OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.

Objective:To systematically evaluate the correlation between maternal arsenic exposure during pregnancy and congenital heart disease (CHD) in offspring.Methods:Literature search was performed through databases such as PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and VIP.com to include epidemiological literature on association between maternal arsenic exposure during pregnancy and offspring CHD published domestically and internationally. The search was conducted from database establishment until November 2, 2022. Stata MP15 software was used for meta-analysis of binary variables, and I 2 statistics and Q test were used for heterogeneity test, fixed effect model or random effect model was selected based on the test results. Using OR value (95% CI) as the effect evaluation indicator, subgroup analysis was conducted based on CHD subtypes [conotruncal defects (CTD), atrioventricular septal defect (AVSD), total anomalous pulmonary venous return (TAPVR), left ventricular outflow tract obstruction (LVOTO), right ventricular outflow tract obstruction (RVOTO), atrial septal defect (ASD)/ventricular septal defect (VSD), and patent ductus arteriosus (PDA)]. Results:Nine articles were finally included, including two Chinese and seven English articles. Among them, 8 articles had CHD as the outcome, 5 articles had ASD/VSD as the outcome, 4 articles had CTD as the outcome, 3 articles had LVOTO as the outcome, 2 articles had PDA as the outcome, and 1 article had RVOTO as the outcome. An analysis was conducted on 8 articles with CHD as the outcome. After heterogeneity testing, I 2 = 88.5% and P < 0.001, indicating significant heterogeneity. A random effect model was used for meta-analysis, and the combined OR value (95% CI) was 1.51 (1.40 - 1.62). The results of CHD subgroup analysis showed that the combined OR values (95% CI) for ASD/VSD, CTD, LVOTO, PDA, and RVOTO were 1.68 (1.53 - 1.84), 1.64 (1.29 - 2.09), 2.89 (1.82 - 4.61), 1.78 (1.53 - 2.08), and 0.81 (0.64 - 1.03), respectively. Conclusion:Maternal arsenic exposure during pregnancy is associated with development of offspring CHD, including ASD/VSD, CTD, LVOTO, and PDA as the common lesions in offspring CHD.

ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction （GDFMD） in the development of liver fibrosis in Wilson's disease （WD）. MethodFirst， 30 TX-j mice were randomly divided into the model group， high-dose， medium-dose， and low-dose GDFMD groups， and penicillamine group， with six mice in each group， and another six wild-type mice were used as the normal group. The high-dose， medium-dose， and low-dose GDFMD groups were intragastrically administered drugs of 13.92， 6.96， 3.48 g·kg^-1. In the penicillamine group， 0.1 g·kg^-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline， once a day， for four consecutive weeks. Samples were collected four weeks after gavage， and enzyme-linked immunosorbent assay （ELISA） was used to detect type Ⅲ procollagen peptide （PCⅢ）， collagen type Ⅳ （Col Ⅳ）， hyaluronic acid （HA）， and laminin （LN）. Hematoxylin-eosin （HE）， Masson， and picric acid-Sirus red collagen （Sirus Red） staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry， and Western blot were used to observe the expressions of α-smooth muscle actin （α-SMA） and collagen type Ⅰ （Col Ⅰ）， which were related to the activation of hepatic stellate cells （HSCs）. The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 （ULK1） and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group， the four items of liver fibrosis （PCⅢ， Col Ⅳ， HA， and LN） in the model group were significantly abnormal （P<0.01）， and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated （P<0.05， P<0.01）， and miR-29b-3p expression was down-regulated （P<0.01）. ULK1， p-ULK1， autophagy-related gene 13 （Atg13）， p-Atg13， Beclin-1， FAK family kinase-interacting protein of 200 kDa （FIP200）， activating molecule in BECN1-regulated autophagy protein 1 （AMBKA1）， and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ） were up-regulated （P<0.05， P<0.01）. p62 protein expression was down-regulated （P<0.01）. Compared with the model group， the four items of liver fibrosis in the high-dose， medium-dose， and low-dose GDFMD groups and the penicillamine group were significantly improve （P<0.01）， and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated （P<0.05， P<0.01）， and the expression of miR-29b-3p was up-regulated （P<0.01）. ULK1， p-ULK1， Atg13， p-Atg13， Beclin-1， FIP200， AMBKA1， and LC3Ⅱ/Ⅰ were down-regulated （P<0.05， P<0.01）， and p62 protein expression was up-regulated （P<0.01）. The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured （P<0.01）. ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.

Objective To evaluate the accuracy and clinical application value of the fluorescence quantitative PCR melting curve meth-od for detecting fungal nucleic acid.Methods 460 suspected or confirmed patients with respiratory fungal infections were enrolled in the study.The fluorescence quantitative PCR melting curve method was used as the test method,and the fungal 26S rRNA gene nucleic acid detection kit combined with Sanger sequencing was used as the reference method.Sputum samples from each study subject were collected and detected by the test method and reference method,respectively.The Kappa value of the two methods was calculated to evaluate the consistency of the results.Results Compared with the reference method,the overall conformity rate of the test method was 92.83%(427/460).Compared with the reference method,the positive conformity rates,negative conformity rates,and overall conformity rates of the test method for detecting 8 fungi,including Candida albicans,Candida glabrata,Candida krusei,Candida trop-icalis,Candida parapsilosis,Cryptococcus neoformans,Candida guilliermondii,and Aspergillus,were 97.34%(183/188),97.06%(264/272),and 97.17%(447/460),100.00%(33/33),99.77%(426/427),and 99.78%(459/460),100.00%(16/16),99.55%(442/444),and 99.57%(458/460),98.11%(52/53),99.75%(442/444),and 99.57%(458/460),95.08%(58/61),99.50%(397/399),and 98.91%(455/460),100.00%(9/9),99.56%(449/451),and 99.57%(458/460),85.00%(17/20),99.32%(437/440),and 98.70%(454/460),and 97.59%(81/83),97.88%(369/377),and 97.83%(450/460),respectively.The Kappa values for the consistency evaluation of the two methods'detection results were both greater than 0.8.Upon retesting the inconsistent re-sults of the two methods,it was found that 53.7%(22/41)of the detection results were consistent with the test method,and the others were consistent with the reference method.Conclusion The fluorescence quantitative PCR melting curve method can simultaneously detect 8 kinds of fungi,and the detection results are highly consistent with the reference method.It has unique advantages in fungal de-tection and important clinical application value.

For muscle-invasive bladder cancer (MIBC) patients, preoperative neoadjuvant chemotherapy (NAC) can reduce the tumor stage, treat micrometastases, prolong the median survival, and improve the prognosis.However, NAC is associated with side effects such as renal impairment, thromboembolism and drug toxicity.NAC itself suffers from deficiencies such as renal function impairment, thromboembolism, and drug toxicity.Its therapeutic efficacy is affected by factors such as tumor pathology type, DNA repair gene defects, whether it is primary MIBC, and TNM staging, so there are certain limitations in its use.Based on the cisplatin treatment regimen, more and more studies are exploring the limitations and shortcomings of NAC in MIBC treatment regimen.Therefore, this paper provides an overview and outlook of the application of NAC in MIBC treatment.

Objective To study the levels and clinical significance of serum angiopoietin-like protein 8(ANGPTL8)and neopurine in children with hormone sensitive primary nephrotic syndrome(NS).Methods A total of 159 children with hormone sensitive primary NS treated in the hospital from January 2018 to January 2021 were selected as the study subjects(NS group).After 1 year of follow-up,based on whether frequent recurrence occurred,they were divided into the non frequent recurrence subgroup(n=93)and the frequent recurrence subgroup(n=66).Additionally,60 children with oblique hernia who underwent e-lective surgery in the Department of Pediatrics in the hospital were selected as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of ANGPTL8 and neopterin.The ser-um levels of ANGPTL8 and neopterin in each group were compared.Multivariate Logistic regression analysis was used to analyze risk factors for frequent recurrence in children with hormone sensitive primary NS.The predictive value of serum ANGPTL8 and neopterin in predicting frequent recurrence in children with hormone sensitive primary NS was analyzed by receiver operating characteristic(ROC)curve.Results The serum lev-els of ANGPTL8 and neopterin in the NS group were higher than those in the control group,and the differ-ences were statistically significant(t=20.948,44.288,P＜0.001,0.001).The serum ANGPTL8,neopterin levels,CD8+T cells,24 h urine protein quantification,and urine protein conversion time in the frequent recur-rence subgroup were significantly higher than those in the non frequent recurrence subgroup,while the blood albumin,CD4+T cells,CD4+/CD8+T cell ratios were lower than those in the non frequent recurrence sub-group,and the differences were statistically significant(all P＜0.05).The serum levels of ANGPTL8 and neopterin in NS patients were significantly positively correlated with 24 h urine protein and CD8+T cells,while they were significantly negatively correlated with serum albumin,CD4+T cells,CD4l+/CD8+(all P＜0.05).Serum ANGPTL8 and neopterin were independent risk factors for frequent recurrence in children with hormone sensitive primary NS.The area under the curve(AUC)of the combined model of serum ANGPTL8 and neopurine for predicting frequent recurrence in hormone sensitive primary NS patients was 0.852(95％CI:0.813-0.889),which was higher than 0.764(95％CI:0.722-0.812)of ANGPTL8,and 0.749(95％CI:0.711-0.790)of neopurine,and the differences were statistically significant(Z=3.623,3.987,P=0.003,＜0.001).Conclusion Elevated levels of serum ANGPTL8 and neopterin are risk factors for frequent recurrence hormone sensitive primary NS.The combination detection of serum ANGPTL8 and neopterin has high predictive value for frequent recurrence in children with hormone sensitive primary NS.

Objective To study the expression of serum interleukin(IL)-17A,calcium binding protein S100A8 and S100A9 in children with severe Mycoplasma pneumoniae pneumonia(SMPP)and their prognostic significance.Methods A total of 116 children with SMPP who were diagnosed and treated in this hospital from March 2019 to March 2021 were enrolled as the SMPP group.According to the pediatric critical cases score,the SMPP children divided into non-critical group(43 cases),critial group(40 cases),extremely critical group(33 cases).According to the prognosis of 28 d after admission,the SMPP children were divided into a good prognosis group with 82 children and a poor prognosis group with 34 children.A total of 60 physical ex-amination of healthy children in the same hospital during the same period were enrolled as the control group.The levels of serum IL-17A,S100A8,S100A9,procalcitonin(PCT),C-reactive protein(CRP),IL-6 and tumor necrosis factor(TNF)-α were detected in each group.Pearson correlation analysis was used to analyze the cor-relation between serum levels of IL-17A,S100A8,S100A9 and PCT,CRP,IL-6,and TNF-α.Multivariate Lo-gistic regression analysis was used to analyze the factors affecting the poor prognosis of children with SMPP.The receiver operating characteristic(ROC)curve was used to analyze the value of each index in predicting the poor prognosis of children with SMPP.Results The SMPP group had significantly higher serum levels of IL-17A,S100A8,S100A9,PCT,CRP,IL-6,and TNF-α than the control group(P<0.05).In children with SMPP,the serum levels of IL-17A,S100A8,and S100A9 were positively correlated with PCT,CRP,IL-6,and TNF-α(P<0.05).The serum levels of IL-17A,S100A8 and S100A9 in extremely critical group were signifi-cantly higher than those in critical group and non-critical group(P<0.05).Elevated serum levels of IL-17A,S100A8 and S100A9 were independent risk factors for poor prognosis in children with SMPP.The area under the curve(AUC)of combined detection of serum IL-17A,S100A8 and S100A9 for predicting poor prognosis in children with SMPP was 0.895,which was higher than that of single detection of serum IL-17A,S100A8 and S100A9(0.833,0.764,0.810),the differences were all statistically significant(Z=3.780,6.723,5.012,P<0.059).The sensitivity and specificity of combined detection were 0.891 and 0.755,respectively.Conclu-sion The serum levels of IL-17A,S100A8 and S100A9 are increased in children with SMPP,which are related to the severity of SMPP.The combined detection of the three indicators has a high predictive value for the poor prognosis of SMPP.

Hepatolenticular degeneration (HLD) is a rare genetic metabolic disorder of the nervous system with complex and diverse clinical phenotypes and is difficult to diagnose. The common lesions of HLD brain area are basal ganglia, thalamus, cerebellum and other anatomical structures, the classic manifestations of brain magnetic resonance imaging are symmetrical bilateral lenticular nucleus with low signal on T 1WI and high signal on T 2WI, and it is extremely rare for cases with high signal intensity on diffusion weighted imaging (DWI) of the brain stem, bilateral cerebral peduncles, thalamus, and basal ganglia. This article reported a case of HLD with high signal on DWI for clinical reference.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Objective To systematically integrate qualitative studies on health promoting behaviors of stroke patients and provide references for the development of relevant behavioral interventions.Methods Qualitative studies on health promotion behaviors of stroke patients were retrieved from CNKI,Wanfang,China Biomedical Database,VIP,PubMed,Web of Science,the Cochrane Library,and Embase from the inscription to February 2023.The JBI Model of Evidence-Based Healthcare was employed to assess the quality of the acquired literature,with the results treated with meta-integration.Results A total of 9 articles were included in the study.From the literature acquired 49 complete themes were abstracted and 3 novel types of literature were yielded.By meta-integration,11 factors affecting the health promoting behaviors of the stroke patients were concluded,including ability of patients such as physical dysfunction,disease cognition,disease risk management,motivation such as negative emotional distress,positive emotional experience,psychological self-regulation,and opportunity such as family caring degree,iatrogenic support,peer mutual support,access to information,and environmental restrictions.Conclusions The factors influencing health promoting behaviors of stroke patients consist of ability,motivation,and opportunity.Medical staff should care about their mental and physical experience,establishing a multi-social support system and working hard to promote the transformation of their health behaviors.