WTAP-mediated abnormal m6A modification promotes cancer progression by remodeling the tumor microenvironment: bibliometric and database analyses.

Background: Wilms' tumor 1 associated protein (WTAP) is an essential component of the m6A methyltransferase complex. The research on WTAP has been continuously developed and promoted in recent years. It is needed to make systematic specific bibliometric and database analyses on WTAP, to identify the cooperation and impact of authors, countries, institutions and journals, to evaluate the knowledge base and find the hotspot trends, and to detect the emerging topics regarding WTAP research. Methods: The related articles and reviews of WTAP in the Web of Science Core Collection from January 1999 to June 2022 were retrieved, and CiteSpace and VOSviewer were used to perform bibliometric and knowledge-map analyses. Multiple databases were used to explore the expression level of WTAP in pan-cancers and its correlation with prognosis and immune infiltration. Results: In recent years, the number of publications on WTAP research has increased rapidly. Among the journals publishing WTAP research, Frontiers in Cell and Developmental Biology had the most papers, while Nature papers were most cited. The country with the highest number of publications on WTAP was China, and China Medical University was the institution with the most publications. The most prominent author was Haruo Sugiyama from Japan. Four main aspects of WTAP research included m6A modification, tumor association, cancer therapy, and regulatory mechanisms. The research frontiers and hotspots were m6A modification, methyltransferase, demethylation, tumor microenvironment (TME), and immunotherapy. Bioinformatics analysis showed that the expression of WTAP was up-regulated in a variety of tumors and closely related to TME and survival prognosis. Conclusions: From the bibliometric and database analyses on the researches on WTAP, it is suggested that up-regulated WTAP in cancers may promote cancer progression by mediating abnormal m6A modifications to reshape the TME, thereby affecting the survival prognosis of the patients. The information would provide helpful references for scholars focusing on WTAP and provide new insights for WTAP as a prognostic evaluation and immunotherapy for tumors in the future.

Humoral and cellular immune response to severe acute respiratory syndrome coronavirus-2 vaccination in haemodialysis and kidney transplant patients.

End-stage renal disease (ESRD) patients are amongst the vulnerable groups and thus prioritized in the Coronavirus disease-2019 vaccination programmes. However, this cohort was excluded from vaccine-trials and yet shares the same vaccination scheme with the general population. Here, we explore trends of immune response-proportions amongst ESRD patients on renal replacement therapy for up to 4 weeks post-vaccination completion with Pfizer/Moderna vaccines. From inception to 10 July 2021, we searched six online-databases for articles reporting humoral and cellular immune response proportions for up to 4 weeks post booster-vaccination. We pooled the responders' proportions by meta-analysis and conducted a meta-regression stratifying outcomes by significant confounders. Twenty-seven eligible studies reported 2789 ESRD patients. 1337, 1452 and 477 were on haemodialysis, received kidney transplantation, and healthy controls, respectively. Haemodialysis patients' proportions of humoral and cellular immune responses varied from 87.29% (80.77-93.81)-88.78% (86.76-90.80) and 62.86% (56.56, 69.17)-85.78% (78.99, 92.57), respectively, between first- and fourth-weeks. Kidney transplant patients' proportions of humoral and cellular immune responses ranged from 2.6% (0.06-13.48)-29.87% (27.68, 32.07) and 5.13% (0.63-17.3)-59.84% (54.57-65.10), respectively, between first- and fourth-weeks. All healthy controls maintained ≥93% proportions of both responses throughout the follow-up. Study design and country of study influenced the pooled response proportions. Conclusively, haemodialysis and kidney transplant patients have lower proportions of humoral and cellular immune responses than healthy controls. However, haemodialysis patients' response proportions improve, reaching near healthy-control levels by the fourth week. Kidney transplant patients' lower responses' proportions also improve but remain significantly lower than healthy controls throughout four-weeks. The "one-size-fits-all" vaccination scheme might be inadequate for kidney transplant patients.

Factor analysis of the relationship between PANSS score and family burden of patients with schizophrenia.

OBJECTIVE: This study aims to investigate the burden of family caregivers of patients with schizophrenia, and its influencing factors METHODS: A total of 105 patients with schizophrenia and their caregivers were investigated using the positive and negative symptom scale (PANSS) and family burden scale of disease (FBS) RESULTS: There was a strong correlation between the patient's recovery and family burden, especially between positive and negative symptoms and family financial burden, family daily activities, family recreational activities, and family relationship CONCLUSION: There is a strong correlation between the patient's recovery and family burden, and this is especially correlated to family economic burden, family daily activities, family recreational activities, and family relationship. Medical staff should pay attention to the psychological characteristics of patients and fully understand and avoid the adverse effects of family burden on the rehabilitation of patients.

Keyhole Approach Endoscopic Surgery versus Stereotactic Aspiration plus Urokinase in Treating Basal Ganglia Hypertensive Intracerebral Hemorrhage / 中国医学科学院学报

To compare the short-and long-term effect of two minimal invasive surgical therapies including keyhole approach endoscopic surgery(KAES)and stereotactic aspiration plus urokinase(SAU)in treating basal ganglia hypertensive intracerebral hemorrhage(hICH). The clinical data of 117 hICH patients(63 received KAES and 54 received SAU)were retrospectively analyzed.The operation time,blood loss during surgery,and drainage time were compared between two groups.The residual hematoma volume,hematoma clearance rate(HCR),Glasgow coma scale(GCS)score,and National Institute of Health Stroke Scale(NIHSS)score were recorded at baseline and in the ultra-early stage,early stage,and sub-early stage after surgery.The 30-day mortality and serious adverse events were assessed and the 6-month modified Rankin scale(mRS)score was rated. Baseline data showed no significant difference between these two groups.Compared with the SAU group,the KAES group had significantly longer operation time,more intraoperative blood loss,and shorter drainage time(all 0.05).In the ultra-early and early stage,the GCS and NIHSS scores showed no significant differences between two groups(all >0.05),whereas in the sub-early stage,the NIHSS score was better in the SAU group(=0.034).The 30-day mortality and incidences of serious adverse events showed no significant difference(all >0.05).The good recovery(mRS≤3)at 6-months follow-up showed no significant difference between the two groups(=0.413). Both KAES and SAU are safe and effective in treating basal ganglia hICH.In the ultra-early stage after surgery,KAES achieves better residual hematoma volume and HCR,and patients undergoing SAU quickly catch up.The short-and long-term effectiveness of SAU is comparable or even superior to KAES.

Glycyrrhizic acid activates chicken macrophages and enhances their Salmonella-killing capacity in vitro / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#Salmonella enterica remains a major cause of food-borne disease in humans, and Salmonella Typhimurium (ST) contamination of poultry products is a worldwide problem. Since macrophages play an essential role in controlling Salmonella infection, the aim of this study was to evaluate the effect of glycyrrhizic acid (GA) on immune function of chicken HD11 macrophages.@*METHODS@#Chicken HD11 macrophages were treated with GA (0, 12.5, 25, 50, 100, 200, 400, or 800 μg/ml) and lipopolysaccharide (LPS, 500 ng/ml) for 3, 6, 12, 24, or 48 h. Evaluated responses included phagocytosis, bacteria-killing, gene expression of cell surface molecules (cluster of differentiation 40 (CD40), CD80, CD83, and CD197) and antimicrobial effectors (inducible nitric oxide synthase (iNOS), NADPH oxidase-1 (NOX-1), interferon-γ (IFN-γ), LPS-induced tumor necrosis factor (TNF)-α factor (LITAF), interleukin-6 (IL-6), and IL-10), and production of nitric oxide (NO) and hydrogen peroxide (H2O2).@*RESULTS@#GA increased the internalization of both fluorescein isothiocyanate (FITC)-dextran and ST by HD11 cells and markedly decreased the intracellular survival of ST. We found that the messenger RNA (mRNA) expression of cell surface molecules (CD40, CD80, CD83, and CD197) and cytokines (IFN-γ, IL-6, and IL-10) of HD11 cells was up-regulated following GA exposure. The expression of iNOS and NOX-1 was induced by GA and thereby the productions of NO and H2O2 in HD11 cells were enhanced. Notably, it was verified that nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways were responsible for GA-induced synthesis of NO and IFN-γ gene expression.@*CONCLUSIONS@#Taken together, these results suggested that GA exhibits a potent immune regulatory effect to activate chicken macrophages and enhances Salmonella-killing capacity.

Effects of atorvastatin on serum levels of inflammatory factors, pulmonary function and right ventricular remodeling in patients with chronic obstructive pulmonary disease complicated with pulmonary hypertension / 药物评价研究

Objective To investigate the effect of atorvastatin on serum levels of inflammatory cytokines,pulmonary function and right ventricular remodeling in patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary hypertension.Methods From December 2013 to December 2016,106 patients with COPD complicated with pulmonary hypertension were randomly divided into treatment and control groups,each with 53 cases.Patients in control group were treated with routine basic therapy for three months,and patients in treatment group were treated with atorvastatin on the basis of control group.The pulmonary function,right ventricular remodeling function and inflammatory factors were detected,and the clinical efficacy of two groups was evaluated.Results The total effective rate was 94.34％ in the treatment group and 79.25％ in the control group,difference between the two groups was significant (P ＜ 0.05).The levels of FEV1 and FVC were not significantly different between two groups before treatment.The levels of FVC and FEV1 in treatment group were significantly higher than those in the control group after treatment (P ＜ 0.05).After treatment,the LVED,LVPW,TRVmax and RVEF of treatment group were significantly higher than those of control group (P ＜ 0.05),and the difference was statistically significant.Compared with before treatment,LVID,LVPW and TRVmax were increased,RVAD decreased,and the difference was statistically significant (P ＜ 0.05).The levels of CRP,ET and IL-6 in the treatment group were significantly lower than those in the control group (P ＜ 0.05),and difference was statistically significant.Conclusion The effect of atorvastatin on serum inflammatory factors,pulmonary function and right ventricular remodeling in patients with COPD combined with pulmonary hypertension is significant and can be popularized.

Clinical effect of fasudil in heart failure induced by chronic pneumocardial disease and the influence in serum level of NO and ET-1 / 药物评价研究

Objective To investigate the clinical effect of fasudil in heart failure induced by chronic pneumocardial disease and the influence in serum level of NO and ET-1.Methods 100 cases of patients with heart failure induced by chronic pneumocardial disease in our hospital from September 2013 to September 2016 were selected and divided into observation group and control group,50 cases in each group.Patients in the control group were treated with conventional therapy,and in the observation group were treated with fasudil based on the conventional therapy.Compared the clinical effect,blood oxygen partial pressure (PaO2),CO2 partial pressure (PaCO2),tricuspid regurgitation speed,fight ventricular outflow tract inside diameter(RVOT),left ventricular ejection fraction (LVEF) and serum biochemical indexes (NO and ET-1) levels.Results After treatment,the total effective rate of the observation group was significantly higher than control group (P ＜ 0.05).PaO2,LVEF,serum level of NO of the two groups were significantly higher,PaCO2,tricuspid regurgitation speed,RVOT,serum level of ET-1 significantly lower than before treatment (P ＜ 0.05),and the PaO2,LVEF,serum level of NO of observation group were significantly higher,PaCO2,tricuspid regurgitation speed,RVOT,serum level of ET-1 of observation group were significantly lower than control group (P ＜ 0.05).Conclusion Fasudil had remarkable clinical effect in heart failure induced by chronic pneumocardial disease,and improve the patient's clinical symptoms,adjust the serum level of NO and ET-1.

Saccharomyces boulardii and Bacillus subtilis B10 modulate TLRs mediated signaling to induce immunity by chicken BMDCs.

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play a critical role to activate immune response. They may be targeted for immunomodulation by microbes, including probiotics. In this study, chicken bone marrow dendrite cells (chi-BMDCs) were stimulated with lipopolysachride (LPS), Saccharomyces boulardii (Sb), Bacillus subtilis B10 (Bs), co-culture of Sb + Bs and phosphate buffer saline (PBS) as a control group (Ctr) at 3, 6, and 12 h intervals. Results revealed that treatment groups modulated the phenotype and biological functions of chi-BMDCs. Scan electron microscopy showed attachment of probiotics on the surface of chi-BMDCs. Additionally transmission electron microscopy (TEM) revealed efficiently engulfing and degradation of probiotics. Gene expression levels of MHC-II, CD40, CD80 and CD86 up-regulated in stimulated groups. Furthermore, toll-like receptors TLR1, TLR2, TLR4, and chicken specific TLR15 expressions were improved and downstream associated factors MyD88, TRAF6, TAB1, and NFκ-B mRNA levels increased in all treatment groups as compared to control. Surprisingly, NFκ-B response was noted significant higher in LPS treatment among all groups. Moreover, IL-1ß, IL-17, IL-4, TGF-ß, and IL-10 production levels were found higher, and lower concentration of INF-γ and IL-8 were observed in Sb, Bs, and Sb + Bs treatment groups. In contrast, LPS groups showed prominent increase in IL-12, INF-γ, and IL-8 concentration levels as compared to control group. Altogether, these results emphasize a potentially important role of Saccharomyces boulardii and Bacillus subtilis B10 in modulating immunological functions of chi-BMDCs by targeting specific toll like receptors (TLRs) and associated factors. The role of probiotics on chi-BMDCs functionality in a non-mammalian species have been presented for the first time.

Discussion of anti-inflammatory mechanism of cyclooxygenase (COX-2) inhibitor in improving cardiovascular safety / 中国中药杂志

The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1β and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.

Stability analysis of the pelvis and fracture fixation in standing position / 医用生物力学

Objective To develop the three-dimensional (3D) finite element (FE) models of pelvis and fracture fixation, and test their validity. Methods Based on CT scan images, the 3D FE model of the pelvis was built by software of Mimics, ANSYS ICEM, Hypermesh and ABAQUS. A uniformly distributed load of 600 N was applied in vertical direction on the upper lamina of S1 vertebrae to simulate the stresses on the pelvis in standing position and to verify the validity of the pelvis model. T-shaped acetabular fracture models with 3 types of fixation were also established to verify the validity of internal fixation. ResultsBoth the stress and displacement distributions were found to be bilaterally symmetrical on the pelvis in standing position, with the Von Mises stresses mainly distributed in the beginning of arcuate line, pubic branch and posterior-superior area of acetabulum. The largest displacement occurred in the center of the sacral crest, and became relatively smaller in iliac fossa and femur, which was reduced gradually to the femur. Each of the three fixation types in acetabulum showed good biomechanical stability. Conclusions The established hexahedral grid-3D FE model can accurately simulate mechanical properties of the femur in standing position, which would provide an intuitive basis for clinical study.

The lignins from Torreya grandis cv. Merrilli / 药学学报

<p><b>AIM</b>To separate and identify the chemical constituents of the aril of Torreya grandis cv. Merrilli.</p><p><b>METHODS</b>Three lignins were isolated by chromatography and their chemical structures were elucidated by IR, EI-MS, 1HNMR, 13CNMR, DEPT and 2D-NMR spectral methods.</p><p><b>RESULTS</b>Three lignins were identified as pinonesinol, dihydrodehydrodiconiferylalcohol and (7,8-cis-8,8'-trans)-2',4'dihydroxyl-3, 5-dimethoxy-lariciresinol.</p><p><b>CONCLUSION</b>These compounds were isolated from this plant for the first time, and compound III is a new compound.</p>

Study of correlation and effect of smoking on semen quality of men / 中华男科学杂志

<p><b>OBJECTIVES</b>To study the correlation and effect of smoking on the semen quality of men.</p><p><b>METHODS</b>61 men, non-smoker, who had one or more children as normal fertility control group and adult males attending the infertility clinic, including 110 non-smokers and 191 smokers, were recruited for the study. The smokers were divided into subgroups according to the amount and duration of smoking. Semen parameters(volume, sperm density, viability, motility and morphology) were examined and seminal plasma contents of Zn, Cu and superoxide dismutase (SOD) were determined.</p><p><b>RESULTS</b>The semen volume, pH, sperm density, viability and forward progression, as well as the seminal plasma contents of Zn, Cu and SOD were much lower in the medium, heavy and long-term smokers than in the non-smokers(P < 0.01). The sperm density, viability and forward progression, and the seminal plasma Zn, Cu and SOD levels were negatively correlation with the amount and duration of cigarette smoking(P < 0.001).</p><p><b>CONCLUSIONS</b>The effect of smoking on semen parameters of infertile men were dose-effect and time-effect relationship. Medium, heavy and long-term smoking adversely affected the semen quality in a population of men visiting the infertility clinic.</p>