including 5-HT, angiotensin II (Ang II), and urotensin II (UII). Thus, the potential synergistic effects of the different components of XXMD on the regulation of vasoconstriction and vasodilation were further investigated by molecular docking based on network pharmacology. We constructed and analyzed a database comprising 963 compounds of XXMD and studied the interactions between five vascular GPCRs (5-HT1A receptor (5-HT1AR), 5-HT1B receptor (5-HT1BR), Ang II type 1 receptor (AT1R), beta 2-adrenergic receptor (β2-AR), and UII receptor (UTR)) and the various herbal constituents of XXMD using molecular docking. By constructing and analyzing the compound-target networks of XXMD, we found that Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, and Paeoniae Radix Alba were the three major herbs that contained a large number of compounds with high docking scores. We additionally observed that several constituents of XXMD, including gallotannin, liquiritin apioside, nariutin, 1,2,3,4,6-pentagalloylglucose, folic acid, and ginsenoside Rb1, targeted multiple vascular GPCRs. Moreover, the interactions between the components of XXMD and the targets related to vascular tone constituted the comprehensive cerebrovascular regulatory function of XXMD and provided a material basis of the vasoregulatory function of XXMD. The study reports the contributions of various components of XXMD to the regulatory effects on vascular tone and provides scientific evidence for the multicomponent and multitargeting characteristics of XXMD.

BACKGROUND: Neonatal sepsis is one of the major public health problems globally, particularly, in developing countries. Klebsiella, Staphylococcus aureus, Coagulase-negative Staphylococcus, and Escherichia coli are the common pathogens for neonatal sepsis in developing countries. However, the pooled estimate of common pathogens causing neonatal sepsis in developing countries is still unknown. Therefore, this study is aimed at computing the pooled proportion of the leading cause of pathogens for neonatal sepsis in developing countries. METHODS: We strictly followed the Preferred Reporting Items for Systemic Reviews and Meta-analysis guidelines to report this systematic review and meta-analysis. PubMed, Cochrane Library, Web of Science, CINAHL, Science Direct, and other search engines such as Google Scholar, Africa Journals Online, and Hinari were used to obtain studies related to the leading cause of pathogens for neonatal sepsis in developing countries. The search was done from October 1 to December 30, 2018, by considering both published and gray literature. Studies were evaluated based on the PRISMA guideline checklist by using their titles, abstracts, and full texts. Studies were extracted using Microsoft Excel spreadsheets, and STATA software version 14 was used to analyze data. Heterogeneity between studies was checked based on Cochran's Q-test and the corresponding I 2 statistic test. RESULTS: The pooled prevalence of the leading cause of pathogens of neonatal sepsis in developing countries were Klebsiella (26.36%), Staphylococcus aureus (23.22%), Coagulase-negative Staphylococcus (23.22%), and Escherichia coli (15.30%). Common pathogens were varied across regions; for instance, pooled isolated Coagulase-negative Staphylococcus was 25.98% in Africa, 16.62% in Asia, and 36.71% in Latin America, and Klebsiella was 29.80% in Africa, 23.21% in Asia, and 22.00% in Latin America. Also, Staphylococcus aureus was 27.87% in Africa and 18.28% in Asia, and Escherichia coli was 22.97% in Asia and 9.43% in Africa. CONCLUSIONS: This study highlights that the more prevalent common isolated pathogens in developing countries were Klebsiella, Staphylococcus aureus, Coagulase-negative Staphylococcus, and Escherichia coli, Klebsiella, and Staphylococcus aureus pathogens were predominantly high in Africa as compared to other Asian and Latin American countries. At the same time, Coagulase-negative Staphylococcus was more prevalent in Latin America compared to other regions. Escherichia coli is more dominant in Asia as compared to Africa and Latin America.

This study was aimed at investigating the effects of myocardial infarction- (MI-) associated extracellular vesicle- (EV-) delivered miR-208b on human umbilical vein endothelial cells (HUVECs). EVs were isolated and subsequently stained with PHK67. A dual-luciferase reporter gene assay was used to determine the target of miR-208b. Afterwards, HUVECs were transfected with either MI-associated EVs or miR-208b mimics, and cell viability, migration, and apoptosis were subsequently measured. Real-time quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expressions of the tested genes. NanoSight, transmission electron microscopy, and western blotting showed that EVs were successfully isolated. Among the potential microRNA biomarkers for MI, miR-208b was chosen for subsequent experiments. We found that MI-associated EVs could be taken up by HUVECs and confirmed that CDKN1A was a direct target of miR-208b. Additionally, miR-208b mimics and MI-associated EVs significantly inhibited the viability and migration of HUVECs (P < 0.05) and promoted cell apoptosis, as well as reduced S phase and increased G2/M phase cell distribution. RT-qPCR revealed that both miR-208b mimics and MI-associated EVs upregulated the expressions of CDKN1A, FAK, Raf-1, MAPK1, and Bax but downregulated the expression of Bcl2 and reduced the Bcl2/Bax ratio. Our study concludes that MI-associated EVs delivered miR-208b to HUVECs, and EV-delivered miR-208b could affect the growth of HUVECs by regulating the miR-208b/CDKN1A pathway; thus, miR-208b can be therefore served as important therapeutic targets for MI treatment.

BACKGROUND: Ischemia-reperfusion injury is one of the most critical phenomena in lung transplantation and causes primary graft failure. Its pathophysiology remains incompletely understood, although the inflammatory response and apoptosis play key roles. Lidocaine has anti-inflammatory properties. The aim of this research is to evaluate the effect of intravenous lidocaine on the inflammatory and apoptotic responses in lung ischemia-reperfusion injury. METHODS: We studied the histological and immunohistochemical changes in an experimental model of lung transplantation in pigs. Twelve pigs underwent left pneumonectomy, cranial lobectomy, caudal lobe reimplantation, and 60 minutes of graft reperfusion. Six of the pigs made up the control group, while six other pigs received 1.5 mg/kg of intravenous lidocaine after induction and a 1.5 mg/kg/h intravenous lidocaine infusion during surgery. In addition, six more pigs underwent simulated surgery. Lung biopsies were collected from the left caudal lobe 60 minutes after reperfusion. We conducted a double study on these biopsies and assessed the degree of inflammation, predominant cell type (monocyte-macrophage, lymphocytes, or polymorphous), the degree of congestion, and tissue edema by hematoxylin and eosin stain. We also conducted an immunohistochemical analysis with antibodies against CD68 antigens, monocyte chemoattractant protein-1 (MCP-1), Bcl-2, and caspase-9. RESULTS: The lungs subjected to ischemia-reperfusion injury exhibited a higher degree of inflammatory infiltration. The predominant cell type was monocyte-macrophage cells. Both findings were mitigated by intravenous lidocaine administration. Immunohistochemical detection of anti-CD68 and anti-MCP-1 showed higher infiltration in the lungs subjected to ischemia-reperfusion injury, while intravenous lidocaine decreased the expression. Ischemia-reperfusion induced apoptotic changes and decreased Bcl-2 expression. The group treated with lidocaine showed an increased number of Bcl-2-positive cells. No differences were observed in caspase-9 expression. CONCLUSIONS: In our animal model, intravenous lidocaine was associated with an attenuation of the histological markers of lung damage in the early stages of reperfusion.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic condition that manifests as inflammation of synovial joints, leading to joint destruction and deformity. METHODS: We identified single-cell RNA-seq data of synovial fibroblasts from RA and osteoarthritis (OA) patients in GSE109449 dataset. RA- and OA-specific cellular subpopulations were identified, and enrichment analysis was performed. Further, key genes for RA and OA were obtained by combined analysis with differentially expressed genes (DEGs) between RA and OA in GSE56409 dataset. The diagnostic role of key genes for RA was predicted using receiver operating characteristic (ROC) curve. Finally, we identified differences in immune cell infiltration between RA and OA patients, and utilized flow cytometry, qRT-PCR, and Western blot were used to examine the immune cell and key genes in RA patients. RESULTS: The cluster 0 matched OA and cluster 3 matched RA and significantly enriched for neutrophil-mediated immunity and ECM receptor interaction, respectively. We identified 478 DEGs. In the top 20 degrees of connection in the PPI network, the key genes for RA were obtained by comparing with the gene markers of cluster 0 and cluster 3, respectively. ROC curve showed that CCL2 and MMP13 might be diagnostic markers for RA. We found aberrant levels of CD8+T, neutrophil, and B cells in RA fibroblasts, which were validated in clinical samples. Importantly, we also validated the differential expression of key genes between RA and OA. CONCLUSION: High expression of CCL2 and MMP13 in RA may be a diagnostic and therapeutic target.

BACKGROUND: Subjective cognitive decline (SCD) is the earliest symptom stage of Alzheimer's disease (AD). Previous studies have shown that the study setting is an important influence factor of SCD. However, the effect of this factor among a Chinese population with SCD is not clear. Here, we aim to compare the clinical characteristics of SCD between a convenience and a population-based sample in China. METHODS: We included a convenience sample of 212 SCD subjects and a population-based sample of 110 SCD subjects. We performed univariate analysis to evaluate the between-group differences in sociodemographic characteristics, neuropsychological performance, psychiatric conditions, different cognitive domains, and the SCD-plus criteria. Multiple linear regression model was established, adjusted for sex, age, and education, and compared the neuropsychological performance between the groups. RESULTS: The convenience sample had more years of education, a higher family history of dementia, and higher neuropsychological and anxiety depression score than the population-based sample. Using sex, age, education, group as the independent variables, and neuropsychological score as the dependent variable, multiple linear regression model was established; a statistically significant neuropsychological score difference (MoCA-B, AVLT-H-N4, AVLT-H-N5, AVLT-H-N7, AFT, and STT-B) was found between the two samples. In the SCD cognitive domains, the population-based sample had more complaints about declines in their language and planning domains. For SCD-plus criteria in memory domain, the convenience sample had more complaints, worry, and cognitive decline within the last 5 years, along with medical help-seeking. CONCLUSION: There were some different characteristics among SCD individuals between convenience samples and population-based samples in China.

BACKGROUND: To ascertain the seasonal pattern and global public interest in osteoporosis by evaluating search term popularity changes of the disease over a decade. METHODS: We applied Google Trends to retrieve search popularity scores for the term "osteoporosis" between January 01, 2004, and December 31, 2019. Cosinor analyses were conducted to examine the seasonality of osteoporosis, and analysis on osteoporosis-related topics including hot topics and rising-related topics was also performed. RESULTS: The cosinor analyses demonstrated a statistically significant seasonal variation in relative search volume of the "osteoporosis" in the world (p = 0.0083), USA (p < 0.001), UK (p < 0.001), Canada (p < 0.001), Ireland (p < 0.001), Australia (p < 0.001), and New Zealand (p < 0.001), with a peak in the late winter months and trough in the summer months. The peaks in late winter and valley in summer presented an approximately 6-month difference between hemispheres. The top 11 rising topics were denosumab, FRAX, hypocalcaemia, zoledronic acid, ibandronic acid, osteomyelitis, osteopenia, osteoarthritis, bone, calcium, and bone density. CONCLUSIONS: Google search query volumes related to osteoporosis follow strong seasonal patterns with late winter peaks and summer troughs. Further studies aimed at elucidating the possible mechanisms behind seasonality in osteoporosis are needed. Moreover, Internet data including the top rising topics may alert physicians to strengthen the propaganda of osteoporosis timely, so as to further promote the development of public health interventions.

Reduction in isometric strength of the scapulohumeral muscles is a commonly seen impairment in overhead athletes afflicted with shoulder impingement syndrome (SIS). The purpose of this study was to compare the effects of two different treatment programs: progressive resistance exercises plus manual therapy (PRE plus MT) and motor control exercises (MCE), on isometric strength of upper trapezius (UT), middle trapezius (MTr), lower trapezius (LT), serratus anterior (SA), supraspinatus (Supr.), anterior deltoid (A.D), and latissimus dorsi (LD). 80 male university-level overhead athletes clinically diagnosed with SIS were randomly allocated into either of the two groups: PRE plus MT and MCE group. Athletes in the PRE plus MT group underwent graduated exercises with resistance elastic band, stretching exercises, and mobilization of the thoracic and shoulder joints. MCE group was submitted to motor control exercises in varied planar positions. Athletes in both groups underwent management 3 times a week for 8 weeks. Isometric strength of UT, MTr, LT, Supr, A.D, SA, and LD was measured at three-time points: baseline, 4th week, and 8th week. Relative to baseline, both interventions were found to be effective in increasing and optimizing the isometric strength of muscles (p < 0.05) except for supraspinatus in the MCE group (p > 0.05). However, athletes in PRE plus MT group presented a more pronounced increase in isometric strength than those in the MCE group. Between groups analysis found the largest isometric strength improvement in PRE plus MT group for A.D, followed by Supr. and UT muscles (p < 0.05; effect size: 0.39 to 0.40). The study concluded that compared to MCE, PRE plus MT provides greater improvement in the isometric strength of scapulohumeral muscles.

INTRODUCTION: As the clinical manifestation of neonatal infection is nonspecific and characterised by varied clinical features, it is highly problematic to establish an early diagnosis. Recently, hopes have been raised by the new acute-phase protein-pentraxin 3 (PTX3). PTX3 belongs to the family of long pentraxins, which is synthesized in numerous cells like endothelial cells, macrophages, and monocytes infiltrating sites of inflammation. Material and Methods. In our research, we have enrolled 29 newborns with infection as the study group and 47 healthy ones as the control group, as well as their mothers. The C-reactive protein (CRP), procalcitonin (PCT), and PTX3 levels were determined in venous blood samples from all investigated neonates and their mothers. Moreover, PTX3 concentrations were assessed in the umbilical cord. RESULTS: There were statistically significant differences in PTX3 levels between healthy and sick newborns both in the umbilical cord (p = 0.02) and venous blood (p = 0.01). The highest PTX3 concentrations were observed in children with infection in the presence of premature rupture of membranes (PROM). PTX3 concentrations in this group were significantly higher compared to those in healthy children without PROM. We observed elevated PCT levels in newborns with infection. No differences in CRP levels in 12 hours of life were noticed between the investigated groups. A comparison of ROC curves for PTX3 and PCT concentrations revealed similar sensitivity and specificity in the prediction of infection in neonates. CONCLUSIONS: Serum PTX3 is an important and specific biomarker of early infection. It is already elevated in the umbilical cord, so measuring PTX3 concentration might be useful in the early prediction of infection in newborns.

Low back pain which resulted from intervertebral disc degeneration (IDD) is a common health problem that afflicts people all over the world. Due to the lack of an overall understanding of the molecular interactions involved in IDD, we hope to better understand the pathogenetic mechanisms that drive the degenerative process. The purpose of this study is to obtain mRNAs, miRNAs, lncRNAs, and circRNAs associated with IDD gained from public databases and to establish an interaction network. According to the results of microarray analysis and bioinformatics analysis from the contrast of IDD and normal nucleus pulposus tissues, a total of 49 mRNAs, 10 miRNAs, 30 lncRNAs, and 4 circRNAs were obtained and a lncRNA/circRNA-miRNA-mRNA interaction network was constructed. NEAT1-miR-5100-COL10A1 and miR663AHG/HEIH/hsa-circ-0003600-miR-4741-HAS2/HYAL1/LYVE1 might be potential interaction axes of the molecular mechanism in IDD. The increased expression of NEAT1 might inhibit miR-5100 and subsequently upregulate the expression of COL10A1, which leads to IDD, while the increased expression of miR663AHG/HEIH/hsa-circ-0003600 might inhibit miR-4741 and indirectly upregulate HAS2/HYAL1/LYVE1, and leads to the protection from IDD. More interaction axes are to be exploited to provide theoretical bases for further study on IDD.

OBJECTIVE: To investigate the expression of microRNA-122 (miR-122) in the progression of chronic hepatitis B virus- (HBV-) infected liver diseases, thus determining the role of serum miR-122 as a marker of HBV-caused liver injury. METHODS: Sera were collected from patients with different stages of HBV infection (n = 63) and healthy volunteers (n = 11). And the serum miR-122 levels were detected using RT-qPCR. Moreover, an analysis was applied for identifying the specific correlation of the miR-122 level with HBV DNA, HBeAg, and ALT levels. After liver biopsy, Ishak scoring was utilized for evaluation of the fibrosis stage and the histological activity index (HAI). RESULTS: We confirmed, in the serum, increased miR-122 expression in HBV-infected patients and its highest expression in chronic HBV carriers, based on such comparison between the healthy controls and patients. The correlation analysis results were taken as confirmation of the positive relationship of miR-122 with HBV DNA (r = 0.354, P = 0.005) and ALT (r = 0.331, P = 0.009). But no correlation of this molecule with HBeAg levels was found (P = 0.187). In comparison with the HBeAg-negative patients, serum miR-122 expression showed an increase in the HBeAg-positive patients (P = 0.001). miR-122 expression, in addition, was of a significant correlation with HAI, but not with the liver fibrosis score. CONCLUSION: The peak of the serum miR-122 expression normally occurs in the early stage of the progression from the HBV carrier phase to chronic hepatitis to cirrhosis. This molecule can be considered as a marker for evaluation of HBV-caused liver injury.

BACKGROUND: Cervical radiculopathy is defined as a disorder involving dysfunction of the cervical nerve roots characterised by pain radiating and/or loss of motor and sensory function towards the root affected. There is no consensus on a good definition of the term. In addition, the evidence regarding the effectiveness of manual therapy in radiculopathy is contradictory. OBJECTIVE: To assess the effectiveness of manual therapy in improving pain, functional capacity, and range of motion in treating cervical radiculopathy with and without confirmation of altered nerve conduction. METHODS: Systematic review of randomised clinical trials on cervical radiculopathy and manual therapy, in PubMed, Web of Science, Scopus, PEDro, and Cochrane Library Plus databases. The PRISMA checklist was followed. Methodological quality was evaluated using the PEDro scale and RoB 2.0. tool. RESULTS: 17 clinical trials published in the past 10 years were selected. Manual therapy was effective in the treatment of symptoms related to cervical radiculopathy in all studies, regardless of the type of technique and dose applied. CONCLUSIONS: This systematic review did not establish which manual therapy techniques are the most effective for cervical radiculopathy with electrophysiological confirmation of altered nerve conduction. Without this confirmation, the application of manual therapy, regardless of the protocol applied and the manual therapy technique selected, appears to be effective in reducing chronic cervical pain and decreasing the index of cervical disability in cervical radiculopathy in the short term. However, it would be necessary to agree on a definition and diagnostic criteria of radiculopathy, as well as the definition and standardisation of manual techniques, to analyse the effectiveness of manual therapy in cervical radiculopathy in depth.

This study is aimed at proving the clinical benefit of the MELISA® test in the minimization or complete elimination of health problems in patients with confirmed hypersensitivity to metals used for tissue replacements. A group of 305 patients aged 20-75 years with previously proven metal hypersensitivity (initial MELISA® test), mainly to titanium and then to another fifteen metals, was chosen from the database at the Institute of Dental Medicine. From these patients, a final group of 42 patients agreed to participate in the study, 35 of which were female and 7 were male. The patients completed a special questionnaire aimed at information regarding change of health status from their last visit and determining whether the results of the initial MELISA® test and recommendations based on it were beneficial for patients or not. They were clinically examined, and peripheral blood samples were taken to perform follow-up MELISA® tests. Questionnaire data was processed, and the follow-up MELISA® test results were compared with the results of the initial MELISA® tests. For statistical analysis, the Fisher's exact test and paired T-test were used. Thirty-two patients reported that they followed the recommendations based on the results of the initial MELISA® tests, and of these, 30 patients (94%) confirmed significant health improvement. Six patients did not follow the recommendation, and from these, only one patient reported an improvement in his health problems. By comparison of the initial and follow-up MELISA® test results, it can be stated that the hypersensitivity to the given metal decreased or disappeared after the therapeutic interventions performed based on the initial MELISA® test results. The evaluation of the data obtained from patients in this study confirmed a significant clinical benefit of MELISA® test.

Erratum for Biomed Res Int. 2021 Mar 29;2021:6688855.

OBJECTIVE: To clarify the role and molecular mechanism of mitochondrial calcium uniporter (MCU) in the malignant biological behaviors of oral squamous cell carcinoma (OSCC) cells through clinical and cellular experiments. METHODS: Immunohistochemistry and qRT-PCR techniques were used to observe the expression of MCU, nuclear factor erythroid 2-related factor 2 (Nrf2), mitochondrial calcium uptake 1 (MICU1), and MICU2 in OSCC and normal tissues. After treatment with si-MCU, spermine, and/or sh-Nrf2, malignant biological behaviors of OSCC cells including proliferation, migration, and apoptosis were detected by clone formation, migration, and mitochondrial membrane potential (MMP) assays. Furthermore, MCU, MICU1, MICU2, Nrf2, and other proteins related to malignant biological behaviors were examined using western blot, immunohistochemistry, and immunofluorescence assays. RESULTS: MCU, Nrf2, and MICU1 were strongly expressed in OSCC as compared to normal tissues, while MICU2 was relatively weakly expressed in OSCC tissues. Knockdown of MCU distinctly weakened proliferation and migration and lowered MMP level in CAL 27 cells. Conversely, its activation reinforced migrated capacity and increased MMP level in CAL 27 cells, which was reversed after cotransfection with sh-Nrf2. After treatment with si-MCU or spermine, Nrf2 expression was not affected in CAL 27 cells. However, MCU expression was distinctly suppressed in CAL 27 cells transfected with sh-Nrf2. Furthermore, knockdown of Nrf2 significantly reversed the increase in expression of MICU1 and MICU2 induced by MCU activation in CAL 27 cells. CONCLUSION: MCU, as a novel oncogene of OSCC, augments malignant biological behaviors of OSCC cells, which could be transcriptionally regulated by Nrf2.

This single-center prospective randomized controlled trial explores the effect of prophylactic norepinephrine infusion on the incidence of complications and hospitalization time in elderly patients (60-85 years old) undergoing posterior lumbar spinal fusion. In total, 129 elderly patients were randomized into two groups: a group that received norepinephrine during general anesthesia and a control group not receiving norepinephrine. The primary outcomes were in-hospital complications and 90-day postoperative complications and hospitalization time. The results show that in-hospital complications occurred in 24 of 60 patients (40%) in the control group versus 11 of 60 patients (18.3%) in the norepinephrine group (RR, 2.182; 95% CI, 1.177-4.045; P = 0.015). Cardiac events occurred significantly more frequently in the control than in the norepinephrine group. Total number of patients experiencing complications within 90 days postoperatively was lower in the norepinephrine (11 of 60; 18.3%) than in the control group (26 of 60; 43.3%; RR, 2.364; 95% CI, 1.288-4.339; P = 0.005). The median length of hospital stay was 17 days (11-27) in the control group and 15 days (10- 23) in the norepinephrine group (P = 0.01). The secondary outcomes were serum levels of syndecan-1, hyaluronic acid, heparan sulfate, and brain natriuretic peptide. Logistic regression analysis is used to describe the relationship between selected independent variables and in-hospital complications. Intraoperative total fluid, crystalloid, and colloid volumes were significantly higher in the control than in the norepinephrine group. The patients in the norepinephrine group had a higher MAP but a lower heart rate than those in the control group after the induction of anesthesia and intraoperatively. Syndecan-1, hyaluronic acid, and heparan sulfate serum levels showed a different course in the two groups. In conclusion, prophylactic norepinephrine infusion during posterior lumbar spinal fusion is preferable for elderly patients undergoing lumbar spinal fusion under general anesthesia. It can reduce postoperative complications and hospitalization time by reducing the injury to the vascular endothelium. This trial is registered with Clinical Trial Registration http://www.chictr.org.cn/showproj.aspx?proj=33660, identifier ChiCTR-1900021309.

Hepatocellular carcinoma (HCC) is one of the most common and aggressive tumors in the world while the accuracy of the present tests for detecting HCC is poor. A novel diagnostic and prognostic biomarker for HCC is urgently needed. Overwhelming evidence has demonstrated the regulatory roles of small nucleolar RNA (snoRNA) in carcinogenesis. This study is aimed at analyzing the expression of a snoRNA, SNORA52, in HCC and exploring the correlation between its expression and various clinical characteristics of HCC patients. By using quantitative real-time PCR, we found that SNORA52 was downregulated in HCC cell lines (P < 0.05) and HCC tissues (P < 0.001). Correlation analysis showed that the expression of SNORA52 was obviously associated with tumor size (P = 0.011), lesion number (P = 0.007), capsular invasion (P = 0.011), tumor differentiation degree (P = 0.046), and TNM stage (P = 0.004). The disease-free survival (DFS) and overall survival (OS) analysis showed that patients with lower SNORA52 expression had a worse prognosis (P < 0.001). Univariate and multivariate Cox regression analysis showed that SNORA52 expression was a completely independent prognostic factor to predict DFS (P = 0.009) and OS (P = 0.012) of HCC patients. Overall, our findings showed SNORA52 expression levels were downregulated in HCC tissues and correlated with multiple clinical variables, and SNORA52 was an independent prognostic factor for HCC patients, which suggested that SNORA52 could function as a potential diagnostic and prognostic biomarker for HCC patients.

BACKGROUND: Antenatal depression is the major obstetric problem that led to significant maternal and perinatal morbidity and mortality worldwide, especially in the third world. However, in Ethiopia this prevalence and association were not studied, as result, this study investigated the prevalence and associated factors of antenatal depression among pregnant mothers who had intimate partner violence during pregnancy. Methodology. An institution-based cross-sectional study was done among 409 pregnant mothers who had intimate partner violence during pregnancy from May to July 2019 at Gondar University Hospital. All pregnant mothers who came for ANC follow-up during the study period approached for screening of intimate partner violence during pregnancy using standard and validated screening method and instrument of the WHO multicountry study on women's health and domestic violence to evaluate intimate partner violence, and we use EPDS for the evaluation of antenatal depression validated in Ethiopia with a cut point of 13. RESULT: Prevalence of depression among pregnant mothers who had any form of intimate partner violence during pregnancy was 35%: physical abuse (AOR = 1.8; 95% CI: 1.19, 3.30), more than one type of abuse (AOR = 10.18; 95% CI: 7.10, 16.18), poor social support (AOR = 5.81; 95% CI: 1.12, 13.12), and pregnant mothers whose partner drunk for the past twelve months (AOR = 7.16; 95% CI: 183, 8.00) were significantly associated with antenatal depression. CONCLUSION: High prevalence of antenatal depression among pregnant mothers who had intimate partner violence during pregnancy was highly associated with physical abuse, more than one type of abuse, lack of social support, and partner of pregnant mothers who is a drunk. Hence, this is important to create a screening program and prevention strategy of intimate partner violence during pregnancy at the time of antenatal follow-up to prevent and early identify its morbidity and mortality.

BACKGROUND: Despite recent advances in scientific knowledge and clinical practice, management, and treatment of breast cancer, as one of the leading causes of female mortality, breast cancer remains a major burden. Recently, methods employing stem cells and their derivatives, i.e., exosomes, in gene-based therapies hold great promise. Since these natural nanovesicles are able to transmit crucial cellular information which can be engineered to have robust delivery and targeting capacity, they are considered one of the modes of intercellular communication. miR-145, one of the downregulated microRNAs (miRNAs) in various cancers, can regulate tumor cell invasion, metastasis, apoptosis, and proliferation and stem cell differentiation. OBJECTIVES: The aim of this study was to investigate the role of exosomes secreted from adipose tissue-derived mesenchymal stem cells (MSCs) for miR-145 transfection into breast cancer cells in order to weaken their expansion and metastasis. METHODS: Here, we exploited the exosomes from adipose tissue-derived mesenchymal stem cells (MSC-Exo) to deliver miR-145 in the T-47D breast cancer cell line. Lentiviral vectors of miR-145-pLenti-III-enhanced green fluorescent protein (eGFP) and empty pLenti-III-eGFP as the backbone were used to transfect MSCs and T-47D cells. In order to find the efficiency of exosomes as a delivery vehicle, the expression level of some miR-145 target genes, including Rho-Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1), Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2), Matrix Metalloproteinase 9 (MMP9), and Tumor Protein p53 (TP53), was compared in all treatment groups (T-47D cells treated by miR-145-transfected MSCs and their derivatives or their backbone) and control group (untransfected T-47D cells) using real-time PCR. RESULTS: The obtained data represented the inhibitory effect of miR-145 on apoptosis induction and metastasis in both direct miR-treated groups. However, exosome-mediated delivery caused an improved anticancer property of miR-145. CONCLUSION: Restoration of miR-145 using MSC-Exo can be considered a potential novel therapeutic strategy in breast cancer in the future.

In this COVID-19 pandemic, there is a dire need for cost-effective and less time-consuming alternatives for SARS-CoV-2 testing. The RNA extraction-free method for detecting SARS-CoV-2 in saliva is a promising option. This study found that it has high sensitivity (85.34%), specificity (95.04%), and was comparable to the gold standard nasopharyngeal swab (NPS) sample tests. The method showed good agreement between salivary and NPS samples, with a kappa coefficient of 0.797. However, there are variations in the sensitivity and specificity based on the RT-PCR kit used. The Thermo Fisher Applied Biosystems showed high sensitivity, positive predictive value (PPV), and negative predictive value (NPV) but also showed a higher percentage of invalid reports. On the other hand, the BGI kit showed high specificity, better agreement (kappa coefficient) between the results of saliva and NPS samples, and higher correlation between the Ct values of saliva and NPS samples. Thus, the RNA extraction-free method for salivary sample serves as an effective alternative screening method for COVID-19.

This study is aimed to investigate the mechanisms of radiation-induced mouse models of premature ovarian insufficiency (POI). Wistar female rats were grouped into the control, 3.2 Gy, 4.0 Gy, and 4.8 Gy groups. Overall ovarian functions were assessed with the H&E staining and ELISA. Proinflammatory cytokine secretion was analyzed ELISA, and the reactive oxygen species (ROS) levels were analyzed with immunohistochemistry. Protein expressions were analyzed by Western blot analysis. The 4.0 Gy and 4.8 Gy groups had significantly lower ovarian weight coefficients than the control and 3.2 Gy groups (after only one irradiation therapy). The 3.2 Gy radiation group induced periodic disturbance and hormone change at 4 weeks after radiation. In the 4.0 Gy and 4.8 Gy groups, the preantral follicles and antral follicles were decreased, while Atresia follicles were increased. E2 was decreased, while FSH and LH secretions were increased. The ovaries in the 4.0 Gy group were not completely atrophied, and some preantral follicles remained. Ovarian atrophy and follicular Atresia were found in the 4.8 Gy group. Inflammatory and oxidative markers were upregulated. PI3K and AKT were downregulated in the 4.0 Gy and 4.8 Gy groups, while FOXO3a was upregulated. Ovarian injuries may lead to oxidative damages and inflammatory injuries, downregulate the expression of P13k and Akt, upregulate the expression of FOXO3a, and lead to follicular atresia in the ovary.

OBJECTIVES: To investigate the clinical efficacy and safety of Shenxiong glucose injection combined with edaravone in the treatment of acute large-area cerebral infarction. METHODS: 156 patients with acute large-area cerebral infarction admitted to our hospital from July 2015 to January 2017 were included in the analysis. The patients were randomly divided into experimental (78 cases) and control (78 cases) groups. Patients in the experimental group were given a 30 mg injection of edaravone in 100 ml of 0.9% sodium chloride solution by intravenous drip, twice a day within 30 minutes and a daily 200 ml injection of Shenxiong glucose by intravenous drip. Patients in the control group were given a 30 mg edaravone injection in 100 ml of 0.9% sodium chloride solution by intravenous drip, twice a day, and the drip was completed within 30 minutes. Patients in both groups were treated for 2 weeks. The levels of fibrinogen (FIB), D-dimer, interleukin 6 (IL-6), P-selectin (CD62P), and hypersensitive C-reactive protein (hs-CRP) were evaluated in the two groups of patients. Neurological disability was evaluated using the modified Rankin scale (mRS) and the neurological deficit score (National Institute of Health Stroke Scale, NIHSS). Adverse reactions to the treatments were also recorded. RESULTS: No significant differences in age, gender, medical histories, and blood biochemical indices were observed between the two groups before treatment (P > 0.05). After treatment, the levels of FIB, D-dimer, IL-6, CD62P, and hs-CRP were significantly lower following treatment and compared to the control group (P < 0.05). Also, the mRS and NIHSS scores were significantly lower after treatment and compared with the control group (P < 0.05). The total effective rate of the treatment in the experimental group was significantly higher compared to the control group (P < 0.05). During the treatment period, no obvious adverse reactions were observed in the two groups of patients. CONCLUSIONS: In addition to the routine basic treatment of acute large-area cerebral infarction, the addition of Shenxiong glucose injection combined with edaravone injection can improve platelet aggregation and reduce inflammation by affecting P-selectin, D-dimer, and FIB. This treatment approach promotes the recovery of nerve defect function without obvious adverse reactions in patients with acute large-area cerebral infarction.

Real-time genome monitoring of the SARS-CoV-2 pandemic outbreak is of utmost importance for designing diagnostic tools, guiding antiviral treatment and vaccination strategies. In this study, we present an accurate method for temporal and geographical comparison of mutational events based on GISAID database genome sequencing. Among 42523 SARS-CoV-2 genomes analyzed, we found 23202 variants compared to the reference genome. The Ti/Tv (transition/transversion) ratio was used to filter out possible false-positive errors. Transition mutations generally occurred more frequently than transversions. Our clustering analysis revealed remarkable hotspot mutation patterns for SARS-CoV-2. Mutations were clustered based on how their frequencies changed over time according to each geographical location. We observed some clusters showing a clear variation in mutation frequency and continuously evolving in the world. However, many mutations appeared in specific periods without a clear pattern over time. Various important nonsynonymous mutations were observed, mainly in Oceania and Asia. More than half of these mutations were observed only once. Four hotspot mutations were found in all geographical locations at least once: T265I (NSP2), P314L (NSP12), D614G (S), and Q57H (ORF3a). The current analysis of SARS-CoV-2 genomes provides valuable information on the geographical and temporal mutational evolution of SARS-CoV-2.

Management of diarrhea has evolved over the years from relatively inadequate interventions in the early years to more successful physiological approaches. The use of herbal medicinal products and supplements has grown significantly over the past three decades, with more than half of the global population depending on it for some aspect of their primary health care needs. This study is aimed at formulating solid and liquid oral dosage forms of the ethanolic extract of Cola nitida seeds for the treatment of diarrhea. The flow property of the dried ethanolic extract was determined and subsequently formulated into granules for encapsulation. The ethanolic extract was also used in formulating an oral suspension. Pharmacopeia tests such as uniformity of weight, disintegration, drug content, and dissolution were carried out on the formulated capsules. The formulated suspension was also assessed using the following parameters; viscosity, flow rate, drug content, dissolution, sedimentation rate, and sedimentation volume. The dried ethanolic extract and formulated granules exhibited good flow properties. The formulated capsules exhibited optimal in vitro release of extract (>90% after 45 minutes) and passed the uniformity of weight, disintegration, and drug content tests. The formulated suspension also passed the drug content test and had a good sedimentation rate, sedimentation volume, and flow rate. The formulated suspension also exhibited pseudoplastic flow, optimal viscosity, and a good in vitro release profile (>90% after 45 minutes). Capsules and suspension of the ethanolic extract of Cola nitida seeds have been successfully formulated and can be used as standard dosage forms for the management of diarrhea.

INTRODUCTION: This study was aimed to investigate the effects of N-acetylcysteine (NAC) on chronic obstructive pulmonary disease (COPD) and the change of Th17/Treg cytokine imbalance. Material and Methods. A total of 121 patients with stable COPD at the stage of C or D were consecutively enrolled and randomly divided into 2 groups. Patients in the treatment group received NAC granules (0.2 g × 10 bags, 0.4 g each time, 3 times/d) for half a year. The control group was treated with the same amount of placebo therapy. The peripheral blood of the patient was collected and the cytokine, T lymphocyte subsets were detected. RESULTS: We found the oral administration of NAC could regulate Th17/Treg balance to resist inflammation in COPD patients. Serum testing showed that the proportion of Treg in CD4+ T cells has increased and the Th17/Treg ratio has decreased during the NAC treatment. In vitro studies, we found that NAC regulated Th17/Treg balance through Hypoxia Inducible Factor-1α pathway. CONCLUSIONS: Our result could provide new diagnosis and treatment for elderly patients with COPD from the perspective of immunity ideas.

Vaccination has been identified as one of the most effective ways to prevent the transmission of infectious diseases in humans and animals. One of the most critical steps in vaccine development is the selection of a suitable adjuvant. Although various adjuvant candidates have been evaluated in the past few decades, only a limited amount of them are nontoxic and safe for human use. Astragalus polysaccharide (APS), due to its lack of toxicity, has been used as an immunomodulator to enhance immune responses. On the other hand, the immune effects of APS on ovalbumin are yet to be examined. Thus, in this study, we analyzed APS's effects on the immune response to ovalbumin in BALB/c mice. We have also used the classic adjuvant CpG oligodeoxynucleotide as the positive control.

Erratum in Biomed Res Int. 2021 Oct 23;2021:9762405.

BACKGROUND: Acute kidney injury (AKI) is a common clinical syndrome carrying high morbidity and mortality. Body mass index (BMI) is a common health indicator, and a high BMI value-obesity has been shown to be associated with the outcomes of several diseases. However, the relationship between different BMI categories and mortality in all critically ill patients with AKI is unclear and needs further investigation. Therefore, we evaluated the ability of BMI to predict the severity and all-cause mortality of AKI in critically ill patients. METHODS: We extracted clinical data from the MIMIC-III v1.4 database. All adult patients with AKI were initially screened. The baseline data extracted within 24 hours after ICU admission were presented according to WHO BMI categories. Logistic regression models and the Cox proportional hazards models were, respectively, constructed to assess the relationship between BMI and the severity and all-cause mortality of AKI. The generalized additive model (GAM) was used to identify nonlinear relationships as BMI was a continuous variable. The subgroup analyses were performed to further analyze the stability of the association between BMI category and 365-day all-cause mortality of AKI. RESULT: A total of 15,174 patients were extracted and were divided into four groups according to BMI. Obese patients were more likely to be young and male. In the fully adjusted logistic regression model, we found that overweight and obesity were significant predictors of AKI stage III (OR, 95 CI: 1.17, 1.05-1.30; 1.32, 1.18-1.47). In the fully adjusted Cox proportional hazards model, overweight and obesity were associated with significantly lower 30-day, 90-day, and 365-day all-cause mortality. The corresponding adjusted HRs (95 CIs) for overweight patients were 0.87 (0.77, 0.99), 0.84 (0.76, 0.93), and 0.80 (0.74, 0.88), and for obese patients, they were 0.87 (0.77, 0.98), 0.79 (0.71, 0.88), and 0.73 (0.66, 0.80), respectively. The subgroup analyses further presented a stable relationship between BMI category and 365-day all-cause mortality. CONCLUSIONS: BMI was independently associated with the severity and all-cause mortality of AKI in critical illness. Overweight and obesity were associated with increased risk of AKI stage III; however, they were predictive of a relatively lower mortality risk in these patients.

BACKGROUND: Autophagy is likely altered in patients with endometriosis. Ovarian steroid hormones seem to affect this changing of the autophagic process. OBJECTIVE: To study the effect of combined oral contraceptive (COC) pills on the expression of autophagic-related gene BECN1 and LC3B in the ectopic and eutopic endometria of patients with endometriosis. Material and Methods. The present quasiexperimental study recruited 36 women (18-45 years old) with endometrioma and nonendometrioma who were scheduled for surgery. Patients with endometrioma were randomly assigned to either a no-treatment group (n = 12) or a COC group (n = 12). The COC group was prescribed a daily oral pill composed of 3 mg drospirenone and 0.03 mg ethinyl estradiol for 6 weeks before surgery. The control group (n = 12) was composed of women without endometrioma. Ectopic endometriotic and endometrium tissues were collected from the no-treatment and COC groups, whereas the only endometrium was collected from the control group. These tissues were used for real-time PCR to measure the expression of the BECN1 and LC3B genes. RESULTS: The baseline demographic data were not different among the three groups. The BECN1 gene expression in endometrium tissue in the COC group was significantly less than that in the no-treatment and control groups (P = 0.011 and 0.029, respectively). No significant difference of endometriotic cyst BECN1 and LC3B gene expression was found between COC and no treatment. CONCLUSIONS: Oral COC pills for 6 weeks continuously before surgery decreased the eutopic endometrial expression (mRNA) of the BECN1 gene compared to those from healthy normal women and nontreated patients with an endometriotic cyst. The change in the expression of autophagy-related genes was more distinct in eutopic than ectopic endometria. This trial is registered with TCTR20170720002. Registered and enrolled the first patient on 20 July 2017.

Anoxybacillus kamchatkensis NASTPD13 isolated from Paudwar hot spring of Myagdi, Nepal, upon morphological and biochemical analysis revealed to be Gram-positive, straight or slightly curved, rod-shaped, spore-forming, catalase, and oxidase-positive facultative anaerobes. It grows over a wide range of pH (5.0-11) and temperature (37-75°C), which showed growth in different reduced carbon sources such as starch raffinose, glucose, fructose, inositol, trehalose, sorbitol, mellobiose, and mannitol in aerobic conditions. Furthermore, the partial sequence obtained upon sequencing showed 99% sequence similarity in 16S rRNA gene sequence with A. kamchatkensis JW/VK-KG4 and was suggested to be Anoxybacillus kamchatkensis. Moreover, whole-genome analysis of NASTPD13 revealed 2,866,796 bp genome with a G+C content of 41.6%. Analysis of the genome revealed the presence of 102 RNA genes, which includes sequences coding for 19 rRNA and 79 tRNA genes. While the 16S rRNA gene sequence of strain NASTPD13 showed high similarity (>99%) to those of A. kamchatkensis JW/VK-KG4, RAST analysis of NASTPD13 genome suggested that A. kamchatkensis G10 is actually the closest neighbor in terms of sequence similarity. The genome annotation by RAST revealed various genes encoding glycoside hydrolases supporting that it can utilize several reduced carbon sources as observed and these genes could be important for carbohydrate-related industries. Xylanase pathway, particularly the genomic region encoding key enzymes for xylan depolymerization and xylose metabolism, further confirmed the presence of the complete gene in xylan metabolism. In addition, the complete xylose utilization gene locus analysis of NASTPD13 genome revealed all including D-xylose transport ATP-binding protein XylG and XylF, the xylose isomerase encoding gene XylA, and the gene XylB coding for a xylulokinase supported the fact that the isolate contains a complete set of genes related to xylan degradation, pentose transport, and metabolism. The results of the present study suggest that the isolated A. kamchatkensis NASTPD13 containing xylanase-producing genes could be useful in lignocellulosic biomass-utilizing industries where pentose polymers could also be utilized along with the hexose polymers.

The aim of the study was to compare the microbiota composition and bacterial diversity of subgingival plaque in chronic periodontitis patients with and without gingival erosive oral lichen planus. The subgingival plaque samples of 20 chronic periodontitis patients with gingival erosive oral lichen planus (CP-OLP group) and 19 chronic periodontitis patients without gingival erosive oral lichen planus (CP group) were analyzed by 16S rRNA gene high-throughput sequencing. Compared with the CP group, the richness and diversity of subgingival plaque microflora in the CP-OLP group decreased significantly. There were some differences between the two groups in the composition of microflora on the levels of phylum and genus. Distributions of Prevotella and Leptotrichia in the CP-OLP group were significantly lower than those in the CP group. The dominant genera in CP-OLP group were Pseudomonas and Granulicatella. These results indicated that gingival erosive oral lichen planus may influence the structure and proportion of subgingival plaque microflora.

MATERIALS AND METHODS: Rat L6 skeletal muscle cells were cultured in 25 cm2 flasks. These differentiated cells were treated, and then, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (probe-based) was used to measure the relative mRNA expression level for metabolic, inflammatory, and nuclear receptor genes including peroxisome proliferator-activated receptor gamma (PGC-1α), carnitine palmitoyl transferase 1 beta (CPT1B), long-chain acyl-CoA de hydrogenase (LCAD), acetyl-CoA carboxylase beta (ACCβ), pyruvate dehydrogenase kinase 4 (PDK4), hexokinase II (HKII), phosphofructokinase (PFK), interleukin-6 (IL-6), and nuclear receptor subfamily 4, group A (NR4A) at different treatment conditions. RESULTS: Adenosine-5'-N-ethyluronamide (NECA), a stable adenosine analogue, significantly stimulate inflammatory mediator (IL-6) (p < 0.001) and nuclear receptors (NR4A) (p < 0.05) and significantly modulate metabolic (PFK, LCAD, PGC-1α, and CPT1B) gene expressions in skeletal muscle cells (p < 0.05, p < 0.05, p < 0.001, and p < 0.01, respectively). This present study shows that there is a noteworthy crosstalk between NECA and insulin at various metabolic levels including glycolysis (HKII), fatty acid oxidation (ACCβ), and insulin sensitivity (PDK4). CONCLUSIONS: A novel crosstalk between adenosine analogue and insulin has been demonstrated for the first time; evidence has been gathered in vitro for the effects of NECA and insulin treatment on intracellular signaling pathways, in particular glycolysis and insulin sensitivity in skeletal muscle cells.

Nigella sativa (NS) is a well-known plant for its various benefits and multiuse in traditional medicine. This study is aimed at investigating the chemical composition of the different NS fractions by using GC-MS for the esterified fatty acids or HPLC-UV for organic fraction and at evaluating the inhibitory effect on pancreatic α-amylase (in vitro, in vivo) and intestinal glucose absorption. Among all the investigated fractions, it was shown that they are rich with different molecules of great interest. The n-hexane fraction was characterized by the presence of linoleic acid (44.65%), palmitic acid (16.32%), stearic acid (14.60%), and thymoquinone (8.7%), while among the identified peaks in EtOH fraction we found catechin (89.03 mg/100 g DW), rutin (6.46 mg/100 g DW), and kaempferol (0.032 mg/100 g DW). The MeOH fraction was distinguished with the presence of gallic acid (19.91 mg/100 g DW), catechin (13.79 mg/100 g DW), and rutin (21.07 mg/100 g DW). Finally, the aqueous fraction was marked by the existence of different molecules; among them, we mention salicylic acid (32.26 mg/100 g DW), rutin (21.46 mg/100 g DW), and vanillic acid (3.81 mg/100 g DW). Concerning the inhibitory effect on pancreatic α-amylase, it was found that in the in vitro study, the best IC50 registered were those of EtOH (0.25 mg/ml), MeOH (0.10 mg/ml), aqueous (0.031 mg/ml), and n-hexane fraction (0.76 mg/ml), while in the in vivo study an important inhibition of α-amylase in normal and diabetic rats was observed. Finally, the percentage of intestinal glucose absorption was evaluated for all tested extracts and it was ranging from 24.82 to 60.12%. The results of the present study showed that the NS seed fractions exert an interesting inhibitory effect of α-amylase and intestinal glucose absorption activity which could be associated with the existent bioactive compounds. Indeed, these compounds can be used as antidiabetic agents because of their nontoxic effect and high efficacy.

Gastric cancer is a common and deadly cancer in the world. The gold standard for the detection of gastric cancer is the histological examination by pathologists, where Gastric Histopathological Image Analysis (GHIA) contributes significant diagnostic information. The histopathological images of gastric cancer contain sufficient characterization information, which plays a crucial role in the diagnosis and treatment of gastric cancer. In order to improve the accuracy and objectivity of GHIA, Computer-Aided Diagnosis (CAD) has been widely used in histological image analysis of gastric cancer. In this review, the CAD technique on pathological images of gastric cancer is summarized. Firstly, the paper summarizes the image preprocessing methods, then introduces the methods of feature extraction, and then generalizes the existing segmentation and classification techniques. Finally, these techniques are systematically introduced and analyzed for the convenience of future researchers.

OBJECTIVE: The aim of this study was to investigate the correlation between polymorphisms in the FTO gene and TSH level in Uyghur patients with type 2 diabetes in the Xinjiang region. Material and Methods. This cohort was made up of 498 Uyghur patients with type 2 diabetes who underwent genotype screening for rs8050136 and rs9939609 using the Sequenom MassARRAY system. The distribution frequencies of the genotypes and alleles at rs8050136 and rs993960 were compared between two patient groups, those with TSH < 2.5 mU/L and those with TSH ≥ 2.5 mU/L group. We further evaluated the relationships between these different genotypes and FT3, FT4, TSH, FPG, and HbA1c expression. RESULTS: The results suggested the TSH level was 2.281 times higher in rs8050136 CC+CA carriers than in AA genotype (95%CI = 1.024~5.080, P = 0.044) and was 2.417 times higher in rs9939609 TT+TA carriers than in AA genotype (95%CI = 1.257~4.649, P = 0.008) after adjusting for age, sex, and BMI under the recessive model. TSH levels were significantly different between T2DM patients with different FTO genotypes, rs8050136 (P = 0.008) and rs9939609 (P = 0.003), with TSH levels in rs8050136 CC genotype carriers showing a significant increase compared to those in the AA genotype carriers (P = 0.005). Additionally, rs9939609 TT and TA genotype carriers had a significant increase in the TSH level when compared to AA genotype carriers (P = 0.001 and P = 0.031, respectively). The TSH level was also significantly different in these male patients with different genotypes of rs8050136 (P = 0.026) and rs9939609 (P = 0.019). And TSH levels in rs8050136 CC genotype male carriers showing a significant increase compared to those in the AA genotype carriers (P = 0.013) and rs9939609 TT genotype male carriers had a significant increase in TSH level when compared to AA genotype carriers (P = 0.004). CONCLUSION: The polymorphisms at rs8050136 and rs9939609 are associated with changes in the TSH level with rs8050136 CC and rs9939609 TT genotypes identified as potential risk factors for increased TSH levels in these male patients.

The present study is developed a new approach using a computer diagnostic method to diagnosing diabetic diseases with the use of fluorescein images. In doing so, this study presented the growth region algorithm for the aim of diagnosing diabetes, considering the angiography images of the patients' eyes. In addition, this study integrated two methods, including fuzzy C-means (FCM) and genetic algorithm (GA) to predict the retinopathy in diabetic patients from angiography images. The developed algorithm was applied to a total of 224 images of patients' retinopathy eyes. As clearly confirmed by the obtained results, the GA-FCM method outperformed the hand method regarding the selection of initial points. The proposed method showed 0.78 sensitivity. The comparison of the fuzzy fitness function in GA with other techniques revealed that the approach introduced in this study is more applicable to the Jaccard index since it could offer the lowest Jaccard distance and, at the same time, the highest Jaccard values. The results of the analysis demonstrated that the proposed method was efficient and effective to predict the retinopathy in diabetic patients from angiography images.

OBJECTIVE: To compare the effects of sevoflurane inhalation and intravenous anesthesia on hemodynamics, serum myocardial enzymes, and myocardial markers in elderly patients undergoing hysterectomy. METHODS: Group A and group B were established randomly regarding a total of 126 elderly patients who underwent an elective hysterectomy. Patients in group A were given full anesthesia with sevoflurane, and patients in group B were given anesthesia with intravenous anesthesia. The operation time, anesthesia time, and recovery time in Postanesthesia Care Unit (PACU) were compared; plasma cortisol concentration, hemodynamics, serum myocardial enzymes, and myocardial markers were detected and compared between the two groups of patients before anesthesia (T 0), after anesthesia (T 1), and after surgery (T 2). RESULTS: Group A observed a longer extubation time and recovery time in PACU than group B (P < 0.05). Results show a lower systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and plasma cortisol concentration of T 1 by comparison with those of T 0 (P < 0.05), but no significant difference remains in terms of intergroup SBP, DBP, and HR (P > 0.05), and there was no interaction effect of groups and time (P > 0.05). The two groups showed no great disparity in the levels of lactate dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), and CK-MB as a subtype of CK before surgery between the two groups of patients (P > 0.05). After surgery, LDH, AST, CK, and CK-MB levels in both groups were witnessed a surge, in which group A obtained higher levels of LDH, AST, CK, and CK-MB (all P < 0.05). CONCLUSION: Total intravenous anesthesia will not increase the hemodynamic fluctuation of elderly patients undergoing hysterectomy and can reduce the damage to the myocardium of patients with surgical trauma, which can protect the myocardium of elderly patients to a certain extent, so it can be adopted as the optimal anesthesia protocol for surgery.

Nonnutritive sweeteners (NNSs) are sugar substitutes widely used to reduce the negative health effects of excessive sugar consumption. Dental caries, one of the most prevalent chronic diseases globally, results from a pathogenic biofilm with microecological imbalance and frequent exposure to sugars. Some research has shown that certain NNSs possess less cariogenic potential than sucrose, indicating their putative effect on oral microbiome. To uncover the alterations of acidogenic pathogens and alkali-generating commensals, as well as the biofilm cariogenic potential under the influence of NNSs, we selected four common NNSs (acesulfame-K, aspartame, saccharin, and sucralose) and established single-, dual-, and multispecies in vitro culture model to assess their effects on Streptococcus mutans (S. mutans) and/or Streptococcus sanguinis (S. sanguinis) compared to sucrose with the same sweetness. The results showed that NNSs significantly suppressed the planktonic growth, acid production, and biofilm formation of S. mutans or S. sanguinis compared with sucrose in single-species cultures. Additionally, decreased S. mutans/S. sanguinis ratio, less EPS generation, and higher pH value were observed in dual-species and saliva-derived multispecies biofilms with supplementary NNSs. Collectively, this study demonstrates that NNSs inhibit the cariogenic potential of biofilms by maintaining microbial equilibrium, thus having a promising prospect as anticaries agents.

OBJECTIVE: Little observational data exist regarding the use of cisplatin, etoposide, and bleomycin (BEP) chemotherapy regimen in patients with gestational trophoblastic neoplasia (GTN). METHODS: This is a retrospective study of 95 patients with GTN in our center from June/2010 to June/2018. All patients received at least 2 cycles of BEP chemotherapy. The primary outcomes were the rate of complete remission (CR) and overall survival (OS). The secondary outcomes were disease-free survival (DFS), pregnancy rates after BEP exposure, drug resistance rate, and other adverse events. RESULTS: Of the 95 patients included, 66 (69.5%) patients received BEP as primary treatment and 29 (30.5%) were Salvage chemotherapy. The median age at diagnosis was 37 years (range 29.75-46) and 34 years (range 27-40) in two groups, respectively. The median WHO prognostic scores were 6 (range 3.5-8), and 77.32% of patients were FIGO stage III-IV in the primary treatment group. The median WHO prognostic scores were 5 (range 3-9), and 66.55% of patients were FIGO stage III-IV in the salvage treatment group. Median cycles of BEP treatment were 4 (3, 5) and 3 (2, 4) in two groups, respectively. In the primary chemotherapy group, 18.2% received additional hysterectomy, 4.5% received UAE for vaginal bleeding, and 1.52% received whole-brain radiotherapy. In the salvage chemotherapy group, 20.7% received hysterectomy, 6.9% received lobectomy, 3.4% received hysteroscopic lesion resection, and 3.4% received whole-brain radiotherapy. CR rates to initial chemotherapy were 86.4%, including 87.9% in the primary chemotherapy group and 82.8% in the salvage chemotherapy group. No predictive factor of chemotherapy resistance was identified. The rate of 5 year-DFS was 96.52% (95% CI 86.78-99.12) in the primary chemotherapy group and 92.44% (95% CI 73.02-98.06) in the salvage chemotherapy group. The rate of 5 year-OS was 98.31% (95% CI 88.57-99.76) and 95.65% (95% CI 79.93-99.38) in the two groups, respectively. During the treatment, neutropenia, thrombocytopenia, anemia, and liver dysfunction occurred in 80.3%, 6.1%, 25.8%, and 50% primary chemotherapy patients and 82.8%, 31%, 10.3%, and 86.2% salvage chemotherapy patients. In patients with fertility requirements, live birth rates were 100% (10/10) in primary chemotherapy patients and 80% (4/5) in salvage chemotherapy patients. CONCLUSIONS: BEP regimen was effective in the treatment of GTINs. The treatment was well tolerated, with no safety concerns on patients' fertility.

BACKGROUND: Early diagnosis of hypoxic-ischaemic encephalopathy (HIE) is crucial in preventing neurodevelopmental disabilities and reducing morbidity and mortality. The study was to investigate the plasma metabolic signatures in the peripheral blood of HIE newborns and explore the potential diagnostic biomarkers. METHOD: In the present study, 24 newborns with HIE and 24 healthy controls were recruited. The plasma metabolites were measured by gas chromatography-mass spectrometry (GC-MS), and the raw data was standardized by the EigenMS method. Significantly differential metabolites were identified by multivariate statistics. Pathway enrichment was performed by bioinformatics analysis. Meanwhile, the diagnostic value of candidate biomarkers was evaluated. RESULT: The multivariate statistical models showed a robust capacity to distinguish the HIE cases from the controls. 52 metabolites were completely annotated. 331 significantly changed pathways were enriched based on seven databases, including 33 overlapped pathways. Most of them were related to amino acid metabolism, energy metabolism, neurotransmitter biosynthesis, pyrimidine metabolism, the regulation of HIF by oxygen, and GPCR downstream signaling. 14 candidate metabolites showed great diagnostic potential on HIE. Among them, alpha-ketoglutaric acid has the potential to assess the severity of HIE in particular. CONCLUSION: The blood plasma metabolic profile could comprehensively reflect the metabolic disorders of the whole body under hypoxia-ischaemic injury. Several candidate metabolites may serve as promising biomarkers for the early diagnosis of HIE. Further validation based on large clinical samples and the establishment of guidelines for the clinical application of mass spectrometry data standardization methods are imperative in the future.

OBJECTIVES: To evaluate the value of the whole volume apparent diffusion coefficient (ADC) histogram in distinguishing between benign and malignant breast lesions and differentiating different molecular subtypes of breast cancers and to assess the correlation between ADC histogram parameters and Ki-67 expression in breast cancers. METHODS: The institutional review board approved this retrospective study. Between September 2016 and February 2019, 189 patients with 84 benign lesions and 105 breast cancers underwent magnetic resonance imaging (MRI). Volumetric ADC histograms were created by placing regions of interest (ROIs) on the whole lesion. The relationships between the ADC parameters and Ki-67 were analysed using Spearman's correlation analysis. RESULTS: Of the 189 breast lesions included, there were significant differences in patient age (P < 0.001) and lesion size (P = 0.006) between the benign and malignant lesions. The results also demonstrated significant differences in all ADC histogram parameters between benign and malignant lesions (all P < 0.001). The median and mean ADC histogram parameters performed better than the other ADC histogram parameters (AUCs were 0.943 and 0.930, respectively). The receiver operating characteristic (ROC) analysis revealed that the 10th percentile ADC value and entropy could determine the human epidermal growth factor receptor 2 (HER-2) status (both P = 0.001) and estrogen receptor (ER)/progesterone receptor (PR) status (P = 0.020 and P = 0.041, respectively). Among all breast cancer lesions, 35 tumours in the low-proliferation group (Ki - 67 < 14%) and 70 tumours in the high-proliferation group (Ki - 67 ≥ 14) were analysed with ROC curves and correlation analyses. The ROC analysis revealed that entropy and skewness could determine the Ki-67 status (P = 0.007 and P < 0.001, respectively), and there were weak correlations between ADC entropy (r = 0.383) and skewness (r = 0.209) and the Ki-67 index. CONCLUSION: The volumetric ADC histogram could serve as an imaging marker to determine breast lesion characteristics and may be a supplemental method in predicting tumour proliferation in breast cancer.

The recent outbreak of the deadly coronavirus disease 19 (COVID-19) pandemic poses serious health concerns around the world. The lack of approved drugs or vaccines continues to be a challenge and further necessitates the discovery of new therapeutic molecules. Computer-aided drug design has helped to expedite the drug discovery and development process by minimizing the cost and time. In this review article, we highlight two important categories of computer-aided drug design (CADD), viz., the ligand-based as well as structured-based drug discovery. Various molecular modeling techniques involved in structure-based drug design are molecular docking and molecular dynamic simulation, whereas ligand-based drug design includes pharmacophore modeling, quantitative structure-activity relationship (QSARs), and artificial intelligence (AI). We have briefly discussed the significance of computer-aided drug design in the context of COVID-19 and how the researchers continue to rely on these computational techniques in the rapid identification of promising drug candidate molecules against various drug targets implicated in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The structural elucidation of pharmacological drug targets and the discovery of preclinical drug candidate molecules have accelerated both structure-based as well as ligand-based drug design. This review article will help the clinicians and researchers to exploit the immense potential of computer-aided drug design in designing and identification of drug molecules and thereby helping in the management of fatal disease.

Titanium dioxide nanoparticles (TiO2) were used in various fields such as food industry, cosmetics, medicine, and agriculture. Despite the many advantages of nanotechnology, the adverse effects of nanoparticles are inevitable. The present study was conducted to evaluate the protective effect of bee bread on titanium dioxide (TiO2) nanoparticle toxicity. Male rats were randomly divided into four groups: Group 1 received daily by gavage (10 mL/kg bw) of distilled water, Group 2 received bee bread ethanolic extract (100 mg/kg bw), Group 3 received TiO2 (100 mg/kg bw) and distilled water (10 mL/kg bw), and Group 4 received TiO2 (100 mg/kg bw) and bee bread ethanolic extract (100 mg/kg bw). All treatments were given daily by gavage during 30 days. At the end of the experiment period, blood samples were collected to analyze fasting blood glucose, lipid profile (TC, TG, LDL-C, HDL-C, and VLDL-C), liver enzymes (AST, ALT, and LDH), total protein, urea, albumin, creatinine, sodium, potassium, and chloride ions. In addition, histological examinations of the kidneys, liver, and brain were investigated. The results showed that the subacute administration of TiO2 alone (100 mg/kg bw) had induced hyperglycemia (309 ± 5 mg/dL) and elevation of hepatic enzyme levels, accompanied by a change in both lipid profile and renal biomarkers as well as induced congestion and dilatation in the hepatic central vein and congestion in kidney and brain tissues. However, the cotreatment with bee bread extract restored these biochemical parameters and attenuated the deleterious effects of titanium nanoparticles on brain, liver, and kidney functions which could be due to its rich content on functional molecules. The findings of this paper could make an important contribution to the field of using bee bread as a detoxifying agent against titanium dioxide nanoparticles and other xenobiotics.

Cytochrome P450 family 2 subfamily J member 2 (CYP2J2), a member of the monooxygenase cytochrome P450 (CYP) family and the only member of the human CYP2J subfamily, has many functions, including regulation of oxidative stress, inflammation, apoptosis, and immune responses. However, its role in cancer development has not been clearly elucidated. In this study, expression levels of CYP2J2 in various cancer types were determined using the Oncomine, the Gene Expression Profiling Interactive Analysis (GEIPA), DriverDBv3, UALCAN, and Tumor Immune Estimation Resource (TIMER) databases. The prognostic value of CYP2J2 for KIRC was analyzed using GEPIA, UALCAN, OSkirc, and DriverDBv3 databases. We evaluated the expression levels of CYP2J2 transcript, protein, and promoter methylation at different clinical characteristics in KIRC through the UALCAN database. Simultaneously, CYP2J2 network-related functions were evaluated using the GeneMANIA interactive tool while the biological processes involved in CYP2J2 and its interactive genes were investigated through Metascape and FunRich. Then, we used TIMER to determine the correlation between CYP2J2 expression levels and immune infiltration levels in KIRC. In KIRC, the CYP2J2 gene, RNA, and protein were found to be overexpressed. However, the methylation level of CYP2J2 promoter in KIRC was lower than in normal tissues. Surprisingly, elevated expression levels of CYP2J2 exhibited better prognostic outcomes in KIRC. Evaluation of protein-protein interaction networks and biological processes revealed that CYP2J2 was principally involved in immune responses, apoptosis, and other metabolic processes. Moreover, we found that the expression levels of CYP2J2 were positively correlated with infiltration levels of B cells, CD8 + T cells, neutrophils, and dendritic cells in KIRC. Therefore, we speculated that the overexpression of CYP2J2 prolonged the survival outcome of KIRC patients, which may be related to the change of tumor immune microenvironment. Moreover, all these new understandings of CYP2J2 may provide important value for the early diagnosis and new targeted drug therapy of KIRC.

BACKGROUND: Child marriage is a major public health problem globally, and the prevalence remains high in sub-Saharan African countries, including Mali. There is a dearth of evidence about factors associated with child marriage in Mali. Hence, this studyaimed at investigating the individual/household and community-level factors associated with child marriage among women in Mali. METHODS: Using data from the 2018 Mali Demographic and Health Survey, analysis was done on 8,350 women aged 18-49 years. A Chi-square test was used to select candidate variables for the multilevel multivariable logistic regression models. Fixed effects results weree xpressed as adjusted odds ratios (aOR) at 95% confidence intervals (CI). Stata version 14 software was used for the analysis. RESULTS: The results showed that 58.2% (95% CI; 56.3%-60.0%) and 20.3% (95%; 19.0%-21.6%) of women aged 18-49 years were married before their 18th and 15th birthday, respectively. Educational status of women (higher education: aOR = 0.25, 95% CI; 0.14-0.44), their partner's/husband's educational status (higher education: aOR = 0.64, 95% CI; 0.47-0.87), women's occupation (professional, technical, or managerial: aOR = 0.50, 95% CI; 0.33-0.77), family size (five and above: aOR = 1.16, 95% CI; 1.03-1.30), and ethnicity (Senoufo/Minianka: aOR = 0.73, 95% CI; 0.58-0.92) were the identified individual/household level factors associated with child marriage, whereas region (Mopti: aOR = 0.27, 95% CI; 0.19-0.39) was the community level factor associated with child marriage. CONCLUSIONS: This study has revealed a high prevalence of child marriage in Mali. To reduce the magnitude of child marriage in Mali, enhancing policies and programs that promote education for both girls and boys, creating employment opportunities, improving the utilization of family planning services, and sensitizing girls and parents who live in regions such as Kayes on the negative effects of child marriage is essential. Moreover, working with community leaders so as to reduce child marriage in the Bambara ethnic communities would also be beneficial.

Deep venous thrombosis (DVT) is a common complication in patients with lower extremity fractures, causing delays in recovery short-term and possible impacts on quality of life long-term. Early prediction and prevention of thrombosis can effectively reduce patient pain while improving outcomes. Although research on the risk factors for thrombosis is prevalent, there is a stark lack of clinical predictive models for DVT occurrence specifically in patients with lower limb fractures. In this study, we aim to propose a new thrombus prediction model for lower extremity fracture patients. Data from 3300 patients with lower limb fractures were collected from Wuhan Union Hospital and Hebei Third Hospital, China. Patients who met our inclusion criteria were divided into a thrombosis and a nonthrombosis group. A multivariate logistic regression analysis was carried out to identify predictors with obvious effects, and the corresponding formulas were used to establish the model. Model performance was evaluated using a discrimination and correction curve. 2662 patients were included in the regression analysis, with 1666 in the thrombosis group and 996 in the nonthrombosis group. Predictive factors included age, Body Mass Index (BMI), fracture-fixation types, energy of impact at the time of injury, blood transfusion during hospitalization, and use of anticoagulant drugs. The discriminative ability of the model was verified using the C-statistic (0.676). For the convenience of clinical use, a score table and nomogram were compiled. Data from two centers were used to establish a novel thrombus prediction model specific for patients with lower limb fractures, with verified predictive ability.

Despite benefits of physical activity, the level of physical activity is not desirable in patients with type 2 diabetes. The aim of this study is the using of integration of intervention based on the theory of protection motivation and implementation intention in order to improve the level of activity in patients with diabetes. This field trial study has been performed on 125 patients with type 2 diabetes. Samples have been randomly selected, and they are divided into two intervention and control groups. In the intervention group, training sessions were conducted based on the protection motivation theory and implementation intention. Physical activity levels, VO2 max, and hemoglobin A1C were measured before and three months after the intervention in the two groups. Data were analyzed by using SPSS 18, and independent t-test, paired t-test, and equivalent nonparametric tests were used for analyzing abnormal data. The results of this study showed that the level of physical activity was higher in the intervention group (p = 0.02). Also, the amount of hemoglobin A1c in the intervention group has been decreased significantly three months later (p < 0.001). In this study, VO2 max and blood lipids were not significantly different in the two groups. However, there was higher VO2 max compared to before the intervention in the intervention group. The present study showed that combining motivational interventions and implementing intention intervention can be effective in promoting the physical activity of patients with type 2 diabetes.

BACKGROUND: Mitral valve disease surgery is an evolving field with multiple possible interventions. There is an increasing body of evidence regarding the optimal strategy in secondary mitral regurgitation where the pathology lies within the ventricle. We conducted a systematic review to identify the benefits and limitations of each surgical option. METHODS: A systematic review of the literature was performed to identify pertinent randomized controlled trials (RCTs), propensity-matched observational series, and meta-analyses which were considered initially and followed by unmatched observational series using the MEDLINE, Ovid EMBASE, and Cochrane Library. RESULTS: We identified 6 different strategies for treating secondary mitral valve regurgitation: mitral valve replacement, restrictive mitral annuloplasty, surgical revascularization (with and without mitral annuloplasty), subvalvular procedures (papillary muscle approximation, papillary muscle relocation, ring and string procedure), and procedures directly targeting the mitral valve (edge-to-edge repair and anterior leaflet enlargement) alongside transcatheter heart valve therapy. We also highlighted the role of left ventricular assist devices in the management of this condition. The benefits and limitations of each intervention are highlighted. CONCLUSION: There is currently no unanimous and shared strategy for the optimal treatment of patients with secondary IMR. The management of patients with secondary mitral regurgitation must be entrusted to a multidisciplinary Heart Team to ensure ideal intervention and patient matching for the best outcomes.

OBJECTIVE: The objective of this systematic review was to investigate the quality and outcome of studies into artificial intelligence techniques, analysis, and effect in dentistry. MATERIALS AND METHODS: Using the MeSH keywords: artificial intelligence (AI), dentistry, AI in dentistry, neural networks and dentistry, machine learning, AI dental imaging, and AI treatment recommendations and dentistry. Two investigators performed an electronic search in 5 databases: PubMed/MEDLINE (National Library of Medicine), Scopus (Elsevier), ScienceDirect databases (Elsevier), Web of Science (Clarivate Analytics), and the Cochrane Collaboration (Wiley). The English language articles reporting on AI in different dental specialties were screened for eligibility. Thirty-two full-text articles were selected and systematically analyzed according to a predefined inclusion criterion. These articles were analyzed as per a specific research question, and the relevant data based on article general characteristics, study and control groups, assessment methods, outcomes, and quality assessment were extracted. RESULTS: The initial search identified 175 articles related to AI in dentistry based on the title and abstracts. The full text of 38 articles was assessed for eligibility to exclude studies not fulfilling the inclusion criteria. Six articles not related to AI in dentistry were excluded. Thirty-two articles were included in the systematic review. It was revealed that AI provides accurate patient management, dental diagnosis, prediction, and decision making. Artificial intelligence appeared as a reliable modality to enhance future implications in the various fields of dentistry, i.e., diagnostic dentistry, patient management, head and neck cancer, restorative dentistry, prosthetic dental sciences, orthodontics, radiology, and periodontics. CONCLUSION: The included studies describe that AI is a reliable tool to make dental care smooth, better, time-saving, and economical for practitioners. AI benefits them in fulfilling patient demand and expectations. The dentists can use AI to ensure quality treatment, better oral health care outcome, and achieve precision. AI can help to predict failures in clinical scenarios and depict reliable solutions. However, AI is increasing the scope of state-of-the-art models in dentistry but is still under development. Further studies are required to assess the clinical performance of AI techniques in dentistry.

Acute lung injury (ALI) is a life-threatening clinical syndrome with high morbidity and mortality. The main pathological features of ALI are increased alveolar-capillary membrane permeability, edema, uncontrolled migration of neutrophils to the lungs, and diffuse alveolar damage, resulting in acute hypoxemic respiratory failure. Glucocorticoids, aspirin, and other anti-inflammatory drugs are commonly used to treat ALI. Respiratory supports, such as a ventilator, are used to alleviate hypoxemia. Many treatment methods are available, but they cannot significantly ameliorate the quality of life of patients with ALI and reduce mortality rates. Herbal active ingredients, such as flavonoids, terpenoids, saponins, alkaloids, and quinonoids, exhibit advantages for ALI prevention and treatment, but the underlying mechanism needs further study. This paper summarizes the role of herbal active ingredients in anti-ALI therapy and progresses in the understanding of their mechanisms. The work also provides some references and insights for the discovery and development of novel drugs for ALI prevention and treatment.

Erratum in Biomed Res Int. 2021 Aug 23;2021:9789613.

OBJECTIVE: The objective of the present review is to assess the implant survival, marginal bone loss, and biomechanical features of narrow-diameter implants (2.5-3.5 mm) supporting or retaining full-arch fixed or removable restorations. MATERIALS AND METHODS: Three operators screened the literature (PubMed, Cochrane Library, and Google Scholar) and performed a hand search on the main journals that focus on implantology until 24 March 2019. Only articles that considered full-arch restorations supported or retained by narrow-diameter implants (2.5-3.5 mm) were considered if they have a minimum of 10 patients and a mean follow-up of at least 6 months. The outcome variables were survival of implants and marginal bone loss. The review was performed according to the PRISMA statements. Risk of bias assessment was evaluated. Failure rates were analyzed using random effect Poisson regression models to obtain the summary estimate of 5-year survival rate and marginal bone loss. RESULTS: A total of nine papers were finally selected, reporting a high survival rate of the implants. Eight studies focused only on the mandible while one study reported data from both mandible and maxilla. All studies reported on removable restorations; none focused on fixed rehabilitations. The estimated survival rate for 5 years of follow-up was calculated to be 92.25% for the implants. The estimated marginal bone loss after 5 years was calculated to be 1.40 mm. No study reported implant fractures. CONCLUSIONS: With the limitations of the present study, there is evidence that 2.5-3.5 mm narrow-diameter implants retaining a removable restoration can be a successful treatment in fully edentulous patients. No data on fixed restorations was available.

BACKGROUND: The pathogenic variant, POU class 4 transcription factor 3 (POU4F3), is reported to cause autosomal dominant nonsyndromic hearing loss (ADNSHL). Previously, we have examined a four-generation midfrequency sensorineural hearing loss (MFSNHL) family (no. 6126) and established POU4F3 c.602T>C (p.Leu201Pro) as a potential disease-causing variant. OBJECTIVES: We explored the structural and functional alterations that the c.602T>C (p.Leu201Pro) variant enforces on the POU4F3 protein. METHODS: We utilized wild-type (WT) and mutant (MUT) POU4F3 c.602T>C plasmid incorporation into HeLa cells to assess functional changes, by immunofluorescence and luciferase assays. To predict protein structural alterations in the MUT versus WT POU4F3, we also generated 3D structures to compare both types of POU4F3 proteins. RESULTS: The WT POU4F3 is ubiquitously present in the nucleus, whereas the MUT form of POU4F3 exhibits a more restricted nuclear presence. This finding is different from other publications, which report a cytoplasmic localization of the MUT POU4F3. We also demonstrated that, as opposed to WT POU4F3, the MUT POU4F3 had 40% reduced luciferase activity. CONCLUSIONS: The reduced nuclear presence, combined with reduced transcriptional activity, suggests that the POU4F3 c.602T>C variant alters cellular activity and may contribute to the pathogenicity of POU4F3-related hearing loss. It, also, provides more evidence of the pathophysiological characteristics of MFSNHL.

BACKGROUND: Carotid plaque is an undefined risk factor in ischemic stroke and is driven by inflammation. Mounting evidence suggests that neutrophil-to-lymphocyte ratio (NLR) is crucial not only for cerebrovascular events but also in atherosclerosis progression. Here, we aimed to explore the association between the admission NLR and carotid plaque vulnerability as well as the occurrence of vulnerable carotid plaque detected by carotid ultrasonography in patients with acute ischemic stroke (AIS) among Chinese. METHODS: We conducted a retrospective study composed of 588 patients with AIS and 309 healthy controls free of carotid plaque in the Department of Neurology in The Second Hospital of Lanzhou University from March 2014 to February 2015. All patients were classified as nonplaque, stable plaque, and vulnerable plaque groups on the basis of carotid ultrasonography results. The baseline information was collected and compared among the four different groups. The correlation between variables and carotid plaque vulnerability was tested by Spearman linear correlation analysis. To identify the independent predictors for vulnerable carotid plaque, univariate and multivariate logistic regression analysis was performed. RESULTS: The comparisons of age, sex proportion, history of hypertension, diabetes, and smoking, the levels of HDL-C, Lp(a), BMI, SBP, DBP, Fib, CRP, leukocyte, and NLR among the four groups showed a statistically significant difference (P < 0.05); in particular, the NLR was significantly higher in the vulnerable plaque group as compared to the control (P = 0.043), nonplaque (P = 0.022), and stable plaque groups (P = 0.015). The Spearman correlation analysis presented a positive correlation between carotid plaque vulnerability and age (r = 0.302; P < 0.001), SBP (r = 0.163; P < 0.001), and NLR (r = 0.087; P = 0.034), while the lymphocyte was negatively related to the carotid plaque vulnerability (r = -0.089; P = 0.030). The multivariate logistic regression analysis adjusted for confounding factors revealed that age (odds ratio [OR], 1.042; 95% confidence interval [CI], 1.025-1.060; P < 0.001), male gender (OR, 2.005; 95% CI, 1.394-2.884; P < 0.001), diabetes (OR, 1.481; 95% CI, 1.021-2.149; P = 0.039), SBP (OR, 1.012; 95% CI, 1.003-1.021; P = 0.010), and NLR (OR, 1.098; 95% CI, 1.018-1.184; P = 0.015) are independent predictors of vulnerable carotid plaque in patients with AIS. CONCLUSION: The admission NLR is a novel and meaningful biomarker that can be used in predicting carotid plaque vulnerability and the presence of vulnerable carotid plaque assessed by carotid ultrasonography in patients with AIS among Chinese.

OBJECTIVE: The abnormal expression of LncRNA H19 and miR-140-5p has been linked to ovarian cancer (OC). Whether H19 directly regulates miR-140-5p in ovarian cancer cells has been unclear. In this study, we deeply explored the relationship between H19 and miR-140-5p in ovarian cancer and the mechanism of action in regulating OC progression. METHODS: A total of 66 patients with OC admitted to the hospital from June 2017 to June 2019 were selected as the research group (RG), and meanwhile, 60 cases of healthy subjects were selected as the control group (CG). In addition, OC cells and normal ovarian epithelial cells were used to detect H19 and miR-140-5p expression levels and to analyze the effect of H19 on OC cells. The activation of the PI3K/AKT pathway and downstream proteins were analyzed by western blot. RESULTS: H19 was highly expressed while miR-140-5p was lowly expressed in OC patients and cell lines (P < 0.050). The proliferation, invasion, migration ability, and epithelial-mesenchymal transition (EMT) of OC cells were reduced after inhibiting H19 expression, and the apoptosis rate was increased. Transfection of cells with miR-140-5p mimics brought opposite effects. Online prediction and dual-luciferase reporter (DLR) confirmed that H19 directly binds miR-140-5p. Western blot assay indicated overexpression activated the PI3K/AKT signaling pathway in OC cells. Moreover, overexpression promoted tumor growth in nude mice and was suppressed by PI3K inhibitor. CONCLUSION: LncRNA H19 downregulation of miR-140-5p to activate the PI3K/AKT signaling pathway and promote the proliferation, invasion, migration and EMT of OC.

Hearing loss is a sensory deprivation that can affect the quality of life. Currently, only rehabilitation devices such as hearing aids and cochlear implants are used, without a definitive cure. However, in chronic hearing-deprived patients, in whom secondary auditory neural degeneration is expected, a relatively poor rehabilitation prognosis is projected. Stem cell therapy for cochlear neural structures would be an easier and feasible strategy compared with cochlear sensory cells. Considering the highly developed cochlear implantation technology, improving cochlear neural health has significant medical and social effects. Stem cell delivery to Rosenthal's canal in an acutely damaged mouse model has been performed and showed cell survival and the possibility of differentiation. The results of stem cell transplantation in chronic auditory neural hearing loss should be evaluated because neural stem cell replacement therapy for chronic (long-term) sensorineural hearing loss is a major target in clinics. In the present study, we established a mouse model that mimicked chronic auditory neural hearing loss (secondary degeneration of auditory neurons after loss of sensory input). Then, mouse embryonic stem cells (mESCs) were transplanted into the scala tympani and survival and distribution of transplanted cells were compared between the acute and chronic auditory neural hearing loss models induced by ouabain or kanamycin (KM), respectively. The mESC survival was similar to the acute model, and perilymphatic distribution of cell aggregates was more predominant in the chronic model. Lastly, the effects of mESC transplantation on neural signal transduction observed in the cochlear nucleus (CN) were compared and a statistical increase was observed in the chronic model compared with other models. These results indicated that after transplantation, mESCs survived in the cochlea and increased the neural signaling toward the central auditory pathway, even in the chronic (secondary) hearing loss mouse model.

Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae that contain the largest genome among RNA viruses. Their genome encodes 4 major structural proteins, and among them, the Spike (S) protein plays a crucial role in determining the viral tropism. It mediates viral attachment to the host cell, fusion to the membranes, and cell entry using cellular proteases as activators. Several in vitro models have been developed to study the CoVs entry, pathogenesis, and possible therapeutic approaches. This article is aimed at summarizing the current knowledge about the use of relevant methodologies and cell lines permissive for CoV life cycle studies. The synthesis of this information can be useful for setting up specific experimental procedures. We also discuss different strategies for inhibiting the binding of the S protein to the cell receptors and the fusion process which may offer opportunities for therapeutic intervention.

OBJECTIVE: The aim of this research was to compare three cephalometric analyses and their correlation with the airway volume in subjects with different skeletal classes using 2D and 3D images. Study Design. Cross-sectional descriptive study. Material and Method. Steiner, McNamara, and Ricketts analyses and the airway volume were compared in 115 subjects who were candidates for orthognathic surgery under diagnosis using cone beam computed tomography (CBCT); 46 males (40%) and 69 females (60%) were included. The sagittal positions of the maxilla and mandible, the angulation of the mandibular plane, the sagittal positions of the upper and lower incisors, measurements of the largest or shortest airway area, and the volume were compared using Spearman's test considering a p value < 0.05. RESULTS: Differences were observed between the Steiner and McNamara techniques for the sagittal position of the maxilla (p = 0.01). For mandibular angulation, there was a greater difference between values for Steiner and Ricketts techniques (p = 0.001). In the upper incisor, the results for McNamara and Ricketts techniques were significantly different (p = 0.004). Analysing the airway, subjects with a class II skeletal pattern had a smaller volume than those with a class III pattern (p = 0.034). CONCLUSION: It may be concluded that skeletal class II patients have a significantly smaller airway volume than class III patients. The skeletal parameter does not always relate to the airway volume; however, the high mandibular angle could be related to the airway conditions.

The increase in the average age of our society represents a growing medical and social problem, which requires concentration on the issue concerning balance disorders. The aquatic environment has a number of complex properties that have miscellaneous effects on the human body. In the light of the above, water is becoming an ideal environment to learn correct neuromuscular communication, and a properly prepared training session in water helps to practice balance and movement coordination. The objective of the study was to assess the impact of rehabilitation in the aquatic environment on patients' balance and compare the results obtained with patients who received rehabilitation at a gym. The study was carried out among patients hospitalised in the "Krzeszowice" Rehabilitation Centre. It encompassed 137 patients, randomly assigned to either the study group (the aquatic environment) or the control group (the gym). The preliminary examination included general medical history and a test on the stabilometric platform. The patients attended training sessions for 4 weeks, 5 times a week for 30 minutes. It was a single-blinded study wherein the authors did not know which group a given patient had been assigned to. Upon completion of a monthly therapy, the stabilometric test was carried out again. The study revealed that the patients from both groups experienced a significant improvement in balance. However, the improvement was slightly greater in those exercising in the pool. Physiotherapy in the aquatic environment makes a greater contribution to the improvement of body balance compared to physical exercises performed at a gym.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by lung inflammation and remodeling. Macrophage polarization is associated with inflammation and tissue remodeling, as well as immunity. Therefore, this study attempts to investigate the diagnostic value and regulatory mechanism of macrophage polarization-related genes for COPD by bioinformatics analysis and to provide a new theoretical basis for experimental research. METHODS: The raw gene expression profile dataset (GSE124180) was collected from the Gene Expression Omnibus (GEO) database. Next, a weighted gene coexpression network analysis (WGCNA) was conducted to screen macrophage polarization-related genes. The differentially expressed genes (DEGs) between the COPD and normal samples were generated using DESeq2 v3.11 and overlapped with the macrophage polarization-related genes. Moreover, functional annotations of overlapped genes were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resource. The immune-related genes were selected, and their correlation with the differential immune cells was analyzed by Pearson. Finally, receiver operating characteristic (ROC) curves were used to verify the diagnostic value of genes. RESULTS: A total of 4922 coexpressed genes related to macrophage polarization were overlapped with the 203 DEGs between the COPD and normal samples, obtaining 25 genes related to COPD and macrophage polarization. GEM, S100B, and GZMA of them participated in the immune response, which were considered the candidate biomarkers. GEM and S100B were significantly correlated with marker genes of B cells which had a significant difference between the COPD and normal samples. Moreover, GEM was highly associated with the genes in the PI3K/Akt/GSK3β signaling pathway, regulation of actin cytoskeleton, and calcium signaling pathway based on a Pearson correlation analysis of the candidate genes and the genes in the B cell receptor signaling pathway. PPI network analysis also indicated that GEM might participate in the regulation of the PI3K/Akt/GSK3β signaling pathway. The ROC curve showed that GEM possessed an excellent accuracy in distinguishing COPD from normal samples. CONCLUSIONS: The data provide a transcriptome-based evidence that GEM is related to COPD and macrophage polarization likely contributes to COPD diagnosis. At the same time, it is hoped that in-depth functional mining can provide new ideas for exploring the COPD pathogenesis.

OBJECTIVE: Many intracranial aneurysms often have branch arteries, and it is especially important to protect them during embolization. The purpose of the present study was to evaluate the curative effect and safety of the "stilted building" technique. METHODS: 25 patients with intracranial aneurysms with branch arteries that have been treated by coil embolization with the "stilted building" technique were retrospectively reviewed. Clinical follow-up was performed after endovascular treatment. RESULTS: All 25 patients successfully underwent aneurysm embolization. During the operation, the ruptured sac and most of the body of the aneurysm were embolized using the "stilted building" technique. Immediate imaging showed that the blood flow to the branch arteries from the neck or sidewall of the aneurysm was unobstructed. The mRS scores of the 25 patients during the follow-up period were mRS 0 for twenty-one patients, mRS 1 for three patients, and mRS 6 for one patient. No aneurysms recurred among the patients who completed the follow-up. CONCLUSIONS: In an aneurysm with a branch artery, when a balloon or stent cannot be effectively used to protect the branch artery, the use of "stilted building" embolization can achieve good therapeutic effects, and the short-term follow-up results are satisfactory; the technique can effectively protect branch arteries originating from aneurysms.

Erratum for Biomed Res Int. 2020 Jul 31;2020:7147824.

This study was conducted to evaluate the prognostic value of receptor-interacting protein kinase 4 (RIPK4) in ovarian cancer (OC) and its role in tumorigenesis. RNA expression and the corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The relationship between clinical-pathological characteristics and RIPK4 expression was analyzed using the Wilcoxon signed-rank test and logistic regression. The Cox regression and the Kaplan-Meier method were used to evaluate the relationship between clinicopathological features and overall survival (OS). Gene set enrichment analysis (GSEA) was performed using Molecular Signatures Database. Scratch assay, transwell assay, and cell transfection were used to verify the function of RIPK4. Overexpression of RIPK4 was associated with the stage of OC and distant metastasis. Survival analysis revealed that patients with OC and higher expression of RIPK4 had a poorer prognosis. Univariate and multivariate analyses indicated that high expression of RIPK4 was associated with poor OS, as well as age and stage of OC. The areas under the curve (AUC) at 1, 4, and 8 years were 0.737, 0.634, and 0.669, respectively, according to the established OS prediction model. GSEA revealed that adherens junction, cadherin binding, and Wnt signaling pathway were enriched in the high RIPK4 expression group. Cell transfection confirmed RIPK4 was involved in the Wnt signaling pathway. RIPK4 can act as a potential prognostic molecular marker for poor survival in OC. Moreover, RIPK4 is associated with tumor metastasis and implicated in the regulation of the Wnt signaling pathway.

BACKGROUND: Acute kidney injury (AKI) is one of most prevalent and serious complications of leptospirosis, a prevalent zoonotic disease in tropical countries. Prompt diagnosis of the leptospirosis-associated AKI is a challenge as there are no proper diagnostic tools that can identify patients in the early stage. Kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1) are widely used novel AKI biomarkers that are studied in various disease conditions with AKI, but not in leptospirosis. Thus, this study is aimed at seeking the importance of KIM-1 and MCP-1 in determining the leptospirosis-associated AKI. METHODS: Leptospirosis-suspected patients who were admitted to medical wards of two selected hospitals in the Western province of Sri Lanka were recruited. Leptospirosis was confirmed by three diagnostic tests: PCR, MAT, and culture, and the status of AKI was determined by Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Of 170 leptospirosis-suspected patients, 79 were leptospirosis confirmed, and among them, 24.05% of patients were diagnosed to have AKI according to KDIGO criteria. Median serum KIM-1 (p < 0.0001), urine KIM-1 (0.0053), serum MCP-1 (0.0080), and urine MCP-1 (0.0019) levels in those developing AKI were significantly higher than in patients not developing AKI. The biomarker levels associated with leptospirosis AKI had AUC-ROC of 0.8565, 0.7292, 0.7024, and 0.7282 for serum KIM-1, urine KIM-1, serum MCP-1, and urine MCP-1, respectively. CONCLUSION: This study revealed serum KIM-1 as a promising marker for leptospirosis-associated AKI among the tested biomarkers. Thus, further validation is recommended with a larger study group.

In the present study, we hypothesized that buckwheat honey (BH) should be regarded as a potential alternative to antibacterial and antioxidant agent in liquid storage of boar semen. To this end, boar semen was firstly studied for in vitro dose tolerability to BH by measuring sperm progressive motility. The optimum progressive motility of boar spermatozoa was observed in extender with 0.5% and 0.6% BH addition. Afterward, sperm quality parameters, bacterial profile and composition, total antioxidant (T-AOC), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels of control, BH supplementation, antibiotics supplementation, and incorporated supplementation were compared during liquid storage period, to further investigate antibacterial and antioxidant properties of BH. The results showed that BH supplementation significantly improved sperm motility, acrosome integrity, plasma membrane integrity, inhibited opportunistic bacterial growth, and altered microbial compositions at the end of preservation. Additionally, T-AOC, SOD, and CAT levels were significantly higher in the BH supplementation group than those in the control and antibiotic supplementation group, whereas MDA level exhibited opposite change pattern. Importantly, BH addition to the extender was able to exert a synergistic effect in combination of antibiotic use. Our findings suggested that the appropriate concentrations (0.5% and 0.6%) of BH were added to the extender could act antibacterial and antioxidant roles in liquid preservation of boar semen.

As a powerful antioxidant in the human body, uric acid (UA) has been the subject of increasing research that focused on its influence on Alzheimer's disease (AD) in recent years. The latest literature was gathered to describe the influence of serum uric acid (SUA) level on the onset and progression of AD and to analyze the possibility that SUA is a biomarker of Alzheimer's disease. A large number of existing studies suggested that the SUA level was lower or tended to decrease in patients with AD, and increased SUA level may have a protective effect in AD, which could reduce the risk of onset and slowing the course of the disease. However, some Mendelian randomization analyses suggested that genetically determined uric acid was not associated with AD risk. Existing research results are contradictory due to the high inconsistency of the studies, the selection of subjects, and other factors. UA also showed a strong association with cognitive function, and there appeared to be a gender-selective neuroprotective action. Due to its potent antioxidant properties, the low uric acid level may contribute to oxidative stress to accelerate disease progression. But some preclinical data showed a possibility that in some special cases, UA had a prooxidant properties. The possibility was raised in the discussion of the underlying mechanism that both the low uric acid level and the rapidly progressive course of the disease were the consequence of malnutrition. This paper reviews recent advances in the study of SUA and AD which offers the possibility of new biomarker, new prevention, and treatment strategies for Alzheimer's disease.

Statins can help COVID-19 patients' treatment because of their involvement in angiotensin-converting enzyme-2. The main objective of this study is to evaluate the impact of statins on COVID-19 severity for people who have been taking statins before COVID-19 infection. The examined research patients include people that had taken three types of statins consisting of Atorvastatin, Simvastatin, and Rosuvastatin. The case study includes 561 patients admitted to the Razi Hospital in Ghaemshahr, Iran, during February and March 2020. The illness severity was encoded based on the respiratory rate, oxygen saturation, systolic pressure, and diastolic pressure in five categories: mild, medium, severe, critical, and death. Since 69.23% of participants were in mild severity condition, the results showed the positive effect of Simvastatin on COVID-19 severity for people that take Simvastatin before being infected by the COVID-19 virus. Also, systolic pressure for this case study is 137.31, which is higher than that of the total patients. Another result of this study is that Simvastatin takers have an average of 95.77 mmHg O2Sat; however, the O2Sat is 92.42, which is medium severity for evaluating the entire case study. In the rest of this paper, we used machine learning approaches to diagnose COVID-19 patients' severity based on clinical features. Results indicated that the decision tree method could predict patients' illness severity with 87.9% accuracy. Other methods, including the K-nearest neighbors (KNN) algorithm, support vector machine (SVM), Naïve Bayes classifier, and discriminant analysis, showed accuracy levels of 80%, 68.8%, 61.1%, and 85.1%, respectively.

The baseline levels of various inflammatory mediators and their changes during anesthesia in swine are not known. The aim of this animal study was to measure the baseline values and kinetics of interleukin-6, procalcitonin, and tumor necrosis factor-alpha in healthy Landrace-Large White swine anesthetized with propofol-based total intravenous anesthesia. We included 8 healthy male pigs with an average weight of 19 ± 2 kg (aged 10-15 weeks) that were subjected to propofol-based total intravenous anesthesia for 8 hours. Complete blood count, serum chemistry, and serum levels of interleukin-6, procalcitonin, and tumor necrosis factor-alpha were analyzed, and serum levels were quantified hourly. Blood was also collected for bacterial culturing. Baseline values of interleukin-6 and procalcitonin were 18 pg/ml and 21 ng/ml, respectively, while tumor necrosis factor-alpha was not detectable during collection of baseline samples. A statistically significant difference was observed in interleukin-6 levels between time points (p < 0.0001). Procalcitonin increased with time, but there were no significant differences between time points (p = 0.152). Tumor necrosis factor-alpha increased until the 3rd hour of propofol-based total intravenous anesthesia, while after the 4th hour, it gradually decreased, reaching its baseline undetectable values by the 7th hour (p < 0.001). Our results can serve as the basis for further translational research.

OBJECTIVE: Our purpose was to characterize distinct molecular subtypes of diffuse large B cell lymphoma (DLBCL) patients treated with rituximab-CHOP (R-CHOP). METHODS: Two gene expression datasets of R-CHOP-treated DLBCL patients were downloaded from GSE10846 (n = 233, training set) and GSE31312 (n = 470, validation set) datasets. Cluster analysis was presented via the ConsensusClusterPlus package in R. Using the limma package, differential expression analysis was utilized to identify feature genes. Kaplan-Meier survival analysis was presented to compare the differences in the prognosis between distinct molecular subtypes. Correlation between molecular subtypes and clinical features was analyzed. Based on the sets of highly expressed genes, biological functions were explored by gene set enrichment analysis (GSEA). Several feature genes were validated in the molecular subtypes via qRT-PCR and western blot. RESULTS: DLBCL samples were clustered into two molecular subtypes. Samples in subtype I displayed poorer overall survival time in the training set (p < 0.0001). Consistently, patients in subtype I had shorter overall survival (p = 0.0041) and progression-free survival time (p < 0.0001) than those in subtype II. Older age, higher stage, and higher international prognostic index (IPI) were found in subtype I. In subtype I, T cell activation, lymphocyte activation, and immune response were distinctly enriched, while cell adhesion, migration, and motility were significantly enriched in subtype II. T cell exhaustion-related genes including TIM3 (p < 0.001), PD-L1 (p < 0.0001), LAG3 (p < 0.0001), CD160 (p < 0.001), and CD244 (p < 0.001) were significantly highly expressed in subtype I than subtype II. CONCLUSION: Two molecular subtypes were constructed in DLBCL, which were characterized by different clinical outcomes and molecular mechanisms. Our findings may offer a novel insight into risk stratification and prognosis prediction for DLBCL patients.

The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.

BACKGROUND: Polymicrobial Klebsiella pneumoniae bloodstream infection (KP-BSI) has been reported to account for more than 10% of all KP-BSI, but few studies have characterized polymicrobial KP-BSI. Our study investigated the clinical characteristics, risk factors, and outcomes of polymicrobial KP-BSI by comparing with monomicrobial KP-BSI. METHODS: We conducted a single-center retrospective cohort study of patients with KP-BSI from 1 January 2013 to 31 December 2018 and collected the clinical data by reviewing electronic medical records. RESULTS: Of the 818 patients with KP-BSI recruited, 13.9% (114/818) were polymicrobial KP-BSI. The severity of illness in polymicrobial and monomicrobial KP-BSI was similar, while the rate of resistance to carbapenems was obviously higher in polymicrobial KP-BSI (78.1% vs. 65.6%, p = 0.009). On multivariate analysis, hospitalization in burn ward (odds ratio (OR) 6.13, 95% confidence interval (CI) 2.00-18.76, p = 0.001) and intensive care unit (OR 2.39, 95% CI 1.05-5.43, p = 0.038) was independently associated with polymicrobial KP-BSI. Gram-negative bacteria accounted for the highest proportion (68.9%) among copathogens of polymicrobial KP-BSI, whereas gram-positive bacteria (22.9%) and Candida (8.2%) ranked the second and the third, respectively, with Acinetobacter baumannii being the most common (23.0%). Patients with polymicrobial KP-BSI had longer hospital days after BSI onset and total hospital days than patients with monomicrobial KP-BSI (median (interquartile range (IQR)), 19 (5, 39) vs. 12 (6, 25), 37 (21, 67) vs. 29 (16, 53), respectively, p < 0.05). The mortality did not differ between polymicrobial KP-BSI and monomicrobial KP-BSI (all p > 0.05). CONCLUSIONS: It was observed that polymicrobial KP-BSI accounted for a significant proportion among all KP-BSI in the current study. Hospitalization in burn ward and intensive care unit was an independent risk factor for the development of polymicrobial KP-BSI. The patients with polymicrobial KP-BSI had a higher rate of carbapenem-resistant K. pneumoniae and might have poor outcomes compared to monomicrobial KP-BSI.

BACKGROUND: COVID-19 is a pandemic disease worldwide. Although cutaneous manifestations may present in affected patients, there have been limited studies on the cutaneous findings and hair and nail abnormalities after discharge. OBJECTIVE: To establish the cutaneous manifestations, hair and scalp disorders, and nail abnormalities in patients who recovered from COVID-19 infections. METHODS: A retrospective chart review and telephone interviews were conducted to determine the cutaneous manifestations, hair and scalp disorders, and nail abnormalities of patients aged over 18 years who were diagnosed with COVID-19 infections at Siriraj Hospital, Bangkok, Thailand, between January and June 2020. RESULTS: Ninety-three patients with prior COVID-19 infections participated in the study. The COVID-19 severity had been mild for most (71%). Cutaneous manifestations were reported in 8 patients (8.6%), with the common skin conditions being maculopapular rash and urticaria. The onsets of the skin conditions were before admission (1%), during admission (4.3%), and after discharge (3.2%). Increased hair shedding was also reported in 22 patients (23.7%), with a female predominance. Three patients were affected during admission, while the others were affected after discharge. The patients with moderate, severe, and critical COVID-19 infections experienced significantly more hair shedding than those with asymptomatic and mild diseases. Only 2 patients with mild COVID-19 disease reported nail abnormalities (chromonychia and brittle nails). CONCLUSIONS: Cutaneous manifestations, hair disorders, and nail abnormalities can occur in patients with COVID-19 after their discharge from hospital. Patients should therefore be followed up in anticipation of dermatological problems.

The present study is aimed at determining the effects of intensity-modified recreational volleyball training on health markers and physical fitness in healthy middle-aged men. Thirty-four healthy untrained men aged 25-55 years were randomized to either a modified recreational volleyball group (MRV, n = 17) or a recreational volleyball group (RV, n = 17). Both groups performed volleyball training twice a week over 12 weeks, with participants in MRV playing a modified game with higher intensity due to shorter breaks between rallies. The small to moderate improvements of both groups were observed in SBP (MRV g av = -0.50 [-0.67, -0.33] vs. RV g av = -0.37 [-0.55, -0.20]) to a similar extent (p = 0.12). However, only the MRV significantly improved (p < 0.001) the mean body weight (g av = -0.35 [-0.52, -0.18]) and BMI (g av = -0.39 [-0.56, -0.22]) to a moderate extent and the YYIR1 performance (g av = 2.45 [2.22, 2.69]) to a large extent. Even though both groups significantly improved the rest HR, the mean change of rest HR was significantly greater in MRV as compared to the RV (p < 0.001,  ŋ p 2 = 0.47). The study revealed that an intensity-modified type of recreational volleyball, involving shorter breaks between rallies, improves cardiorespiratory fitness and health markers for men aged 25-55 years.

Expanded polytetrafluoroethylene (ePTFE) is commonly used in cardiovascular surgery, but usually causes postoperation complications. Although great efforts have been done to relieve these complications or to understand their mechanism, there are no applicable strategies available and no understanding mechanisms, especially in the myocardium. Here, ePTFE membranes are implanted into the right ventricular outflow tract of rabbits, and the implant-related myocardium is dissected and analyzed by histology and transcriptome sequencing. ePTFE implantation causes myocardium inflammation and fibrosis. There are 1867 differently expressed mRNAs (DEmRNAs, 1107 upregulated and 760 downregulated) and 246 differently expressed lncRNAs (DElncRNAs, 110 upregulated and 136 downregulated) identified. Bioinformatic analysis indicates that the upregulated DEmRNAs and DElncRNAs are mainly involved in inflammatory, immune responses, and extracellular matrix remodeling, while the downregulated DEmRNAs and DElncRNAs are predominantly functioned in the metabolism and cardiac remodeling. Analysis of coexpression and regulatory relationship of DEmRNAs and DElncRNAs reveals that most DElncRNAs are trans-regulated on the relevant DEmRNAs. In conclusion, ePTFE implantation causes severe myocardial tissue damages and alters the transcriptome profiles of the myocardium. Such novel data may provide a landscape of mechanisms underlying the adverse reactions caused by ePTFE implantation and uncover new therapeutic targets for inhibiting the ePTFE-related complications.

BACKGROUND: Parkinson's disease (PD) patients are at increased risk for central auditory processing (CAP) deficits and cognitive dysfunction. However, behavioral assessments of CAP and cognitive processing used in a previous study by our research team found few significant differences in performance between early-stage PD patients and age-matched control subjects. The objective of this study is to use auditory event-related potentials (AERPs) to compare CAP and cognitive functions in a population of PD patients with a group of age-matched control subjects. METHODS: AERPs in response to tonal and speech stimuli were recorded from 35 adults who had a medical diagnosis of PD (23 males and 12 females; mean age = 66.9 ± s.d.11.2 years), and 35 age-matched control subjects who did not have PD or any other neurological disorders (31 males and 4 females; mean age = 65.4 ± s.d.12.3 years). Auditory stimuli included pure tones (500 and 1000 Hz) to elicit the P300 response and a dichotic digits paradigm to elicit the N200 processing negativity. RESULTS: Compared to control subjects, PD patients exhibited significantly longer latencies of P300 and N200 components and smaller amplitude N200 components. Latency and amplitude of the N200 component were significantly correlated with participants' age. N200 amplitude was correlated with results from the Rey Auditory Verbal Learning Test (RAVLT) of cognitive ability. Latency of the P300 and amplitude of the N200 components were significantly correlated with results from the Spatial Release From Masking (SRM) behavioral CAP assessment. CONCLUSIONS: AERP assessments used in this study appear to be sensitive indicators of CAP and cognitive deficits exhibited by early-stage PD patients. While few significant differences in performance on behavioral CAP and cognitive tests were previously observed between this population of PD patients and age-matched control subjects, N200 and P300 components recorded in the present study revealed impaired neural processing by the PD group.

PURPOSE: The aim of this work was to analyze the complete genome of probiotic bacteria Lactobacillus plantarum 8 RA 3, Lactobacillus fermentum 90 TC-4, Lactobacillus fermentum 39, Bifidobacterium bifidum 791, Bifidobacterium bifidum 1, and Bifidobacterium longum 379 and to test their activity against influenza A and SARS-CoV-2 viruses. METHODS: To confirm the taxonomic affiliation of the bacterial strains, MALDI TOF mass spectrometry and biochemical test systems were used. Whole genome sequencing was performed on the Illumina Inc. MiSeq platform. To determine the antiviral activity, A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798) and A/common gull/Saratov/1676/2018 (H5N6) (EPI_ISL_336925) influenza viruses and SARS-CoV-2 virus strain Australia/VIC01/2020 (GenBank: MT007544.1) were used. RESULTS: All studied probiotic bacteria are nonpathogenic for humans and do not contain the determinants of transmission-type antibiotic resistance and integrated plasmids. Resistance to antibiotics of different classes is explained by the presence of molecular efflux pumps of the MatE and MFS families. Cultures of L. fermentum 90 TC 4, L. plantarum 8 RA 3, and B. bifidum 791 showed a pronounced activity against influenza A viruses in MDCK cells. Activity against the SARS-CoV-2 virus was demonstrated only by the L. fermentum 90 TC 4 strain in VERO cells. CONCLUSIONS: The studied probiotic bacteria are safe, have antiviral activity, and are of great importance for the prevention of diseases caused by respiratory viruses that can also infect the human intestine.

With the continuous development of artificial intelligence technology, "brain-computer interfaces" are gradually entering the field of medical rehabilitation. As a result, brain-computer interfaces (BCIs) have been included in many countries' strategic plans for innovating this field, and subsequently, major funding and talent have been invested in this technology. In neurological rehabilitation for stroke patients, the use of BCIs opens up a new chapter in "top-down" rehabilitation. In our study, we first reviewed the latest BCI technologies, then presented recent research advances and landmark findings in BCI-based neurorehabilitation for stroke patients. Neurorehabilitation was focused on the areas of motor, sensory, speech, cognitive, and environmental interactions. Finally, we summarized the shortcomings of BCI use in the field of stroke neurorehabilitation and the prospects for BCI technology development for rehabilitation.

Species of Tulipa (Liliaceae) are of great horticultural importance and are distributed across Europe, North Africa, and Asia. The Tien Shan Mountain is one of the primary diversity centres of Tulipa, but the molecular studies of Tulipa species from this location are lacking. In our study, we assembled four Tulipa plastid genomes from the Tien Shan Mountains, T. altaica, T. iliensis, T. patens, and T. thianschanica, combined with the plastid genome of T. sylvestris to compare against other Liliaceae plastid genomes. We focussed on the species diversity and evolution of their plastid genomes. The five Tulipa plastid genomes proved highly similar in overall size (151,691-152,088 bp), structure, gene order, and content. With comparative analysis, we chose 7 mononucleotide SSRs from the Tulipa species that could be used in further population studies. Phylogenetic analyses based on 24 plastid genomes robustly supported the monophyly of Tulipa and the sister relationship between Tulipa and Amana, Erythronium. T. iliensis, T. thianschanica, and T. altaica were clustered together, and T. patens was clustered with T. sylvestris, with our results clearly demonstrating the relationships between these five Tulipa species. Our results provide a more comprehensive understanding of the phylogenomics and comparative genomics of Tulipa.

OBJECTIVE: To observe the changes in the mechanical withdrawal threshold (MWT) and the proportion of GABA-immunoreactive neurons in spinal dorsal horn (SDH) of the spared nerve injury (SNI) rat model. METHODS: Thirty-six healthy male SD rats were randomly divided into a sham-operated group (group D, n = 18) and an SNI group (group S, n = 18). The left sciatic nerve trunk and three branches were exposed, two of which, known as tibial and the peroneal nerve, were ligated and cut off. The sural nerve was preserved to build the SNI model in group S. The left sciatic nerve trunk and three branches were only exposed in group D. MWT tests were performed on the medial and lateral sides of the rats' left hindpaw 1 day before surgery and at 7th, 14th, and 28th day after surgery. RESULTS: In group S, compared with the baseline measured 1 day before surgery, MWT on the medial and lateral sides of the rats' left hindpaw decreased significantly on the 7th, 14th, and 28th days after surgery (P < 0.05), while in group D, there was no statistically significant difference (P > 0.05). Compared with right SDH, there were not statistically significant reductions in the proportions of GABAergic neurons of left SDH on 7th and 28th day after SNI (P > 0.05); however, the proportion of GABAergic neurons in left SDH significantly decreased, compared with that in right side on 14th day after SNI (P < 0.05). On the same way, the proportions of GABAergic neurons on 7th, 14th, and 28th day after surgery were not statistically different (P > 0.05) in group D. CONCLUSION: The SNI model could reduce the proportion of GABA-immunoreactive neurons in the rat's spinal dorsal horn on the nerve-injured side, and this change was lasting, which might be related to the transformation of the GABA-immunoreactive neurons.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) are a family of enzymes. However, the clinical and functional roles of PLOD3 in colon adenocarcinoma (COAD) have not been investigated. The present study found that PLOD3 was highly upregulated in COAD, which may be resulted from its aberrant DNA methylation. The upregulation of both PLOD3 mRNA and protein was confirmed in our tissue samples. Moreover, high PLOD3 was identified to be associated with unfavorable prognosis in COAD. As genome instability is a hallmark of cancer, PLOD3 was expressed higher in COAD samples with high chromosomal instability (CIN-high) than those with low CIN (CIN-low) and higher in those with low MSI than high MSI, indicating that PLOD3 expression was associated with tumor genomic instability. Furthermore, immune cells showed significantly different infiltrating levels between the high and low PLOD3 expression groups, and the immune score was negatively correlated with PLOD3 expression and higher in samples with low PLOD3 expression, suggesting that high PLOD3 expression was associated with reduced immune cell infiltrating levels in COAD. To further uncover the underlying mechanism of PLOD3 in PLOD3, we compared the COAD samples of high PLOD3 expression with those of low PLOD3 expression and found that high expression of PLOD3 was associated with reduced expression of immune regulators and enhanced activities of two tumor-promoting pathways, including gluconeogenesis and TGF-beta signaling in epithelial-mesenchymal transition (EMT), suggesting that high expression of PLOD3 causes poor prognosis in COAD by weakening the immune cell infiltration and enhancing activities of tumor-promoting pathways. In summary, the present study highlights the importance of PLOD3 and provides the evidence about the functional role of PLOD3 in COAD.

OBJECTIVE: Autophagy and long noncoding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma. METHODS: We downloaded RNA sequencing data and clinical information of melanoma from the Cancer Genome Atlas. The coexpression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate Cox regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups. RESULTS: According to the results of the univariate Cox analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate Cox analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p < 0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism. CONCLUSION: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNA risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

Argonaute (AGO) proteins play a pivotal role in plant growth and development as the core components of RNA-induced silencing complex (RISC). However, no systematic characterization of AGO genes in wheat has been reported to date. In this study, a total number of 69 TaAGO genes in the hexaploid bread wheat (Triticum aestivum cv. Chinese Spring) genome, divided into 10 subfamilies, were identified. Compared to all wheat genes, TaAGOs showed a significantly lower evolutionary rate, which is consistent with their high conservation in eukaryotes. However, the homoeolog retention was remarkably higher than the average, implying the nonredundant biological importance of TaAGO genes in bread wheat. Further homoeologous gene expression bias analyses revealed that TaAGOs may have undergone neofunctionalization after polyploidization and duplication through the divergent expression of homoeologous gene copies, to provide new opportunities for the generation of adaptive traits. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) analyses indicated that TaAGO gene expression was involved in response to heat, drought, and salt stresses. Our results would provide a theoretical basis for future studies on the biological functions of TaAGO genes in wheat and other gramineous species.

Single nucleotide polymorphisms (SNPs) play a significant role in microRNA (miRNA) generation, processing, and function and contribute to multiple phenotypes and diseases. Therefore, whole-genome analysis of how SNPs affect miRNA maturation mechanisms is important for precision medicine. The present study established an SNP-associated pre-miRNA (SNP-pre-miRNA) database, named miRSNPBase, and constructed SNP-pre-miRNA sequences. We also identified phenotypes and disease biomarker-associated isoform miRNA (isomiR) based on miRFind, which was developed in our previous study. We identified functional SNPs and isomiRs. We analyzed the biological characteristics of functional SNPs and isomiRs and studied their distribution in different ethnic groups using whole-genome analysis. Notably, we used individuals from Great Britain (GBR) as examples and identified isomiRs and isomiR-associated SNPs (iso-SNPs). We performed sequence alignments of isomiRs and miRNA sequencing data to verify the identified isomiRs and further revealed GBR ethnographic epigenetic dominant biomarkers. The SNP-pre-miRNA database consisted of 886 pre-miRNAs and 2640 SNPs. We analyzed the effects of SNP type, SNP location, and SNP-mediated free energy change during mature miRNA biogenesis and found that these factors were closely associated to mature miRNA biogenesis. Remarkably, 158 isomiRs were verified in the miRNA sequencing data for the 18 GBR samples. Our results indicated that SNPs affected the mature miRNA processing mechanism and contributed to the production of isomiRs. This mechanism may have important significance for epigenetic changes and diseases.

3D printing has been in use for a long time and has continued to contribute to breakthroughs in the fields of clinical, physical, and rehabilitation medicine. In order to evaluate the role of 3D printing technology in treating spinal disorders, this paper presents a systematic review of the relevant literature. 3D printing is described in terms of its adjunctive function in various stages of spinal surgery and assistance in osteoporosis treatment. A review of metal 3D printed materials and applications of the technology is also provided.

BACKGROUND: Human tongue squamous cell carcinoma (TSCC) is the most common oral cancer with the highest human papillomavirus (HPV) infection rate in oral cancer. The purpose of this study was to research the correlation between HPV and TSCC. METHOD: Plasmid pEGFP/HPV16 E6E7 and plasmid pEGFP/no HPV16 E6E7 were constructed. TSCC cell lines SCC9 and SCC15 were infected by liposome transfection and would be highly selected by antibiotic. Fluorescence imaging, PCR, and Western blot were used to detect the expression of HPV16 E6E7 in cells. The biological characteristics were detected by CCK-8, wound healing assay, qRT-PCR, and Western blot. RESULT: TSCC cell lines transfected with HPV16 E6E7 gene were successfully established and identified. And the proliferation and migration ability of the TSCC cell lines infected with HPV16 E6E7 gene were significantly stronger than that of the blank group. CONCLUSION: TSCC cell lines infected with HPV16 E6E7 with significantly higher ability of proliferation and migration were more malignant than those not infected with HPV16 E6E7.

Tumor immune escape plays an essential role in both cancer progression and immunotherapy responses. For prostate cancer (PC), however, the molecular mechanisms that drive its different immune phenotypes have yet to be fully elucidated. Patient gene expression data were analyzed from The Cancer Genome Atlas-prostate adenocarcinoma (TCGA-PRAD) and the International Cancer Genome Consortium (ICGC) databases. We used a Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis and an unsupervised clustering analysis to identify patient subgroups with distinct immune phenotypes. These distinct phenotypes were then explored for associations for differentially expressed genes (DEGs) and both epigenetic and genetic landscapes. Finally, we used a protein-protein interaction analysis to identify key hub genes. We identified two patient subgroups with independent immune phenotypes associated with the expression of Programmed death-ligand 1 (PD-L1). Patient samples in Cluster 1 (C1) had higher scores for immune-cell subsets compared to Cluster 2 (C2), and C2 samples had higher specific somatic mutations, MHC mutations, and genomic copy number variations compared to C1. We also found additional cluster phenotype differences for DNA methylation, microRNA (miRNA) expression, and long noncoding RNA (lncRNA) expression. Furthermore, we established a 4-gene model to distinguish between clusters by integrating analyses for DEGs, lncRNAs, miRNAs, and methylation. Notably, we found that glial fibrillary acidic protein (GFAP) might serve as a key hub gene within the genetic and epigenetic regulatory networks. These results improve our understanding of the molecular mechanisms underlying tumor immune phenotypes that are associated with tumor immune escape. In addition, GFAP may be a potential biomarker for both PC diagnosis and prognosis.

Increasing attention has been paid to the possible link between periodontal disease and atherosclerosis over the past decade. The aim of this study is to investigate the presence of five periopathogens: Porphyromonas gingivalis (P.g.), Aggregatibacter actinomycetemcomitans (A.a.), Tannerella forsythia (T.f.), Treponema denticola (T.d.), and Prevotella intermedia (P.i.) in atheromatous plaques obtained from the carotid and coronary arteries in patients who underwent coronary artery bypass graft surgery and carotid endarterectomy. Group I (carotid arteries) consisted of 30 patients (mean age: 54.5 ± 14.8), and group II (coronary arteries) consisted of 28 patients (mean age: 63 ± 12.1). Clinical periodontal examinations consisted of plaque index, gingival index, sulcus bleeding index, and periodontal probing depth and were performed on the day of vascular surgery. The presence of periopathogens in periodontal pockets and atherosclerotic vessels was detected using polymerase chain reaction. In both subgingival plaque and atherosclerotic plaque of carotid arteries, P.g., A.a., T.f., T.d., and P.i. were detected in 26.7%, 6.7%, 66.7%, 10.0%, and 20.0%, respectively, while for coronary arteries, P.g. was detected in 39.3%, A.a. in 25%, T.f. in 46.4%, T.d. in 7.1%, and P.i. in 35.7%. The presence of five periopathogens in carotid and coronary atherosclerotic vessels showed correlation in regard to the degree of periodontal inflammation. The present study suggests the relationship between periodontal pathogenic bacteria and atherogenesis. Further studies are necessary in relation to the prevention or treatment of periodontal disease that would result in reduced mortality and morbidity associated with atherosclerosis.

In this study, four Gaussian process regression (GPR) approaches by various kernel functions have been proposed for the estimation of biodiesel density as the functions of pressure, temperature, molecular weight, and the normal melting point of fatty acid esters. Comparing the actual values with GPR outputs shows that these approaches have good accuracy, but the performance of the rational quadratic GPR model is better than others. In this GPR model, RMSE = 0.47, MSE = 0.22, MRE = 0.04, R 2 = 1, and STD is equal to 0.3. In addition, for the first time, this study shows that the effective parameters affect the biodiesel density. According to this analysis, it was shown that among the input parameters, pressure has the greatest effect on the target values with a relevancy factor of 0.59. This study can be used as a suitable and valuable work/tool for chemical and petroleum engineers who attempt environment protection and recovery improvement.

The last decade (2010-2021) has witnessed the evolution of robotic applications in orthodontics. This review scopes and analyzes published orthodontic literature in eight different domains: (1) robotic dental assistants; (2) robotics in diagnosis and simulation of orthodontic problems; (3) robotics in orthodontic patient education, teaching, and training; (4) wire bending and customized appliance robotics; (5) nanorobots/microrobots for acceleration of tooth movement and for remote monitoring; (6) robotics in maxillofacial surgeries and implant placement; (7) automated aligner production robotics; and (8) TMD rehabilitative robotics. A total of 1,150 records were searched, of which 124 potentially relevant articles were retrieved in full. 87 studies met the selection criteria following screening and were included in the scoping review. The review found that studies pertaining to arch wire bending and customized appliance robots, simulative robots for diagnosis, and surgical robots have been important areas of research in the last decade (32%, 22%, and 16%). Rehabilitative robots and nanorobots are quite promising and have been considerably reported in the orthodontic literature (13%, 9%). On the other hand, assistive robots, automated aligner production robots, and patient robots need more scientific data to be gathered in the future (1%, 1%, and 6%). Technological readiness of different robotic applications in orthodontics was further assessed. The presented eight domains of robotic technologies were assigned to an estimated technological readiness level according to the information given in the publications. Wire bending robots, TMD robots, nanorobots, and aligner production robots have reached the highest levels of technological readiness: 9; diagnostic robots and patient robots reached level 7, whereas surgical robots and assistive robots reached lower levels of readiness: 4 and 3, respectively.

OBJECTIVE: To screen glycolytic genes linked to the glioma prognosis and construct the prognostic model. METHODS: The relevant data of glioma were downloaded from TCGA and GTEx databases. GSEA of glycolysis-related pathways was carried out, and enriched differential genes were extracted. Screening out prognostic-related genes with conspicuous significance and construction of the prognostic model were conducted by multivariate Cox regression analysis and Lasso regression analysis. The model was evaluated, and cBioPortal was used to analyze the mutation of the model gene. The expression of the model gene in tumor and normal colon tissue was analyzed. The model was used to evaluate the prognosis of patients in different groups to verify the applicability of the model. RESULTS: 339 differentially glycolytic-related genes were enriched in REACTOME_GLYCOLYSIS, GLYCOLYTIC_PROCESS, HALLMARK_GLYCOLYSIS, and other pathways. We obtained 9 key prognostic genes and constructed the prognostic evaluation model. The 3-year AUC values of the ROC curve display model are greater than 0.75, which indicates that the accuracy of the model is good. The relation of age and risk score to prognosis is shown by univariate and multivariate Cox analysis. The expression of SRD5A3, MDH2, and B3GAT3 genes was significantly upregulated in the tumor tissues, while the HDAC4 and G6PC2 genes were downregulated. The mutation rate of MDH2 and HDAC4 genes was the highest. This model could effectively distinguish the risk of poor prognosis of patients in any age stage. CONCLUSION: The prognostic assessment models based on glycolysis-related nine-gene signature could accurately predict the prognosis of patients with GBM.

Microbial infections are increasing worldwide, and the widespread emergence of antibiotic-resistant pathogens poses a severe threat to public health. Medicinal plants are well-known sources of bioactive ingredients. This study was designed to determine the antimicrobial and antioxidant activities of extracts from Platycerium stemaria. The serial exhaustive extraction method using a solvent of increasing polarity from nonpolar (hexane) to polar (water) was designed to prepare crude extracts; liquid-liquid partition was used to fractionate of active extracts. The extracts and fractions were screened for antimicrobial activity on bacteria and yeasts using the microdilution method. The antioxidant activity was done using DPPH and FRAP assays. Out of the sixteen extracts screened, four (PsHex, PsH2O(H), PsMeOH(EA), and PsMeOH) exhibited potency with minimal inhibitory concentration (MIC) values ranging from 31.25 to 500 μg/mL. Out of the four extracts, two, including PsMeOH and PsMeOH(EA), exhibited DPPH radical scavenging activity with the antiradical power of 8.94 × 10-5 and 47.96 × 10-5, respectively, and ferric reducing antioxidant power values ranging from 0.34 to 61.53 μg equivalent Vit C/g of extract. The phytochemical screening of the promising crude extracts revealed flavonoids, glycosides, phenols, tannins, terpenoids, saponins, and anthraquinones. This study reports the antimicrobial and antioxidant activities of P. stemaria for the first time. The results showed that the serial exhaustive extraction approach used in this study allowed capturing the antimicrobial and antioxidant metabolites beyond the single extraction, indicating the need for a rigorous choice of an appropriate solvent and method for extracting P. stemaria. Further investigation is needed to characterize the active ingredients present in the promising extracts.

Hepatotoxicity was found in different case reports and studies in tenofovir disoproxil fumarate- (TDF-) based regimen. However, there was no data regarding liver enzymes, glucose, and hemoglobin in Ethiopian patients receiving TDF-based regimen. The aim of this study was to determine elevated liver enzymes and its associated factors as well as elevated fasting plasma glucose and anemia. A hospital-based observational prospective cohort study was conducted on conveniently selected 63 patients in Tikur Anbessa Specialized Hospital (TASH) from January to September 2019. Laboratory values were determined at pre-TDF-based regimen baseline and six-month follow-up. The data was analyzed by using SPSS version 21.0, and multivariate logistic regression was used to determine associated factors with elevated liver enzymes. The overall elevated liver enzymes were found in 26 (41.3%) participants. From this, elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) comprise 3 (4.8%), 3 (4.8%), and 20 (31.8%), respectively. Elevated fasting plasma glucose (FPG) was found in 9 (14.3%) and 14 (22.2%) of participants at baseline and six-month visit, respectively. At six-month visit, 4 (6.4%) of participants experienced anemia. The mean value of ALP and FPG at six months was significantly higher than their respective baseline mean values (mean difference (MD) = +63.38, 95% CI (39.84, 86.92), p = 0.0001; MD = +6.64, 95% CI (2.63, 10.64), p = 0.002, respectively). The mean value of ALT, AST, and Hg at six months was slightly increased compared to their respective baseline mean values, but the difference was not significant. In multivariate analysis, only female sex was significantly associated with elevated ALP (AOR = 4.5, 95% CI (1.03, 19.6), p = 0.045). Overall mild and moderate hepatotoxicity was found to be high (26, 41.3%) in the present study, and from this, the majority was comprised by elevated ALP (20, 31.8%). The proportion of participants with hyperglycemia was increased at the end of follow-up compared to its baseline value, but anemia was not. Female sex was significantly associated with elevated ALP. This study warrants monitoring of liver enzymes and glucose in TDF-based regimen.

Hydroxycitronellal (HC) is a monoterpene present in essential oils of aromatic plants of different species, obtained from semisynthesis of citronellal, and is widely used as a fragrance in cosmetics. The objective of this work was to evaluate the possible anxiolytic-like activity of HC and its possible mechanism of action using in vivo and in silico methodologies. Swiss male mice (Mus musculus) were treated with HC (12.5, 25, and 50 mg/kg, i.p.) and subjected to the rota rod, elevated plus maze, and open field tests. No significant impairments were observed in the rota rod tests for the motor activity of the animals treated with HC at 12.5, 25, and 50 mg/kg, i.p., indicating no myo-relaxing or sedative effects. In the elevated plus maze, HC (in the three doses) induced significant increases in the percentage of entries (respectively, 34.8%, 33.8%, and 38.6%) and in the length of stay (respectively, 49.9%, 56.1%, and 57.0%) in the open arms of the EPM, as well as the number of crossings in the open field tests. The mechanism of action of the compound's anxiolytic-like activity can be attributed to the involvement of GABAA receptors, and this interaction was observed in in vivo and in silico studies. For HC, the results suggest anxiolytic-like effects, possibly via modulation of the GABAergic system. The use of natural products to treat anxiety can become an alternative to existing synthetic products.

BACKGROUND: Cannabinoid system affects memory and has anticonvulsant effects in epileptic models. In the current study, the role of cannabinoid 1 (CB1) receptors was investigated in amelioration of the effects of low-frequency stimulation (LFS) on learning and memory impairments in kindled rats. METHODS: Electrical stimulation of the hippocampal CA1 area was employed to kindle the animals. LFS was applied to the CA1 area in four trials following the last kindling stimulation. One group of animals received intraperitoneal injection of AM251 (0.1 μg/rat), a CB1 receptor antagonist, before the LFS application. Similarly, CB1 agonist WIN55-212-2 (WIN) was administrated to another group prior to LFS. The Morris water maze (MWM) and the novel object recognition (NOR) tests were executed 48 h after the last kindling stimulation to assess learning and memory. RESULTS: Applying LFS in the kindled+LFS group restored learning and memory impairments in the kindled rats. There was a significant difference between the kindled and the kindled+LFS groups in learning and memory. The application of AM251 reduced the LFS effects significantly. Adversely, WIN acted similarly to LFS and alleviated learning and memory deficits in the kindled+WIN group. In addition, WIN did not counteract the LFS enhancing effects in the KLFS+WIN group. CONCLUSIONS: Improving effects of LFS on learning and memory impairments are mediated through the activation of the endocannabinoid (ECB) system.

BACKGROUND: Conscious patients admitted to intensive care units (ICU) suffer from anxiety and agitation for various reasons, which can affect their recovery processes. AIMS: To compare the effects of lavender and Citrus aurantium essential oils on anxiety and agitation of conscious patients admitted to ICUs. DESIGN: A randomized parallel placebo-controlled trial. METHODS: One hundred and fifty conscious patients admitted to ICUs were selected by convenience sampling and were randomly divided into three groups, groups of lavender aromatherapy and Citrus aurantium aromatherapy, in addition to the routine care and inhalation of five drops of lavender or Citrus aurantium essential oils for 30 minutes. The placebo group, in addition to routine care, was provided with 5 drops of normal saline for 30 minutes. Anxiety was assessed with the state subscale of State-Trait Anxiety Inventory, and agitation was examined with Richmond Agitation-Sedation Scale before, immediately, one hour, and three hours after the intervention. RESULTS: All three groups suffered from relatively severe state anxiety before the intervention. The level of anxiety in the lavender and Citrus aurantium groups was significantly lower than that of the placebo group immediately and three hours after the intervention (P < 0.05). No significant difference was observed between the two groups of lavender and Citrus aurantium. The majority of the samples in all three groups were agitated before the intervention, but agitation of all three groups decreased after the intervention. Restless/agitation reduced significantly in all three groups. Although restless/agitation of the lavender and Citrus aurantium groups reduced more than that of the placebo, no significant difference was found between the three groups. CONCLUSION: The results of the present study showed the positive effects of lavender aromatherapy and Citrus aurantium aromatherapy on reducing the anxiety of patients admitted to ICUs. Relevance to Clinical Practice. Aromatherapy can be used as an effective and safe intervention to reduce anxiety in ICUs.

BACKGROUND: Acute appendicitis (AA) might be amenable to conservative antibiotic treatment, whereas a perforated appendix (PA) necessitates surgery. We investigated the value of clinical-laboratory markers in distinguishing AA from a PA. METHODS: Retrospectively obtained preoperative parameters for 306 consecutive patients (<18 years) with histologically confirmed appendicitis (AA (n = 237) vs. PA (n = 69)), treated at our institution between January 2014 and December 2017. RESULTS: A PA was associated with male preponderance, younger age, decreased sodium level and increased white blood cell count, Tzanakis score, C-reactive protein (CRP) level, and CRP-to-lymphocyte ratio (CLR). Upon discrimination analysis, CLR and CRP displayed the highest accuracy in differentiating a PA from AA. Regression analysis identified levels of CRP, sodium, and the Tzanakis score as independent predictors for a PA. CONCLUSION: Levels of CLR, CRP, sodium, and Tzanakis score might support decision-making regarding treatment options for pediatric appendicitis.

Melatonin (ML) is a potent antioxidant that reduces oxidative stress. This study was designed to examine the protective effect of melatonin on potassium dichromate- (PDC-) induced male reproductive toxicity. Forty rats were divided into five groups: the control group, rats administered PDC orally (10 mg/kg body weight) for eight weeks, rats administered ML intraperitoneally at doses of either 2.5 or 5 mg/kg followed by the administration of PDC, and rats administered 5 mg/kg ML only. The treatment of rats with PDC led to a decrease in the levels of plasma sex hormones, glutathione, superoxide dismutase, catalase, carnitine, sperm count, and motility. Testicular malondialdehyde levels, nitric oxide concentrations, and abnormalities increased significantly in the PDC group. Melatonin administration to the PDC-treated rats reduced the increase of malondialdehyde and restored the activity of antioxidant enzymes (superoxide dismutase and catalase), glutathione, and sex hormone levels. Moreover, ML attenuated PDC-induced increase in levels of tumor necrosis factor-alpha or interleukin-6. ML alleviated histopathological changes and an increase of p53-positive immune reaction due to PDC. Furthermore, ML inhibited PDC-induced decrease in the DNA content of spermatogenic cells. This study proposed that melatonin may be useful in mitigating oxidative stress-induced testicular damage due to potassium dichromate toxicity.

Obesity can induce chronic low-grade inflammation via oxidative stress. Tetrahydrocurcumin (THC) is a major curcumin metabolite with anti-inflammatory and antioxidant effects, but little is known about its effects on the skin of obese individuals. Thus, the aim of this study was to investigate the effects of THC on inflammatory cytokine production, oxidative stress, and autophagy in the skin of mice with high-fat diet- (HFD-) induced obesity. Eight-week-old C57BL/6J mice were fed a regular diet, HFD (60% of total calories from fat), or HFD supplemented with THC (100 mg/kg/day orally) for 12 weeks. We measured their body weights during the experimental period. After 12-week treatments, we performed western blotting and real-time polymerase chain reaction analyses on skin samples to evaluate the expression of inflammatory cytokines, oxidative stress markers, and autophagy markers. We observed higher tumor necrosis factor-α (TNF-α), NADPH oxidase 2 (Nox2), Nox4, and phosphorylated p65 levels; lower nuclear factor erythroid 2-related factor 2 (Nrf2) expression; and higher light chain 3 (LC3), autophagy-related 5 (Atg5), and Beclin 1 expression in the skin of HFD mice compared to the corresponding levels in the skin of mice fed with regular diet. THC administration decreased TNF-α, Nox2, Nox4, and phosphorylated p65 levels and activated the Nrf2 pathway. Interestingly, THC administration suppressed the expression of the autophagy markers LC3, Atg5, and Beclin 1. Overall, HFD-fed mice exhibited an elevation in inflammation, oxidative stress, and autophagy in their skin. THC ameliorated obesity-related skin pathology, and therefore, it is a potential therapeutic agent for obesity-related inflammatory skin diseases.

Diabetes represents a challenge in implant therapy because hyperglycemia may negatively affect bone regeneration, directly compromising clinical outcomes and increasing clinical failures. The aim of this retrospective study is to analyse the prognostic significance of HbA1c levels in patients undergoing implant placement associated with horizontal guided bone regeneration. Thirty-four patients were divided into 3 groups according to their HbA1c levels: nondiabetic normoglycemic patients (HbA1c < 5.7%), nondiabetic hyperglycemic patients (HbA1c < 6.5%), and controlled diabetic patients (HbA1c < 7%). Primary outcomes were dimensional changes in height (VDH) and width (DW) of the peri-implant defect. Secondary outcomes were evaluations of periodontal parameters of adjacent tooth sites, wound healing, marginal bone loss (MBL), and survival and success rates. At T 1 (6 months), mean VDH values in groups 1, 2, and 3 were, respectively, 0.07, 0.5, and 0.25 mm. Mean DW values in those same groups were, respectively, 0.07, 0.38, and 0.33 mm. HbA1c levels were not statistically related to VDH and DW values at T 1. No statistically significant differences were observed in MBL between groups (p = 0.230). Implant survival and success rates were, respectively, 98% and 96%. Simultaneous guided bone regeneration is a feasible procedure for the treatment of horizontal bone deficiencies in controlled diabetic patients.

The objective of the study was to investigate the suitability of the Plantago ovata (PO) husk as a pharmaceutical excipient. Various phytoconstituents of the husk were determined according to the standard test procedures. The Plantago ovata husk was evaluated for various pharmaceutical parameters related to flow, swelling index, and compressibility index. Orodispersible tablets (ODTs) were prepared, containing different concentrations (2.5, 3, 5, 7.5, 10, and 15% w/w) of the Plantago ovata husk. Before compression, all the formulations were evaluated for their flow. Compressed ODTs were evaluated for physical characteristics (physical appearance, weight and weight variation, thickness, and moisture content), mechanical strength (crushing strength, specific crushing strength, tensile strength, and friability), disintegration behavior (disintegration time and oral disintegration time), drug content, and in vitro drug release. Phytochemical evaluation of the Plantago ovata husk confirmed the presence of various phytoconstituents like alkaloids, tannins, glycosides, saponins, flavonoids, and phenols. SEM photograph of the Plantago ovata husk showed that it has a fibrous structure, with a porous and rough surface. The Plantago ovata husk had a high swelling index (380%) which decreased by pulverization (310%). Precompression evaluation of the powder blend for all the formulations of ODTs showed good flow properties, indicating that the Plantago ovata husk improved the rheological characteristics of the powder blend. Compressed ODTs had good mechanical strength, and their friability was within the official limits (<1%). Best disintegration was observed with formulation F-6 containing 10% w/w of the Plantago ovata husk. It is concluded that the Plantago ovata husk can be used as a disintegrant in the formulation of ODTs.

Trypanosomes are the causative agents of animal African trypanosomiasis (AAT) and human African trypanosomiasis (HAT), the former affecting domestic animals prevalent in Sub-Saharan Africa. The main species causing AAT in cattle are T. congolense, T. vivax, and T. b. brucei. Northern Uganda has been politically unstable with no form of vector control in place. The return of displaced inhabitants led to the restocking of cattle from AAT endemic areas. It was thus important to estimate the burden of trypanosomiasis in the region. This study was designed to compare the prevalence of animal African trypanosomes in cattle in Lira District using microscopy and polymerase chain reaction amplification (PCR) methods. In this cross-sectional study, a total of 254 cattle from the three villages of Acanakwo A, Barropok, and Acungkena in Lira District, Uganda, were selected by simple random sampling technique and screened for trypanosomiasis using microscopy and PCR methods. The prevalence of trypanosomiasis according to microscopic results was 5/254 (2.0%) as compared to 11/254 (4.3%) trypanosomiasis prevalence according to PCR analysis. The prevalence of trypanosomiasis infection in the animal studied is 11/254 (4.3%). Trypanosoma congolense was the most dominant trypanosome species with a proportion of 9/11 (81.8%), followed by T. vivax 1/11 (9.1%) and mixed infection of T. congolense/T. vivax1/11 (9.1%). Barropok village had the highest prevalence of trypanosomiasis with 6/11 (54.5%). There is a statistically significant relationship (OR = 6.041; 95% CI: 1.634-22.331; p < 0.05) between abnormal PCV and trypanosome infection. Polymerase reaction amplification was the most reliable diagnostic method due to its high sensitivity and specificity as compared to the conventional microscopic method. Polymerase reaction amplification appears to have adequate accuracy to substitute the use of a microscope where facilities allow. This study, therefore, underscores the urgent need for local surveillance schemes more especially at the grassroots in Uganda to provide data for reference guideline development needed for the control of trypanosomiasis in Uganda.

Infective endocarditis is a sinister condition with considerable morbidity and mortality. Its relevance in the current era is compounded by the increased use of implanted devices such as replacement valves or cardiac implantable electronic devices. These infections are caused by multiple different bacteria with different virulence, pathogenicity, and antimicrobial resistance. Unlike in native endocarditis, the presence of foreign tissue permits sustenance by inflammatory and thrombotic processes as the artificial surfaces promote inflammatory responses and hypercoagulability. Prevention of these infections has been suggested with the use of homografts in combination with antibiotics. Others have attempted to use "low fouling coats" with little clinical success thus far. The use of antibiotic prophylaxis plays a pivotal part in reducing the incidence of prosthesis-related endocarditis. This remains especially crucial with the increasing use of transcatheter heart valve therapies. The widespread use of cardiac implantable electronic devices such as permanent pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapy devices has also heralded a noticeable increase in cases of infectious endocarditis affecting complex equipment which can be difficult to treat. Multimodality strategies are needed with input from surgeons and cardiologists to ensure treatment is both prompt and successful, tailored to the individual needs of the patients.

World Health Organization (WHO) has approved only one treatment for schistosomiasis, praziquantel (PZQ), but some poor efficacy was noticed in patients during the early stage of infection. Therefore, researchers have intensified their efforts to research new alternative medicines to treat schistosomiasis. In the present study, in vitro as well as in vivo studies have been accomplished to evaluate the effect of Origanum majorana, Ziziphus spina-christi, and Salvia fruticosa extracts in a different concentration 500, 250, 125, 62.5, and 31.25 μg/ml on golden hamster infected by Egyptian strains of schistosome (Schistosoma haematobium). In vitro, the adult worms and schistosomula of S. haematobium were investigated in RPMI-1640 medium for 48 hrs. The results showed that the concentration 500, 250, and 125 μg/ml of Origanum majorana, and Ziziphus spina-christi caused dead of 100% of Egyptian Schistosoma strains of adult worm and schistosomula of S. haematobium within 6 to 12 hrs of incubation. On the other hand, the extract of Salvia fruticosa at concentrations 500, 250, and 125 μg/ml showed death 100% parasites after 12 to 24 hrs of incubation. Inclusion, Origanum majorana, and Ziziphus spina-christi showed effectiveness against Egyptian Schistosoma strains (S. haematobium), a slight decrease in Salvia fruticosa was observed. Therefore, these medical plant extracts may be used as a safe and effective treatment for schistosomiasis.

Analysis and diagnosis according to the collected physical data are an important part in the physical examination. Through the data analysis of the physical examination results and expert diagnoses, the physical condition of a specific physical examination unit can be achieved which may guide individual health development. However, in general, the application of physical examination data is insufficient in most of the current physical examination organizations. Therefore, in the present study, statistical analysis and intelligent diagnosis were applied to maximize the utilization of physical examination data. The physical examination data collected from different departments of Dalian University of Technology were statistically analyzed and then synthesized for stimulating the thinking mode and knowledge framework of medical experts by a learning model on machine, resulting in the construction of an intelligent physical examination diagnosis method with 93.4% accuracy confirmed by experts. In conclusion, a potential artificial intelligence model of psychical examination data on health analysis and intelligent diagnosis was established, which may become more and more accurate with data accumulation in the near future.

PURPOSE: This study is aimed at analyzing the application experience and feedback of the patients with poststroke ankle dorsiflexion disorders for 3D printed AFO with three different materials. METHODS: 15 patients were randomly divided into three groups; 3D printed AFO with 3 different materials (PA2200, Somos NeXt, and PA12) was used to each group, according to the crossover study design, in order to ask the three groups of patients to use three different materials of 3D printed AFO. Assessment was taken by the end of each test round. Through statistical processing, the patient feedback data of the three groups of materials of 3D printed AFO were obtained. RESULTS: In the material comfort assessment of the AFO, Somos NeXt was compared with PA2200, and the p value was <0.05; in the item of surface smoothness of the AFO, Somos NeXt was compared with PA2200, and the p value was <0.01; at the same time, PA12 was compared with PA2200, and the p value was <0.05. CONCLUSION: The 3 different materials of 3D printing AFO bring different experience, and we also have sufficient reason to believe that there will be differences in the auxiliary effect of this on patients, which leads the patient's selection too. The material Somos NeXt is much popular and has certain clinical advantages.

Accurate screening on cancer biomarkers contributes to health assessment, drug screening, and targeted therapy for precision medicine. The rapid development of high-throughput sequencing technology has identified abundant genomic biomarkers, but most of them are limited to single-cancer analysis. Based on the combination of Fisher score, Recursive feature elimination, and Logistic regression (FRL), this paper proposes an integrative feature selection algorithm named FRL to explore potential cancer genomic biomarkers on cancer subsets. Fisher score is initially used to calculate the weights of genes to rapidly reduce the dimension. Recursive feature elimination and Logistic regression are then jointly employed to extract the optimal subset. Compared to the current differential expression analysis tool GEO2R based on the Limma algorithm, FRL has greater classification precision than Limma. Compared with five traditional feature selection algorithms, FRL exhibits excellent performance on accuracy (ACC) and F1-score and greatly improves computational efficiency. On high-noise datasets such as esophageal cancer, the ACC of FRL is 30% superior to the average ACC achieved with other traditional algorithms. As biomarkers found in multiple studies are more reliable and reproducible, and reveal stronger association on potential clinical value than single analysis, through literature review and spatial analyses of gene functional enrichment and functional pathways, we conduct cluster analysis on 10 diverse cancers with high mortality and form a potential biomarker module comprising 19 genes. All genes in this module can serve as potential biomarkers to provide more information on the overall oncogenesis mechanism for the detection of diverse early cancers and assist in targeted anticancer therapies for further developments in precision medicine.

The rapid progress of the combination of medicine and engineering provides better chances for the clinical treatment and healthcare engineering. Traumatic brain injury (TBI) and its related symptoms have become a major global health problem. At present, these techniques has been widely used in the rehabilitation of TBI. In this review article, we summarizes the progress of the combination of medicine and industry in the rehabilitation of traumatic brain injury in recent years, mainly from the following aspects: artificial intelligence (AI), brain-computer interfaces (BCI), noninvasive brain stimulation (NIBS), and wearable-assisted devices. We believe the summary of this article can improve insight into the combination of medicine and industry in the rehabilitation of traumatic brain injury.

OBJECTIVE: Alzheimer's disease is a progressive, age-related, and neurodegenerative disease characterized by mental decline. The exact cause of Alzheimer's disease is unclear, but cholinergic dysfunction, protein accumulation, and oxidative stress are among the most important hypotheses. The main purpose of our study was to investigate the effects of aqueous and hydroalcoholic extract combination of these two medicinal plants, black pepper and cumin (as a related formulation in traditional Persian medicine), on memory and learning of an immobilized stress animal model. METHODS: In this study, hydroalcoholic and aqueous extracts of cumin and black pepper fruits were prepared. Six groups of mice were treated orally for 2 weeks: control group, immobility stress, and stress-induced immobility mice received different doses of the hydroalcoholic extract (100 and 200 mg/kg) and aqueous extract (100 and 200 mg/kg). The shuttle box, novel object detection, and rotarod test were used to evaluate memory and learning. The activities of acetylcholinesterase, catalase (CAT), and superoxide dismutase (SOD) and the level of reduced glutathione (GSH) and malondialdehyde (MDA) were measured in the brain tissue. RESULTS: Immobility stress significantly reduced learning and motor coordination. Furthermore, MDA levels and acetylcholinesterase activity were significantly increased, while CAT and SOD activities were significantly reduced in the brain of immobility-induced stress mice. Other findings indicated that hydroalcoholic and aqueous extracts (100 and 200 mg/kg) of cumin and black pepper fruits have an improving effect on animal motor coordination and learning ability, GSH content, and CAT, SOD, and acetylcholinesterase enzyme function in comparison with stress groups (p < 0.05). CONCLUSION: The hydroalcoholic and aqueous extracts of cumin and black pepper fruits have protective effects against stress-induced memory deficit and oxidative stress and may have beneficial therapeutic effect in the treatment of neurodegenerative diseases.

Worldwide, iron deficiency is a common form of micronutrient deficiency with a high individual and societal cost. There are considerable knowledge and practice gaps in the diagnosis and treatment of iron deficiency. Bibliometric analysis examines the published body of knowledge of a subject in an objective fashion. The Web of Science Core Collection was searched to retrieve the 100 most cited papers on the topic of iron deficiency, and the key metrics of each paper were extracted. A keyword study was performed using VOSviewer 1.6.10 software, which provided a visual mapping of the network of keyword cooccurrences. The papers were published between 1964 and 2017 and were cited an average of 636 times. They were contributed by authors from 119 different countries/regions, with the largest contributing country being the United States. 29 institutions contributed at least 6 publications each, and 4 researchers authored or coauthored at least 5 papers. Keyword analysis suggests that the most cited topics could be grouped into 4 categories: (1) epidemiologic research of the global burden of iron deficiency, (2) clinical aspects of iron deficiency anemia, (3) iron metabolism, and (4) the impact of iron deficiency on children. Identification of the most impactful studies in the field of iron deficiency may be helpful to practitioners interested in improving their knowledge base. Compared to bibliometric studies performed on other topics, the medical literature of iron deficiency is mature, as evidenced by the high citation rate of the top 100 papers. Despite the high worldwide prevalence of iron deficiency, the top cited papers are dominated by a relatively small number of countries and institutions. Interestingly, however, the most cited authors in this study do not overlap with the most cited institutions.

BACKGROUND: Healthcare-associated infection (HAI) is a serious threat to the safety of patients worldwide. The prevalence survey is widely used to explore and study the characteristics of HAI. However, the annual continuous prevalence survey of hospital-acquired infections has not been reported so far. AIM: This study is aimed at examining the occurrence and development trend of HAIs dynamically and accurately. METHODS: An annual continuous HAI prevalence survey based on the real-time monitoring system was conducted in representative hospitals from different regions in Shandong in China. Findings. A total of 64 hospitals participated in the survey, and 2,741,433 patients were monitored in 2018. The highest prevalence of HAIs in Shandong was 3.83% (February 15), the lowest was 1.85% (February 28), and the average was 2.45%. The percentile distribution of prevalence of HAIs in this study was as follows: P10, 2.23%; P25, 2.31%; P50, 2.41%; P75, 2.55%; and P90, 2.73%. CONCLUSION: This study dynamically and accurately showed the occurrence and development trend of HAIs in Shandong in 2018. The results of this study can be used as a reference for the HAI prevalence survey in various medical institutions in Shandong and provide the basis for the regional HAI prevention and control strategy.

BACKGROUND: This study investigated and analyzed the current situation of sharp injuries among health care workers (HCWs) in China's Shandong Province. METHODS: By means of questionnaire survey, the incidence of sharp injuries among HCWs from 36 hospitals in China's Shandong Province in October 2019 was investigated, and the results of this survey were compared with those of October 2012. RESULTS: A total of 48165 HCWs were investigated. 549 cases of sharp injuries occurred. The incidence of sharp injuries was 1.14%, which was significantly lower than that in October 2012 (9.71%). In the occupational distribution of sharp injuries among HCWs, the proportion of nurses was 58.65%, doctors 23.32%, and interns 12.02%. Among the distribution of sharp injury departments, general wards, operating rooms, intensive care units, disinfection supply centers, and outpatient clinics were the high-incidence sites of occupational exposure among HCWs. The main instruments causing sharp injuries in HCWs were syringes, scalp steel needles, surgical suture needles, vacuum blood collection needles, and glass slides. Drug administration, double-handed loop needle cap, blood extraction, surgical suture needle, and arteriovenous needle extraction were high-risk operations causing sharp instrument injuries in HCWs. CONCLUSION: The incidence of sharp injuries among HCWs from 36 hospitals in Shandong Province in October 2019 was significantly lower than that in October 2012. Sharp injuries were a common type of occupational exposure for HCWs. The occurrence of sharp injuries should be effectively reduced by changing wrong habitual behavior and implementing standard protective measures.

Erratum for Biomed Res Int. 2021 Mar 26;2021:6642826.

BACKGROUND: Primary cutaneous lymphomas (PCLs) refer to cutaneous lymphomas that primarily develop in the skin with no evidence of extracutaneous disease at the time of diagnosis. The epidemiological and clinical data of PCLs in Thailand are lacking. OBJECTIVES: To evaluate the frequency, demographic data, and clinical characteristics of different subtypes of PCLs in a tertiary care university hospital. METHODS: In total, 137 patients with PCLs diagnosed in our hospital in 2008-2017 were retrospectively reviewed. RESULTS: Of the 137 patients, 57 (41.6%) were male and 80 (58.4%) were female (M : F = 1 : 1.4). The median age at diagnosis was 40 years. Most patients (134, 97.8%) had cutaneous T-cell lymphomas (CTCLs). Three patients (2.2%) had cutaneous B-cell lymphomas (CBCLs). The most common subtype was mycosis fungoides (MF) (67.9%), followed by subcutaneous panniculitis-like T-cell lymphoma (SPTCL) (21.2%), primary cutaneous anaplastic large cell lymphoma (pcALCL) (3.6%), lymphomatoid papulosis (LyP) (1.5%), primary cutaneous gamma/delta T-cell lymphoma (pcGDTCL) (1.5%), Sézary syndrome (SS) (0.7%), extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) (0.7%), primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS) (0.7%), primary cutaneous diffuse large B-cell lymphoma, leg type (pcDLBCL-LT) (1.5%), and primary cutaneous follicle center lymphoma (pcFCL) (0.7%). Most patients with MF presented with early-stage disease (84.0%), with hypopigmented MF the most common variant (42.6%). CONCLUSIONS: Compared to earlier Caucasian and Asian studies, the present study revealed a higher proportion of CTCL patients with a younger age at onset and a female predominance. MF was the most common CTCL subtype, followed by SPTCL. More than 80% of MF patients were diagnosed at an early stage.

BACKGROUND: The emergence and spread of multi-drug resistant (MDR) bacteria have become a public health problem in recent years. For the last many years, carbapenem antibiotics have been used successfully to treat infections caused by MDR Enterobacteriaceae. However, recently, Enterobacteriaceae producing carbapenemases have emerged, which confer broad resistance to most β-lactam antibiotics including carbapenems. Therefore, this study is aimed at determining the magnitude of MDR and carbapenemase-producing Enterobacteriaceae (CPE) isolated from various clinical specimens in Addis Ababa, Ethiopia. METHODS: A cross-sectional study was conducted from January to April 2018. A total of 312 Enterobacteriaceae isolates were identified from various clinical specimens. The Phoenix automated system (BD Phoenix100) was used for bacterial identification and antimicrobial susceptibility testing. Potential carbapenemase producers were confirmed by the modified carbapenem inactivation test, and KPC, MBL, and OXA-48 were phenotypically characterized by the disk diffusion method. The data obtained were entered and analyzed using SPSS version 20 software. Descriptive statistics, chi square, bivariate and multivariable logistic regression analyses were performed. P value ≤ 0.05 with corresponding 95% confidence interval was considered for statistical significance. RESULTS: A total of 312 Enterobacteriaceae were recovered. Of these isolates, 68.6% were MDR and 2.6% were CPE with different classes including OXA-48 1.6% (5/312), MBL 0.6% (2/312), and KPC and OXA-48 0.3% (1/312). The predominant bacterial isolates were E. coli 72.4% (226/312) followed by K. pneumoniae 13.8% (43/312). The antibiotic resistance rates of CPE isolates were significantly higher than other MDRE including ampicillin (100% versus 77.6%), cefoxitin (75% versus 20.6%), and piperacillin/tazobactam (50% versus 13.1%). CONCLUSION: In this study, a relatively higher prevalence of MDR was observed, and the highest resistance was recorded against ampicillin, amoxicillin with clavulanic acid, and sulfamethoxazole-trimethoprim. Detection of CPE is important for implementing appropriate antimicrobial therapy and in controlling the spread of the infection. Furthermore, continuous screening and investigations, including genotypic characterization of CPE, are required for the prevention and control of the spread of antimicrobial-resistant pathogens.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck, with strong local invasiveness and cervical lymph node metastasis. The purpose of this study was to investigate the role of LINC01296 in oral squamous cell carcinoma and its possible mechanism. MATERIALS AND METHODS: GEPAI database analysis and clinical samples were used to detect the expression of LINC01296 in head and neck cancer. In vivo experiment, MTT, clone formation assay, and transwell were used to detect the proliferation, migration, and invasion of oral squamous cell carcinoma. The effect of LINC01296 on EMT was detected by western blot and qRT-PCR to measure the expression of epithelial and mesenchymal phenotypic markers. BALB/c nude mice were used to carry out in vitro treatment experiment. In terms of mechanism, the binding relationship between LINC01296 and SRSF1 was predicted and verified by the RBPDB database and RNA pull-down assay. RESULTS: LINC01296 was highly expressed in clinical samples and cell lines of oral squamous cell carcinoma. Overexpression of LINC01296 promoted the proliferation, invasion, and migration of oral squamous cell carcinoma cells and accelerated the formation of xenografts, while silencing LINC01296 inhibited tumor progression. In mechanism, LINC01296 plays a tumor-promoting role by binding to SRSF1 protein. CONCLUSION: LINC01296 promotes malignant lesions in oral squamous cell carcinoma by binding to SRSF1 protein, which provides important experimental data and theoretical basis for the prevention, diagnosis, and treatment of oral squamous cell carcinoma.

OBJECTIVE: According to reports, liver enzymes might play a role in the incidence and development of cardiometabolic diseases such as metabolic syndrome (MetS), hypertension (HTN), and cardiovascular diseases (CVD). We conducted a study to investigate this hypothesis among the Iranian Kurdish population. METHODS: We analyzed data from the baseline phase of the Ravansar noncommunicable disease (RaNCD) cohort. The association between liver enzymes (ALT, AST, ALT/AST ratio, GGT, and ALP) with cardiometabolic disease risk factors was investigated by multiple linear regression. The odds ratio of cardiometabolic diseases in each quartile category of liver enzyme concentration was estimated using multivariable logistic regression. RESULTS: The mean age of participants was 47.3 ± 4.1 years (48.1 years in males and 51.8 years in females). In the adjusted model, all enzymes were positively associated with MetS, HTN, and CVD risk factors except for the ALT/AST ratio with SBP and DBP. In the adjusted model, subjects in the fourth quartile for GGT, ALT/AST ratio, ALT, ALP, and AST had 3.29-, 2.94-, 2.45-, 2.00-, and 1.19-fold increased risk for MetS compared with subjects in the first quartile. Increased levels of GGT and ALP were positively associated with the risk of HTN (ORs = 1.33, 95%CI = 1.03-1.71 for GGT; ORs = 1.32, 95%CI = -1.68 for ALP). An increased GGT level was significantly associated with CVD (ORs = 1.54, 95%CI = 1.03-1.68). Within the normal range quartile, ALT had a significant correlation with the incidence of MetS. CONCLUSION: According to the present study, the levels of liver enzymes could be considered for early diagnosis of MetS, HTN, and CVD.

The aim of our study was to investigate the effects of single-dose Ougan (Citrus reticulata cv. Suavissima) juice application on the pharmacokinetics of erlotinib in vivo. Twelve Sprague-Dawley rats were randomly divided into the Ougan juice and control groups (n = 6 each). The rats were given a single dose of 1 mL/100 g Ougan juice or 1 mL/100 g normal saline (NS) by intragastric administration, followed by a single oral administration of 20 mg/kg erlotinib. The plasma concentration of erlotinib in rats was determined using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Erlotinib-d6 was used as the internal standard for chromatographic analysis on the UPLC BEH C18 analysis column (2.1 mm × 50 mm, 1.7 μm). The mobile phase was composed of acetonitrile and 0.1% formic acid eluting by gradient. Different pharmacokinetic (PK) parameters of erlotinib were calculated. The Ougan juice promoted the absorption of erlotinib and reduced the clearance of the drug. The area under the curve of erlotinib in the single-dose Ougan juice pretreatment group was approximately 1.87 times higher, and the maximum blood concentration (Cmax) was approximately 1.34 times higher than that in the control group. The mean residence time of erlotinib in the Ougan juice group was larger, and the clearance rate was smaller than those in the control group; the difference was statistically significant (P < 0.05). Ougan juice affected the PK spectrum of erlotinib in rats by improving the bioavailability of the drug and significantly increasing its plasma concentration.

Mineral malnutrition as a prevalent public health issue can be alleviated by increasing the intake of dietary minerals from major staple crops, such as rice. Identification of the gene responsible for mineral contents in rice would help breed cultivars enriched with minerals through marker-assisted selection. Two segregating populations of backcross inbred lines (BIL) were employed to map quantitative trait loci (QTLs) for macronutrient contents in brown and milled rice, BC1F5, and BC2F4:5 derived from an interspecific cross of Xieqingzao B (Oryza sativa) and Dongxiang wild rice (O. rufipogon). Phenotyping the populations was conducted in multiple locations and years, and up to 169 DNA markers were used for the genotyping. A total of 17 QTLs for P, K, Na, Ca, and Mg contents in brown and milled rice distributed on eight regions were identified in the BC1F5 population, which is explained to range from 5.98% to 56.80% of phenotypic variances. Two regions controlling qCa1.1 and qCa4.1 were validated, and seven new QTLs for Ca and Mg contents were identified in the BC2F4:5 population. 18 of 24 QTLs were clustered across seven chromosomal regions, indicating that different mineral accumulation might be involved in common regulatory pathways. Of 24 QTLs identified in two populations, 16 having favorable alleles were derived from O. rufipogon and 10 were novel. These results will not only help understand the molecular mechanism of macronutrient accumulation in rice but also provide candidate QTLs for further gene cloning and grain nutrient improvement through QTL pyramiding.

The incidence of stomach diseases is very high, which has a significant impact on human health. Damaged gastric mucosa is more vulnerable to injury, leading to bleeding and perforation, which eventually aggravates the primary disease. Therefore, the protection of gastric mucosa is crucial. However, existing drugs that protect gastric mucosa can cause nonnegligible side effects, such as hepatic inflammation, nephritis, hypoacidity, impotence, osteoporotic bone fracture, and hypergastrinemia. Autophagy, as a major intracellular lysosome-dependent degradation process, plays a key role in maintaining intracellular homeostasis and resisting environmental pressure, which may be a potential therapeutic target for protecting gastric mucosa. Recent studies have demonstrated that autophagy played a dual role when gastric mucosa exposed to biological and chemical factors. More indepth studies are needed on the protective effect of autophagy in gastric mucosa. In this review, we focus on the mechanisms and the dual role of various biological and chemical factors regulating autophagy, such as Helicobacter pylori, virus, and nonsteroidal anti-inflammatory drugs. And we summarize the pathophysiological properties and pharmacological strategies for the protection of gastric mucosa through autophagy.

OBJECTIVE: To observe the therapeutic effect of Carvacrol on oral squamous cell carcinoma (OSCC) and dissect underlying molecular mechanisms. METHODS: Keap1/Nrf2, NALP3, Vimentin, and E-cadherin expression was detected in OSCC and normal oral mucosa (NOM) tissues using immunofluorescence or western blot. When treated with Carvacrol or tert-butylhydroquinone (TBHQ) that activates Nrf2, the expression of Keap1/Nrf2/HO-1, epithelial-mesenchymal transition- (EMT-) related proteins, and NALP3 was examined in OSCC cells. Nrf2 was silenced by treatment with sh-Nrf2 or ML385. After silencing Nrf2 or Carvacrol treatment, cell proliferation and migration were assessed by clone formation and scratch and transwell tests in OSCC cells. Moreover, the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 was detected. RESULTS: Keap1/Nrf2, NALP3, Vimentin, and E-cadherin proteins were all significantly upregulated in OSCC than NOM tissues. Carvacrol significantly suppressed Keap1/Nrf2/HO-1 activation. Carvacrol or silencing Nrf2 markedly inhibited the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 inflammasome in OSCC cells. Furthermore, clone formation and migration capacities were suppressed following treatment with Carvacrol or Nrf2 depletion. The opposite results were found when there is overexpression of Nrf2. However, Carvacrol distinctly improved the cancer-promoting effect induced by Nrf2 overexpression. CONCLUSION: Our findings suggested that Carvacrol ameliorated inflammation, proliferation, and migration for OSCC, which was related to inhibition of the Nrf2/Keap1 pathway.

The intervertebral disc degeneration (IDD) is considered to be an initiator of a series of spinal diseases, among which changes in the nucleus pulposus (NP) are the most significant. NP cells reside in a microenvironment with a lack of blood vessels, hypoxia, and low glucose within the intervertebral disc. Due to the strong activity of HIF-1α, glycolysis is the main pathway for energy metabolism in NP cells. Our previous study found that higher SIRT1 expression is beneficial to delay the degeneration of NP cells. In order to find the downstream genes by which SIRT1 acts on NP cells, we used iTRAQ sequencing to detect the differences between degenerated NP cells overexpressing SIRT1 and a control group (human NP cells were derived from surgery) and found that the expression of LDHA changed in the same direction with SIRT1. This suggests that SIRT1 may delay the degeneration of NP cells by regulating glycolysis. We then used a Seahorse XFe24 analyzer to measure the bioenergetic parameters of NP cells and obtained three findings: (a) glycolysis is the main energy metabolism pathway in NP cells, (b) there is a large difference in ATP production between senescent cells and young cells, and (c) SIRT1 can regulate the production of ATP from glycolysis by regulating LDHA. We also found that SIRT1 in NP cells has a positive regulatory effect on c-Myc which is an upstream gene of LDHA. Through observing IDD-related indicators such as apoptosis, proliferation, senescence, and extracellular matrix, we found that SIRT1 can delay degeneration, and interference with c-Myc and LDHA, respectively, weakens the protective effect of SIRT1. Interfering with LDHA alone can also inhibit glycolysis and accelerate degeneration. Overall, we found that the inhibition of glycolysis in Np cells significantly affects their normal physiological functions and determined that LDHA is a potential therapeutic target for the treatment of IDD.

BACKGROUND: DNA methylation is an important part of epigenetic modification, and its abnormality is closely related to esophageal adenocarcinoma (EAC). This study was aimed at using bioinformatics analysis to identify methylation-driven genes (MDGs) in EAC patients and establish a risk model as a biological indicator of EAC prognosis. METHOD: Downloaded EAC DNA methylation, transcriptome, and related clinical data from TCGA database. MethylMix was used to identify MDGs. R package clusterProfiler and the ConsensusPathDB online database were used to analyze the rich functions and pathways of these MDGs. The prognostic risk model was established by univariate Cox regression, Lasso regression, and multivariate Cox regression analysis. Finally each MDG in the model were carried out through the survival R package. RESULTS: A total of 273 MDGs were identified, which were enriched in transcriptional regulation and embryonic organ morphogenesis. Cox regression analysis established a risk model consisting of GPBAR1, OLFM4, FOXI2, and CASP10. In addition, further survival analysis revealed that OLFM4 and its two related sites were significantly related to the EAC patients' survival. CONCLUSION: In summary, this study used bioinformatics methods to identify EAC MDGs and established a reliable risk prognosis model. It provided potential biomarkers for the early treatment and prognosis evaluation of EAC.

Galvanic skin response (GSR) Biofeedback uses training to reduce tension and anxiety and improve concentration and self-regulation. The study was aimed to evaluate this method as a form of rehabilitation and quantify the outcomes achieved by patients undergoing training using this technique. Six schizophrenic patients were enrolled in the study and underwent training based on the relaxation training module (CENTER), concentration training module (BALANCE), and self-regulation training module (INSECTS). Training sessions were held twice a week for 6 weeks. From the total group of subjects involved in the study, two patients had a statistically significant increase in measured values after the CENTER exercise, indicating that relaxation was achieved. Four patients showed a statistically significant decrease in measured values after the BALANCE exercise, which was reflective of an improvement in concentration. Three patients had a statistically significant decrease in measured values after the INSECTS exercise, which indicated an improvement in self-regulation. GSR Biofeedback may be used to complement the pharmacological treatment of patients diagnosed with schizophrenia.

This study is aimed at assessing the effects of exposure parameters and voxel size for cone-beam computed tomography (CBCT) on the image matching accuracy with an optical dental scan image. CBCT and optical scan images of a dry human mandible were obtained. Different CBCT settings were used: tube voltage, 60, 80, and 100 kVp; tube current, 6 and 8 mA; and voxel size, 100, 200, and 300 μm. Image matching between the CBCT and optical scan images was performed using implant planning software by dental professionals (n = 18). The image matching accuracy in each combination of CBCT settings was evaluated by assessing the linear discrepancy between the three-dimensionally reconstructed radiological image and the registered optical scan image using an image analysis software program. The Kruskal-Wallis test and a post hoc Mann-Whitney U test with Bonferroni correction were used to compare the accuracy of image registration between the groups (α = 0.05). Overall, the image matching accuracy was not significantly different between tube voltage and current settings; however, significantly higher image registration errors were found at the combination of 100 kVp tube voltage/8 mA tube current (F = 8.44, P < 0.001). Changes in voxel sizes did not significantly interfere with the image registration results. No interaction was found among voltage, current, and voxel size in terms of image registration accuracy (F = 2.022, P = 0.091). Different exposure parameter settings in tube voltage and tube current did not significantly influence the image matching accuracy between CBCT and optical dental scan images; however, a high radiation dose could be inappropriate. The image matching accuracy was not significantly affected by changing the voxel sizes of CBCT.

AIM: This study is aimed at constructing the competing endogenous RNA (ceRNA) network in chromophobe renal cell carcinoma (ChRCC). METHODS: Clinical and RNA sequence profiles of patients with ChRCC, including messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), were obtained from The Cancer Genome Atlas (TCGA) database. "edgeR" and "clusterProfiler" packages were utilized to obtain the expression matrices of differential RNAs (DERNAs) and to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Weighted gene coexpression network analysis (WGCNA) was performed to screen the highly related RNAs, and miRcode, StarBase, miRTarBase, miRDB, and TargetScan datasets were used to predict the connections between them. Univariate and multivariate Cox proportional hazards regressions were performed in turn to elucidate prognosis-related mRNAs in order to construct the ceRNA regulatory network. RESULTS: A total of 1628 DElncRNAs, 104 DEmiRNAs, and 2619 DEmRNAs were identified. WGCNA showed significant correlation in 1534 DElncRNAs, 98 DEmiRNAs, and 2543 DEmRNAs, which were related to ChRCC. Fourteen DEmiRNAs, 113 DElncRNAs, and 43 DEmRNAs were screened. Nine mRNAs (ALPL, ARHGAP29, CADM2, KIT, KLRD1, MYBL1, PSD3, SFRP1, and SLC7A11) significantly contributed to the overall survival (OS) of patients with ChRCC (P < 0.05). Furthermore, two mRNAs (CADM2 and SFRP1) appeared to be independent risk factors for ChRCC. CONCLUSION: The findings revealed the molecular mechanism of ChRCC and potential therapeutic targets for the disease.

Nanomaterials have been widely used in many fields in the last decades, including electronics, biomedicine, cosmetics, food processing, buildings, and aeronautics. The application of these nanomaterials in the medical field could improve diagnosis, treatment, and prevention techniques. Graphene oxide (GO), an oxidized derivative of graphene, is currently used in biotechnology and medicine for cancer treatment, drug delivery, and cellular imaging. Also, GO is characterized by various physicochemical properties, including nanoscale size, high surface area, and electrical charge. However, the toxic effect of GO on living cells and organs is a limiting factor that limits its use in the medical field. Recently, numerous studies have evaluated the biocompatibility and toxicity of GO in vivo and in vitro. In general, the severity of this nanomaterial's toxic effects varies according to the administration route, the dose to be administered, the method of GO synthesis, and its physicochemical properties. This review brings together studies on the method of synthesis and structure of GO, characterization techniques, and physicochemical properties. Also, we rely on the toxicity of GO in cellular models and biological systems. Moreover, we mention the general mechanism of its toxicity.

BACKGROUND: The aim of this study was to investigate the application of computer-aided design and 3D printing technology for percutaneous fixation of femoral neck fractures using cannulated compression screws. METHODS: Using computed tomography data, an individualized proximal femur model was created with a 3D printer. The reduction of the femoral neck fracture and the placement of the cannulated compression screws were simulated on a computer. A 3D printing guide plate was designed to match the proximal femur. After demonstrating the feasibility of the 3D model before the surgical procedure, the guide needles and cannulated compression screws were inserted with the aid of the 3D-printed guide plate. RESULTS: During the procedure, the 3D-printed guide plate for each patient matched the bone markers of the proximal femur. With the aid of the 3D-printed guide plate, three cannulated compression screws were accurately inserted into the femoral neck to treat femoral neck fractures. After screw placement, intraoperative X-ray examination showed results that were consistent with the preoperative design. The time taken to complete the procedure in the guide plate group was 35.3 ± 2.1 min, the intraoperative blood loss was 6.3 ± 2.8 mL, and X-ray fluoroscopy was only performed 9.1 ± 3.5 times. Postoperative radiographs showed adequate reduction of the femoral neck fractures. The entry point, entry direction, and length of the three cannulated compression screws were consistent with the preoperative design, and the screws did not penetrate the bone cortex. CONCLUSION: Using computer-aided design and 3D printing technology, personalized and accurate placement of cannulated compression screws can be realized for the treatment of femoral neck fractures. This technique can shorten the time required for the procedure and reduce damage to the femoral neck cortex, intraoperative bleeding, and the exposure of patients and healthcare staff to radiation.

BACKGROUND: This paper reports the corrosion behavior of uncoated commercially pure titanium and Ti-6Al-4V samples and these coated with hydroxyapatite, partial stabilized zirconia (PSZ), and the mixture of partial stabilized zirconia and hydroxyl-apatite by measuring passivation current density and see if there are any differences between them using electrochemical polarization tests in 37°C Hank's solution. MATERIALS AND METHODS: The electrophoretic deposition method (EPD) was elected to keep the coating materials which are HA, PSZ, and the mixture of 50% HA and 50% PSZ on Cp Ti and Ti-6Al-4V alloy samples. The electrochemical corrosion test was achieved by exposing the coated and uncoated samples to Hank's solution which prepared in the laboratory and measuring the polarization potential, passivation current density, and the open circuit potential for all samples. RESULTS: The results indicated that the passivation current density for all Cp Ti and Ti-6Al-4V alloy groups that coated with HA, PSZ, and with mixture of 50/50 HA and PSZ was less than uncoated groups. There are no significant differences between all Cp Ti groups when compared with all Ti-6Al-4 V alloy groups. The open circuit potential (OCP) for both Cp Ti and Ti -6Al -4V samples was in the following sequence PSZ > HA > mixture of HA and PSZ > uncoated. CONCLUSIONS: Coating significantly decreased the passivation current density of Cp Ti and Ti-6Al-4V alloy.

OBJECTIVE: To observe the protective effect of AC-YVAD-CMK on sepsis-induced acute kidney injury in mice and to explore its possible mechanisms primarily. METHODS: Eighteen male C57BL/6 mice were randomly divided into sham-operated group (Control), cecal ligation and puncture group (CLP), and CLP model treated with AC-YVAD-CMK group (AC-YVAD-CMK) (n = 6 in each group). Mice were sacrificed at 24 h after operation, and blood and kidney tissue samples were collected for analyses. Histologic changes were determined microscopically following HE staining. The expression of Ly-6B and CD68 was investigated using immunohistochemistry. Serum concentrations of creatinine (sCR) and blood urea nitrogen (BUN) were measured. Serum levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), TNF-α, and interleukin-6 (IL-6) were determined by ELISA. The expressions of Caspas-1, NLRP-1, IL-1β, and IL-18 in renal tissues were investigated using Western blot. Immunofluorescence staining was used to detect the expression of GSDMD protein in renal tissues. RESULTS: AC-YVAD-CMK treatment significantly alleviates sepsis-induced acute kidney injury, with decreased histological injury in renal tissues, suppresses the accumulation of neutrophils and macrophages in renal tissues, and decreased sCR and BUN level (P < 0.05). Attenuation of sepsis-induced acute kidney injury was due to the prohibited production of inflammatory cytokines and decrease expression of Caspas-1, NLRP-1, IL-1β, and IL-18 in renal tissues. In addition, AC-YVAD-CMK treatment significantly reduced the expression of GSDMD in renal tissues compared to those observed in controls (P < 0.05). CONCLUSIONS: We demonstrated a marked renoprotective effect of caspase-1-inhibitor AC-YVAD-CMK in a rat model of sepsis by inhibition of pyroptosis.

BACKGROUND: Left atrial appendage (LAA) occlusion has been established as an alternative to systemic anticoagulation for stroke prevention in patients with atrial fibrillation; however, limitations of current devices have slowed adoption. We present preclinical evaluations of a novel device, the Conformal Left Atrial Appendage Seal (CLAAS). METHODS: An in vitro assessment of conformability was conducted to evaluate the two CLAAS devices (regular 27 mm and large 35 mm) and a Watchman 2.5 (27 mm). Devices were placed within silicone tubes and compressed in a vise submerged in a water bath at 37°C. Changes in device diameter and visual seal were noted. Acute (n = 1) and chronic 60-day (n = 6) canine studies with gross and histologic assessment were performed. RESULTS: Conformability bench tests demonstrated that the regular CLAAS implant was able to seal oval orifices from 20 × 30 mm to 15 × 33 mm and the large from 30 × 35 mm to 20 × 40 mm. As the CLAAS implant was compressed in the minor diameter, it increased in the major diameter, thereby filling the oval space, whereas the Watchman 2.5 showed gaps and maintained its round configuration when compressed in one direction. Seven devices were successfully implanted in the canine model with complete seal without thrombus. Histologic examination showed complete neointima covering with minimal inflammation at 60 days. CONCLUSIONS: Preclinical testing demonstrated the conformability of the CLAAS implant and its ability to seal the LAA. Clinical studies are ongoing to characterize the utility of the CLAAS implant in the treatment of patients with atrial fibrillation.

INTRODUCTION: Proteus mirabilis is a biofilm-forming agent that quickly settles on the urinary catheters and causing catheter-associated urinary tract infections. Thus, the spread of multidrug-resistant P. mirabilis isolates, with the ability to form a biofilm that carries integron, extended-spectrum β-lactamases (ESBLs), and plasmid-mediated colistin resistance genes (mcr), represents a severe threat to managing nosocomial infectious diseases. This study is aimed at surveying the prevalence of ESBL, integrase, and mcr genes of P. mirabilis, isolated from the catheter, to assess the differences in their antimicrobial susceptibility and clonal dissemination. METHOD: Microtiter plate assay was adopted to measure biofilm formation. The antimicrobial susceptibility was assessed by the disk diffusion method. Antimicrobial resistance genes (intI1, intI2, intI3, bla TEM, bla CTX-M, bla SHV, mcr1, and mcr2) were detected by PCR. All of the isolates were characterized by repetitive sequence-based PCR. RESULT: From 385 collected catheters in patients admitted to the intensive care unit (ICU), 40 P. mirabilis were isolated. All of the isolates could form a biofilm. Proteus spp. had intrinsic resistance to tetracycline (95%) and nitrofurantoin (92.5%), which explains the high resistance prevalence. The most widely resistant antibiotic was trimethoprim-sulfamethoxazole (75%). Thirty-three (82.5%) isolates were classified as multidrug resistance (MDR). The prevalence of intI1 and intI2 genes was 60% and 25%, respectively. In 6 (15%) isolates, both genes were detected. The most frequent ESBL gene detected in all of the isolates was blaTEM . Also, no detection for mcr1 and mcr2 antibiotic resistance genes was reported. Rep-PCR identified 39(GTG)5 types (G1-G39) of 40 isolates that 38 isolates had unique patterns. CONCLUSION: In this study, 82.5% of isolates were MDR with high antibiotic resistance to trimethoprim-sulfamethoxazole. The intI1 and bla TEM were the most prevalent genes in the integrase and ESBL gene family. High diversity was seen in the isolates with Rep-PCR. The increasing rate of MDR isolates with a high prevalence of resistance genes could be alarming and demonstrate the need for hygienic procedures to prevent the increased antibiotic resistance rate in the future.

INTRODUCTION: Rate pressure product (the product of heart rate and systolic blood pressure) is a measure of cardiac workload. Resting rate pressure product (rRPP) varies from one individual to the next, but its biochemical/cellular phenotype remains unknown. This study determined the degree to which an individual's biochemical/cellular profile as characterized by a standard blood panel is predictive of rRPP, as well the importance of each blood biomarker in this prediction. METHODS: We included data from 55,730 participants in this study with complete rRPP measurements and concurrently collected blood panel information from the Health Management Centre at the Affiliated Hospital of Hangzhou Normal University. We used the XGBoost machine learning algorithm to train a tree-based model and then assessed its accuracy on an independent portion of the dataset and then compared its performance against a standard linear regression technique. We further determined the predictive importance of each feature in the blood panel. RESULTS: We found a fair positive correlation (Pearson r) of 0.377 (95% CI: 0.375-0.378) between observed rRPP and rRPP predicted from blood biomarkers. By comparison, the performance for standard linear regression was 0.352 (95% CI: 0.351-0.354). The top three predictors in this model were glucose concentration, total protein concentration, and neutrophil count. Discussion/. CONCLUSION: Blood biomarkers predict resting RPP when modeled in combination with one another; such models are valuable for studying the complex interrelations between resting cardiac workload and one's biochemical/cellular phenotype.

Nonpharmacological therapies with a good tolerability and safety profile are of interest to many patients with allergic rhinitis, as a relevant proportion of them have reservations about guideline-concordant pharmacological therapies due to their local irritations and side effects. Ectoine is a bacterial-derived extremolyte with an ability to protect proteins and biological membranes against damage caused by extreme conditions of salinity, drought, irradiation, pH, and temperature. Evidence from preclinical and clinical studies attests its effectiveness in the treatment of several inflammatory diseases, including allergic rhinitis. In this review, we analyzed 14 recent clinical trials investigating ectoine nasal spray in patients with allergic rhinitis and/or conjunctivitis, including sensitive patient groups like children or pregnant women. Some studies investigated monotherapy with ectoine; others investigated combination therapy of ectoine and an antihistamine or a corticosteroid. Analysis of the study results demonstrated that patients with mild-to-moderate symptoms of allergic rhinitis can be successfully treated with ectoine-containing nasal spray. When applied as monotherapy, ectoine exerted noninferior effects compared to first-line therapies such as antihistamines and cromoglicic acid. Using ectoine as an add-on therapy to antihistamines or intranasal glucocorticosteroids accelerated symptom relief by days and improved the level of symptom relief. Importantly, concomitant treatment with ectoine was proven beneficial in a group of difficult-to-treat patients suffering from moderate-to-severe rhinitis symptoms. Taken together, the natural substance ectoine represents a viable alternative for allergic rhinitis and conjunctivitis patients who wish to avoid local reactions and side effects associated with pharmacological therapies.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causes coronavirus disease-19 (COVID-19), which is characterized by clinical manifestations such as pneumonia, lymphopenia, severe acute respiratory distress, and cytokine storm. S glycoprotein of SARS-CoV-2 binds to angiotensin-converting enzyme II (ACE-II) to enter into the lungs through membrane proteases consequently inflicting the extensive viral load through rapid replication mechanisms. Despite several research efforts, challenges in COVID-19 management still persist at various levels that include (a) availability of a low cost and rapid self-screening test, (b) lack of an effective vaccine which works against multiple variants of SARS-CoV-2, and (c) lack of a potent drug that can reduce the complications of COVID-19. The development of vaccines against SARS-CoV-2 is a complicated process due to the emergence of mutant variants with greater virulence and their ability to invoke intricate lung pathophysiology. Moreover, the lack of a thorough understanding about the virus transmission mechanisms and complete pathogenesis of SARS-CoV-2 is making it hard for medical scientists to develop a better strategy to prevent the spread of the virus and design a clinically viable vaccine to protect individuals from being infected. A recent report has tested the hypothesis of T cell immunity and found effective when compared to the antibody response in agammaglobulinemic patients. Understanding SARS-CoV-2-induced changes such as "Th-2 immunopathological variations, mononuclear cell & eosinophil infiltration of the lung and antibody-dependent enhancement (ADE)" in COVID-19 patients provides key insights to develop potential therapeutic interventions for immediate clinical management. Therefore, in this review, we have described the details of rapid detection methods of SARS-CoV-2 using molecular and serological tests and addressed different therapeutic modalities used for the treatment of COVID-19 patients. In addition, the current challenges against the development of vaccines for SARS-CoV-2 are also briefly described in this article.

BACKGROUND: The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue mainly characterized by joint hypermobility. Patients with hEDS suffer joint pain, in particular low back pain, commonly resistant to drug therapy. The aim of this research was to evaluate a neurocognitive rehabilitation approach based not only on the motion and function recovery but also on the pain management. METHODS: In this nonrandomized clinical trial, eighteen hEDS patients (4 males and 14 females) with mean age 21 years (range 13-55) were recruited and evaluated before and after three months of rehabilitation treatment. RESULTS: The outcome scores showed significant statistical results after treatment in reducing pain symptoms (numerical rating scale, P = 0.003; McGill (total score), P = 0.03), fatigue (fatigue severity scale, P = 0.03), fear of movement (Tampa scale, P = 0.003), and pain-associated disability (Oswestry disability index, P = 0.03). CONCLUSION: The clinical results observed in our study seem to confirm the role of a specific neurocognitive rehabilitation program in the chronic pain management in the Ehlers-Danlos syndrome; the rehabilitation treatment should be tailored on patient problems and focused not only in the recovery of movement but also on pain perception.

OBJECTIVE: To better understand the immune-related heterogeneity of tumor microenvironment (TME) and establish a prognostic model for breast cancer in clinical practice. METHODS: For the 2620 breast cancer cases obtained from The Cancer Genome Atlas and the Molecular Taxonomy of Breast Cancer International Consortium, the CIBERSORT algorithm was performed to identify the immunological pattern, which underwent consensus clustering to curate TME subtypes, and biological profiles were explored by enrichment analysis. Random forest analysis, least absolute shrinkage, and selection operator analysis, in addition to uni- and multivariate COX regression analyses, were successively employed to precisely select the significant genes with prediction values for the introduction of the prognostic model. RESULTS: Three TME subtypes with distinct molecular and clinical features were identified by an unsupervised clustering approach, of which the molecular heterogeneity could be the result of cell cycle dysfunction and the variation of cytotoxic T lymphocyte activity. A total of 15 significant genes were proposed to construct the prognostic immune-related score system, and a predictive model was established in combination with clinicopathological characteristics for the survival of breast cancer patients. For immunological signatures, proactivity of CD8 T lymphocytes and hyperangiogenesis could be attributed to heterogeneous survival profiles. CONCLUSIONS: We developed and validated a prognostic model based on immune-related signatures for breast cancer. This promising model is justified for validation and optimized in future clinical practice.

BACKGROUND: Obesity causes different diseases, eventually. In our study, the results of resistance exercises were examined on selected biochemical markers in Abha City, Saudi Arabia, which is at the height of 2,270 meters above sea level. METHODS: A randomized controlled research was conducted with 60 participants equally divided into three groups, 20 subjects in each group: group 1 was composed of obese people who received resistance training exercise, group 2 was composed of the obese control group who did not receive resistance training exercise, and group 3 was composed of normal individuals who received resistance exercise training. The resistance exercises were done in the 6th and 12th weeks. Biochemical blood tests were done. RESULTS: Comparing to the control group, glucose decreased very little with insulin also showing little difference. It has been seen that TC, TG, and LDL reduced to a reasonable extent after resistance exercise, while HDL was increased (p ≤ 0.01). Plasma urea and creatinine showed no differences. Interleukin-6 and leptin decreased significantly (p ≤ 0.01), while there was a significant elevation in adiponectin and testosterone (p ≤ 0.01) once comparing group 1 with group 2 and group 3. CONCLUSION: We have seen that resistance exercise helps in reducing lipid profile which will result in a decrease of the cardiac and related risk factors when conducted in obese patients in high-altitude regions. Also, alterations of the levels of interleukin-6, leptin, adiponectin, and testosterone showed that resistance exercise is of benefit and favourable in obese persons in high-altitude regions, which can also pave the way for added development of drugs related to the above parameters.

Gliomas are the most common type of primary brain tumor, yet the prognosis for glioma patients remains poor. Mutations in the promoter region of the telomerase reverse transcriptase gene (TERTp) are associated with diagnosis and poor prognosis in gliomas. Here, we developed a precise and rapid Sanger sequencing assay to screen or TERTp mutations. We established the Sanger sequencing approach for the detection of TERTp mutations based on human glioma cell lines U251 and assessed the analytical validation by determining the accuracy, sensitivity, precision, and specificity. In our study, we verified the accuracy of Sanger sequencing by the real-time polymerase chain reaction method. Our data showed that TERTp mutations were detected at an analytical sensitivity of 10% per mutant. The precision and specificity validation also showed the desired results. In total, 147 glioma patients were investigated for TERTp mutations, and of each patient, clinical data and molecular characteristics were analyzed. We found that anaplastic oligodendroglioma had the highest frequency of TERTp mutations (66.7%). No differences in TERTp mutation frequency were observed between frozen tissue specimens and formalin-fixed and paraffin-embedded tissue. TERTp mutations were associated with older patients (≥45 years), whereas isocitrate dehydrogenase (IDH) mutations were inclined to a younger age (<45 years), frontal location, and pathologic stage II-III patients. IDH mutations were significantly associated with O6-methylguanine-DNA methyltransferase (MGMT) methylation (P = 0.003) and lower Ki-67 protein expression (P = 0.011). Moreover, MGMT methylation was enriched in IDH-mutant/TERTp-mutant gliomas, and Ki-67 protein expression was the highest in the IDH-wild type/TERTp-mutant group. Taken together, the findings of this study indicate the establishment of a rapid, precise, and practical Sanger sequencing technique for TERTp mutations in gliomas that may show promising results in clinical applications.

Antibacterial activity of ethanolic and aqueous extracts of two medicinal plants including Oxalis corniculata (EtOc, AqOc) and Artemisia annua (EtAa, AqAa) as well as A. annua essential oil (EoAa) was investigated on multi-drug resistance (MDR) E. coli. Microdilution and agar well diffusion methods were used to determine the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) as well as the inhibition zone. The phytconstituents of these products were analyzed using Reverse-phase High- performance liquid chromatography (RP-HPLC) and gas chromatography-mass spectrometry (GC-mass). The order of bacteriostatic and bacteriocide rate of the products can be shown as follows: EoAa>AqOc>EtAa = AqAa>EtOc, but the bactericidal effect of A. annua extracts is higher than of O. corniculata based on the MIC/MBC ratio and the order is as follows: EoAa>EtAa = AqAa>EtOc>AqOc. The most potent product, i.e. EoAa with a 56.7% inhibition of all isolates, has the potential to substitute 13 used antibiotics including oxacillin, amoxicillin, ampicillin, amoxicillin-clavulanic acid, tetracycline, streptomycin, ciprofloxacin, ceftriaxone, cefazolin, cefuroxime, cefotaxime, ceftazidime and cefixime (P <0.05). Different terpenoids were detected and measured in EoAa and catechin flavonoids in extracts of both plants, quercetin in extracts of O. corniculata but it was only possible to detect chlorogenic acid polyphenol in AqAa. Due to the antibacterial activities of the studied products, more effective than some antibiotics and their edible consumption, these products can be suggested as an alternative to some antibiotics and food preservatives to fight against MDR E. coli.

BACKGROUND: Citation analysis has emerged to play a significant role in recognition of the most useful areas of research. Endodontic microbiology has been a topic of interest for endodontists as well as periodontists and oral surgeons. This bibliometric analysis is aimed at identifying and reporting the characteristics of the top 50 cited articles on endodontic microbiology. METHODS: The articles were identified through a search on Web of Science (WoS), property of Clarivate Analytics database published on endodontic microbiology. The citation information of the selected articles was recorded. The Journal of Endodontics, International Endodontic Journal, Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, Dental Traumatology, and Australian Endodontic Journal were searched in the search title. Descriptive and bivariate analyses were performed using a statistical software package SPSS. Statistical analysis was performed using Shapiro-Wilk, Kruskal-Wallis, Post hoc, Mann-Kendall trend, and Spearman-rank tests. RESULTS: The 50 most cited articles were published from 1965 to 2012 with citation count varying from 1065 to 103 times. The total citation counts of articles recorded were 11,525 (WoS), 12,602 (Elseviers' Scopus), and 28,871 (Google Scholar). The most prolific years in terms of publications were 2001, 2002, and 2003, with five publications each, followed by 2005 with four. The year with most citations was 1998, with 1,330 citations, followed by 1965 and 2001, with 1,065 and 1,015 citations, respectively. A total of 136 authors contributed to the top 50 most cited articles with 27 corresponding institutions from 12 different countries. The most common methodological design was in vitro study, followed by clinic-laboratory study, literature review, systematic review and meta-analysis, and animal study. CONCLUSIONS: The present study provided a detailed list of the top 50 most cited and classic articles on microbiology in endodontics. This will help researchers, students, and clinicians in the field of endodontics as an impressive source of information.

We have previously reported that F1012-2, a sesquiterpene lactone isolated from the Chinese herbal medicine Eupatorium lindleyanum DC., exhibits strong effects against Triple Negative Breast Cancer (TNBC). In this study, we found F1012-2 effectively inhibited cell migration and invasion detected by wound healing and transwell assays. In order to elucidate the potential mechanisms of F1012-2, we further studied its effect on DNA damage in TNBC cell lines. Using single cell gel electrophoresis (comet assay), immunofluorescence, and western blotting assays, we found that F1012-2 treatment induced significant DNA strand breaks and γ-H2AX activation. Moreover, exposure to F1012-2 led to overproduction of reactive oxygen species (ROS). NAC treatment completely eliminated ROS, which may be due to the interaction between NAC and F1012-2. A further study of the molecular mechanisms demonstrated that the MAPK signaling pathway participated in the anti-TNBC effect of F1012-2. Pretreatment with specific inhibitors targeting JNK (SP600125) and ERK (PD98059) could rescue the decrease in cell viability and inhibit expressions of JNK and ERK phosphorylation, but SB203580 had no effects. Finally, in the acute toxicity experiment, there were no obvious symptoms of poisoning in the F1012-2 treatment group. An in vivo study demonstrated that F1012-2 significantly suppressed the tumor growth and induced DNA damage. In conclusion, the activity of F1012-2-induced DNA damage in TNBC was found in vivo and in vitro, which might trigger the MAPK pathway through ROS accumulation. These results indicate that F1012-2 may be an effective anti-TNBC therapeutic agent.