Depression is a serious psychological disorder with a rapidly increasing incidence in recent years. Clinically, selective serotonin reuptake inhibitors are the main therapy. These drugs, have serious adverse reactions, however. Traditional Chinese medicine has the characteristics of multiple components, targets, and pathways, which has huge potential advantages for the treatment of depression. The antidepressant potential of the herbal combination of Bupleurum chinense DC (Chaihu) and Paeonia lactiflora Pall (Baishao) has been extensively studied previously. In this review, we summarized the antidepressant active components and mechanism of Chaihu-Baishao herb pair. We found that it works mainly through relieving oxidative stress, regulating HPA axis, and protecting neurons. Nevertheless, current research of this combined preparation still faces many challenges. On one hand, most of the current studies only stay at the level of animal models, lacking of sufficient clinical double-blind controlled trials for further verification. In addition, studies on the synergistic effect between different targets and signaling pathways are scarce. On the other hand, this preparation has numerous defects such as poor stability, low solubility, and difficulty in crossing the blood-brain barrier.

Baicalin (BA) is a major flavone from Scutellaria baicalensis Georgi and has showed significant curative effects in Parkinson's and Alzheimer's diseases. In the present study, we investigated the effects of BA on antineuroinflammation and related signaling cascade in lipopolysaccharide- (LPS-) induced BV-2 microglial model. The results showed that BA significantly attenuated inflammatory mediators (NO, iNOS, IL-1β, COX-2, and PGE2) and suppressed the expression of miR-155. More crucially, BA could regulate the expression of related proteins in Toll-like receptor 4 (TLR4)/myeloid differentiation protein 88 (MyD88)/nuclear factor κB (NF-κB) pathway and suppress the phosphorylation of mitogen-activated protein kinase (MAPK) family. In addition, molecular docking analysis indicated that BA binds to the amino acids Lie 63 and Tyr 65 of TLR4 by π-σ and π-π T-shaped interaction. Thus, BA suppressed the LPS-stimulated neuroinflammation in BV-2 microglia by blocking the TLR4-mediated signal transduction through TLR4/MyD88/NF-κB and MAPK pathways and inhibiting the miR-155 expression. Our findings demonstrated that BA could be a valuable therapeutic for the treatment of neuroinflammation and neurodegenerative diseases.

OBJECTIVE: As a highly malignant tumour, malignant rhabdoid tumours of the kidney (MRTK) are prone to metastasis and invasion, while tumour metastasis and invasion are inseparable from matrix metalloproteinases (MMPs) and epithelial-mesenchymal transformation (EMT). Moreover, the key to EMT is remodelling of the cytoskeleton. Therefore, our study is aimed at investigating whether doxycycline hydrochloride (DCH), an inhibitor of MMPs, could reverse EMT in MRTK to exert an antitumour effect by regulating MMPs and the cytoskeleton. METHODS: The existence of EMT in MRTK cells was verified by bioinformatics analysis, immunofluorescence, and western blotting (WB). In vitro, the proliferation, migration, and invasion abilities of G401 cells were examined by Cell Counting Kit-8 (CCK-8), scratch, and Transwell assays, respectively. The effect of DCH on tumour growth in tumour-bearing mice was explored in in vivo experiments, and the expression of MMP2 and MMP9 and EMT correlation indexes was measured by immunofluorescence and WB, and the changes in cytoskeletal F-actin and β-tubulin were measured by fluorescence. RESULTS: The altered extracellular matrix (ECM) composition, EMT, and high expression of MMP2 and MMP9 existed in MRTK. DCH inhibited the proliferation, migration, and invasion of G401 cells in vitro. In vivo, DCH inhibited tumour growth in mice, downregulated the expression of MMP2 and MMP9, and partially reversed EMT. Alternatively, DCH resulted in cytoskeletal rearrangements of G401 cells. CONCLUSIONS: DCH, as an MMP inhibitor, is used for the first time in MRTK research, showing good antitumour effects by reversing EMT and potentially providing new therapeutic measures for MRTK treatment.

BACKGROUND: Accurate, cost-effective, and noninvasive alternative molecular methods are needed for detecting low malaria parasitemia. The currently-used nested polymerase chain reaction (nPCR) requires blood as well as skilled personnel in order to minimise the risk of bloodborne disease transmission. Therefore, this study is aimed at assessing the accuracy of a noninvasive and more affordable malaria diagnosis with saliva using the loop-mediated isothermal amplification (LAMP) technique. METHODS: A cross-sectional study was conducted in the Centre and Southwest regions of Cameroon. Matched blood and saliva samples collected from symptomatic and asymptomatic participants were tested for malaria using rapid diagnostic tests, microscopy, PCR, and LAMP. Statistics were performed using R studio software at 95% confidence interval. RESULTS: A total of 100 participants (65% symptomatic and 35% asymptomatic) aged between 1 and 74 years with a balanced gender distribution ratio of 1.08 were included in our study. The prevalence of malaria was 61%, 57%, 59%, 42%, 35%, 17%, and 16% for blood-RDT, blood-PCR, blood-LAMP, blood-RT-LAMP, saliva-PCR, saliva-RT-LAMP, and saliva-LAMP, respectively. Both saliva and blood showed a sensitivity of 43.90% and respective specificities of 68.75% and 57.62%. When using RT-LAMP, sensitivities of 49.38% and 48.21% and specificities of 94.11% and 66.67% were recorded for saliva and blood, respectively. Sensitivities of 70.23% and 73.49% and specificities of 62.5% and 76.47% were recorded, respectively, for saliva-LAMP and saliva-RT-LAMP when compared to saliva-PCR as the gold standard. Saliva-LAMP and saliva-RT-LAMP had a fair agreement (к = 0.221 and 0.352, respectively) with saliva-PCR. Homemade LAMP and RT-LAMP technologies match the WHO recommendations and after proper validation in a larger sample size, could serve for malaria diagnosis in developing countries.

To investigate the regulatory mechanism of pterygium formation, we detected differentially expressed messenger RNAs (DE-mRNAs) and differentially expressed circular RNAs (DE-circRNAs) in pterygium-associated conjunctival epithelium (PCE) and normal conjunctival epithelium (NCE). Genome-wide mRNA and circRNA expression profiles of PCE and NCE were determined using high-throughput sequencing. Bioinformatics analyses, including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) analysis, were conducted. The microRNAs (miRNAs) interacting with the hub DE-mRNAs and DE-circRNAs were predicted and verified using real-time quantitative PCR (RT-qPCR). The data showed that there were 536 DE-mRNAs (280 upregulated and 256 downregulated mRNAs) and 78 DE-circRNAs (20 upregulated and 58 downregulated circRNAs) in PCE. KEGG enrichment analysis indicated that the DE-mRNAs were mainly involved in the following biological processes: IL-17 signalling pathway, viral protein interaction with cytokine and cytokine receptor, cytokine-cytokine receptor interaction, ECM-receptor interaction, and focal adhesion. The GSEA results revealed that the epithelial mesenchymal transition (EMT) process was significantly enriched in upregulated mRNAs. The pterygium-associated circRNA-miRNA-mRNA network was established based on the top 10 DE-circRNAs, 4 validated miRNAs (upregulated miR-376a-5p and miR-208a-5p,downregulated miR-203a-3p and miR-200b-3p), and 31 DE-mRNAs. We found that miR-200b-3p, as a regulator of FN1, SDC2, and MEX3D, could be regulated by 5 upregulated circRNAs. In addition, we screened out EMT-related DE-mRNAs, including 6 upregulated DE-mRNAs and 6 downregulated DE-mRNAs. The EMT-related circRNA-miRNA-mRNA network was established with the top 10 circRNAs, 8 validated miRNAs (upregulated miR-17-5p, miR-181a-5p, and miR-106a-5p, downregulated miR-124-3p, miR-9-5p, miR-130b-5p, miR-1-3p, and miR-26b-5P), and 12 EMT-related DE-mRNAs. We found that hsa_circ_0002406 might upregulate FN1 and ADAM12 by sponging miR-26b-5p and miR-1-3p, respectively, thus promoting EMT in pterygium. Briefly, the study provides a novel viewpoint on the molecular pathological mechanisms in pterygium formation. CircRNA-miRNA-mRNA regulatory networks participate in the pathogenesis of pterygium and might become promising targets for pterygium prevention and treatment.

Liver hepatocellular carcinoma (LIHC) remains a lethal disease for humans. Immune checkpoint inhibitors (ICIs) targeting PD1/PD-L1 and CTLA4 offered new hopes for advanced-stage patients. Novel immune biomarkers and therapeutic targets are urgently needed. For the first time, we evaluated the expression and prognostic value of Layilin (LAYN) using in silico analyses and uncovered the carcinogenic role of LAYN in LIHC. The HCG18/hsa-mir-148a/LAYN axis was predicted as the upstream mechanism. Moreover, gene set enrichment analysis (GSEA) revealed that LAYN and its coexpressed genes primarily participated in immune response pathways, and LAYN expression was found significantly correlated with tumor immune cell infiltration in LIHC tissues. In general, our data provided evidence that HCG18/hsa-mir-148a-regulated high expression of LAYN is associated with immune cell infiltration and unfavorable prognosis of LIHC patients.

INTRODUCTION: In recent times, Bangladesh has made significant improvements in various health outcomes, but not so much in maternal death. The current flat trend in reducing maternal mortality in Bangladesh has been mainly due to the lower coverage of maternal health care. To improve the coverage, it is essential to find biosocial factors related to adequate maternal health care. Therefore, this study is aimed at finding out the socioeconomic correlates of adequate maternal health care in Bangladesh. METHODS: The study used data from the Bangladeshi demographic and health survey 2017-18. The total unweighted sample of 4012 women who reported pregnancy before three years of the survey was analyzed. A composite binary indicator of adequate maternal care has been constructed using the variables-access to maternal care service, four antenatal care visits, at least one visit with qualified providers, and institutional delivery. A binary logistic regression model was employed to find out the socioeconomic correlate of adequate maternal care. RESULTS: Only 24.4% percent of sample women received adequate maternal care. The result of the logistic regression model shows that urban, Khulna, Rajshahi, and Rangpur were associated with an increase in the odds of having adequate maternal care. High education and health care decisions taken by the partner or husband were also associated with an increased odd of adequate maternal care. Islam and lower wealth status were associated with a lower probability of adequate maternal care. CONCLUSIONS: Policymakers and health administration should pay attention to the variation in the utilization of maternal health care across residence, region, religion, education, and wealth status to ensure safe motherhood.

PURPOSE: This study aims at constructing a clinical predictive model that predicted the risk factors for leg numbness after spinal endoscopic surgery. METHODS: We collected the clinical data of patients, including general information, imaging parameters, and clinical score, from our hospital's electronic database. Based on the postoperative leg numbness visual analog scale (LN-VAS), the clinical data were divided into the leg numbness group (≥25) and the improvement group (<25). All parameters were included in the least absolute shrinkage and selection operator (LASSO) regression analysis, while the parameters with the area under the curve (AUC) greater than 0.7 were selected to construct nomograms. Furthermore, the accuracy and validity of the model were evaluated using the C-index, decision curve analysis (DCA), calibration curve, and receiver operating characteristic curve (ROC). RESULTS: A total of 73 patients' clinical data were included in the training set, where 51 patients were assigned to the improvement group and 22 to the leg numbness group. The nomogram was constructed using four selected parameters, including symptom duration, lumbar spinal stenosis (LSS), pelvic incidence (PI), and preoperative low back pain visual analog scale (LBP-VAS). The nomogram predictions were found to range between 0.01 and 0.99. The values of the C-index, AUC, and internally validated C-index were 0.96, 0.96, and 0.94, respectively. Our result showed that the clinical net benefit of the nomogram ranged between 0.01 and 0.99. CONCLUSION: Our clinical prediction model demonstrated high predictive ability and clinical validity. Moreover, we found that symptom duration, LSS, PI, and preoperative LBP-VAS were the predictive risk factors for leg numbness after spinal endoscopic surgery.

OBJECTIVES: The jaw angle plays an important role in facial beauty. Therefore, this study is aimed at comparatively determining the range of most attractive female intergonial widths and gonial heights on Perceptometric frontal-view and three-quarter-view images, from the perspective of orthodontists, oral maxillofacial (OMF) surgeons, and laypeople of different ages and sexes. METHODS: This prospective multivariate Perceptometric study was performed on 4191 esthetic scores given by 127 individuals to 33 Perceptometric face images. Frontal view and three-quarter-view photographs of a normal young woman were modified by image editing software to create two Perceptometric sets, one for the 24 gradual changes of intergonial width on the frontal view, and the other for the 9 vertical changes of the jaw angle on the three-quarter view. An online questionnaire was designed including 24 frontal and 9 oblique view photographs. The questionnaires' internal consistencies were almost perfect. Enrolled were 127 raters, including 33 orthodontists, 32 OMF surgeons, and 62 laypeople. The esthetics of different images were compared across different professions, across different ages, and between the sexes using 2-way MANCOVA, ANCOVA, and Bonferroni; the zones of esthetic jaw angles and also the sensitivity of judges to Perceptometric anatomical changes were assessed using 2-way RM-ANCOVA and Bonferroni (α = 0.05, α = 0.0056, α = 0.0021, and β = 0.05). RESULTS: Orthodontists and surgeons gave the highest attractiveness scores to intergonial: interzygomatic ratio of 72.53%, while the best ratio was 74.45% for the laypeople. The range of beautiful intergonial is as follows: interzygomatic ratio was 72.53% to 86.03%. OMF surgeons and orthodontists gave the highest score to a gonial height of 4.5 mm above the mouth corner, while the laypeople gave the highest score to the gonial height of 4.5 mm below the mouth corner. The range of beautiful gonial height was from 4.5 mm above the mouth corner to 9 mm below the mouth corner. The education of observers may affect their perception of beauty; orthodontists tended differ from laypeople, overall and also specifically in the case of the highly attractive frontal images concerning the intergonial width changes. However, no such differences were detected between surgeons with orthodontists or laypeople. Although age did not affect the overall esthetic scores, it did affect the sensitivity of the judges to the anatomic changes. So did expertise, i.e., the expertise of judges affected their sensitivity to anatomical changes; orthodontists showed steeper slopes of esthetic preference alterations to anatomical changes, while laypeople had the gentlest slope of preference changes. Judges' sex did not affect either their overall esthetic preferences or their sensitivity to anatomic changes. CONCLUSION: Narrower female jaw angles and jaw angles that are vertically close to the level of the mouth corner may be unanimously more desirable. Thus, treatments aiming at widening the jaw angle of a woman or lowering it should be discouraged, at least in Persians. Orthodontists, but not surgeons, are more sensitive than laypeople to anatomic changes of the jaw angle. The judges' age can affect this perceptive sensitivity, but their sex cannot.

PURPOSE: Our study is aimed at analyzing the relationships between water loss and a professional soccer team's internal and external training load throughout the first three months of a season, covering all the preseason and the first two months of the competitive season. METHODS: This study followed an observational analytic design. Twenty-seven athletes (age: 25.5 ± 4.1 years, height: 180.7 ± 8.2 cm, and body mass: 78.4 ± 8.7 kg) were included in the study, conducted over the first three months of the season. Players were weighed at the beginning and end of all training sessions to estimate fluid losses. They were asked to complete a wellness questionnaire and indicate the color of the first urine of the day upon their arrival at the practice session. Additionally, all sessions were monitored for locomotor demands. RESULTS: We found a positive correlation between urine color and sprint distance (r = 0.46, p = 0.01) and a positive correlation between dehydration and rating of perceived exertion (r = 0.44, p = 0.015), whereas a negative correlation between dehydration and number of acceleration (r = -0.39, p = 0.034). CONCLUSIONS: Dehydration increased perceived physical exertion. Regularly monitoring training load and changes in body mass, as well as raising awareness about hydration, can contribute to cognitive and physical performance.

OBJECTIVE: To compare the effects of propofol-dexmedetomidine versus propofol-remifentanil for endoscopic ultrasonography (EUS). Design, Setting, and Participants. A single-center, randomized trial from August 20, 2020 to August 20, 2021, in patients undergoing EUS. Interventions. Propofol-dexmedetomidine (PD) versus propofol-remifentanil (PR). Outcome Measures. The primary outcome was the endoscopist satisfaction level. The secondary outcomes included patient satisfaction, the incidence of adverse events, induction time, and time to achieve postanesthesia discharge score (PADS) ≥9. METHODS: Total of 200 patients were enrolled and randomized into PD and PR groups. A bolus dose of 0.5 μg/kg dexmedetomidine was injected intravenously for 5 min. Subsequently, a continuous infusion of 0.5 μg/kg/h for the PD group. Remifentanil was continuously infused at 1.5 μg/kg/h for the PR group. A bolus dose of 1 mg/kg propofol was administered to both groups and then continuously infused. RESULTS: The endoscopist satisfaction level was higher in the PR group than in the PD group (P = 0.009). Patient satisfaction was not significantly different between the groups (P = 0.738). No patients required mask ventilation or tracheal intubation in both groups. All patients were relatively hemodynamically stable. The incidence of body movements during the procedure in the PD group was higher than in the PR group (P = 0.035). The induction time and time taken to achieve PADS ≥9 in the PD group were longer than in the PR group (P < 0.05). CONCLUSIONS: PR sedation can increase the satisfaction level of the endoscopist by providing faster induction time and lower body movement and that of the patient by achieving faster PADS than PD sedation. Trial registration number: http://www.chictr.org.cn (ChiCTR2000034987).

Pectin is a high molecular weight polymer which is present in virtually all plants where it contributes to the cell structure. Pectin is a high valuable food ingredient widely used as a gelling agent and thickening agent with limited use in the pharmaceutical industry. The objective of this study is to evaluate the suspending properties of pectin from watermelon rind. Tragacanth was used as a standard suspending agent to which the suspending properties of pectin from watermelon rinds were compared with. The extracted pectin was subjected to phytochemical and physiochemical characterization for its safety and suitability to use as a suspending agent. Paracetamol suspensions were formulated using tragacanth concentrations of 0.5% w/v, 1% w/v, and 2% w/v and compared with paracetamol suspensions containing the same concentrations of watermelon pectin. The suspensions were all tested for their pH, sedimentation rate, sedimentation volume, flow rate, and ease of redispersibility over a period of 4 weeks. At the end of the 4-week period, all formulated suspensions had no changes in their pH values. Suspensions containing the extracted pectin had a lower rate of sedimentation and ease of redispersibility compared to that of tragacanth. In addition, their sedimentation volumes as well as flow rates were comparable to that of the tragacanth formulations. Ultimately, pectin from watermelon rind can serve as a suitable alternative to tragacanth in formulation of pharmaceutical suspensions.

BACKGROUND: The leading cause of cancer-related fatalities globally is lung cancer; lung adenocarcinoma (LUAD) is the most common histological type in it. The spliceosome plays an important role in a majority of malignancies. However, it is yet unclear how spliceosome-related genes affect patients with LUAD in terms of treatment course and prognosis. METHODS: Spliceosome-related genes were assessed from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database to obtain clinical information and gene expression in patients with LUAD. A spliceosome-related gene signature and prognostic model were constructed by using the least absolute shrinkage and selection operator (LASSO), time-dependent receiver operating characteristic (ROC), and nomogram. Immune infiltrate levels, mutation analysis, and pathway enrichment were predicted potential mechanisms of the signature by using single-sample gene set enrichment analysis (ssGSEA), Gene Set Cancer Analysis (GSCA) database, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) database. Then, a protein-protein interaction (PPI) network and transcription factor- (TF-) hub gene and drug mining network were also established by Cytoscape software. RESULTS: Firstly, we constructed a prognostic model for 11 spliceosome signature genes. Based on the prognostic risk score, we stratified patients with LUAD into high- and low-risk groups. The high- and low-risk groups were closely related to the OS, tumor immune infiltration level, immune checkpoint molecules, and tumor mutation burden (TMB) of LUAD patients. Based on PPI networks, we also predict relevant TF genes that may regulate signature prognostic genes. Finally, drugs including oxaliplatin, arsenic trioxide, cisplatin, and sunitinib were excavated for the treatment of the 11 spliceosome signature genes in LUAD patients. CONCLUSION: In conclusion, this study is the first to explore the importance of spliceosome-related genes in the prognosis and treatment of LUAD. Through our study, we have innovatively provided potential prognosis genes and new therapeutic drug targets for the treatment of LUAD patients.

BACKGROUND AND AIMS: Abnormal expression of lncRNAs is relevant to the occurrence and development of gastric cancer (GC), but the significance remains inconclusive. We performed a diagnostic meta-bioinformatics analysis to elucidate the association between lncRNA expression and GC risk. METHODS: Published datasets were selected from PubMed, Embase, CNKI, and Web of Science, up to 1st December 2021. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the diagnostic value. RNA sequencing data were downloaded for validation. RESULTS: 54 studies with 4671 patients and 4652 matched controls were included in the meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC were 0.71, 0.76, 2.9, 0.39, 8, and 0.79, respectively. Subgroup analyses showed that the DOR and AUC of intergenic lncRNAs, circulating lncRNAs, larger sample size (>200), and high-quality (NOS score ≥ 7) groups were superior to antisense lncRNAs, tissue lncRNAs, smaller sample size (≤200), and low-quality (NOS score < 7) groups, respectively. However, only circulating lncRNAs had significantly higher diagnostic utility than that tissue lncRNAs. Nine differentially expressed lncRNAs in the meta-analysis were verified in TCGA-STAD. PVT1 was the most effective single lncRNA, with AUC of 0.949, SEN of 0.808, and SPE of 0.969, while PVT1 and C5orf66-AS1 were the most effective combination, with AUC of 0.972, SEN of 0.941, and SPE of 0.937. CONCLUSION: Abnormally expressed lncRNAs, especially circulating lncRNAs, might be potential diagnostic biomarkers for GC risk. A novel combined model of lncRNAs might achieve better GC diagnosis performance.

OBJECTIVE: Henoch-Schönlein purpura nephritis (HSPN) is considered a major cause of chronic renal failure and is the most common secondary glomerular disease in children. Huaiqihuang (HQH), a traditional Chinese herbal formula, exhibits therapeutic effects against HSPN in clinical practice. However, the potential molecular targets and mechanisms underlying HSPN treatment remain unclear. METHODS: By constructing a protein-protein interaction (PPI) network, core targets related to HQH and HSPN were identified. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to identify the main pathways related to HSPN based on the core targets. To screen the main active ingredients of HQH against HSPN, an ingredient-target-pathway network was constructed using the top 10 main pathways associated with HSPN. Then, molecular docking was performed to explore the interactions and binding patterns between molecules and proteins. RESULTS: Clinical data showed that HQH combined with conventional medicine significantly reduced 24-hour urine protein excretion, urine microalbumin levels, and erythrocyte counts in the urine sediment of HSPN patients. By constructing PPI models, 15 potential core targets were identified. The top 10 main pathways showed higher enrichment ratios, including the cytokine-cytokine receptor interaction and signaling pathways related to NOD-like receptor, IL-17, etc. Through the ingredient-target-pathway network and molecular docking, we revealed that five active ingredients of HQH had good affinities with three core targets, AKT1, MMP9, and SERPINE1, which may be vital in treating HSPN. CONCLUSIONS: The study preliminarily explored the active ingredients, targets, and pathways involved in HQH therapy for HSPN. The mechanism of HQH therapy may be attributed to the modulation of inflammatory response, immune response, and oxidative stress. Combined with clinical data, our results indicate that HQH is highly effective in treating HSPN.

BACKGROUND: To report the pregnancy and neonatal outcomes in patients with twin pregnancies who underwent ultrasound-indicated cerclage (UIC) and to compare them to patients with singleton pregnancies undergoing the same procedures. METHODS: Patients who underwent UIC between January 2010 and December 2020 at Kangnam Sacred Heart Hospital were reviewed. We compared characteristics, pregnancy, and neonatal outcomes between patients with singleton and twin pregnancies. RESULTS: A total of 94 women (56 singleton and 38 twin pregnancies) underwent UIC were included. The mean gestational age (GA) at cerclage and preoperative cervical length (CL) were not significantly different. Twin pregnancies were more likely to deliver at earlier median gestations than singletons (singleton, 36 + 1 weeks vs twin, 32 + 6 weeks, and p = 0.004). The frequency of preterm delivery <34 weeks in twin group was higher than in singleton group (15 (26.8%) vs 20 (52.6%) and p =0.016). However, the frequency of preterm delivery <32, <28, and <24 weeks was not significantly different between two groups. Although neonatal weights in singleton pregnancies were heavier than twin pregnancies, neonatal mortality and morbidities were not significantly different between two groups. Among various factors contributing to preterm birth, preoperative CL ≤ 15 mm was independently associated with a higher risk of preterm delivery before 34 weeks. Furthermore, pregnancy and neonatal outcomes of twin pregnancies with cervical length ≤ 15 mm are comparable with those of singleton pregnancies (GA at delivery, singleton, 35 + 1 weeks vs twin, 32 + 5 weeks, and p = 0.24; neonatal mortality, singleton, 3.4% vs twin, 4.8%, and p = 0.64). CONCLUSION: The pregnancy and neonatal outcomes of UIC in twin pregnancies were comparable to those in singleton pregnancies, especially when CL is ≤15 mm. UIC might be considered a safe procedure for twin pregnancies.

BACKGROUND: Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is an integral membrane protein overexpressed in various cancers and may function as a prognostic tumor marker. The present study is aimed at understanding the clinical significance of serum LAPTM4B in breast cancer (BC). METHODS: Serum LAPTM4B level was evaluated in 426 BC patients, 40 benign breast disease, and 80 healthy controls by ELISA. We used the receiver operator characteristic (ROC) curve to assess the diagnostic significance. 46 BC patients were recruited to monitor the dynamic change of serum LAPTM4B during adjuvant therapy (AT). In addition, sera from a subset of 330 patients undergoing AT, including anti-HER2 treatment, were collected to evaluate the association between LAPTM4B levels and AT efficacy. Descriptive and explorative statistical analyses were used to assess LAPTM4 B's potential as a diagnostic and prognostic marker in BC. RESULTS: Serum LAPTM4B level was significantly increased in BC patients than benign group and controls. It could well discriminate BC from healthy controls with diagnostic accuracy with an AUC of 0.912, a sensitivity of 85.9%, and a specificity of 83.8%. Compared with pre-AT, serum LAPTM4B concentration remarkably decreased after AT. In addition, patients in the invalid response group (PD + SD) showed higher LAPTM4B levels than the valid response group (PR + CR). CONCLUSION: Our results proposed that serum LAPTM4B had a high diagnostic and prognostic impact as a circulating biomarker in BC.

Multilevel lumbar fusion with posterior pedicle screw fixation is a widely performed surgical procedure for the management of adult spinal deformity. However, there has not been a comprehensive biomechanical study on the different types of fusion levels in terms of stability and possible complications. We aimed to investigate the biomechanical properties of multilevel lumbar fusion according to different types of upper and lower fusion levels. Six different types of fusions were performed using three-dimensional finite element models. Type A and B referred to the group of which upper fusion level was L1 and T10, respectively. Subtype 1, 2, and 3 referred to the group of which lower fusion level was L5, S1, and ilium, respectively (A1, L1-L5; A2, L1-S1; A3, L1-ilium; B1, T10-L5; B2, T10-S1; B3, T10-ilium). Flexion, extension, axial rotation, and lateral bending moments were applied, and the risk of screw loosening and failure and adjacent segment degeneration (ASD) was analyzed. Stress at the bone-screw interface of type B3 was lowest in overall motions. The risk of screw failure showed increasing pattern as the upper and lower levels extended in all motions. Proximal range of motion (ROM) increased as the lower fusion level changed from L5 to S1 and the ilium. For axial rotation, type B3 showed higher proximal ROM (16.2°) than type A3 (11.8°). In multilevel lumbar fusion surgery for adult spinal deformity, adding iliac screws and increasing the fusion level to T10-ilium may lower the risk of screw loosening. In terms of screw failure and proximal ASD, however, T10-ilium fusion has a higher potential risk compared with other fusion types. These results will contribute for surgeons to provide adequate patient education regarding screw failure and proximal ASD, when performing multilevel lumbar fusion.

High-risk human papillomavirus (HR-HPV) is the main etiological factor for cervical cancer. Accumulating evidence has suggested the active role of metabolites in the initiation and progression of cancers. This study explored the plasma metabolic profiles of HPV-16 positive (HPV16 (+)), HPV-18 positive (HPV18 (+)), and HPV negative (CTL) individuals using a nontargeted metabolomics approach. C8 ceramide-1-Phosphate (d18 : 1/8 : 0) was found to inhibit cervical cancer cell proliferation and migration in vitro, evidenced by CCK8 experiments, a cell migration test, RT-qPCR, and western blotting. The underlying mechanism demonstrated that C8 inhibited proliferation and migration in cervical cancer cells via the MAPK/JNK1 signaling pathway. These findings may contribute to the clinical treatment of HR-HPV-induced cervical cancer by intervening in its initiation and progression.

PURPOSE: To investigate the baseline parameters of peripapillary regions in both eyes of patients with unilateral branch retinal vein occlusion (BRVO) using optical coherence tomography angiography (OCTA) and their association with best-corrected visual acuity (BCVA). METHODS: Forty-eight unilateral BRVO patients were enrolled. The 4.5 × 4.5 mm disc angiogram was acquired in the BRVO eyes and fellow eyes using the OCTA. Radial peripapillary capillary (RPC), whole vessel density, and retinal nerve fiber layer (RNFL) thickness in different regions and optic nerve head (ONH) analysis were automatically calculated. The partition includes the whole image, peripapillary, superior hemifield, inferior hemifield, eight equally divided sectors, and nine evenly divided square areas. RESULTS: All vessel density and capillary vessel density in the whole and peripapillary regions of BRVO eyes were significantly lower than those in fellow eyes. The RNFL peripapillary thickness in BRVO eyes was significantly higher than those in fellow eyes. In eyes with supertemporal vein occlusion, all vessel density both in the superior hemifield and in the G12 region was significantly reduced compared with that in the fellow eyes. The capillary vessel density was significantly lower in the superior hemifield, superior temporal (ST), superior nasal (SN), and temporal superior (TS) areas than in the fellow eyes. The RNFL thickness in the NI, IN, TI, and TS sectors was significantly higher than in fellow eyes (all P < 0.05). CONCLUSIONS: OCTA provided quantitative information on peripapillary vascular density and RNFL thickness changes in BRVO. Branch retinal vein occlusion not only affects the blood vessel density in the macular area but also decreases the radial peripapillary capillaries. The capillary density is mainly affected in the affected hemifield but not in the unaffected hemifield.

Any bodily movement produced by skeletal muscle which requires energy expenditure is known as physical activity (PA). WHO has recommended that at least 150 minutes of moderate or 75 minutes of vigorous-intensity PA or a combination of both per week is required for health benefits. Physical inactivity is one of the strongest risk factors for noncommunicable diseases (NCDs) and other conditions and is attributable to 6% of global premature death. However, data on the PA of teachers are unavailable in Nepal. They are considered one of the risk groups for NCDs because of the less active nature of their job. So, we aimed to evaluate the effect of the educational intervention based on the theory of planned behaviour on PA intention among secondary school teachers in Bhaktapur district, Nepal. For this study, we recruited 126 teachers from 6 schools. Each intervention and control group contained three randomly selected secondary schools. All the teachers from the selected schools were enrolled in the respective groups. A quasiexperimental (pretest-posttest control group) study design was used to test the effectiveness of the intervention on attitude, behaviour control, subjective norms, and intention for engaging in regular PA. Both groups underwent baseline and follow-up assessments at four weeks using the self-administered questionnaire developed for this study. The intervention group delivered a one-hour lecture session supported by audio-video materials for PA promotion. The effect was analysed by comparing the changes in the theory of planned behaviour (TPB) constructs within and between intervention and control groups. The difference in scores between and within the groups was tested using Student's t-test. Adjusted difference-in-difference scores were calculated through linear regression. Data analysis was done using Statistical Package for Social Science version 26.0. The adjusted mean score increase in TPB constructs due to the interaction of time and intervention increased from 0.641 to 1.381. The highest gain (beta = 1.381) was seen in the intention score, while a minor improvement was seen in perceived behavioural control (beta = 0.641). After the intervention, the net increase in PA intention score was 9.35% compared to the control group. Thus, the promotion package was effective in increasing PA intention. The findings of this study and educational package could be helpful in encouraging teachers to engage in PA in other schools.

BACKGROUND: Antinuclear antibody (ANA) is often used as a screening test for autoimmune comorbidities in patients with chronic spontaneous urticaria (CSU). However, the relationship of ANA status and the clinical course of the disease have not been fully described. OBJECTIVES: To compare clinical features of CSU patients who are positive and negative for ANA. METHODS: This was a retrospective cohort study that enrolled CSU patients attending the Urticaria Clinic at Siriraj Hospital from 2013 to 2019. Demographics, clinical characteristics, laboratory investigations, and treatments were collected until July 2021. All patients were investigated for ANA. Clinical feature data was compared between CSU patients with positive ANA and negative ANA groups using the 2-sample t-test and the Mann-Whitney U test for quantitative variables. The chi-squared test or Fisher's exact test was conducted to explore the association of qualitative variables. Disease relapse and remission were analysed via Kaplan-Meier survival analysis. RESULTS: Of 323 CSU patients, 31% had positive ANA. There were no significant differences in disease severity or impairment in quality of life. Patients with a positive ANA test had significantly lower prevalence of allergic rhinitis (p = .048) and significantly higher level of erythrocyte sedimentation rate (p = 0.007). Kaplan-Meier survival analysis showed that 2% of ANA positive CSU patients achieved remission status after one year and 28% did so after five years. There was no statistically significant difference in time to remission and time to relapse between ANA-positive and negative groups. CONCLUSION: Positive ANA in CSU patients could not indicate the differences in main disease characteristics from the ANA-negative CSU patients. Investigation for ANA may be useful in CSU patients who are suspected of having autoimmune diseases.

OBJECTIVE: To evaluate the incidence and risk factors for complications following volar locking plate (VLP) fixation of unstable distal radius fracture (DRF). METHODS: This retrospective study identified patients who underwent VLP fixation of unstable DRF between 2017 and 2020 with a minimum 12-month follow-up assessments. By reviewing electronic medical records and follow-up notes, patients were categorized complication or noncomplication group. Differences in variables were detected by using univariate analyses, and independent factors were identified using multivariate logistic regression analysis. RESULTS: During this study period, 423 patients were included, and 63 (rate, 14.9%) complications in 58 patients were documented. Wound infection (17, 4.0%) was most common, followed in decreasing frequency by carpal tunnel syndrome (13, 3.1%), tendon rupture/irritation (10, 2.4%), complex regional pain syndrome (8, 1.9%), and plate/screw-related complications (5, 1.7%). In the univariate analyses, 18 variables were found to be significantly different (p < 0.05). Logistic regression analysis identified 5 independent factors, including being male (OR, 3.5; p = 0.014), type C fracture (vs. type A, OR: 2.7, and p = 0.035), general anesthesia (vs. regional, OR: 2.4, and p = 0.045), bone grafting (OR, 6.3; p < 0.001), and surgery performed by less experienced surgeons (OR, 3.1; p = 0.003). The goodness-of-fit of the final model was acceptable. CONCLUSIONS: These factors will help surgeons individualize and stratify the risk of complications and help patients for risk counselling; especially, an informed clinical decision targeting those modifiable factors (anesthesia mode, bone grafting, and surgeon experience) can be considered, when indicated.

Transfersomes (TFS) are the promising carriers for transdermal delivery of various low and high molecular weight drugs, owing to their self-regulating and self-optimizing nature. Herein, we report synthesis and characterization of TFS loaded with meloxicam (MLX), an NSAID, and dexamethasone (DEX), a steroid, for simultaneous transdermal delivery. The different formulations of TFS containing varying amounts of lecithin, Span 80, and Tween 80 (TFS-1 to TFS-6) were successfully prepared by thin-film hydration method. The size of ranged between 248 and 273 nm, zeta potential values covering from -62.6 to -69.5 mV, polydispersity index (PDI) values in between 0.329 and 0.526, and entrapment efficiency of MLX and DEX ranged between 63-96% and 48-81%, respectively. Release experiments at pH 7.4 demonstrated higher cumulative drug release attained with Tween 80 compared to Span 80-based TFS. The scanning electron microscopy (SEM) of selected formulations -1 and TFS-3 revealed spherical shape of vesicles. Furthermore, three optimized transfersomal formulations (based on entrapment efficiency, TFS-1, TFS-3, and TFS-5) were incorporated into carbopol-940 gels coded as TF-G1, TF-G3, and TF-G5. These transfersomal gels were subjected to pH, spreadability, viscosity, homogeneity, skin irritation, in vitro drug release, and ex vivo skin permeation studies, and the results were compared with plain (nontransfersomal) gel having MLX and DEX. TFS released 71.72% to 81.87% MLX in 12 h; whereas, DEX release was quantified as 74.72% to 83.72% in same time. Nevertheless, TF-based gels showed slower drug release; 51.54% to 59.60% for MLX and 48.98% to 61.23% for DEX. The TF-G systems showed 85.87% permeation of MLX (TF-G1), 68.15% (TF-G3), and 68.94% (TF-G5); whereas, 78.59%, 70.54%, and 75.97% of DEX was permeated by TF-G1, TF-G3, and TF-G5, respectively. Kinetic modeling of release and permeation data indicated to follow Korsmeyer-Peppas model showing diffusion diffusion-based drug moment. Conversely, plain gel influx was found mere 26.18% and 22.94% for MLX and DEX, respectively. These results suggest that TF-G loaded with MLX and DEX can be proposed as an alternate drug carriers for improved transdermal flux that will certainly increase therapeutic outcomes.

Glutaminyl cyclase (QC) is responsible for converting the N-terminal glutaminyl and glutamyl of the proteins into pyroglutamate (pE) through cyclization. It has been confirmed that QC catalyzes the formation of neurotoxic pE-modified Aβ in the brain of AD patients. But the effects of upregulated QC in diverse diseases have not been much clear until recently. Here, RNA sequencing was applied to identify differentially expressed genes (DEGs) in PC12 cells with QC overexpressing or knockdown. A total of 697 DEGs were identified in QC overexpressing cells while only 77 in QC knockdown cells. Multiple bioinformatic approaches revealed that the DEGs in QC overexpressing group were enriched in endoplasmic reticulum stress (ERS) related signaling pathways. The gene expression patterns of 23 DEGs were confirmed by RT-qPCR, in which the genes related to ERS showed the highest consistency. We also revealed the protein levels of GRP78, PERK, CHOP, and PARP-1, and caspase family was significantly upregulated by overexpressing QC. Moreover, overexpressing QC significantly increased apoptosis of PC12 cells in a time dependent manner. However, no significant alteration was observed in QC knockdown cells. Therefore, our study indicated that upregulated QC could induce ERS and apoptosis, which consequently trigger diseases by catalyzing the generation of pE-modified mediators.

OBJECTIVE: To investigate the current situation of self-perceived burden in patients with urostomy, analyze the correlation between self-perceived burden and quality of life, and explore the intermediary role of resilience and social support. METHODS: The convenience sampling method was used to select 303 patients with urostomy of outpatient departments of the three tertiary hospitals in Yinchuan, Ningxia region, China, from April 1, 2020, to October 1, 2020, who then completed a survey questionnaire. The survey questionnaire contained a general data questionnaire and self-perceived burden scale, city of hope-quality of life-ostomy questionnaire, Connor-Davidson resilience scale, and social support rating scale. RESULTS: Self-perceived burden was present among 89.8% patients with urostomy; the quality of life of patients with urostomy is low. The results showed that the self-perceived burden and quality of life, resilience, and social support are related in pairs; self-perceived burden was significantly negatively correlated with quality of life，resilience, and social support; there was a significant positive correlation between quality of life, resilience, and social support; resilience and social support were parallel mediators. CONCLUSIONS: Patients with urostomy had a heavy self-perceived burden and low quality of life. Reducing the self-perceived burden of patients with urostomy by improving the level of resilience and social support, could raise the level of quality of life. This study could provide empirical basis for nurses to take continuous nursing intervention measures in order to reduce the self-perceived burden of patients with urostomy and ultimately to improve the quality of life.

BACKGROUND: Lung squamous cell carcinoma (LUSC) has poor survival prognosis and few clinical treatment options. We urgently need to explore new therapeutic drugs in clinical practice. Cepharanthine (CEP) has been shown to have anticancer effects in several tumors, but the mechanism of CEP in treating LUSC has not been reported. METHODS: SwissTargetPrediction, PharmMapper, and GeneCards were used to identify targets of CEP and LUSC. Further topological analysis was used to obtain hub genes via Cytoscape. Molecular docking was carried out to verify the combination of CEP with hub targets. Based on bioinformatics, we first analyzed the expression and survival of hub targets in LUSC and further analyzed the correlation between hub targets and cancer stemness, immune cell infiltration, and tumor mutation burden (TMB). RESULTS: A total of 41 targets were identified. Further topological analysis identified 6 hub genes: AURKA, CCNA2, CCNE1, CDK1, CHEK1, and PLK1. Molecular docking analysis showed that CEP had stable binding to all these 6 target proteins. In-depth bioinformatics analysis of these 6 targets showed that high expression of these targets were positively correlated with cancer stemness index and negatively correlated with tumor infiltrating immune cells. In immune subtype analysis, the expressions of these targets were significantly decreased in inflammatory tumors. In addition, we also found that the expressions of these targets were positively correlated with TMB. CONCLUSION: Based on multidisciplinary analysis, we preliminarily identified potential targets of CEP for LUSC treatment and suggested that CEP may play a role in regulating LUSC stemness.

Level of toxic heavy metal concentration like lead (Pb), chromium (Cr), cadmium (Cd), iron (Fe), copper (Cu), zinc (Zn), and nickel (Ni) in thirty-six soft and hard organs and their impact on lipid profile of Hypophthalmichthys molitrix and Catla catla fish species inhibiting in Tanda Dam reservoir were investigated. The heavy metal concentrations in water, sediment, and fish of the different regions in the reservoir were determined with atomic absorption spectrophotometer. Lipid profile was carried out by AOAC official methods. The results showed that Pb was dominant among all the heavy metals in six organs, and its maximum concentration of Pb (22.5 mg kg-1 and 32.9 mg kg-1) was observed in scales in Hypophthalmichthys molitrix and tail of Catla catla, respectively. The maximum concentrations of Cd were observed in the head, scales, fins, and gills of Catla catla. The bioaccumulation of heavy metals was significantly different at (p ≤ 0.01) within the organs and between the fish species. The lipid concentration was minimum in those organs where the concentrations of heavy metals were maximum. It is clear from the findings that heavy metal accumulation reduces the lipid content of fish. It is inevitable to monitor the Tanda Dam reservoir to safeguard human health.

Erratum for J Biomed Biotechnol. 2011;2011:219060.

This study is aimed at examining the prognostic value of blood neutrophil-to-lymphocyte ratio (NLR) in patients with hepatocellular carcinoma (HCC). Demographic and clinical data of 543 HCC patients treated with interventional therapies were retrospectively analyzed. Preoperative NLRs were determined and receiver operating characteristic (ROC) curves were plotted for survival time in patients with high (NLR ≥3.8) and low (NLR<3.8) NLR. The median overall survival (OS) was 1241 days after interventional therapies and was significantly reduced in the high NLR group when compared to the low NLR group. The median progression-free survival time (PFST) of patients was also significantly shorter in the high NLR group than in the low NLR group. Univariate analysis revealed that tumor type, therapy method, maximum tumor size (>3 mm), and NLR (>3.8) were risk factors for OST and PFST (P < 0.05). Multivariate analysis indicated that tumor type, maximum tumor diameter, therapy method, and NLR (>3.8) were independent risk factors for PFST (P < 0.05). Our results demonstrate that preoperative NLR has prognostic value for patients with HCC undergoing interventional therapies, and high NLR is an indication of poor prognosis.

Bone defect repair remains a challenge in orthopedics. This study describes the development and potential effectiveness of vascular endothelial growth factor (VEGF)/bone morphogenetic protein-2 (BMP-2) shell-core microspheres for promoting bone regeneration. Poly(L-lactic acid)/polylactic-co-glycolic acid (PLLA/PLGA) core-shell microspheres loaded with VEGF and BMP-2 were prepared by a coaxial electrospray technique, and their surface morphology, core-shell distribution, and particle size were examined. Different groups of microspheres were prepared with different placement of the growth factors, and the encapsulation efficiency and in vitro release curves were measured. Additionally, the effects of the different groups of microspheres on the proliferation and differentiation of osteoblasts and vascular endothelial cells were investigated. The prepared microspheres had a core-shell structure with good homogeneity and dispersion, a clear boundary, and a smooth surface. On scanning electron microscopy, the mean diameter of the microspheres was similar for all six preparations (P > 0.05). During in vitro release, growth factor was initially released via a brief burst release from the outer shell of the microsphere followed by a slower sustained release. The release of growth factors from the inner core remained relatively slow and sustained. Sequential release of different growth factors was achieved through the inconsistent release rates from the microsphere shell and inner core. All groups of microspheres showed no cytotoxicity, good biocompatibility, and the ability to promote osteoblast proliferation. The microspheres loaded with BMP-2 also promoted osteoblast differentiation, and VEGF-loaded microspheres promoted the proliferation and differentiation of vascular endothelial cells. The BMP-2 (core)/VEGF (shell) microsphere group best promoted osteoblast differentiation. The microspheres prepared in this study exhibited slow sequential release of BMP-2 and VEGF and showed good biocompatibility along with the ability to promote osteoblast differentiation and vascular endothelial cell proliferation.

BACKGROUND: Diarrhea caused by bacterial pathogens such as Shigella spp. is one of the prominent public health concerns. The evolution of vast antibiotic resistance by these pathogens, leading to failure in the infections eradication, has made an impetus to seek and develop novel approaches. Recently, some alternative therapies such as phage therapy have been investigated. Bacteriophages are viruses that target specific bacterial species. The objective of this study was to assess the therapeutic effect of phages obtained from hospital sewage against Shigella sonnei (S. sonnei) ATCC® 9290 and S. flexneri ATCC 12022 standard and clinical strains. METHODS: Four various lytic bacteriophages were isolated from animal fecal and sewage samples and propagated using S. sonnei and S. flexneri as host organisms. The phages' morphology was determined using transmission electron microscopy (TEM). The lytic potential and host specificity of isolated phages were evaluated using double layer plaque assay and spot test. Moreover, bacterial turbidity values were evaluated in coculture with phages in the Luria Bertani (LB) medium for 24 hours at time intervals of 30 min. RESULTS: Phage cocktails (Shs1, Shs2, Shf1, and Shf2) exhibited higher antimicrobial activity than single phage application against S. sonnei and S. flexneri standard strains. The phages belonged to Podoviridae and Myoviridae families according to TEM-assisted morphological features analysis. In addition, the phages exhibited host specificity using the spot test against 18 Shigella clinical isolates. CONCLUSION: In this study, phage cocktail of Podoviridae and Myoviridae families from sewage conferred substantial antibacterial effects against S. sonnei and S. flexneri. However, single phage effects were unstable in the LB coculture. Moreover, the phages had host specificity using the spot test performed against Shigella spp. clinical isolates.

BACKGROUND: Neonatal sepsis is a leading cause of morbidity and mortality in low-and middle-income countries (LMICs). There are several sophisticated biomarkers; however, they are still insufficient in precision. In this perspective, our study aims to search for a pragmatic diagnostic biomarker in the age category. METHODS: A cross-sectional study was conducted over six months(April-September 2018). All neonates with a diagnosis of probable sepsis were included. Logistic regression analysis of demographic variables was done to elucidate any association with confirmed sepsis cases. The median with interquartile range (IQR)] and mean with standard deviation (SD) were calculated, and then compared. The area under the receiver operating characteristic curve (AUROC) of the commonly opted biomarker tests [distribution width of red blood cells (RDW) and platelets(PDW), mean platelet volume(MPV), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] was compared to the culture-confirmed case. RESULTS: Of the 171 suspected sepsis subjects, we discovered a significant burden of newborn sepsis, with 18.7% of cases being culture-confirmed. 66 Early-onset sepsis(EOS) and 105 Late-onset sepsis(LOS) probable sepsis cases were enrolled. A higher incidence was revealed among male infants 24(14%) compared to females 8(4.7%). On logistic regression analysis, preterm birth [odds ratio (OR): 10.9, 95% confidence interval (CI): 4.5-26.9] and low birth weight (OR: 6.5, 95% CI: 2.4-17.9) were significantly associated. Coagulase-negative Staphylococcus aureus (CoNS) (n =6) among gram-positive, and Pseudomonas aeruginosa (n =6) was among gram-negative, were the leading etiologies. Escherichia coli (n =3) was the predominant bacteria in EOS subjects, while Pseudomonas aeruginosa (n =6) among LOS. Median interquartile range(IQR): platelet count 144.5(99-192), red cell distribution width 18(16.9-20), CRP 6(3-18.3); and mean ± SD: MPV (11.7 ± 1.7); PDW (15.2 ± 3.5) were attained, among confirmed cases. The AUROC, of biomarker tests was attained in the order: PDW(0.86) > MPV(0.81) > RDW(0.76) > CRP(0.67) > ESR(0.59); similarly, the cut-off order was >11.2, >10.4, >16.8, >2.9, >4.5, respectively. CONCLUSIONS: Our finding shows an increment in the width and volume of RBCand platelet: RDW, MPV, and PDW have a diagnostic role in neonatal sepsis.

Convolvulus arvensis L. is rich in phenolic compounds and traditionally used to treat wounds, skin ulcer, and inflammation. The current study is aimed at scientifically potentiating its traditional wound healing use. The methanolic extract of C. arvensis stem (CaME) was analyzed for HPLC and GC-MS analyses. The binding modes of active compounds were investigated against protein targets glycogen synthase kinase-3β (GSK-3β), transforming growth factor-beta (TGF-β), c-myc, and β-catenin by molecular docking followed by molecular dynamic simulations which revealed some conserved mode of binding as reported in crystal structures. The antioxidant potential of CaME was evaluated by in vitro methods such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, hydrogen peroxide scavenging, and ferric reducing power assays. Ointment formulations of 10 and 20% CaME were applied topically and evaluated for wound healing potency against the excisional wound on the skin of Wistar rats. Gentamycin (0.1%) served as standard therapy. The healing process was observed for 20 days in the form of wound size and epithelialization followed by histopathological evaluation of the wound area. Chemical characterization showed the presence of 7-hexadecenoic acid, 2-hexadecylicosan-1-ol, quercetin, gallic acid, ferulic acid, and other compounds. The plant extract exhibited significant in vitro antioxidant activity. The animals treated with 10% ointment showed moderate healing, whereas the treatment with 20% CaME revealed healing potential comparable to the standard 0.1% gentamycin as coevidenced from histopathological evaluation of skin. The study corroborates promising potential of C. arvensis on the healing of wounds, which possibly will be attributed to its antioxidant activity, fatty acids, quercetin, and gallic and caffeic acids, and binding potential of its phytoconstituents (phenolic acids) with wound healing targets.

Saikosaponin D (SSD), a saponin derivative, is extracted from Bupleurum falcatum. It exhibits an inhibitory effect on a number of tumor cells and is relatively safe when used at therapeutic doses. However, its effects on glioblastoma multiforme (GBM) have not been fully explored. This study is aimed at investigating the cytotoxic effects of SSD in GBM cell lines. SSD induces apoptosis and autophagy by activating endoplasmic reticulum (ER) stress in GBM cells. GBM cell proliferation activity and morphology were observed using the Cell Counting Kit-8 assay and hematoxylin and eosin staining. Hoechst 33258 fluorescence staining and flow cytometry were performed to assess apoptosis. Western blotting and immunocytochemical staining were used to detect protein expression and distribution. SSD significantly inhibited the proliferation of RG-2, U87-MG, and U251 cells in a dose-dependent manner, and the proportion of apoptotic cells increased significantly. Additionally, the expressions of ER-, apoptosis-, and autophagy-related proteins were significantly upregulated and distributed in the cytoplasm and nucleus. Therefore, SSD may be considered a novel treatment option for GBM. This study demonstrated the anti-GBM effect of SSD from the perspectives of cell apoptosis and autophagy.

OBJECTIVE: Mingmu Dihuang Pill (MMDHP) is a traditional Chinese formula that has shown remarkable improvements of dry eyes, tearing, and blurry vision; however, the mechanisms underlying MMDHP treatment for diabetic retinopathy have not been fully understood. This study is aimed at identifying the molecular targets and active ingredients of MMDHP for the treatment of diabetic retinopathy based on network pharmacology. METHODS: All active ingredients of MMDHP were retrieved from TCMSP and BATMAN-TCM databases, and the targets of active ingredients of MMDHP were predicted on the SwissTargetPrediction website. Diabetic retinopathy-related target sets were retrieved from GeneCards and OMIM databases, and the intersecting targets between targets of active ingredients of MMDHP and potential therapeutic targets of diabetic retinopathy were collected to generate the traditional Chinese medicine-ingredient-target-diabetic retinopathy network and to create the protein-protein interaction network. In addition, GO terms and KEGG pathway enrichment analyses were performed to identify the potential pathways, and molecular docking was employed to verify the binding of active ingredients of MMDHP to key targets of diabetic retinopathy. RESULTS: Network pharmacology predicted 183 active ingredients and 904 targets from MMDHP, and 203 targets were intersected with the therapeutic targets of diabetic retinopathy. The top 10 hub targets included PIK3RA, TP53, SRC, JUN, HRAS, AKT1, VEGFA, EGFR, ESR1, and PI3KCA. GO terms and KEGG pathway enrichment analyses identified AGE-RAGE, PI3K-AKT, and Rap1 signaling pathways as major pathways involved in MMDHP treatment for diabetic retinopathy. Molecular docking confirmed a good binding affinity of active ingredients of MMDHP, including luteolin, acacetin, naringenin, and alisol B, with AKT1, SRC, and VEGFA as the three key targets of diabetic retinopathy. CONCLUSION: MMDHP may be effective for the treatment of diabetic retinopathy through active ingredients luteolin, acacetin, naringenin, and alisol B via AKT1, SRC, and VEGFA in AGE-RAGE, PI3K-AKT, and Rap1 signaling pathways.

[This retracts the article DOI: 10.1155/2022/9018379.].

OBJECTIVE: To evaluate and summarize the best evidence for nonpharmacological management of chemotherapy induced nausea and vomiting (CINV). This article aims at serving as a reference for nursing staff to prevent and manage CINV. METHODS: We systematically searched for evidence on CINV in databases such as Cnki and Wanfang, guide websites such as GIN and NZGG, and professional websites such as UICC and ACS. Only articles published between November 2012 and November 2021 were considered for inclusion in the summary. Two researchers evaluated the quality of the literature and extracted the data. RESULTS: A total of 22 articles were included in this study, including 3 clinical decisions, 2 guidelines, 1 evidence summary, 2 recommended practices, 13 systematic reviews, and 1 expert consensus. Finally, 15 pieces of evidence were summarized from 3 perspectives: risk factor assessment, nursing process specification, and nonpharmacological interventions. CONCLUSION: Our research summarizes the best evidence on nonpharmacological management of CINV. During actual clinical application, it is necessary to fully consider the clinical situation, combine professional judgment with patients' wishes, follow the principle of individualization, analyze the obstacles and facilitating factors of the application of evidence, and prudently apply the evidence to the clinical practice.

BACKGROUND: Drug resistance testing in HIV-1 low-level viremia (LLV) samples is challenging yet critical. Our study is aimed at assessing the performance of lentivirus concentration reagent (LCR) in combination with a validated Sanger sequencing (SS) for monitoring drug resistance mutations (DRMs) in LLV samples. METHODS: A series of clinical samples were diluted and amplified for genotypic resistance testing (GRT) to prove the performance of the LCR. The Stanford HIV-1 drug resistance database (HIVdb version 8.9) was used to analyze the mutations. HIV-1 subtypes and CRFs were determined using the COMET online tool. The overall success rate of genotyping was compared with ultracentrifugation combined with SS. Furthermore, the success rates at varied VL of the two concentration methods were evaluated, and the DRMs of diluted samples were compared with those undiluted samples. RESULTS: When LCR was used, the overall success rate was 90% (72/80) in the PR and RT regions and 60% (48/80) in the IN region. In addition, when HIV RNA was 1000 copies/ml, 400 copies/ml, 200 copies/ml, and 100 copies/ml, the success rates of PR and RT regions were 100%, 100%, 95%, and 65%, respectively, while the success rates of IN region were 85%, 60%, 45%, and 50%, respectively. We found that the sample DR-387A2 missed the E138A mutation, and mutations in other samples were consistent with undiluted samples using LCR. CONCLUSIONS: LCR will support monitoring DRMs in HIV-1 patients with LLV and can be an effective alternative for small- and medium-sized laboratories that cannot afford an ultracentrifuge.

BACKGROUND: To explore the normal changes in bone turnover markers (BTMs) and the correlations between the different BTMs after osteoporotic vertebral compression fracture (OVCF). Meanwhile, we explored the related differences that exist between sexes. METHODS: A total of 130 OVCF patients were retrospectively reviewed. Using IBM SPSS 19.0 statistical software, the differences in the levels of BTMs and clinical parameters between sexes were assessed using Student's unpaired t test, and one-way ANOVA was used for the comparison of the three groups of samples. The correlations between P1NP, CTX, and clinical factors were assessed using Pearson's correlation coefficient. RESULTS: P1NP was 52.15 ng/ml within two weeks in male patients, and the level increased to 96.33 ng/ml after 12 weeks; in female patients, the increase was not as obvious as in male patients. CTX in male patients reached as much as approximately twice the initial value after 12 weeks. However, the situation in female patients was diverse. CTX was 0.58 ng/ml within two weeks and increased to 0.61 ng/ml within 2-12 weeks after the onset of OVCF. Subsequently, CTX decreased suddenly after 12 weeks. The increase in P1NP levels within 2 weeks after OVCF was significantly correlated with the levels of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Changes in CTX within 2 weeks after OVCF were considerably related to phosphorus, 25 hydroxyvitamin D (25-OHD), OC, and BAP. CONCLUSION: The levels of P1NP and CTX increased differently in males and females after OVCF. The levels of OC and BAP were correlated with the levels of P1NP and CTX within 2 weeks of OVCF.

OBJECTIVE: Asthma (AS) is a chronic inflammatory disease of the airway, and macrophages contribute to AS remodeling. Our study aims at screening macrophage-related gene signatures to build a risk prediction model and explore its predictive abilities in AS diagnosis. METHODS: Three microarray datasets were downloaded from the GEO database. The Limma package was used to screen differentially expressed genes (DEGs) between AS and controls. The ssGSEA algorithm was used to determine immune cell proportions. The Pearson correlation coefficient was computed to select the macrophage-related DEGs. The LASSO and RFE algorithms were implemented to filter the macrophage-related DEG signatures to establish a risk prediction model. Receiver operating characteristic (ROC) curves were used to assess the diagnostic ability of the prediction model. Finally, the qPCR was used to detect the expression of selected differential genes in sputum from healthy people and asthmatic patients. RESULTS: We obtained 1,189 DEGs between AS and controls from the combined datasets. By evaluating immune cell proportions, macrophages showed a significant difference between the two groups, and 439 DEGs were found to be associated with macrophages. These genes were mainly enriched in the gene ontology-biological process of immune and inflammatory responses, as well as in the KEGG pathways of cytokine-cytokine receptor interaction and biosynthesis of antibiotics. Finally, 10 macrophage-related DEG signatures (EARS2, ATP2A2, COLGALT1, GART, WNT5A, AK5, ZBTB16, CCL17, ADORA3, and CXCR4) were screened as an optimized gene set to predict AS diagnosis, and they showed diagnostic abilities with AUCs of 0.968 and 0.875 in ROC curves of combined and validation datasets, respectively. The mRNA expressions of EARS2, ATP2A2, COLGALT1, and GART in the control group were higher than in AS group, while the expressions of WNT5A, AK5, ZBTB16, CCL17, ADORA3, and CXCR4 in the control group were lower than that in the AS group. CONCLUSION: We proposed a diagnostic model based on 10 macrophage-related genes to predict AS risk.\.

Esophageal squamous cell carcinoma (ESCC) is one of the subtypes of esophageal cancer with Chinese characteristics, and its five-year survival rate is less than 20%. Early diagnosis is beneficial to improving the survival rate of ESCC significantly. Quantitative Real-Time Polymerase Chain Reaction is a high-throughput technique that can quantify tumor-related genes for early diagnosis. Its accuracy largely depends on the stability of the reference gene. There is no systematic scientific basis to demonstrate which reference gene expression is stable in ESCC and no consensus on the selection of internal reference. Therefore, this research used four software programs (The comparative delta-Ct method, GeNorm, NormFinder, and BestKeeper) to evaluate the expression stability of eight candidate reference genes commonly used in other tumor tissues and generated a comprehensive analysis by RefFinder. Randomly selected transcriptome sequencing analysis confirmed the SPP1 gene is closely related to ESCC. It was found that the expression trend of SPP1 obtained by RPS18 and PPIA as internal reference genes were the same as that of sequencing. The results show that RPS18 and PPIA are stable reference genes, and PPIA + RPS18 are a suitable reference gene combination. This is a reference gene report that combines transcriptome sequencing analysis and only focuses on ESCC, which makes the quantification more precise, systematic, and standardized, and promotes gene regulation research and the early diagnosis of ESCC in the future.

BACKGROUND: N7-methylguanosine (m7G) has been implicated in the development of cancer. The role of m7G-related miRNAs in the survival prediction of UCEC patients has not been investigated. Current research was the first to construct an m7G-related miRNA model to accurately predict the survival of patients with uterine corpus endometrial carcinoma (UCEC) and to explore immune cell infiltration and immune activity in the tumor microenvironment. METHODS: RNA-seq data and clinical information of UCEC patients were derived from The Cancer Genome Atlas (TCGA) database. Using the TargetScan online database, we predicted miRNAs linked to the m7G-related genes and identified miRNAs which were significantly associated with the survival in UCEC patients and constructed a risk scoring model. The TCGA-UCEC cases were scored according to the risk model, and the high- and low-risk groups were divided by the median risk value. Gene enrichment analysis and immune cell infiltration and immune function analysis were performed using "clusterProfiler" and "GSVA" packages in R. RESULTS: The survival prediction model consisted of 9 miRNAs, namely, hsa-miR-1301, hsa-miR-940, hsa-miR-592, hsa-miR-3170, hsa-miR-876, hsa-miR-215, hsa-miR-934, hsa-miR-3920, and hsa-miR-216b. Survival of UCEC patients in the high-risk group was worse than that in the low-risk group (p < 0.001). The receiver operating characteristic (ROC) curve showed that the model had good predictive performance, and the area under the curve was 0.800, 0.690, and 0.705 for 1-, 3-, and 5-year survival predictions, respectively. There were differences in the degree of immune cell infiltration and immune activity between the low-risk and high-risk groups. The expression levels of the identified differentially expressed genes correlated with the susceptibility to multiple anticancer drugs. CONCLUSIONS: The survival prediction model constructed based on 9 m7G-related miRNAs had good predictive performance.

BACKGROUND: Studies have shown high early mortality after initiation of highly active antiretroviral therapy (HAART). We examined change in three-year survival and predictors of mortality of patients initiating HAART in Ethiopia since 2007 to 2019. METHODS: A retrospective cohort study was conducted in 47 health facilities (HFs) using records of 11,013 adult patients initiating HAART from 2007 to 2019. Study subjects were stratified as four different cohorts based on their calendar year of HAART initiation: 2007-2010, 2011-2013, 2014-2016, and 2017-2019. HFs were selected using probability proportional to size of patients. Survival rate and predictors of mortality were estimated by the calendar year using the Kaplan-Meier and Cox proportional hazard, respectively. We generated a pooled estimate of survival rate and predicators of mortality. RESULTS: Data from 1881, 3868, 3004, and 2260 patients were retrieved from each of the cohorts. Overall mortality for all cohorts at all times was 10.3%. A gradual decline of mortality was observed in the first three years of follow-up since 2007-2016 which were 21.37%, 10.03%, and 4.34% among patients who initiated HAART in 2007, 2011, and 2014 respectively. A mortality jump of 9.25% was observed among patents initiating HAART in 2017, which coincided with political instability happened in the country. Of the 21,638 person-years of follow-up among 11,013 adults, mortality was 5.23/100 person-years, while disaggregated by the cohorts, it was 14.77, 5.06, 2.12, and 4.17 per 100 person-years, respectively. Among all the cohorts, patients with CD4 count of ≤200 cells/mm3, unsuppressed viral load, poor adherence, and drug resistance in all cohorts, respectively, have overall 2.0 (95%CI = 1.35 - 2.69), 4.66 (95%CI = 2.53 - 6.72), 6.78 (95%CI = 3.4 - 10.3), and 10.02 (95%CI = 6.91 - 13.82) times of mortality risk than those without. Patients with bedridden for cohort initiating HAART during 2007 and 2011 were 2.0 (95%CI = 1.35 - 2.69) times of mortality risk than those without. CONCLUSION: Patients initiating HAART from 2007 to 2016 have continuously improved their survival during three-year cohort follow-up in Ethiopia. The significant decline of survival among those who initiate HAART as of 2017 calls for program intervention. Low CD4 counts, unsuppressed viral load, poor adherence, and drug resistance could be used as predictors for increased mortality to monitor the quality of HAART and improve clinical management of HIV/AIDS patients.

BACKGROUND: High tibial osteotomy (HTO) is an effective surgery in treating medial compartment knee osteoarthritis (KOA) combined with varus deformity. An accurate orthopaedy is the key and challenge to the success of HTO. Therefore, we designed a calibratable patient-specific instrumentation (PSI) to assist surgery and evaluated its accuracy and clinical outcomes by comparing with conventional operation (CO). MATERIALS AND METHODS: 37 patients (39 knees) with medial compartment KOA were randomly divided into the PSI and CO groups and underwent medial open-wedge high tibial osteotomy (MOWHTO) from September 2020 to May 2021. The postoperative radiological outcomes were compared with the preoperative measurements or target values to evaluate the accuracy of correction in the two groups. The American Knee Society Score (AKSS), complication rate, number of intraoperative radiation exposures, blood loss volume, and operative duration were analysed to evaluate the clinical outcomes in the two groups. RESULTS: The designed target values were better achieved in the PSI group than in the CO group. The mean absolute difference between the postoperative measurements and preoperative targets was significantly lower in the PSI group than in the CO group (weight-bearing line (WBL) ratio, 1.97 ± 1.83% vs.5.42 ± 4.41%, P = 0.002; hip-knee-ankle (HKA) angle, 1.12 ± 0.86° vs. 2.27 ± 1.97°, P = 0.018). The operative duration was significantly shorter (P = 0.014), and the number of radiation exposures (P < 0.001) and volume of intraoperative blood loss (P = 0.003) were significantly lower in the PSI group than in the CO group. The clinical AKSS score at 3 and 6 months postoperatively and the functional AKSS score at 3 months postoperatively were significantly higher in the PSI group than in the CO group (P = 0.042, 0.040, and 0.034, respectively). CONCLUSION: For patients with medial compartment KOA, calibratable PSI can assist the surgeon in MOWHTO with superior accuracy and clinical efficacy. This study was conducted under Randomized Controlled Trial Details (RCT) with Registry Number ChiCTR2000038619.

In this study, the antioxidative activity and polyphenolic content of Syzygium aromaticum's flower bud were compared under different extraction solvents including chloroform, ethyl acetate, methanol, and aqueous. The antioxidant activity was assessed via established in vitro assay models such as 2, 2-diphenyl-1-Picrylhydrazyl (DPPH) radical scavenging assay, NO- radical scavenging assay, H2O2 scavenging assay and Fe3+ reducing capacity. Total phenolic content was measured according to Folin-Ciocalteu's method, and total flavonoid content was estimated by using the aluminum chloride colorimetric method. The results showed that aqueous extract possessed the highest TPC (19.11 ± 2.76 mg GAE/g DW) and TFC (15.32 ± 1.53 mg CtE/g DW). Among the extracts, methanol extract exerted the strongest radical DPPH quenching activity with an IC50 value of 303.56 ± 13.14 μg/mL. The highest NO- radical scavenging activity was shown by methanol extract (IC50192.94 ± 1.9 μg/mL) which is stronger than BHT (IC50247.64 ± 12.89 μg/mL). Methanol extract showed a strong H2O2 scavenging activity (IC50233.71 ± 3.72 μg/mL). The highest Fe3+ reducing capacity was shown by methanol extract (Absorbance = 0.36 ± 0.05). Strong and positive correlations were observed between total phenolic and flavonoid contents and the antioxidant assays. The results of the present work revealed that the tested spice demonstrated high antioxidant activity, total phenolics, and flavonoids. Thus, this spice is worth considering as important source of natural antioxidant agents.

[This retracts the article DOI: 10.1155/2022/5213744.].

[This retracts the article DOI: 10.1155/2022/3650213.].

Coronavirus illness 2019 is a significant worldwide health danger that began with severe acute respiratory syndrome coronavirus two infections. It is the largest pandemic of our lifetime to date, affecting millions of people and crippling economies globally. There is currently no viable therapy for this devastating condition. The fast spread of SARS-CoV-2 underlines the critical need for favorable treatments to prevent SARS-CoV-2 infection and dissemination. Regulating the upstream cytokine release might be a possible method for COVID-19 therapy. We propose that more consideration be paid to the dysregulated IFN-I release in COVID-19 and that cGAS and STING be considered therapeutic targets for avoiding cytokine storms and as critical components in host antiviral defense mechanisms.

Glycosphingolipids (GSLs) play numerous roles in cellular processes, including cell proliferation, apoptosis, inflammation, and cell signaling. Alteration of the GSLs metabolism leads to the accumulation of particular species of GSLs, which can lead to various pathologies, including carcinogenesis and metastasis; in essence, all neoplasms are characterized by the synthesis and aberrant organization of GSLs expressed on the cell surface. Secondary brain tumors make up the majority of intracranial cancers and generally present an unfavorable prognosis. In the present work, a native GSL mixture extracted and purified from a secondary brain tumor with primary pulmonary origin was obtained through extraction and purification and analyzed by MALDI TOF mass spectrometry. Research in the field of lipidomics could offer new data for the understanding of brain tropism and metastatic pathways, by studying the glycolipid molecules involved in the process of metastasis in general and in the production of brain metastases in particular. This could shed new light on the pattern of lipid glycosylation in secondary brain tumors, with a great impact on the effectiveness of cancer therapies, which could be adapted to the specific molecular pattern of the tumor.

ADGRD1 (GPR133), an adhesion G protein-coupled receptor (GPCR), has been linked to cancer. However, the prognostic value and regulatory function within non-small-cell lung cancer (NSCLC) is still unclear. This work adopted various bioinformatics methods, including publicly available databases as well as real-time PCR (RT-PCR), for detecting ADGRD1 expression level and investigating the correlation between ADGRD1 expression level and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), immune infiltrating cells, immune-related genes, and targeted regulation mechanisms in NSCLC. According to the results, ADGRD1 expression decreased within NSCLC, which might be the factor predicting prognosis of NSCLC. Meanwhile, ADGRD1 showed significant correlation with TMB and MSI, respectively, as well as immune cell infiltrating levels in lung adenocarcinoma (LUAD), which were primarily linked to macrophage M1, mast cell resting, T cell CD4 memory activated, and T cell CD4 memory resting and were associated with mast cell activated and mast cell resting in lung squamous cell carcinoma (LUSC). The most promising upstream regulation pathways of ADGRD1 were likely miR-142-5p, miR-93-5p, and miR-17-5p, which were overexpressed and associated with poor prognosis in NSCLC. ADGRD1 and immune-related genes correlated with ADGRD1 were shown to be enriched in "positive regulation of leukocyte activation," "external side of plasma membrane," "receptor ligand activity," and "cytokine-cytokine receptor interaction" pathways. ADGRD1 expression and regulation may be critical in determining NSCLC prognosis.

The protease produced by the transmembrane serine protease 2 (TMPRSS2) gene enhances viral infections and has been linked to severe acute respiratory syndrome coronavirus 2 pathogenesis. Therefore, this study evaluated the association between TMPRSS2 and coronavirus disease 2019 (COVID-19) mortality. TMPRSS2 rs12329760 polymorphism was genotyped using the tetraprimer amplification refractory mutation system-polymerase chain reaction method in 592 dead and 693 improved patients. In the current study, the frequency of TMPRSS2 rs12329760 CC than TT genotypes was significantly lower in improved patients than in dead patients. According to the findings of the multivariate logistic regression test, higher levels of mean age, creatinine, erythrocyte sedimentation rate, C-reactive protein, aspartate aminotransferase, lower levels of 25-hydroxyvitamin D, uric acid, and real-time PCR Ct values and TMPRSS2 rs12329760 CC genotype were observed to be associated with increased COVID-19 mortality rates. In conclusion, the TMPRSS2 rs12329760 CC genotype was a polymorphism linked to a significantly higher incidence of severe COVID-19. Further studies are required to corroborate the obtained findings.

Accurate nuclear instance segmentation and classification in histopathologic images are the foundation of cancer diagnosis and prognosis. Several challenges are restricting the development of accurate simultaneous nuclear instance segmentation and classification. Firstly, the visual appearances of different category nuclei could be similar, making it difficult to distinguish different types of nuclei. Secondly, it is thorny to separate highly clustering nuclear instances. Thirdly, rare current studies have considered the global dependencies among diverse nuclear instances. In this article, we propose a novel deep learning framework named TSHVNet which integrates multiattention modules (i.e., Transformer and SimAM) into the state-of-the-art HoVer-Net for the sake of a more accurate nuclear instance segmentation and classification. Specifically, the Transformer attention module is employed on the trunk of the HoVer-Net to model the long-distance relationships of diverse nuclear instances. The SimAM attention modules are deployed on both the trunk and branches to apply the 3D channel and spatial attention to assign neurons with appropriate weights. Finally, we validate the proposed method on two public datasets: PanNuke and CoNSeP. The comparison results have shown the outstanding performance of the proposed TSHVNet network among the state-of-art methods. Particularly, as compared to the original HoVer-Net, the performance of nuclear instance segmentation evaluated by the PQ index has shown 1.4% and 2.8% increases on the CoNSeP and PanNuke datasets, respectively, and the performance of nuclear classification measured by F1_score has increased by 2.4% and 2.5% on the CoNSeP and PanNuke datasets, respectively. Therefore, the proposed multiattention-based TSHVNet is of great potential in simultaneous nuclear instance segmentation and classification.

Knee osteoarthritis (OA) is a common problem in elderly patients. They are often troubled with altered knee function, such as pain and weakness. However, not all these patients are able to receive autologous platelet-rich plasma (PRP) injections as they may be taking antiplatelet or anticoagulant medications. Their physical condition may not allow them to receive total knee replacement surgery as well. Long-term oral intake of nonsteroidal anti-inflammatory drugs may be detrimental to the gastrointestinal tract. As a result, it is crucial to discover new treatment options that can alleviate painful knee symptoms in elderly knee OA patients. In this study, 19 elderly patients diagnosed with moderate degree of knee OA as well as suprapatellar bursitis were recruited. They received low-level laser therapy (LLLT) to their affected knees. Under ultrasound guidance, flexible fiber optic wire was inserted intra-articularly into the knee joint. Red laser followed by infrared irradiation was performed once every 2 weeks for a total of 3 times. The Lequesne index for knee OA and the volume of suprapatellar synovial fluid (SF) were measured. SF proteomic analyses were also performed up to a period of 6 months. The results revealed that after 3 LLLT, the Lequesne index significantly decreased, signifying improvement in the knee joint functional status. The volume of suprapatellar SF and SF proteins associated with inflammation also decreased significantly in the SF. These findings lasted up to a period of at least 3 months. Therefore, LLLT may be considered as a feasible option in treating elderly patients with knee OA who are not suitable for surgical interventions or intra-articular PRP injections.

BACKGROUND: Whole-body vibration (WBV) is a safe and effective exercise system that affects muscle oxygen through several physiological processes, although its effects on different protocols are still unclear. Unfortunately, the COVID-19 pandemic has generated various health problems and controversy or confusion on its possible adverse consequences and impact on performance when wearing a mask during the practice of physical exercise. AIM: To analyze the acute effects of WBV exercise in muscle oxygen variables during different intervention phases with or without a surgical mask and compare protocols that differ in the order of vibration frequencies. METHODS: Forty-seven healthy students participated in WBV training. They were randomly assigned to use or not use a mask between the three intervention groups: group A (8, 12.6, and 20 Hz), group B (12.6, 20, and 8 Hz), and group C (20, 8, and 12.6 Hz). Besides the 3 WBV moments, the intervention had a baseline moment, two rest time and a recovery moment. During the whole intervention, the heart rate (HR), muscle oxygen saturation (SatO2), oxyhemoglobin (O2Hb), and deoxyhemoglobin (HHb) were registered. RESULTS: There were no significant differences between the mask use and not use groups. Significant differences were found between the variables during the seven intervention moments and between intervention groups (A, B, or C). CONCLUSION: HR, SatO2, and Hb were not influenced by the use of a surgical mask, but they reacted differently through the different moments and were sensitive to vibration frequencies and respective order.

The aim of this work was the screening of bacteriocin-producing LABs isolated from fish, the selection of promising/prominent strain(s), the characterization of the bacteriocin produced, and the evaluation of its potential to be used as biopreservative(s). Amplification and sequencing of the 16S rRNA gene of the bacteriocin-producing strain was performed. Then a partial purification of the produced bacteriocin, using a combination of ammonium sulfate and chloroform-methanol precipitation, was done. Its molecular weight was determined by SDS-PAGE. In addition, the action spectrum, the hemolysis test, and its ability to inhibit biofilm formation were analyzed. A total of 88 isolates of lactic acid bacteria (LAB) including one bacteriocin producer, which was identified as Lactococcus lactis F01, were collected. The bacteriocin was partially purified with an estimated yield of 40%. Regarding the SDS-PAGE profile, the secreted bacteriocin has molecular weight of about 3.5 kDa and was identified as class I bacteriocin. The antimicrobial test showed that the bacteriocin inhibits pathogenic and/or spoilage bacteria, 10 Gram-positive and 16 Gram-negative bacterial species. Moreover, it can inhibit biofilm formation from 1.3% (Escherichia coli) to 63.92% (Pseudomonas aeruginosa ATCC15692) depending on the strain. The hemolytic activity of novel bacteriocin was observed at the concentration of 10 μg/ml of bacteriocin crude extract, which was 0.7 ± 0.0029%. In addition, it exhibited good thermal and pH stability with retained antibacterial activity of 85.25% after treatment at 121°C for 20 min, as well as at a pH range between 2.0 and 10.0. Moreover, this bacteriocin showed the ability to inhibit the growth of bacterial culture load in fish sausage stored at 8°C for 28 days. Considering the results obtained, bacteriocin could be potentially exploited as an alternative to chemical preservatives or as a substitute for antibiotics.

The critical medicine residency training in China started in 2020, but no investigation on the practice of tracheal intubation in ICUs in China has been conducted. A survey was sent to the adult ICUs in public hospitals in Shenzhen (SZ) city and Xinjiang (XJ) province using a WeChat miniprogram to be completed by intensive care physicians. It included questions on training on intubation, intubation procedures, and changes in the use of personal protective equipment due to COVID-19. We analyzed 301 valid questionnaires which were from 72 hospitals. A total of 37% of respondents had completed training in RSI (SZ, 40% vs. XJ, 30%; p = 0.066), and 50% had participated in a course on the emergency front of the neck airway (SZ, 47% vs. XJ, 54%; p = 0.256). Video laryngoscopy was preferred by 75% of respondents. Manual ventilation (56%) and noninvasive positive pressure ventilation (34%) were the first-line options for preoxygenation. For patients with a high risk of aspiration, nasogastric decompression (47%) and cricoid pressure (37%) were administered. Propofol (82%) and midazolam (70%) were the most commonly used induction agents. Only 19% of respondents routinely used neuromuscular blocking agents. For patients with difficult airways, a flexible endoscope was the most commonly used device by 76% of respondents. Most participants (77%) believed that the COVID-19 pandemic had significantly increased their awareness of the need for personal protective equipment during tracheal intubation. Our survey demonstrated that the ICU doctors in these areas lack adequate training in airway management.

Aluminum (Al) is an important factor in the environment as it is used in agriculture and several industries leading to hazardous effects via oxidative stress. Bromelain is a cheap extract from the byproduct waste of Ananas comosus stem. It has been used in several biological and therapeutic applications. So, this study was undertaken to assess the hepatoprotective potential of bromelain versus oxidative stress induced by aluminum chloride in rats. Results revealed that administration of AlCl3 reduced the body and liver weights and increased Al concentration in the blood and liver tissue. Also, AlCl3 caused valuable changes in hematological parameters and increased TBARS and H2O2 concentrations in rat liver. Enzymatic (SOD, CAT, GPx, GR, and GST) and nonenzymatic (GSH) antioxidants and protein content were significantly decreased. Furthermore, alterations in liver biomarkers such as bilirubin level and enzyme activities in both serum and liver homogenate (LDH, ALP, AST, and ALT) were detected. AlCl3 also caused inflammation as indicated by upregulation of the inflammation-related genes [interleukin 1 beta (IL-1β)], tumor necrosis factor-alpha (TNF-α), as well as matrix metalloproteinase (MMP9), and downregulation of nuclear factor erythroid 2 (Nrf2) expression. In addition, histopathological examination showed significant variations in the liver that confirms the biochemical results. Otherwise, bromelain intake alone slumped lipid peroxidation and gotten better antioxidant status significantly. Moreover, supplementation with bromelain before AlCl3 intoxication restores enzymatic and nonenzymatic antioxidants as well as biochemical indices and tissue architecture with respect to the AlCl3 group. In conclusion, bromelain proved its remarkable protective power to abolish AlCl3 toxicity. So, it might represent a new strategy in the therapy of metal toxicity by its antioxidant capacity.

This paper has reviewed the global research on the pandemic critical care research during the COVID-19 from 2020 to 2022. To this end, a bibliometric and cluster analysis by full counting has been carried out using VOSviewer software and bibliographic data extracted from the Scopus database. The research found and studied 2778 documents. The types of research documents were limited to an article (81.46%), a letter (9.43%), an editorial (3.92%), a note (3.92%), a conference paper (0.90), and a short survey (0.04%). The results show an incessant increase in the number of research documents published and citations received during the COVID-19 pandemic. The U.S., U.K., Italy, and France have been shown to be the most productive countries, and there is a predominance of European institutions supporting and fostering research on pandemic critical care. Cecconi, M. (Italy) and Shankar-Hari, M. (U.K.) produced the highest number of research documents. Mapping of citation, co-citation, co-authorship, and keyword cooccurrence highlighted the hotspot, knowledge structure, and important themes. Citation dynamics for the top-cited research documents revealed static discourse. By reviewing the evolutionary trends of pandemic critical care research investigated factors, such as the influential works, main research topics, and the research frontiers, this paper reveals the scientific literature production's main research objectives and directions that could be addressed and explored in future studies. This paper reveals the scientific literature production's main research objectives and directions that could be addressed and explored in future studies after reviewing the evolutionary trends of pandemic critical care research during the COVID-19 and the investigated factors, such as influential works, main research topics, and research frontiers.

OBJECTIVE: This study systematically explored the mechanism of Rhizoma Coptidis-Eupatorium fortunei in treating type 2 diabetes mellitus (T2DM) by using network pharmacology and molecular docking methods. METHODS: The TCMSP database was used to screen out the active ingredients and related targets of Rhizoma Coptidis-Eupatorium fortunei (R-E) drug pair. GeneCards, OMIM, DrugBank, and other databases were used to screen the related targets of T2DM, and then, the UniProt database was used to standardize the relevant targets of T2DM. Then, the Venn analysis was performed on the active ingredient-related targets and disease-related targets of R-E drugs to find the intersection targets. Using the STRING database and Cytoscape software, the PPI network and "drug-active ingredient-target-disease" network are constructed by intersecting targets and corresponding active ingredients. Through the cluster profiler package in the R software, GO function enrichment analysis and KEGG pathway enrichment analysis were carried out on the intersection targets and the screened core targets, and the prediction results were verified by molecular docking. RESULTS: Taking OB ≥ 30% and DL ≥ 0.18 as the standard, a total of 25 effective active ingredients of R-E drug pairs were screened, including berberine, palmatine, coptisine, and so on. After corresponding, 19 effective chemical components and 284 targets of the R-E drug pair were obtained. After searching multiple disease databases, 1289 T2DM-related targets were screened. After the summary, 159 common targets were obtained in this study. Finally, in the bioinformatics analysis, this study concluded that quercetin, luteolin, berberine, palmatine, and coptisine are the main chemical components of the R-E drug pair. ESR1, MAPK1, AKT1, TP53, IL6, and JUN are the important core targets. GO and KEGG enrichment analyses showed that Rhizoma Coptidis-Eupatorium fortunei could improve T2DM by regulating multiple biological processes and pathways. Molecular docking results showed that berberine, palmatine, and coptisine had higher binding to the core target, and MAPK1, AKT1, and IL6 could stably bind to the active ingredients of Rhizoma Coptidis-Eupatorium fortunei. CONCLUSION: Rhizoma Coptidis-Eupatorium fortunei may have therapeutic effects on T2DM such as anti-inflammatory and regulating glucose and lipid metabolism through multiple components, multiple targets, and multiple signaling pathways, which provides a scientific basis for further research on the hypoglycemic effect of Rhizoma Coptidis-Eupatorium fortunei drug pair.

This work was carried out to describe the detailed gross anatomy of the iliolumbar ligaments in human cadavers and to shed more light on these disputes regarding the configuration and direction of these ligaments. Twenty partially dissected human formalin-preserved cadavers originating from North America and Europe were investigated in this study. Blunt dissection was made through the ventral and dorsal aspects of the pelvic area of the cadavers. According to the current study, the anterior and posterior portions of the iliolumbar ligament most frequently attached to the 5th lumbar vertebra's transverse process (70% and 80%, respectively). The body of the 4th lumbar vertebra with the 5th lumbar vertebra' transverse process was the attachment of the anterior part (30%). The attachment of the posterior part was the body of the 5th lumbar vertebra (20%). The anterior and posterior parts of the iliolumbar ligament were inserted into the anterior tip of the iliac crest. There is an obvious variation in the morphological appearance of the iliolumbar ligament distinguished in attachments, length, width, thickness, number of bands, and the presence of accessory bands in the anterior part of the ligament. In addition, a new attachment for the anterior band was revealed in one-third of the specimens (body of the 4th lumbar vertebra) which have not been described before. Also, in one-fifth of the specimens, there was a new attachment for the posterior band (body of the 5th lumbar vertebra).

Yinhua pinggan granule (YHPGKL), a traditional Chinese medical compound, could treat pneumonia. Although previous studies demonstrated the protective and therapeutic effects of YHPGKL on pneumonia, its potential molecular mechanisms and its effective components are still elusive. Herein, we performed a network pharmacology analysis to determine the possible signaling pathways involved in the protective effects of components of YHPGKL. A total of 119 components and 257 target proteins of YHPGKL were identified, among which 117 effective components interacted with 113 proteins related to pneumonia. Then, a compound-effective component-target protein network was established to screen the effective hub components. The top three effective components, namely luteolin, kaempferol, and quercetin, were selected. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of 113 proteins revealed a significant enrichment term associated with host immune and anti-infectious responses. Furthermore, by constructing a protein-protein interaction network between common proteins, ten hub proteins were identified, among which three hub components hit eight proteins. A further molecular docking analysis confirmed that the three effective hub components had a good affinity with six hub proteins. Eventually, the interactions were further visualized and screened on account of an infectious macrophage model in vitro. The results noted that three components could inhibit proinflammatory related hub genes but had no effect on survival-related hub genes. Thus, the three effective hub components and corresponding hub genes may play essential roles in the treatment of YHPGKL on pneumonia.

The present study reports the fish fauna of Gomal Zam Dam at three different sites from October 2018 to July 2019. The total sampled fish belong to 18 species, 15 genera, 5 families, and 4 orders. Fourteen species belong to family Cyprinidae, which was the most abundant, while one species belong to each family Mastacembelidae, Channidae, Siluridae, and Sisoridae. The prominent species were Labeo dyochielus (18.6%), Barilius vagra (16.5%), and Barilius pakistanicus (13.8%), while the rare species were Tor zhobensis, Wallago attu, Hyphophthalmicthys molitrix, Ctenophyrngodon idella, and Bagarius bagarius each one forming (0.1%). Species were rich in spring with ideal temperature, followed by summer, whereas species abundance was high in summer with high temperature and minimum abundance was recorded in autumn. In conclusion, the Gomal Zam Dam is a favorable reservoir for the fish particularly for family Cyprinidae. This present study will provide useful information about the diversity of fish fauna of Gomal Zam Dam that could be used in systematic fisheries management and conservation of the country.

OBJECTIVES: To investigate (i) the interrater and test-retest reliabilities of completion time and number of steps in the Narrow Corridor Walking Test (NCWT); (ii) the minimal detectable changes (MDCs) in NCWT results; (iii) the correlations between NCWT results and stroke-specific outcome measures; and (iv) the optimal cut-off values of NCWT results for discriminating the difference in advanced balance ability between people with stroke and healthy older adults. DESIGN: Cross-sectional. SUBJECTS: Thirty people with stroke and 30 healthy older adults. METHODS: People with stroke completed the NCWT on two separate days with a 7- to 10-day interval. The Fugl-Meyer Assessment (FMA), ankle dorsiflexor and plantarflexor muscle strength, Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and the Chinese version of the Community Integration Measure (CIM) were used to assess. The healthy older adults completed the NCWT once. RESULTS: The NCWT completion time and NCWT steps showed excellent interrater reliability and test-retest reliability and significant correlations with FMA, affected ankle dorsiflexor muscle strength, BBS score, and TUG completion time. A cut-off value of 7.40 s for NCWT completion time and 13.33 for the NCWT steps distinguished people with stroke from healthy older adults. The MDCs of the NCWT completion time and NCWT steps were 6.87 s and 5.50, respectively. CONCLUSION: The NCWT is a reliable clinical measurement tool for the assessment of advanced balance ability in people with stroke.

The aim of the present study was to explore the potential pharmacological mechanism of baicalin by combining network pharmacology prediction and the experimental verification of alopecia. Networks of baicalin-associated targets and alopecia-related genes were constructed using the STRING database. Potential targets and pathways associated with the therapeutic efficacy of baicalin were identified via enrichment analysis using Cytoscape and the database for annotation, visualization and integrated discovery (Metascape). The back hair of C57BL/6J mice was removed with depilatory cream to verify the therapeutic effect of baicalin. Human hair dermal papilla cells (HHDPCs) were used to explore the mechanism of action of baicalin. Network pharmacology analysis revealed that the potential targets of baicalin mainly include protein serine/threonine kinase, Src protein, epidermal growth factor receptor, and insulin-like growth factor 1 (IGF1), which were indicated to mediate neutrophil degranulation and regulation of cell-cell adhesion, vesicle lumen, cytoplasmic vesicle, membrane raft, and endopeptidase activity. Multiple pathways were identified, such as proteoglycans in cancer, PI3K/AKT, and forkhead box O signaling pathways. Following baicalin treatment for the experimental mice, the coverage, length, and weight of the hair increased in a baicalin dose-dependent manner. Moreover, the histological evaluation showed that the number of hair follicles increased after baicalin treatment and melanin formation were pronounced. In addition, baicalin induced an increase in the phosphorylated p-AKT, p-glycogen synthase kinase-3β, p-PI3K, TGF-β1, and vascular endothelial growth factor levels. Furthermore, the activation levels of key protein p-AKT were increased. Baicalin induced the proliferation of HHDPCs in vitro and significantly upregulated p-AKT, IGF1, and alkaline phosphatase. In conclusion, the present study revealed that the pharmacological mechanisms of baicalin in alopecia therapy were associated with the proliferation of DPCs, the activation of the AKT pathway, and the transmission of downstream signals, indicating that baicalin is a potential drug candidate for the clinical treatment of hair loss.

OBJECTIVES: The age discrimination, i.e., ageism, is still a current social problem. Therefore, it is justified to conduct studies increasing the knowledge about this phenomenon. The aim of our research was to determine whether the type of personality, manifested mood, and well-being can influence the attitudes towards the elderly. Material and Methods. During the research, we collected information from 923 participants and we used the following tools: demographic questionnaire, Kogan's Attitudes Toward Old People Scale, Euthymia Scale, WHO-5 Well-Being Index, and the author's questionnaire on contacts with an elderly person. RESULTS: We used R 4.0.2 to analyse the data. In our current model study, we did not observe statistically significant relationships between the WHO-5 or ES scores and the KOAP score. CONCLUSIONS: The conducted study did not show any correlation between mood, sense of well-being, or contact with the elderly and attitude towards the elderly. The results of our study may become the basis for further research to find the relationship between the mood and well-being shown in attitudes towards the elderly. Perhaps, however, the assumption should also be made that there is no such relationship.

The incidence of liver cancer is increasing year by year, and how to effectively diagnose early-stage liver cancer and improve the survival rate of liver cancer patients has become one of the current research topics of concern. Aiming at this problem, it is of great significance for the diagnosis of early liver cancer. With the in-depth research on the diagnosis of early-stage liver cancer, the research on growth differentiation factor 15 is gradually carried out, and its performance advantages are of great significance to solve the problem of detection and diagnosis of early-stage liver cancer. This study can improve the accuracy of early diagnosis of liver cancer. The purpose of this paper is to study the application of data mining in the study of clinical value of growth and differentiation factor 15 detection and diagnosis of early liver cancer. In this paper, the data mining algorithm is analyzed, the performance of the algorithm is experimentally analyzed, and the relevant theoretical formulas are used to explain. The results showed that the expression level of GDF-15 was significant in early primary liver cancer (tumor diameter <2.5 cm). Different from normal liver tissue (P < 0.01), there was a significant difference (P < 0.01) compared with adjacent tissue (P < 0.01). Serum GDF-15 can be used as a tumor marker for predicting early stage liver cancer. The high expression of GDF-15 in early stage liver cancer is an independent risk factor affecting the prognosis of liver cancer patients.

The lack of regulations relating to street food remains a real problem in most developing countries. To remedy this, it is essential to have reliable data on the actors and the conditions of streed food activity. The present study is aimed at (i) establishing the sociodemographic profile of producers and vendors of Gbeli in the municipality of Abomey-Calavi, (ii) developing the technical production diagram and assessing the adoption level of good hygienic practices during the production and sale of Gbeli, and finally, (iv) evaluating the microbiological contamination risks associated with Gbeli consumption. Direct observations followed by a semistructured survey on 92 Gbeli vendors were carried out in Abomey-Calavi municipality. A Gbeli sample was collected from each vendor for microbiological analyses according to standard microbiology analytical techniques. Forty vendors were assisted during Gbeli production. The results showed that the production and sale of Gbeli are activities carried out solely by women (100%), mostly adults (97.82%) and unschooled (58.69%). This trade generates income allowing the vendors to contribute to their household expenses and to save. No major difference was noted in the production process of Gbeli contrary to the sale modes (stationary, itinerant, and mixed). Production process, packaging form, and sale condition of Gbeli present enormous hygienic practice deficiencies. Some corrective measures were thus suggested. About 56% of Gbeli samples analyzed were microbiologically not up to standard. The prevalence and abundance of mycotoxinogenic molds, thermotolerant coliforms, and coagulase-positive Staphylococci in these chips are very worrying. The consumption of Gbeli therefore exposes its consumers to a permanent risk of food poisoning. Training of Gbeli vendors on good hygiene and production practices is indispensable.

BACKGROUND: Wenhua Juanbi Recipe (WJR) is widely used for the treatment of rheumatoid arthritis (RA) in China. However, its mechanism of action remains unclear. This study was designed to investigate the potential therapeutic effects of WJR on the proliferation and apoptosis of synovial fibroblasts in RA and its efficacy in inhibiting miRNA-146a-mediated cellular autophagy. METHODS: A collagen-induced arthritis (CIA) Wistar rat model was established. The model rats were administered WJR or methotrexate (MTX) to assess the therapeutic effect of the drugs. The chemical components of WJR were analyzed using UPLC-Q/TOF-MS. Histological changes; miRNA-146a, ATG5, ATG7, ATG12, Beclin1, LC3II, Bax, and Bcl2 expression; synovial apoptosis; and cellular proliferation were assessed. Primary synovial fibroblasts (FLS) were cultured in vitro using tissue block and transfected with miRNA-146a; an autophagy inducer was added to FLS, inhibiting the PI3K/AKT/mTOR pathway. FLS were cocultured with WJR-containing serum to observe the effects of miRNA-146a-mediated autophagy via the PI3K/AKT/mTOR pathway on CIA-affected rats. RESULTS: Forty and thirty-one compounds were identified in WJR in the positive and negative ion modes, respectively. WJR significantly reduced toe swelling, arthritis scores, and expression of miRNA-146a and autophagy genes (ATG5, ATG7, ATG12, Beclin1, LC32, and Bcl2). Moreover, Bax expression, apoptosis, and attenuated proliferation were observed in rats. WJR could, therefore, regulate autophagy by influencing the miRNA-146a-mediated PI3K/AKT/mTOR pathway, which induces apoptosis and proliferation of FLS. CONCLUSION: WJR can inhibit autophagy, apoptosis, and proliferation in a CIA rat model by inhibiting the miRNA-146a-mediated PI3K/AKT/mTOR pathway.

BACKGROUND: Nanotechnology finds broad applications in the field of nanomedicine, an emerging new field used for diagnosis, treatment, prevention of diseases, and improvement of health. OBJECTIVES: To synthesize silver nanoparticles (AgNPs) from Withania somnifera and Fagonia indica and to carry out their antimicrobial, insecticidal, and phytotoxic activities, a step toward the new range of nanomedicines. METHODS: Silver nanoparticles were synthesized from Withania somnifera and Fagonia indica by chemical reduction method, and further biological activities of these nanoparticles were compared with crude methanolic extract, prepared through cold maceration process, at the concentration of 50 mg/ml. RESULTS: Among all tested bacterial pathogens, crude extract of W. somnifera showed a statistically high significant inhibition zone in millimeter against Pseudomonas aeruginosa (21; p < 0.01). AgNPs showed highly significant result against Streptococcus pneumonia (14; p < 0.01). In comparison with crude extracts, AgNPs showed statistically significant (p < 0.01) results against S. pneumonia (AgNPs, 14; crude, 8.33 mm). Crude extract showed significant inhibition zone against two bacterial strains, P. aeruginosa (crude, 21; AgNPs, 11.67 mm) and Klebsiella pneumoniae (crude, 11.33; AgNPs, 8 mm). Crude extracts of F. indica showed the significant activity against Vibrio cholera (p < 0.01; 11.33 mm). Silver nanoparticles of F. indica exhibited the highest significant activity against Aspergillus flavus and Fusarium oxysporum while AgNPs of W. somnifera were active only against A. flavus. Extracts of W. somnifera and F. indica showed increasing phytotoxic activity with increasing concentrations. The highest significant inhibition was obtained for crude extract (46.7) and AgNPs (45.7) of F. indica at 1000 μg/ml. Insecticidal activity of crude and AgNPs of both plants showed significant inhibition against all tested insects with increasing time intervals, and the highest significant result was obtained at 72 hours with a value of p < 0.01 except T. castaneum. CONCLUSIONS: Both crude and AgNPs showed potent activity; however, in comparison, silver nanoparticles showed slightly enhanced activity. Crude and AgNPs of both plants showed good phytotoxic and insecticidal inhibition. Antimicrobial studies of AgNPs on diseases causing pathogens open a door for new antimicrobial agents and could be the answer to antibiotic resistance after further analysis.

OBJECTIVE: Perianal fistulas of the perianal soft tissues are an important cause of morbidity and a significant portion of colorectal surgery. To our knowledge, there is no study evaluating YouTube videos pertaining perianal fistulas. In this study, we aimed to evaluate YouTube video contents on this topic. METHODS: Whether the videos contained real images, animations or presentations, video duration, number of views, comments and likes, uploading date, and daily view were recorded. Reliability of the videos was assessed using the Quality Criteria for Consumer Health Information (DISCERN) scale and quality of the videos using the Global Quality Score (GQS). RESULTS: A total of 100 YouTube videos regarding perianal fistulas were included in the study. Sixty-four (64%) videos were uploaded by healthcare professionals and 36 (36%) videos by nonprofessionals. The mean video length was calculated as 6.70 ± 8.00 minutes for all videos. The mean DISCERN score of all videos was found as 3.92 ± 0.81 and the mean GQS score as 3.97 ± 0.83. According to the DISCERN score, most videos included (94%) were of good quality. There was an excellent agreement between the two surgeons in terms of the DISCERN and GQS scores. CONCLUSION: Most of the videos included in the study were uploaded by health-care professionals. On the other hand, the majority of the videos contained surgical management of perianal fistulas as it is the definitive treatment. Healthcare related content should be audited and filtered by YouTube with new and effective policies.

The aim of this study was to analyse the cytocompatibility of Surefil One (SuO) with respect to the release of monomers from the material. The following reference materials were chosen: SDR Flow Plus (SDR, Dentsply Sirona, Konstanz, Germany), One Q Bond (Q, Dentalica, Milan, Italy), and Ketac (K, 3M-ESPE, USA). Fifteen dentin discs (2 mm thickness and diameter) were obtained from 15 third molars and were used in this study. After dentin disc permeability measurement, murine fibroblasts were grown, and the pulp surface of the dentinal disc was placed in direct contact with the cells immersed in DMEM. The experimental materials were positioned on the occlusal side of each dentinal disc until a uniform thickness of 2 mm was obtained. Then, the discs were inserted into an artificial pulp chamber for 24 hours to assess the cytocompatibility. Afterwards, the moles of monomers leached from the specimens in DMEM were determined using HPLC. Statistical analysis was performed using ANOVA (p < 0.05). Under the experimental conditions, the toxic effect induced by all tested materials was slight or absent. Diurethane dimethacrylate and acrylic acid were not found in the culture media. It is concluded that all materials have good cytocompatibility consistent with the nondeterminability of the monomers released after polymerization.

Cervical cancer is one of the most common malignancies in women with high morbidity and mortality. Human papillomavirus (HPV) infection is the primary cause of cervical cancer, of which HPV 16 is the predominant. Early detection and effective treatment of cervical precancerous lesions are the key to preventing cervical cancer. Vitamin D receptor (VDR) gene polymorphism is considered to be an important cause of cancer development. Here, we studied the association of VDR polymorphisms (FOKI, BsmI, ApaI, and TaqI) in HPV16-positive cervical intraepithelial neoplasia (CIN)2+ patients. HPV16-positive patients who visited the Colposcopy Clinic of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University for biopsy due to abnormal HPV and/or Thinprep cytologic test (TCT) from September 1, 2020 to October 1, 2021 were grouped by pathological results. The fasting blood samples were collected and VDR polymorphisms were detected using TaqMan fluorescent probes, and the three sites of BsmI-ApaI-TaqI were subjected to haplotype analysis. FOKI ff genotype (OR = 2.01; 95% CI = 1.12 - 3.59; p = 0.019) and f allele (OR = 1.48; 95% CI = 1.10 - 1.98; p = 0.009) were found to be associated with the risk of CIN2+. TaqI Tt genotype (OR = 2.03; 95% CI = 1.20 - 3.43; p = 0.008), tt genotype (OR = 2.09; 95% CI = 1.09 - 4.02; p = 0.028), and t allele (OR = 1.35; 95% CI = 1.01 - 1.80; p = 0.041) were associated with the risk of CIN2+. No haplotype was associated with CIN2+ risk. According to the results, FOKI and TaqI polymorphisms are associated with CIN2+ risk.

With the increase in the number of cardiovascular patients in China, this paper must use better detection methods to examine these patients. Blood lipid testing is a quantitative method for the determination of lipids contained in blood (plasma). Blood lipids are the general term for neutral fats (triglycerides and cholesterol) and lipids (phospholipids, glycolipids, sterols, and steroids) in plasma, which are widely present in the human body. At the same time, this paper also applies this technology to different examination procedures at various current stages. Cardiovascular disease, also known as circulatory system disease, is a series of diseases involving the circulatory system. The circulatory system refers to the organs and tissues that transport blood in the human body, mainly including the heart and blood vessels (arteries, veins, and microvessels), which can be subdivided into acute and chronic and are generally related to arteriosclerosis. In recent years, the most widely used is blood lipid measurement. Therefore, this paper proposes a study on the safety evaluation and effect analysis of blood lipid testing in the diagnosis of cardiovascular disease patients. This article focuses on the causes of cardiovascular disease and introduces the purpose, methods, results, and conclusions of blood lipid detection. Combined with the deep learning method combined with wavelet analysis and support vector machine (SVM), the in-depth analysis is carried out, and suitable patients are selected for blood lipid detection. The final experimental results showed that apolipoprotein B (APOB), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and other indicators were significantly different from the control group. The values of apolipoprotein A1 (APOA1) and high-density lipoprotein cholesterol (HDL-C) were significantly different from those in the control group, P < 0.05. This shows that blood lipid examination has a good effect on the diagnosis of cardiovascular patients; it can make accurate diagnosis and prediction of the patient's condition and has good clinical application value.

Millettia speciosa is a plant extensively used as an important component in Chinese herbal medicine and food-based medicines. The present study was carried out to determine the total flavonoid content (TFC), volatile phytoconstituents, and pharmacological activities, i.e., antityrosinase, sunscreen, and anticancer activity, of different fractions of M. speciosa stem. Different organic solvents of increasing polarity, i.e., petroleum ether (PE), ethyl acetate (EtOAc), and methanol (MeOH), were used for extraction. The highest total flavonoid content, i.e., 48.30 ± 0.90%, was reported for PE extract. Various important phytocomponents were revealed by gas chromatography-mass spectroscopy (GC-MS) analysis. Based on abundance, the major compounds were n-hexadecanoic acid (16.654%), n-hexadecanoic acid (14.808%), and beta-sitosterol (6.298%) for PE, EtOAc, and MeOH extract, respectively. The significant antityrosinase activity, i.e., 70.97 ± 0.66%, with an IC50 value of 4.58 mg/mL was noted for PE extract followed by EtOAc extract, i.e., 59.84 ± 0.67%, with IC50 value of 6.10 mg/mL. The maximum sunscreen activity was reported for PE extract exhibiting the maximum absorbance value (0.633 ± 0.06) in the ultraviolet (UV) region, i.e., UVC, while EtOAc extract showed the second highest level of absorbance in the UVB range, i.e., 0.632 ± 0.07. The strongest anticancer activity (49.73 ± 0.49% cell viability) towards MCF-7 breast cancer cell line was reported for PE extract with IC50 197.51 μg/mL. Our results confirmed the presence of potential therapeutic components for each extract with significant biological functions, showing the importance of the M. speciosa stem as a source of biomedicine. To our knowledge, this is the first report on M. speciosa stem extending comprehensive research about its phytochemical profile and various significant pharmacological activities.

BACKGROUND: The association of genetic and dietary factors with occurrence and progression of chronic diseases such as metabolic syndrome (MetS) has long been addressed but there is a lack of evidence for complex interrelationships, including direct and indirect effects of these variables. Hence, this study is aimed at evaluating the mediating role of glycemic indices in the association of melanocortin-4 receptor (MC4R) rs17782313 polymorphism, sociodemographic, and psychological factors with the risk of MetS in obese adults using structural equation modeling. METHODS: We performed a cross-sectional analysis of data from 287 apparently healthy adults. Dietary glycemic index (GI) and glycemic load (GL) were calculated from a validated 147-item food frequency questionnaire (FFQ). MC4R s17782313 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Structural equation modeling was used to explore direct and indirect effects of genetic and nongenetic factors on MetS. RESULTS: MC4R gene variant was directly associated with the risk of MetS (B = 0.010; P = 0.023). On the other hand, this variant was found to be indirectly and positively associated with LDL-C (B = 6.589; P = 0.042) through mediatory effects of GI and GL. Moreover, GI and GL also mediated indirect positive effects of sex and age on LDL-C (B = 3.970; P ≤ 0.01; B = 0.878; P ≤ 0.01, respectively) and HDL (B = 2.203; P ≤ 0.01; B = 0.129; P ≤ 0.01, respectively). MC4R rs17782313 polymorphism had positive effects on GI (B = 1.577; P ≤ 0.01) and GL (B = 1.235; P ≤ 0.01). CONCLUSION: Our data may state a hypothesis of the mediating effect of quantity and quality of carbohydrates consumed in relationship between genetic susceptibility to obesity and cardiometabolic risk factors. Further analyses should be carried out in high-quality cohort studies in order to confirm the findings.

With the development of human genome sequencing and techniques such as intestinal microbial culture and fecal microbial transplantation, newly discovered microorganisms have been isolated, cultured, and researched. Consequently, many beneficial probiotics have emerged as next-generation probiotics (NGPs). Currently, "safety," "individualized treatment," and "internal interaction within the flora" are requirements of a potential NGPs. Furthermore, in the complex ecosystem of humans and microbes, it is challenging to identify the relationship between specific strains, specific flora, and hosts to warrant a therapeutic intervention in case of a disease. Thus, this review focuses on the progress made in NGPs and human health research by elucidating the limitations of traditional probiotics; summarizing the functions and strengths of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, Eubacterium hallii, and Roseburia spp. as NGPs; and determining the role of their intervention in treatment of certain diseases. Finally, we aim to provide a reference for developing new probiotics in the future.

In recent years, 2 major discoveries have modified the traditional understanding of the brain. First, meningeal lymphatic vessels (MLV) were found in the dural sinus, which may absorb and drain cerebrospinal fluid (CSF). Second, the glymphatic system was discovered, composed of para-arterial CSF influx channel, paravenous interstitial fluid (ISF) efflux channel, and the water channel aquaporin-4 (AQP4) in astrocytes connecting the 2 channels. Accumulating evidence demonstrates that the lymphatic system of the brain plays a vital role within the circulation of CSF and, therefore, in the removal of metabolites. Therefore, it is involved in the incidence and development of some central nervous system (CNS) diseases. The optic nerve and retina are the extension of the CNS in the orbit. Whether they have a lymphatic system and how they clear the metabolites of the optic nerve and retina are still unclear. Recent studies have found that the ocular lymphatic system has a crucial impact on bounding eye diseases, like disorders of the optic nerve and retina. Therefore, here we review the recent research progress concerning the structure and function of MLV and glymphatic system. We also discuss the biomarkers for identification of lymphatic vessels, the composition of ocular lymphatic systems, and the possible association with diseases.

Acute hemorrhagic leukoencephalitis (AHLE), also called Hurst disease, is a rare demyelinating disease of the central nervous system (CNS) marked by rapid progression and acute inflammation of the white matter. Due to the correlation in their suspected postinfectious autoimmune pathogenesis, it is regarded as the most severe form of acute disseminated encephalomyelitis (ADEM). Because this clinical scenario has a high mortality rate, aggressive and immediate treatment is required. Although the exact cause of AHLE is unknown, it usually occurs after a bacterial or viral infection, or, less frequently, after a measles or rabies vaccination. AHLE has been reported in patients with coronavirus disease 2019 (COVID-19) as a rare but serious neurological complication. However, due to the lack of evidence-based diagnostic criteria, diagnosis is difficult. The small number of cases described in the literature, which most likely reflects underreporting and/or low incidence, necessitates greater public awareness. Increased clinical suspicion and early imaging identification of this entity may allow clinicians to pursue more aggressive treatment options, potentially reducing fatal outcomes. This study focuses on symptoms and causes of AHLE, difference between AHLE and ADME, diagnosis and treatment of AHLE, and its link with COVID-19.

A topological index is a real number derived from the structure of a chemical graph. It is helpful to determine the physicochemical and biological properties of a wide range of drugs, and it better reflects the theoretical properties of organic compounds. This is accomplished using degree-based topological indices. Vitiligo is a common, acquired skin pigmentation disorder that significantly impacts the quality of life. It frequently embodies a therapeutic challenge, resulting in interest in alternative treatments based on vitamin and herbal supplements. In this article, azathioprine, clobetasol, desonide, hydrocortisone valerate, and other drugs utilized to cure vitiligo have discoursed, and the goal of QSPR revision is to determine the mathematical relationship between properties under investigation (e.g., polarity and enthalpy) and diverse descriptors associated with the drugs' molecule. The QSPR model will help to predict physical properties. In this study, topological indices (TIs) imposed on said drugs were found to have a good correlation with physicochemical properties in this course. Finally, this work can be helpful to design and synthesize new vitiligo treatments and other disease drugs.

Idiopathic generalized epilepsy (IGE) is the most prevalent type of epilepsy with genetic origin. Mutations in ion channel genes have been identified as a common cause of IGE. Several studies have reported various epilepsy risk variants of GABRG2 (gamma-aminobutyric acid type A receptor subunit gamma2 subunit) gene in different ethnic groups, but the results are inconsistent. The purpose of this case-control research is to determine if GABRG2 polymorphisms contribute to IGE susceptibility and antiepileptic drug resistance in Pakistani population. For this purpose, we genotyped exon2, exon5 (C540T and C588T), exon7 (T813C), exon8 (K289M), and exon9 of GABRG2 gene by restriction fragment length polymorphism and Sanger's sequencing in 87 drug-responsive idiopathic generalized epilepsy patients, 55 drug-resistant epilepsy patients, and 83 healthy controls. Restriction fragment length polymorphism (RFLP) and sequencing results indicated only C588T polymorphism in the studied subjects. The comparison of genotypic and allelic frequencies showed significant differences between IGE patients and control groups (P = 0.008 and odds ratio = 4.2) and nonsignificant association of C588T polymorphism in antiseizure medication-resistant patients (P = 0.9). Our findings showed that C588T polymorphism of GABRG2 is a risk variant for IGE in Pakistani population. Further studies are required to validate the results.

BACKGROUND: Plantar warts are a common cutaneous disease of the sole of the foot caused by human papillomavirus. Photodynamic therapy has gained increasing attention in the treatment of plantar warts. OBJECTIVE: To investigate the effect of photodynamic therapy combined with transfer factor capsules in the treatment of multiple plantar warts. METHODS: Sixty-one patients with multiple plantar warts who visited our outpatient department from September 2017 to August 2019 were randomly divided into two groups. Twenty-three patients received photodynamic therapy (treatment group) and thirty-eight received cryotherapy (control group). Both groups also received immune modulator transfer factor capsules. Skin lesion score, numeric rating scale- (NRS-) 10 score, recurrence rate, adverse reactions, and Dermatology Life Quality Index (DLQI) were analyzed in both groups. RESULTS: The mean skin lesion score improved from 13.39 ± 3.88 before treatment to 1.48 ± 2.50 after the last treatment in the treatment group and from 12.47 ± 2.99 before treatment to 4.47 ± 3.67 after the last treatment in the control group. The success rate after 3 months of treatment was 86.96% in the treatment group and 39.47% in the control group. After 3 months of follow-up, the recurrence rate was significantly lower in the treatment group (20%) than in the control group (53.33%). The mean DLQI score at three months after treatment was significantly lower in the treatment group (3.61 ± 1.16) than in the control group (6.31 ± 2.59). CONCLUSION: Photodynamic therapy combined with immunomodulators significantly increased the cure rate and reduced the recurrence rate of multiple plantar warts compared with traditional cryotherapy combined with immunomodulators.

Skin cancer is one of leading cancers globally, divided into two major categories including melanoma and nonmelanoma. Skin cancer is a global concern with an increasing trend, hence novel therapies are essential. The local treatment strategies play a key role in skin cancer therapy. Nanoparticles (NPs) exert potential applications in medicine with huge advantages and have the ability to overcome common chemotherapy problems. Recently, NPs have been used in nanomedicine as promising drug delivery systems. They can enhance the solubility of poorly water-soluble drugs, improve pharmacokinetic properties, modify bioavailability, and reduce drug metabolism. The high-efficient, nontoxic, low-cost, and specific cancer therapy is a promising goal, which can be achieved by the development of nanotechnology. Metallic NPs (MNPs) can act as important platforms. MNPs development seeks to enhance the therapeutic efficiency of medicines through site specificity, prevention of multidrug resistance, and effective delivery of therapeutic factors. MNPs are used as potential arms in the case of cancer recognition, such as Magnetic Resonance Imaging (MRI) and colloidal mediators for magnetic hyperthermia of cancer. The applications of MNPs in the cancer treatment studies are mostly due to their potential to carry a large dose of drug, resulting in a high concentration of anticancer drugs at the target site. Therefore, off-target toxicity and suffering side effects caused by high concentration of the drug in other parts of the body are avoided. MNPs have been applied as drug carriers for the of improvement of skin cancer treatment and drug delivery. The development of MNPs improves the results of many cancer treatments. Different types of NPs, such as inorganic and organic NPs have been investigated in vitro and in vivo for the skin cancer therapy. MNPs advantages mostly include biodegradability, electrostatic charge, good biocompatibility, high drug payload, and low toxicity. However, the use of controlled-release systems stimulated by electromagnetic waves, temperature, pH, and light improves the accumulation in tumor tissues and improves therapeutic outcomes. This study (2019-2022) is aimed at reviewing applications of MNPs in the skin cancer therapy.

Ischemic stroke is a cerebrovascular disease with a high morbidity and mortality rate, which poses a serious challenge to human health and life. Meanwhile, the management of ischemic stroke remains highly dependent on manual visual analysis of noncontrast computed tomography (CT) or magnetic resonance imaging (MRI). However, artifacts and noise of the equipment as well as the radiologist experience play a significant role on diagnostic accuracy. To overcome these defects, the number of computer-aided diagnostic (CAD) methods for ischemic stroke is increasing substantially during the past decade. Particularly, deep learning models with massive data learning capabilities are recognized as powerful auxiliary tools for the acute intervention and guiding prognosis of ischemic stroke. To select appropriate interventions, facilitate clinical practice, and improve the clinical outcomes of patients, this review firstly surveys the current state-of-the-art deep learning technology. Then, we summarized the major applications in acute ischemic stroke imaging, particularly in exploring the potential function of stroke diagnosis and multimodal prognostication. Finally, we sketched out the current problems and prospects.

A simple process based on the dual roles of both magnesium oxide (MgO) and iron oxide (FeO) with boron (B) as precursors and catalysts has been developed for the synthesis of borate composites of magnesium and iron (Mg2B2O5-Fe3BO6) at 1200°C. The as-synthesized composites can be a single material with the improved and collective properties of both iron borates (Fe3BO6) and magnesium borates (Mg2B2O5). At higher temperatures, the synthesized Mg2B2O5-Fe3BO6 composite is found thermally more stable than the single borates of both magnesium and iron. Similarly, the synthesized composites are found to prevent the growth of both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) pathogenic bacteria on all the tested concentrations. Moreover, the inhibitory effect of the synthesized composite increases with an increase in concentration and is more pronounced against S. aureus as compared to E. coli.

BACKGROUND: Roxadustat is a newly listed oral hypoxia-inducible factor-proline enhancing enzyme inhibitor (HIF-PHI) in recent years. There have been some studies that have proved the efficacy of roxadustat on the treatment of renal anemia in patients with chronic kidney disease (CKD), but there are still different conclusions on its safety. METHODS: PubMed, Embase, Cochrane, and ClinicalTrials were searched for randomized controlled trials (RCTs) that assess efficacy and safety of roxadustat treatment for anemia in CKD patients. The Cochrane Literature Quality Evaluation Scale was used to evaluate the quality of included literature. We choose fixed-effects model or random effects model for data processing based on heterogeneity. It was considered statistically significant when p value <0.05. RESULTS: A total of 842 articles were retrieved, and 16 trials in the 15 articles were finally included. Roxadustat treatment significantly increased Hb levels. Iron (SMD 1.43, 95% CI 0.31 to 2.55), total iron-binding capacity (SMD 2.06, 95% CI 0.91 to 3.22), ferritin (WMD 21.33, 95% CI 3.04 to 39.62), transferrin saturation (SMD 4.17, 95% CI 3.90 to 4.45), and LDL-cholesterol (SMD -0.64, 95% CI -0.73 to -0.55) showed statistical significance in dialysis-dependent (DD) study. And hepcidin (SMD -1.56, 95% CI -2.63 to -0.50), transferrin (SMD 1.80, 95% CI 1.53 to 2.06), total iron-binding capacity (SMD 1.62, 95% CI 1.39 to 1.86), total cholesterol (SMD -0.88, 95% CI -1.68 to -0.09), ferritin (WMD -52.68, 95% CI -62.68 to -42.67), transferrin saturation (SMD -5.57, 95% CI -7.47 to -3.68), and LDL-cholesterol (SMD -0.85, 95% CI -1.37 to -0.34) showed statistical significance in not dialysis-dependent (NDD) study. In terms of safety, roxadustat treatment did not increase risk of total adverse events either in dialysis-dependent or not dialysis-dependent patients. CONCLUSION: Roxadustat can effectively improve anemia in patients with chronic kidney disease. There was no significant difference in total adverse events compared with the control group.

We aimed to determine prognostic factors and develop an effective and practical nomogram for predicting cancer-specific survival in gastrointestinal stromal tumor (GIST) patients. Postoperative data were obtained from the SEER database (2000-2018). Patients were divided into training and validation cohorts at random (7 : 3). Prognostic factors were screened, and a prognostic nomogram was established using log-rank testing and Cox regression. We used DCA, ROC curves, C-index, and calibration curves to evaluate our model's predictive performance. The clinical value of the nomogram and the modified National Institute of Health (M-NIH) classification were compared using the NRI and IDI. The Kaplan-Meier method was applied to examine survival by risk group, and log-rank tests were applied to compare variations in survival curves. Independent prognostic risk factors associated with cancer-specific survival on multivariate Cox proportional hazards regression analysis were age, race, and tumor location, size, grade, and stage. Clinically relevant variables need to be considered in addition to statistically significant variables when developing prognostic models to aid clinical decision-making. We included two additional variables (mitotic rate and chemotherapy) when constructing the prognostic model. The C-index was 0.766 (95% confidence interval (CI): 0.737-0.794) in the training cohort and 0.795 (95% CI: 0.754-0.836) in the internal validation group suggesting robustness. The areas under the ROC curve for three-year and five-year survival were >0.700, indicating satisfactory discrimination. The calibration curves showed good agreement between the predictions of the nomogram and the actual results. The NRI (0.346 for 3-year and 0.265 for 5-year cancer-specific survival for patients with GIST (GSS) prediction; validation cohort: 0.356 for 3-year and 0.246 for 5-year GSS prediction) and IDI values (0.047 for 3-year and 0.060 for 5-year GSS prediction; validation cohort: 0.071 for 3-year and 0.084 for 5-year GSS prediction) suggested that the established nomogram performed significantly better than the M-NIH classification. The DCA indicated that the nomogram was clinically useful and had a high discriminative ability in identifying patients who were at high risk of poor outcomes. According to nomogram findings, patients were divided into three groups (high, moderate, and low risk), with significantly different prognoses in both cohorts. Our nomogram satisfactorily predicted survival in postsurgical GIST patients, which may assist clinicians to evaluate the postoperative status and guide subsequent treatments.

OBJECTIVE: To evaluate different concentrations of solvents (tetrahydrofuran (THF) and dimethyl sulfoxide (DMSO) and monomers on the degree of conversion, microtensile bond strength, and mechanical properties of experimental resin infiltrants. MATERIALS AND METHODS: Resin infiltrants were formulated and divided into eleven groups: (1) Icon, (2) 75% TEGDMA (T) +25% UDMA (U), (3) T +25% BIS-EMA (B), (4) T + U +0.5%DMSO, (5) T + U +5% DMSO, (6) T + U +0.5% THF, (7) T + U +5% THF, (8) T + B +0.5% DMSO, (9) T + B +5% DMSO, (10) T + B +0.5% THF, and (11) T + B +5% THF. One hundred and ten bovine mandibular incisors were sectioned, treated, and destined to the degree of conversion, tensile cohesive strength, microtensile bond strength, flexural strength, and elastic modulus. Data were submitted to one-way ANOVA and Tukey's test (α = 0.05). RESULTS: The degree of conversion was lowest for T + B +5%THF (41.9%) and highest for T + U +5%THF (62.1%). In flexural strength and E-modulus, the T + B (96.5 MPa and 0.49 GPa) obtained the highest values and the lowest for T + U +5% DMSO (18.5 MPa and 9.7 GPa). Icon showed the highest bond strength (19.3 MPa) and cohesive strength (62.2 MPa), while T + U +5%DMSO (9.7 MPa) and T + B +5% DMSO (9.8 MPa) the lowest values and T + B +0.5% DMSO (12.3 MPa) the lowest cohesive strength. CONCLUSIONS: The addition of lower concentrations of DMSO or THF (0.5%) did not impair bond strength or significantly affect monomer conversion, but reduced the mechanical properties of resin infiltration.

Electroacupuncture (EA) combines traditional Chinese medicine acupuncture theory with modern scientific technology. It is a promising therapy for the treatment of cerebrovascular diseases such as cerebral infarction. A large number of clinical studies have shown that EA promotes recovery of neurological function after cerebral infarction, however, the underlying mechanisms behind its effects remain unclear. We tested whether EA stimulation of the Zusanli (ST36) and Neiguan (PC6) acupoints activates neuroplasticity in rats with ischemic stroke and whether this involves the regulation of axonal regeneration through the mTOR pathway. 24 h after permanent middle cerebral artery occlusion (p-MCAO) in rats, EA treatment was started for 20 min, daily, for 14 days. We found that EA significantly reduced Modified Neurological Severity Scores (mNSS), cerebral infarct volume, and apoptosis of neuronal cells. EA also significantly increased the expression of the neuroplasticity-associated proteins GAP-43 and SYN and upregulated the phosphorylation levels of AKT, mTOR, S6, and PTEN to promote CST axon sprouting in the spinal cord at C1-C4 levels. The positive effects of EA were blocked by the administration of the mTOR inhibitor Rapamycin. In short, we found that EA of the Zusanli (ST36) and Neiguan (PC6) acupoints in p-MCAO rats induced neuroprotective and neuroplastic effects by regulating the mTOR signaling pathway. It promoted neuroplasticity activated by axon regeneration in the contralateral cortex and corticospinal tract. Activation of such endogenous remodeling is conducive to neurological recovery and may help explain the positive clinical effects seen in patients with infarcts.

The artemisinin partial resistance is believed to be spread to artemisinin-based combination therapy partner drugs. As a result, new antiplasmodial compounds are required to treat resistant malaria infections. In the invention of antimalarial substances, claimed medical plants are precious resources. So, the current study was designed to assess the antiplasmodial effects of Maesa lanceolata in mice. In this study, preliminary phytoconstituent and in vivo acute oral toxicity tests were done. Early infection, established infection, and residual infection tests were employed to determine the antimalarial effects of the test drugs. Three doses (200, 400, and 600 mg/kg) of the extracts were provided orally to the test mice. Analysis of variance (one-way) followed by post hoc Tukey's test was used to analyze the difference between and within groups. Terpenoids, tannins, saponins, flavonoids, and alkaloids were detected in the phytochemical constituent analysis. Both 80% methanolic crude extract and solvent fractions had no toxic result at the 2000 mg/kg dose. All test drug doses suppressed parasite levels in a significant manner at all tests. The activity of chloroform fraction (maximum percentage suppression, 81.28%) overwhelms the crude extract activity. The curative effects of 80% methanolic crude extract, with a maximum of 80.22% parasitemia suppression, were greater than its suppressive and prophylactic effects. The 400 mg/kg dose of chloroform fraction resulted in a maximum survival period (18 days) than other doses of tested materials. The results of this investigation provide support for the activity of M. lanceolata leaf extract against malaria.

Objectives. Preparation of a multifunctional drug-loaded phase-change nanoparticle (NP), pirfenidone perfluoropentane liposome NPs (PPL NPs), and combined with low-intensity focused ultrasound (LIFU) to influence epithelial mesenchymal transition (EMT) for hepatocellular carcinoma (HCC) by inhibiting the activity of activated Hepatic Stellate Cells (a-HSCs). Methods. PPL NPs were prepared by the thin film dispersion method. The appearance, particle size, zeta potential, encapsulation efficiency, drug loading rate, drug release in vitro, and stability of PPL NPs were tested. The role of a-HSCs in HCC metastasis was studied by CCK-8, colony formation assay, apoptosis, cellular uptake assay, wound healing assay, and Transwell assay. Western blot was used to detect the related protein expression levels. In vitro and vivo, the acoustic droplet vaporization (ADV) of PPL NPs was tested at different times and LIFU intensities. Biosafety of the PPL NPs was assessed by measuring nude mouse body weight and hematoxylin and eosin (H&E) staining. Results. The results showed that the PPL NPs had good biosafety, with an average particle size of 346.6 ± 62.21 nm and an average zeta potential of -15.23 mV. When the LIFU power is 2.4 W/cm2, it can improve the permeability of cells, further promote the uptake of drugs by cells, and improve the toxicity of drugs. In vitro experiments showed that PPL NPs could inhibit the proliferation of a-HSCs cells, thereby affecting the metastasis of HCC, and were related to the TGFβ-Smad2/3-Snail signaling pathway. Both in vivo and in vitro PPL NPs enhanced ultrasound imaging by LIFU-triggered ADV. Conclusion. The PPL NPs designed and prepared in this study combined with LIFU irradiation could significantly alter the EMT of HCC by inhibiting LX2. Clinically, PPL NPs will also be considered a promising contrast agent due to their ultrasound imaging capabilities.

OBJECTIVE: To establish better diagnosis thinking and provide advanced understanding of MSK, the CT imaging features, clinical characteristics, and the expression of suspected genes in the kidney spatiotemporal immune zonation and fetal renal development were investigated. METHODS: 17 patients with MSK hospitalized in our hospital were selected as our research subjects. Human Phenotype Ontology, MalaCards: The Human Disease Database, GeneCards: The Human Gene Database, Human Protein Atlas, and Single Cell Expression Atlas were used to analyze this disease. RESULTS: In our 17 patients, the incidence of MSK tended to be the same in male and female, and the onset age of MSK was probably 31-50 years old. The top one related disease of MSK was nephrocalcinosis and the most frequent phenotype related to MSK was nephrolithiasis. In addition, the expression of HNF1B, CLCN5, GDNF, ATP6V0A4, ATP6V1B1, LAMA2, RET, ACAN, and ABCC8 has been implicated in both human kidney immune zonation and fetal kidney development. CONCLUSIONS: HNF1B, CLCN5, GDNF, ATP6V0A4, ATP6V1B1, LAMA2, RET, ACAN, and ABCC8 could be independent indicators for the diagnosis and preventive intervention of MSK patients, and abnormal kidney development due to mutations in key genes was the underlying cause of MSK.

Rhizome-rooted Medicago sativa L. "Qingshui" is an excellent germplasm for establishing grazing and ecological grasslands but inferior in yield, in which both high production and ecological values can be achieved by cross-breeding. We have obtained valuable rhizome-rooted hybrid strains (RSA-01, RSA-02, and RSA-03) by crossing of Qingshui and the high-yielding Medicago sativa L. "WL168." In this study, the Qingshui plants with low production performance were crossed for improvement, and progenies with better production and higher quality than those of Qingshui were selected. The results reveal that the branch number, crude protein (CP) content, and relative feed value (RFV) of RSA-01; the stem thickness, CP content, and ether extract (EE) content of RSA-02; and the plant height, stem thickness, branch number, and dry hay yield of RSA-03 were higher than those of Qingshui. Except for the leaf/stem ratio and plant height of RSA-01, leaf/stem ratio of RSA-02, and plant height of RSA-03, the coefficient of variation (CV) of yield traits of the hybrid strains was lower than those of Qingshui, ranging from 0.1% to 4.28%. In addition to the lignin and acid detergent fiber content of RSA-01 as well as EE content of RSA-02 and RSA-03, the CV of the nutritional traits of the hybrid strains was low, ranging from 0.60% to 3.43%. The tested samples were ranked as follows based on yield performance and nutritional values: WL168 > RSA - 03 > RSA - 01 > RSA - 02 > Qingshui and RSA - 01 > WL168 > RSA - 03 > Qingshui > RSA - 02, respectively. Compared with parental Qingshui, RSA-01, RSA-02, and RSA-03 show better yield performance; meanwhile, RSA-01 and RSA-03 had higher nutritional traits. RSA-01 shows heterosis in branch number, CP content, and RFV; RSA-02 shows heterosis in stem thickness and RSA-03 in plant height, stem thickness, branch number, fresh yield, dry hay yield, and CP content. Notably, the low production performance of Qingshui was improved after crossing it with WL168, substantially resulting in an abundant rhizome-rooted germplasm resource for the establishment of grazing grasslands.

Enterococcus faecalis is a Gram-positive bacterium that is normally found in the gastrointestinal tract of humans and animals. E. faecalis is an opportunistic pathogen that causes a number of invasive and noninvasive infections. The emergence of multidrug resistance and biofilm formation by the bacterium have rendered the treatment of E. faecalis infections very difficult. Due its high rate of resistance and biofilm formation, there are very few options of treatment. Therefore, the current study was designed to evaluate the antibacterial and biofilm activities of juglone derivatives such as 2-methoxy-6-acetyl-7-methyljuglone and 2-ethoxy-6-acetyl-7-methyljuglone against multidrug-resistant (MDR) and biofilm-producing strains of E. faecalis. Agar well diffusion and broth microdilution methods were used to determine the antibacterial activities. Biofilm attachment and preformed biofilm inhibition were determined using crystal violet staining assay. Both juglone derivatives displayed promising antibacterial and antibiofilm activities against E. faecalis. Among these compounds, 2-ethoxy-6-acetyl-7-methyljuglone possessed better inhibitory activity with minimum inhibitory concentration (MIC) of 9.7 ± 3 μM as compared to 2-methoxy-6-acetyl-7-methyljuglone (MIC, 19.5 ± 2 μM). Additionally, 2-ethoxy-6-acetyl-7-methyljuglone also showed stronger antibiofilm activity than 2-methoxy-6-acetyl-7-methyljuglone. Furthermore, both the ligand molecules were docked into the binding site of the enterococcal surface protein, and the results revealed that both the molecules are actively binding in the target site. Based on these findings, juglone derivatives may be considered useful for the treatment of E. faecalis infections; however, further studies are required to elucidate the mechanism of action.

BACKGROUND: In the last years, mesenchymal stem cells (MSCs) have been considered as a useful strategy to treat many diseases such as traumatic brain injury (TBI). The production of inflammatory agents by TBI elicits an inflammatory response directed to other systems of body, such as the heart and the kidneys. In this study, the efficacy of oral mucosal mesenchymal stem cells (OMSCs) prescription after TBI in inflammation and oxidative stress of the heart and kidneys was evaluated. METHODS: Twenty-four male rats were located in groups as follows: sham, TBI, vehicle (Veh), and stem cell (SC). OMSCs were injected intravenously 1 and 24 hours after TBI. Inflammatory, oxidative stress, and histopathological outcomes of the heart and kidney tissues were investigated 48 hours after TBI. RESULTS: TBI caused an increase in the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), malondialdehyde (MDA), and carbonyl protein (PC) of the heart and kidney compared to the sham group. Superoxide dismutase (SOD), total antioxidant capacity (TAC), catalase (CAT), and interleukin-10 (IL-10) of the heart and kidney decreased after TBI. The use of OMSCs after TBI reduced the changes of these factors in both the heart and the kidney. CONCLUSION: Application of OMSCs after TBI can decrease inflammation and oxidative stress of the heart and kidney tissues leading to the reduction of damage. Therefore, this method can be evaluated in the TBI patients in future studies.