BACKGROUND:Bone marrow mesenchymal stem cells(BMSCs)can release a large number of exosomes(Exos).The effect of Exos derived from BMSCs on hepatocyte apoptosis and the specific mechanism has not been fully clarified. OBJECTIVE:To explore the effect of miR-21-5p carried by Exos derived from BMSCs on apoptosis of rat liver cells and its mechanism. METHODS:Rat BMSCs were isolated and miR-21-5p NC or miR-21-5p inhibitor was transfected into BMSCs.The Exos were extracted by ultracentrifugation and named(BMSCs+miR-21-5p NC)-Exos and(BMSCs+miR-21-5p inhibitor)-Exos.BMSCs-derived Exos were co-cultured with rat hepatocytes to observe the effect of inhibiting miR-21-5p expression on the apoptosis of rat hepatocytes.The targeting relationship between miR-21-5p and PIK3R1 was verified by double luciferase reporter gene detection.TUNEL was used to detect the effect of miR-21-5p directly targeting PIK3R1 in Exos to activate the PI3K/AKT signaling pathway on hepatocyte apoptosis in BRL rats. RESULTS AND CONCLUSION:(1)The double luciferase reporting system confirmed that when PI3KR1 wild type vector and miR-21-5p mimics co-transfected 293T cells,the luciferase activity decreased significantly compared with the PI3KR1 mutant vector co-transfected group,indicating that miR-21-5p could target PIK3R1.(2)TUNEL test results showed that compared with(BMSCs+miR-21-5p NC)-Exos group,(BMSCs+miR-21-5p inhibitor)-Exos treatment significantly increased the apoptosis rate.Compared with the(BMSCs+miR-21-5p NC)-Exos group,after the addition of AKT inhibitor LY294002,the apoptosis rate was significantly increased.(3)The results indicate that Exos may inhibit the apoptosis of BRL rat hepatocytes through miR-21-5p,in which miR-21-5p directly targets PIK3R1 to activate PI3K/AKT signaling pathway.

Highly effective oral antiviral therapy with low drug resistance can strongly inhibit HBV replication;however,some patients may still have low-level viremia(LLV)after receiving entecavir,tenofovir disoproxil fumarate,tenofovir alafenamide,or tenofovir amibufenamide for 48 weeks or more.Multiple studies in China and globally show that LLV after antiviral therapy is closely associated with the progression of chronic hepatitis B liver fibrosis,the risk of decompensated liver cirrhosis and hepatocellular carcinoma,and the reduction in long-term survival rate.Therefore,this article reviews the development,risk factors,and clinical harm of LLV after first-line treatment with nucleos(t)ide analogues,as well as different treatment regimens,in order to provide a reference for the treatment of LLV in chronic hepatitis B patients in the future.

Objective:To analyze and explore the clinical characteristics and risk factors related to nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia.Methods:252 hospitalized patients with liver cirrhosis combined with atrial arrhythmia from January 2014 to December 2021 were enrolled, and their clinical characteristics were analyzed. The above-mentioned patients were divided into groups according to their nosocomial mortality rate. Among them, 45 nosocomial mortality cases were classified as the mortality group, and 207 survival cases were classified as the survival group. The differences in clinical data and laboratory data between the two groups were compared. The risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia were analyzed. The t-test, or rank-sum test, was used to compare measurement data. The chi-square test, or Fisher's exact probability method, was used to compare enumeration data. Multivariate analysis was performed by the logistic regression method.Results:Among the 252 cases, the male-to-female ratio was the same (male/female ratio: 126/126). The age range was 26 to 89 (66.77±10.46) years. Han ethnicity accounted for 79.5%. The main type of atrial arrhythmia was atrial fibrillation ( P ?

Hepatitis D is a global public health issue, and the infection rate and genotype of HDV infection vary greatly across different regions. The overlapping infection of hepatitis D virus (HDV) in patients with chronic hepatitis B virus (HBV) infection can accelerate disease progression, but hepatitis D has not been taken seriously to a large extent. Xinjiang in China is an area with a high incidence rate of hepatitis B, but there is a lack of research on hepatitis D. This article discusses the prevalence of HDV infection in Xinjiang and briefly reviews the prevalence rate of HDV infection in Xinjiang, the molecular epidemiology of HDV among different ethnic groups, and the current status of HDV infection in neighboring countries, so as to provide a reference for the conduct of molecular epidemiological research on HDV and disease prevention and control in Xinjiang.

Objective:To investigate the sero-epidemiological characteristics of the hepatitis D virus (HDV) infection among hepatitis B virus (HBV)-infected patients in Xinjiang region.Methods:A single-center cross-sectional analysis method was used to select 264 cases of hepatitis B virus infection who were hospitalized in the Center for Infectious Diseases and Liver Diseases of the First Affiliated Hospital of Xinjiang Medical University from August 2021 to January 2022. All patients were tested for HDV Ag, HDV IgM, HDV IgG, and HDV RNA. The infection status of hepatitis D virus was analyzed by grouping according to their clinical type, HBV viral load, and HBsAg level. A paired t-test was used for data with measurement data conforming to normal distribution. A paired rank sum test was used for data that did not conform to normal distribution before and after treatment.Results:A total of 36 cases (13.64%) and 26 cases (9.85%) were positive for HDV serological markers and HDV RNA. According to clinical type grouping, the positive rates of HDV serum markers in patients with chronic hepatitis B, hepatitis B-related cirrhosis, liver cancer, and liver failure were 13.46%, 12.43%, and 20.83%, respectively, and there was no statistically significant difference among the three groups ( χ2=0.86, P=0.649). The positive rates of HDV RNA were 11.54%, 8.11%, and 20.83%, respectively, and there was no statistically significant difference among the three groups ( χ2=4.015, P=0.134). According to HBV viral load grouping, the positive rates of HDV serum markers among patients with viral loads <20, 20-2 000, and >2 000 IU/ml were 17.15%, 7.81%, and 6.67%, respectively, and the difference was not statistically significant among the three groups ( χ2=4.846, P=0.089). The positive rates of HDV RNA were 9.47%, 10.94%, and 10%, respectively, and the difference was not statistically significant among the three groups ( χ2=0.113, P=0.945). According to HBsAg level grouping, the positive rates of HDV serum markers in HBsAg<0.05, 0.05~250, and >250 IU/ml were 14.29%, 16.67%, and 10.85%, respectively, and there was no statistically significance between the three groups ( χ2=1.745, P=0.418). The positive rates of HDV RNA were 4.76%, 8.77%, and 11.63%, respectively, and there was no statistically significant difference among the three groups ( χ2=1.221, P=0.543). Clinical outcome, disease course, HBV DNA, serological markers of viral hepatitis, routine blood test, biochemical indicators, coagulation function, and other laboratory indicators were compared between HDV serum marker and/or nucleic acid positive and negative patients, and there was no statistically significant difference ( P>0.05). Conclusion:The positive rate of HDV serological markers and HDV RNA is 13.64% and 9.85%, respectively, at a single center in the Xinjiang region, and there is still a high HDV infection rate among the HBV-infected patients with low levels of viral load and HBsAg.

Objective:To investigate the immune response characteristics of helper T cells Th1, Th2, Th17 and their related cytokines in acute, chronic and recovery phases after Brucella infection. Methods:Using prospective study, a total of 130 patients with brucellosis in the First Affiliated Hospital of Medical College of Shihezi University from January 2017 to December 2018 were selected as the research subjects, including acute phase group (49 cases), chronic phase group (44 cases), recovery phase group (37 cases), and 30 cases of healthy physical examination during the same period were included in the control group. The peripheral blood samples of all subjects were collected, and flow cytometry was used to detect Th1, Th2 and Th17 cells in the peripheral blood; the cytometry bead array (CBA) was used to detect the serum cytokines interferon-γ (IFN-γ), interleukin (IL)-4 and IL-17A expression levels.Results:In the control, acute phase, chronic phase and recovery phase groups, the differences of the expression ratios of Th1 [(1.03 ± 0.85)%, (5.46 ± 3.54)%, (4.48 ± 2.26)%, (2.29 ± 2.25)%], Th2 [(4.72 ± 2.36)%, (7.00 ± 3.14)%, (13.99 ± 9.14)%, (5.89 ± 4.69)%], and Th17 cells [(2.09 ± 0.48)%, (3.04 ± 2.17)%, (3.61 ± 2.67)%, (2.74 ± 2.58)%] were statistically significant ( F = 20.95, 21.15, 2.90, P < 0.05). Compared with the control group, the expressions ratio of Th1, Th2, Th17 cells in acute and chronic phase groups and Th1 cells in recovery phase group were significantly higher ( P < 0.05); compared with the recovery phase group, the expressions ratio of Th1, Th2 and Th17 cells in acute and chronic phase groups were significantly higher, but the expression ratio of Th2 cells in acute phase group was lower than that in chronic phase group ( P < 0.05). The expression levels of IFN-γ, IL-4, and IL-17A in serum of control group, acute phase, chronic phase and recovery phase groups were significantly different ( F = 7.79, 15.85, 7.55, P < 0.05); compared with the control group, the expression levels of IFN-γ, IL-4, IL-17A in acute and chronic phase groups and IFN-γ, IL-4 in recovery phase group were significantly higher ( P < 0.05); compared with the recovery phase group, the expression levels of IFN-γ, IL-4, IL-17A in acute phase group and IFN-γ, IL-17A in chronic phase group were significantly higher ( P < 0.05). The expression ratio of Th1 cells in recovery phase patients who finished treatment for less than 12 months was significantly higher than that of recovery phase patients who finished treatment for ≥12 months ( t = 2.26, P < 0.05). Conclusions:After patients are infected with Brucella, Th1 cell immunity is dominant in acute phase, Th2 cell immunity is dominant in chronic phase, and there is no significant difference in the response of Th17 cell immunity between acute and chronic phases. The immune function of patients in the recovery phase may still be abnormal when the treatment time is less than 12 months. Some clinically cured patients in the recovery phase still have a relatively high proportion of Th1 cells, suggesting that the patient's immune function has not fully recovered.

Objective:To analyze the clinical characteristics of HBV-related liver cirrhotic patients with low viral load.Methods:A retrospective analysis on 481 inpatients with HBV-related cirrhosis with low viral load [HBV DNA≤2 000 IU/ml (10 4 copies/ml)] general condition, virological indicators, liver function-related indicators, complications, and incidence of complications were analyzed. The t-test was used to compare the average measurement data, and the χ2 test was used to compare the count data. Results:481 cases were mainly male (male/female: 324/157), aged 20-83 (53.31 ± 11.67) years old. Han nationality accounted for 71.518%. 386 cases were HBsAg positive. 391 cases were HBeAg positive, and 140 cases were HBV DNA positive. The average value of bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, platelets, and prothrombin were 50.59 ± 91.25 (μmol/L), 33.68 ± 7.5 (g/L), and 60.66 ± 106.95(U/L), 63.37 ± 86.19(U/L), 106.65 ± 83.22(×10 9/L), 68.82% ± 25.33%, respectively. CTP class A/B/C had 220/150/111 cases. The average values of CTP, MELD, APRI and FIB-4 were 7.61 ± 2.58, 10.98 ± 5.79, 2.34 ± 3.56, 6.91 ± 8.04, respectively. The overall incidence of complications in HBV-related cirrhotic patients with low viral load, HBV DNA negative, HBV DNA positive, HBsAg negative, and HBsAg positive were 80.0%, 82.7%, 73.6%, 85.3%, and 78.8%, respectively. Among them, 283 cases (58.84%), 197 cases (55.77%), 86 cases (61.43%), 52 cases (54.74%) and 231 cases (59.84%) were of hypersplenism, and 267 cases (55.51%), 197 cases (55.77%), 70 cases (50.00%), 56 cases (58.95%), and 211 cases (54.66%) were of esophagogastric varices. There were 59 cases (12.27%), 48 cases (14.08%), 11 cases (7.86%), 12 cases (12.63%), and 47 cases (12.18%) of rupture of esophageal and gastric varices, respectively. 202 cases (42.00%), 147 cases (43.11%), 55 cases (39.29%), 42 cases (44.21%), and 160 cases (41.45%) were of ascites, respectively. 17 cases (3.53%), 12 cases (3.52%), 5 cases (3.5%), 2 cases (2.11%), 15 (3.89%) cases were of hepatic encephalopathy, respectively. There were 6 cases (1.25%), 3 cases (0.88%), 3 cases (2.14%), 0 cases (0%), 6 cases (1.55%) of liver cancer. 29 cases (6.03%), 21 cases (6.16%), 8 cases (5.71%), 9 cases (9.47%) and 20 cases (5.18%) were of portal vein thrombosis. Compared with the overall incidence of complications, 341 HBV DNA-negative patients and 95 HBsAg-negative patients still had higher incidence of complications. The patients were grouped by age, and in < 40 years old, 40-50 years old, and > 50 years old, the overall complications were 80.8% in 42 cases, 76.8% in 116 cases and 81.7% in 227 cases, and the difference was not statistically significant. Conclusion:HBV infection patients with low viral load, and those whose HBsAg has disappeared, are still at risk of developing liver cirrhosis and even serious complications, and whether such population need antiviral therapy and benefit from it deserves further research.

Objective: To investigate the clinical features of brucellosis with thrombocytopenia. Methods: The clinical data of patients with brucellosis complicated with thrombocytopenia (platelet count < 100 × 10⁹/L) diagnosed by the Department of Infection Disease, the First Affiliated Hospital of Xinjiang Medical University from January 2012 to December 2018 were collected retrospectively, and the demographic characteristics, clinical characteristics, laboratory examinations, treatment and prognosis of the patients were analyzed. Results: All the 21 patients were male and their age was (47.3 ± 12.2) years old, including 3 Uygur, 14 Han and 4 Kazak. Their occupation was dominated by farmers and herdsmen, a total of 16 patients; 11 patients had a history of close contact with cattle and sheep, 5 patients were engaged in slaughter and wool processing industries, and 5 patients were infected for unknown reason. All the 21 patients had fever, hyperhidrosis in 17 patients, fatigue in 16 patients, joint and muscle pain in 7 patients, and decreased body mass in 5 patients. Sheep Brucella blood culture were positive in 12 patients; serum tube agglutination test was positive in 16 patients, titer was 1∶200-1∶800; white blood cell count was normal [(4-10) × 10⁹/L] in 3 patients, white blood cell count reduced in 18 patients. Sixteen patients were treated by orally taking rifampin capsules combined with doxycycline tablets, 3 patients were treated by orally taking baifule tablets combined with doxycycline tablets, and 2 patients were treated by orally taking baifule tablets combined with rifampin capsules; three patients with platelet count < 10 × 10⁹/L were treated with glucocorticoid, gamma globulin and platelet transfusion. After 6 months of follow-up after treatment, 19 patients returned to normal platelet levels, and 2 patients had slightly lower platelet levels. Conclusions The main clinical features of brucellosis with thrombocytopenia are fever, hyperhidrosis, fatigue, joint and muscle pain, decreased body mass, and reduced white blood cell count. Their prognosis is better after treatment.

Objective To evaluate the application of modified MELD score based on the estimated glomerular filtration rate (eGFR) in the prognosis of patients with liver failure.Methods Clinical data of 558 patients with liver failure admitted in the First Affiliated Hospital of Xinjiang Medical University from December 2001 to September 2017 were retrospectively analyzed.Among all patients,238 cases survived (survival group) and 320 died (fatal group) within 3 months.The eGFR was used in the modified model for end stage liver disease (MELD) instead of serum creatinine.Cox regression analyses were fitted with modified MELD or MELD scores by SAS 9.0 PHREG.The receiver operating characteristic (ROC) curve was generated and the values of modified MELD score and MELD score in predicting the prognosis of patients with liver failure in 3 months were compared.Kaplan-Meier method was used to analyze the survival rate of patients with liver failure.Results Cox regression analysis showed that total bilirubin,international normalized ratio (INR) and eGFR were independent prognostic factors for patients with liver failure.The fitted MELD modified score =4.07 × ln total bilirubin (mg/dL) + 12.99 × ln INR-8.32 × ln eGFR.The area under the ROC curve (AUC) of the modified MELD score and the MELD score were 0.814 and 0.757,respectively,and the sensitivity and specificity of the modified MELD score were 70.0％ and 71.4％,respectively.The predictive power of modified MELD scores in patients with liver failure was better than MELD score (Z =4.47,P ＜ 0.01).The 3-month survival rate of patients with modified MELD score ＜-15.38 was significantly higher than those with modified MELD score ≥-15.38 (x2 =99.20,P ＜ 0.01).Conclusions eGFR is an independent risk factor for the prognosis of patients with liver failure.The modified MELD score including eGFR and excluding etiological factors can be more effective and more accurate for prognosis of patients with liver failure.

Objective: To investigate the curative effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of stromal cell-derived growth factor (SDF-1 α) and vascular endothelial growth factor (VEGF) in rats with acute hepatic failure, and to compare the effects of two transplantation pathways. Methods: Eighty-four rats with acute liver failure (ALF) induced by D-galactosamine combined with lipopolysaccharide were randomly divided into control group, tail vein and portal vein transplantation group. The latter two groups were injected allogenic BMSCs into the tail vein and portal vein. Blood samples and liver tissue samples were collected at 24, 72, 120, and 168h after transplantation to detect serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The improvement of liver function before and after BMSCs transplantation was compared. The expression of VEGF and SDF-1a in liver tissue was detected by immunofluorescence and Western blot. Data measurement between two groups was performed by analysis of variance and the correlation analysis was performed by Spearman’s rank correlation coefficient. Results: Serum ALT and AST levels in the tail vein and portal vein transplantation group peaked at 24 h after transplantation, which were (134.60 ± 58.08 IU/L), (179.20 ± 86.68 IU/L), and (131.00 ± 54.47 IU/L), (173.50 ± 93.10 IU/L). In addition, 168h after transplantation it decreased to (46.10 ± 8.40 IU/L), (95.67 ± 13.80 IU/L) and (19.30 ± 1.30 IU/L), (54.30 ± 6.00 IU/L). After 120 and 168 hours of BMSCs transplantation, the levels of serum ALT and AST in tail vein and portal vein transplantation group were significantly higher than control group (F ≥ 12.51, P < 0.01). The results of western blot and immunofluorescence showed that the expression levels of SDF-1α and VEGF protein in the two BMSCs transplantation groups increased with the improvement of liver function, and the difference was statistically significant at 120 and 168 hours after transplantation (F ≥ 9.069, P < 0.05). There was no significant difference in the expression of SDF-1a and VEGF between the tail vein and portal vein transplantation groups (P > 0.05). Correlation analysis showed that the expression levels of SDF-1α and VEGF in liver tissues were positively correlated (r = 0.923, P < 0.05). Conclusion BMSCs transplantation can promote the secretion of VEGF for recovery of liver function to reduce the degree of inflammation and necrosis in rats with ALF.