Progress in the potential therapeutic mechanism of mesenchymal stem cell-derived exosomes for liver fibrosis / 中国临床药理学与治疗学

Liver fibrosis is pathological in most chronic liver diseases. Exosomes secreted by mesenchymal stem cells (MSCs) can regulate liver fibrosis through mechanisms such as inhibition of inflammatory response and proliferation of activated hepatic stellate cells, regulation of immune cells and metabolism. Therefore, MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease, expanding new ideas for the treatment of chronic liver disease. Recent researches on MSC-derived exosomes in the treatment of liver fibrosis are reviewed in this article.

Polyethylene biodegradation: current status and perspectives / 生物工程学报

Polyethylene (PE) is the most abundantly used synthetic resin and one of the most resistant to degradation, and its massive accumulation in the environment has caused serious pollution. Traditional landfill, composting and incineration technologies can hardly meet the requirements of environmental protection. Biodegradation is an eco-friendly, low-cost and promising method to solve the plastic pollution problem. This review summarizes the chemical structure of PE, the species of PE degrading microorganisms, degrading enzymes and metabolic pathways. Future research is suggested to focus on the screening of high-efficiency PE degrading strains, the construction of synthetic microbial consortia, the screening and modification of degrading enzymes, so as to provide selectable pathways and theoretical references for PE biodegradation research.

Screening for scoliosis and associated factors among primary and middle school students in Shanghai / 中国学校卫生

Objective@#To understand the prevalence and influencing factors of scoliosis among primary and middle school students in Shanghai, so as to provide reference for the prevention and control strategies of scoliosis in children and adolescents.@*Methods@#From September to December 2021, a total of 4 531 students from grade four of primary school to grade three of junior high school from 16 primary and middle schools in 4 districts of Shanghai were selected by multi stage stratified cluster sampling to carry out scoliosis screening and questionnaire survey. Independent sample t-test, Chi-squared test, Fisher s exact probability method and nonparametric Mann Whitney U-test were used for statistical analysis, and multivariate Logistic regression was used to analyze the influencing factors of scoliosis.@*Results@#The on the spot detection rate of scoliosis abnormality was 7.4% and the prevalence was 2.2%, mainly for thoracolumbar scoliosis (60.4%) and the scoliosis angle of 10° -<20°(88.1%). The results showed that the detection rate of scoliosis in boys was 1.6% and in girls was 3.3%, with a statistically significant difference ( χ 2=11.84, P < 0.01). There were significant differences in weight and BMI between scoliosis students and students with negative initial screening( t = -3.77, -5.30, P <0.01). And there was a statistically significant difference in the detection rate of scoliosis with different frequency of classroom seating arrangements ( Z =2.02, P <0.05). The results of multivariate Logistic regression showed that the risk of scoliosis in girls was higher than that in boys ( OR =1.87, 95% CI =1.21-2.88). BMI ( OR =0.89, 95% CI =0.83-0.95) and frequency of classroom seating arrangements ( OR =0.49, 95% CI =0.25-0.93) were correlated with lower rate of scoliosis. After stratification by sex, the frequency of classroom seating arrangements ( OR =0.26, 95% CI =0.10-0.67) in boys and the educational stage ( OR =2.35, 95% CI =1.26-4.41) in girls ( P <0.05) was correlated with higher rate of scoliosis, while BMI ( OR =0.86, 95% CI =0.79-0.94) in girls were correlated with lower rate of scoliosis.@*Conclusion@#Regular screening of scoliosis is an effective method for early detection of scoliosis. Girls in junior high school and low BMI should be paid close attention to. According to the occurrence and influencing factors of scoliosis, comprehensive prevention and control based on family, school, society, and other aspects can be carried out.

Current status of surgery for portal hypertension in China: a national multi-center survey analysis / 中华器官移植杂志

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Bioinformatics analysis of key genes and its biofunction of aldosterone producing adenoma / 中华内分泌代谢杂志

Objective:To explore the key genes and its biological functions of aldosterone producing adenoma (APA) using bioinformatics analysis.Methods:Differentially expressed genes of APA were identified from two training datasets GSE60042 and GSE64957 in GEO database. Function and pathway enrichment analyses for differentially expressed genes were performed and transcriptional regulation network among these genes were determined. Hub genes were extracted by node analysis from the protein-protein interaction (PPI) network. The expression of key genes was verified by a testing dataset GSE8514. Receiver operating characteristic(ROC) curve analysis was applied to assess the diagnostic efficiency of key genes in APA. The biofunction of each key gene were determined by gene set enrichment analysis (GSEA).Results:A total of 68 differentially expressed genes, including 33 up-regulated genes and 35 down-regulated genes, were detected from the training datasets. These genes were mainly enriched in aldosterone biosynthetic process, calcium signaling pathway, serotonin receptor signaling pathway, transcriptional activator activity, and regulation of transcription. JUN and VDR were at the center of the transcriptional factor-gene network. Furthermore, we identified nine Hub genes from the PPI network. In testing dataset, CYP11B2 and VDR showed the higher expression, while JUN, NFKBIZ, EGR3, and KLF6 showed lower expression in APA (all P<0.05), and the value of area under ROC curve analysis was 0.936, 0.833, 0.953, 0.854, 0.868, and 0.929, respectively. GSEA indicated the alter of key genes in APA led to up-regulation of the steroid biosynthesis, cell adhesion molecules, immune cells signaling pathway, and complement and coagulation cascades [all normalized enrichment score (NES)>1.5, P<0.05], but down-regulation of the DNA replication, ribosome, and autophagy (all NES<-1.5, P<0.05). Conclusion:Results of bioinformatics indicate that JUN and VDR are key transcriptional factors, and CYP11B2, NFKBIZ, EGR3, and KLF6 are the key genes for APA, which are involved in the steroid biosynthesis, cell adhesion molecules, immune cells signaling pathway in APA.

Mechanism of action of hypoxia-inducible factor 1α in the development and progression of liver fibrosis / 临床肝胆病杂志

Liver fibrosis and end-stage liver cirrhosis are often accompanied by liver hypoxia. As a key transcription factor for regulating the body’s response to hypoxia, hypoxia-inducible factor 1α (HIF-1α) plays an important role in the activation of hepatic stellate cells and the development and progression of liver fibrosis. In addition, downregulation of HIF-1α expression can alleviate liver fibrosis and thus HIF-1α is expected to become a new target for the treatment of liver fibrosis. This article reviews the association between HIF-1α and liver fibrosis-related signaling pathways and genes and further discusses the potential of HIF-1α as a new therapeutic target for liver fibrosis.

Age and Sex Distribution of Chinese Chronic Cough Patients and Their Relationship With Capsaicin Cough Sensitivity

PURPOSE: An older female predominance has been reported among chronic cough patients in Western countries, which is considered to be associated with a higher cough sensitivity in females. However, the characteristics of Chinese chronic cough patients remain unclear. This study aimed to explore the age and sex distribution as well as their relationship with cough reflex sensitivity to capsaicin in Chinese chronic cough patients. METHODS: We analyzed the demographic features of 1,882 consecutive chronic cough patients who attended our cough clinic in Guangzhou, China. Cough sensitivity to capsaicin, which was defined as the lowest concentration of capsaicin causing 5 coughs or more (C5), was measured in 539 of the 1,882 patients and 68 healthy volunteers. RESULTS: The mean age of the patients was 43.0 ± 13.7 years and patients aged <50 years accounted for more than two-thirds of the study population. Around 87% of the patients were never-smokers. The proportion of females (51.5%) was almost equal to that of males (48.5%). The pattern of the age and sex distribution was consistently reflected within most common causes of chronic cough, while a female predominance was shown in patients with cough-variant asthma and patients aged ≥50 years. Female patients had higher cough sensitivity to capsaicin than male patients (log C5: 1.58 ± 0.84 vs. 2.04 ± 0.84 μmol/L, P = 0.001), and patients aged ≥50 years had higher cough sensitivity to capsaicin than patients aged <50 years. CONCLUSIONS: In China, patients with chronic cough have a roughly equal sex distribution and a middle-aged predominance, irrespective of a higher cough sensitivity to capsaicin in females and older patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02591550

Effects of hepatitis B virus on liver function, liver fibrosis and liver pathological staging at different ALT stages / 西安交通大学学报(医学版)

Objective To evaluate the effects of hepatitis B virus on liver function,liver fibrosis,and liver pathological staging at different immune stages.Methods We made a retrospective analysis of 657 patients with chronic hepatitis B diagnosed in the First Hospital of Lanzhou University.Their liver function parameters,liver fibrosis parameters,and hepatitis B virus load were measured by automatic biochemical analyzer,automatic gammaradiation immunity analyzer,and quantitative PCR analyzer,respectively.Effects of hepatitis B virus on liver function,liver fibrosis in different immune stages were analyzed by variance analysis.Effects of hepatitis B virus on liver pathological staging at different immune stages were analyzed by linear trend chi square test analysis.Results In ALT normal chronic hepatitis B patients group,viral load had mild effects on liver function and liver fibrosis parameters.However,in ALT abnormal chronic hepatitis B patients group,viral load had a significant effect on liver function and liver fibrosis parameters,and the effect was most obvious in ALT＞double upper limit of normal group.The specific manifestation was that with viral load increasing,liver function parameters including ALT,AST,TBiL,DBiL,and IBiL increased,while TP and ALB decreased.Liver fibrosis parameters HA,LN,PcⅢ,and CIV all increased (P＜0.05).In ALT normal chronic hepatitis B patients group,viral load had no relationship with liver pathological staging.However,in ALT abnormal chronic hepatitis B patients group,especially ALT≥double upper limit of normal group,viral load was significantly related to liver pathological staging.Conclusion The effects of hepatitis B virus on patients' liver function at different immune stages were different,thus providing evidence-based medicine support for clinical antiviral treatment.

Treatment research progress of cirrhosis of the liver decompensation period, the splenic function and thrombocytopenia after hepatitis C / 中国综合临床

HCV-related decompensated cirrhos,hypersplenism,thrombocytopenia,which not only affect the standard antiviral therapy,fail to achieve the sustained virological response(SVR),but also increase the risk of infection and bleeding.The only successful option is liver transplantation (LT),but the recurrence of HCV after LT remains to be resolved.The patients of HCV genotype 2 are suitable for splenectomy and antiviral therapy following splenectomy,which can achieved a higher SVR and reversed cirrhosis.As an effective alternative to splenectomy,the partial splenic embolization (PSE) can improve the changes of portal hemodynamics and reduce the sequelae of portal hypertension.The appearance of direct antiviral drugs (DAAs)has bring hope for those with decompensated cirrhos and whom IFN is contraindicated or tolerated poorly,those who are waiting for LT or with recurrence of hepatitis C after LT.The treatment of patients with decompensated cirrhos is as follows.

Correlation Study Between Angiotensin II Type1 Receptor Autoantibodies and the Onset Risk in Patients With Essential Hypertension Combining Acute Coronary Syndrome / 中国循环杂志

Objective: To study the correlation between angiotensin II type1 receptor autoantibodies (AT1-AAs) and the onset risk in patients with essential hypertension (EH) combiningacute coronary syndrome (ACS). Methods: Our research included in 4 groups: EH+ACS group,n=28, ACS group, n=29, EH group,n=26 and Control group,n=23 normal subjects. Serum levels of AT1-AAs were examined by ELISA; high sensitivity C-reactive protein (hs-CRP), blood levels of lipids and glucose were also measured and compared among different groups. The correlations between AT1-AAs and blood lipids, glucose, hs-CRP were studied by multiple linear regression analysis. Results: Compared with Control group, ACS group had similar level of AT1-AAs (0.26±0.09) vs (0.21±0.06),P=0.105; while EH+ACS group and HE group had increased AT1-AAs level as (0.40±0.005) and (0.33±0.10),P=0.001 andP=0.02 respectively; AT1-AAs level was higher in EH+ACS group than HE group,P=0.044. In addition, serum AT1-AAs level was positively related to hs-CRP in EH+ACS group, ACS group and EH group (r=0.589,r=0.503 andr=0.273, allP<0.01). Conclusion: Serum AT1-AAs level was positively related to the onset risk in patients with EH combining ACS; AT1-AAs was also related to hs-CRP at certain degree.

Advances in basic research on mesenchymal stem cells and its clinical application in liver cirrhosis / 临床肝胆病杂志

Adult mesenchymal stem cells (MSCs) have the features of high plasticity and low immunogenicity, and hold promise for wide clinical application. This article reviews the basic research on MSCs in bone marrow and umbilical cord blood and their clinical application in liver diseases to lay a theoretical foundation and provide support for their clinical application in liver cirrhosis, and to provide more technical measures for the treatment of end-stage liver disease. However, the safety and efficacy in clinical application still need further studies.

Cells and cellular interactions in the pathogenesis of idiopathic pulmonary fibrosis / 医学研究生学报

Idiopathic pulmonary fibrosis ( IPF) is a kind of Interstitial lung disease with cause unknown,which is aggressive for its increasing prevalence and high morbidity and mortality.At present the pathogenesis of IPF is not entirely clear, but cells and cel-lular interactions play a decisive role on the alveolar inflammation and fibrosis results.We review IPF related cells of interest ( immune competent cells and fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells) , to summarize cells and cellular in-teractions in the pathogenesis of IPF,and discuss new research directions and therapeutic targets.

Hypermethylation of HIC1 and aberrant expression of HIC1/SIRT1 contribute to papillary thyroid carcinoma / 中华内分泌代谢杂志

Objective To explore promoter methylation of HIC1 gene and the expression of HIC1/SIRT1 related to the occurrence, development, and metastasis of papillary thyroid carcinoma. Methods Using Bisulfite sequencing PCR to analyze the promoter methylation of HIC1 gene. Using quantitative real-time PCR and Western blot to analyze expression differences of HIC1 and SIRT1 genes in tissues of papillary thyroid carcinoma(40 cases) and in adjacent normal thyroid(40 cases), of which datas were analyzed by statistics. Results The degree of HIC1 gene promoter methylation was significantly higher than that in adjacent normal tissues(P<0. 01). The degree of HIC1 gene promoter methylation in papillary thyroid carcinoma was related to lymph node metastasis, age, and the tumor-node-metastasis stages(P<0. 01). Compared with the expression of HIC1 mRNA and protein in adjacent normal thyroid tissue, that in papillary thyroid carcinoma was significantly lower(P<0. 01), while the expression of SIRT1 mRNA and protein in papillary thyroid carcinoma was significantly higher(P<0. 01). The lower expression of HIC1 mRNA and protein in the tumor tissues was related to the stage of lymph node metastasis, age, and the tumor-node-metastasis stages(P<0. 05). There was a strong negative correlation between the degree of HIC1 gene promoter methylation and expression of HIC1 in papillary thyroid carcinoma(P<0. 05). The expression of HIC1 mRNA and protein between that of SIRT1 also showed a strong negative correlation(P<0. 01). Conclusion Promoter hypermethylation of HIC1 and aberrant expression of HIC1/SIRT1 in papillary thyroid carcinoma may play a significant role in the oncogenesis and progress of papillary thyroid carcinoma. HIC1 is expected to become a new marker for prevention and treatment of papillary thyroid carcinoma.

Expressions and significance of ZNF217 in papillary thyroid carcinoma / 中华内分泌代谢杂志

Objective To investigate the expression and clinical significance of zinc finger gene 217 (ZNF217) in human papillary thyroid carcinoma.Methods The expressions of ZNF217 mRNA and protein were detected by quantitative realtime PCR and Western blot in papillary thyroid carcinoma tissues (n =20) and adjacent normal tissues (n =20),and the data were analyzed.Results The expressions of ZNF217 mRNA and protein in papillary thyroid carcinoma were significantly higher than those in adjacent normal tissues (96.72 ± 44.19 vs 4.86 ±3.55,0.994 ± 0.172 vs 0.195 ± 0.061,both P＜0.01),being higher in the papillary thyroid carcinoma with capsule invasion compared with that without capsule invasion (P＜0.01).The expressions of ZNF217 mRNA and protein in papillary thyroid carcinoma were not related to gender,age,tumor size,TNM stage or lymph node metastasis (all P＞0.05).Conclusions The overexpression of ZNF217 may be associated with the oncogenesis and progress of papillary thyroid carcinoma and capsule invasion,and thus is expected to become a new target for prevention and treatment of papillary thyroid carcinoma.

Roles of SIRT1 in tumorigenesis and tumor progression / 国际肿瘤学杂志

Silent information regulator 1 (SIRT1) is a kind of histone deacetylase which dependents on nicotinamide adenine dinucleotide.It is involved in the occurrence and development of tumors.Data show that SIRT1 is highly expressed in many tumors,such as gastric cancer,breast cancer,prostate cancer and so on.On the other hand,the expression of SIRT1 is lower in many other types of tumors,including glioblastomas,bladder cancer,ovarian cancer and so on.Therefore,the role of SIRT1 in tumor formation process is still uncertain and controversial.

Expression of mRNA and protein of ZNF217 and EF1α and their significance in pathological scar / 中华医学美学美容杂志

Objective To study the expression of ZNF217 and EF1α gene in the pathological scars and to investigate role and probable mechanism in the pathogenesis of abnormal scar.Methods Quantitative real-time PCR and Western blot were performed to detect the expression and distribution of mRNA and protein of ZNF217 and EF1α in hypertrophic scar (10 cases),keloid (10 cases),normal scar (10 cases),and normal skin (10 cases),and statistics was used to analyze the data.Results The expression of ZNF217 mRNA and protein in the normal skin,normal scar,hypertrophic scar and keloid were 1.46±0.397,1.45±0.265,4.49±0.999,5.47±0.808; 0.276±0.0211,0.299±0.0150,0.743t0.0509 and 0.747±0.0377,respectively.The expression of EF1α mRNA and prorein in the normal skin,normal scar,hypertrophic scar,and keloid were 1.47±0.469,1.47±0.218,5.10±1.68,5.74±1.92; 0.505±0.0371,0.518±0.0153,0.780±0.0369 and 0.792±0.0290,respectively.The positive rate of mRNA and protein of ZNF217 and EF1α was not statistically different between the hypertrophic scar and keloid (P＞0.05),while they were all remarkably significant in comparison between normal scar and abnormal scar (P＜0.01).In pathological scar mRNA and protein of ZNF217 and EF1α showed a strong positive correlation.Conclusions The expression of ZNF217 and EF1α is increased in pathological scar.Therefore,ZNF217 and EF1α overexpression may play an important role in the proliferation of fibroblasts and in the pathogenesis of pathological scar.

HIF-1α and neovascularization in early carotid atherosclerosis plaques in rabbits / 中南大学学报(医学版)

OBJECTIVE@#To explore the relationship between hypoxia-inducible foctor-1α (HIF-1α) and neovascularization in early atherosclerosis plaques by establishing rabbit carotid atherosclerosis models, and to observe the value of contrast-enhanced ultrasound in the detection of neovascularization.@*METHODS@#We provided high-fat diet combined with the implantation of silicone rubber ring to establish carotid atherosclerosis in rat models. On the 14th and 28th days, we detected neovascularization in the carotid atherosclerotic plaques by contrast-enhanced ultrasound, obtained the peak intensity (PI) of the contrast agent in the plaques by time-intensity curve (TIC) and analyzed the difference. We also tested the level of HIF-1α, vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), α-actin, and RAM-11 by immunohistochemical method in each group, analyzed their correlation, and the correlation between PI and CD31 expression.@*RESULTS@#On the 14th day, contrast-enhanced ultrasound showed the neovascularization in the carotid atherosclerotic plaques. On the 14th and 28th days, the intensity of contrast-enhanced ultrasound showed significant difference, the mean optical density of HIF-1α, VEGF, CD31, RAM-11, and α-actin within the carotid atherosclerotic plaques also showed statistical difference. The expressions between HIF-1α and VEGF, HIF-1α and CD31, HIF-1α and RAM-11, HIF-1α and α-actin, as well as PI and CD31 showed highly positive correlations.@*CONCLUSION@#During the process of atherosclerosis evolution, neovascularization in the atherosclerotic plaques has come into being in the early period, and HIF-1α in early atherosclerosis can promote the formation of neovascularization. Contrast-enhanced ultrasound can detect the dynamic changes of neovascularization within early atherosclerotic plaques.

Effect of Mannan Peptide Combined with 5-Fu on the Proliferation and Apoptosis of HepG2 Cells / 中国肿瘤临床

Objective:To investigate the influence of Mannan Peptide combined with 5-Fu on the proliferation and apoptosis of HepG2 cells and to explore the related mechanism.Methods:HepG2 cells were divided into four groups:the control group,5-Fu group,Mannan Peptide group and combination group.Cell proliferation was evaluated by MTT assay.Flow cytometry was used to examine the cell cycle,proliferation index(PI)and apoptosis ratio.The expression of Bcl-2 protein in each group was analyzed by immunocytochemical method.Results:The inhibitive effect of 5-Fu plus Mannan Peptide was significantly stronger than that of Mannan Peptide alone,in a time-and dose-dependent manner. Cells were treated with medicine for 48 hours.Compared with cells in the control group and 5-Fu group,the percentage of cells in G_0/G_1 stage and the apoptosis ratio in the combination group were increased(P<0.01).In immunocytochemical analysis,the combination of Mannan Peptide and 5-Fu could significantly decrease Bcl-2 protein level(P<0.01).Conclusion:The combination of Mannan Peptide and 5-Fu can synergistically suppress the proliferation and induce apoptosis of human hepatoma HepG2 cells.The mechanism might be associated with down-regulation of Bcl-2 protein expression.

Preliminary investigation on corresponding relationship between isolated Q wave of standard limb-lead Ⅲ and sonographic infarct site / 中华超声影像学杂志

Objective To explore the corresponding relationship between isolated Q waves in lead Ⅲ on the electrocardiography(ECG) and echocardiographie segmental diagnosis of myocardial infarction(MI).Methods The shape magnitude of Q waves of 27 patients with MI and the relationship with eehocardiographie features were investigated. Results Twenty-four patients with inferior wall myocardial infarction had close relationship with isolated Q waves in lead Ⅲ on the ECG. Conclusions There is definite corresponding relation between isolated Q waves in lead Ⅲ and inferior wall myocardial infarction.