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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Objective To further clarify the pathogenesis of different types of Kaposi′s sarcoma (KS) by measuring the protein expressions of caspase-3 and E-cad in tumor tissues of Xinjiang Uygur patients with acqured immunodeficiency syndrome (AIDS)-Kaposi′s sarcoma (KS) and classical KS.Methods From July 2011 to October 2014, 38 patients with KS at the First Affiliated Hospital of Xinjiang Medical University and Urumqi Infectious Disease Hospital were enrolled, among whom 28 were male and 10 were female, and all of them were uygur.Immunohistochemical and Western blot methods were used to detect the expressions of caspase-3 and E-cad proteins in 22 cases of AIDS-KS patients and 16 cases of classic KS.The quantitative data of normal distribution were analyzed by t test, while count data were compared with χ2 test with R × C table.Results KS lesions in patients with classic KS were confined to the skin, without mucosal, lymph node or visceral involvement.Lesions in AIDS-KS patients were not only confined to the skin and superficial lymph nodes, but also oral mucosa involved in 12 cases and internal organs involved in 7 cases.Liver and lung involvement was more common.The CD4+T lymphocyte count in patients with AIDS-KS was (200.8±166)/μL.All 15 AIDS cases with CD4+ T cell count less than 200/μL developed opportunistic infections.CD4+ T lymphocyte count of patients with classic KS was (562.52±222.66)/μL and the 16 patients with CD4+T lymphocyte count greater than 350/μL had no opportunistic infections.The results of immunohistochemistry showed that the positive expression rate of caspase-3 protein in KS tissues in patients with AIDS-KS was 68.2%, in patients with classic KS was 100.0%, with significant difference between two groups (χ2=7.37, P=0.01).The positive expression rate of E-cad protein in KS tissues in patients with AIDS-KS was 72.7%, in patients with classic KS was 100.0%, with significant difference between two groups (χ2=5.18, P=0.03).Western blotting showed that the gray value of caspase-3 in the KS tissue of patients with AIDS-KS was 0.55±0.36, and that in patients with classic KS was 0.86±0.56, with significant difference between two groups (t=-2.070, P<0.05).The gray value of E-cad in the KS tissue of patients with AIDS-KS was 0.54±0.41, and that in patients with classic KS was 0.85±0.45, with significant difference between two groups (t=-2.060,P<0.05).Conclusions There are differences in the protein expressions of caspase-3 and E-cad in tumor tissues of patients with AIDS-KS and classical KS in Xinjiang Uygur patients with Kaposi's sarcoma, which may correlate with a faster progression and a higher mortality rate for AIDS-KS.
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Objective To evaluate the efficacy of artificial liver support system ( ALSS) combined with conventional medical treatment for liver failure .Methods Literature retrieval of Wanfang Data , CQVIP, CNKI, Medline, Cochrane Library and PubMed from 2004 to 2014 was conducted to identify all studies on ALSS in treatment of liver failure .The quality of the literature was assessed according to Cochrane systematic guide manual , and meta-analysis was performed using RevMan 5.3.Random-effects or fixed-effects model was performed based on the heterogeneity , and publication bias was evaluated with Begg ’ s funnel pot .Results A total of 20 randomized controlled clinical trials involving 2 356 patients were included for systematic review , among which 1 247 patients were treated with ALSS combined with medical therapy, and 1 109 patients were treated with medical therapy only .Meta-analysis showed that the mortality of patients with liver failure treated with combined therapy was 25.3%(316/1247), which was lower than that with medical treatment alone (524/1 109, 47.2%) ( OR=0.36, 95%CI:0.30-0.43, Z=11.19, P<0.01).The mortality of patients with acute (subacute) and subacute-on-chronic liver failure treated with combined therapy (54/203, 26.6%) was lower than that with medical treatment group (76/188, 40.4%) (OR=0.53, 95%CI:0.34-0.81, Z=2.91, P<0.01).The mortality of patients with chronic liver failure treated with combined therapy was 25.6% (89/347), which was also lower than that with medical treatment group (171/340, 50.3%) (OR=0.32, 95%CI:0.23-0.45, Z=6.73, P<0.01). Mortality in patients received medical treatment plus molecular adsorption recirculation system , plasma exchange or multiple ALSS were 23.6% (26/110), 21.9% (126/575) and 29.7% (80/269), which were significantly lower than those in patients received only medical treatment [38.9%(42/108), 52.2%(257/492) and 45.4%(103/227)] (OR=0.48, 0.24 and 0.45, 95%CI:0.26-0.88, 0.18-0.31 and 0.31-0.67, Z=2.38, 10.14 and 4.02, all P<0.05 or <0.01).Conclusion ALSS combined with medical therapy can reduce the mortality of patients with various types of liver failures .
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BACKGROUND:Studies have shown that bone marrow mesenchymal stem cells have the ability to persistently generate hepatocytes and biliary cells, and thus in the repair process of liver injury, replenish the reduced number of hepatocytes due to damage and participate in damaged liver structure. OBJECTIVE:To investigate the effect of bone marrow mesenchymal stem cells transplantation on acute liver failure and the expression of CD163 and interleukin-10 in rat serum and liver tissue. METHODS:D-galactose and lipopolysaccharidewere used to make acute liver failure models in 60 Sprague-Dawley rats. Then, the rats were divided into control group and transplantation group. Bone marrow mesenchymal stem cells at passage 3 were injected through tail vein in the transplantation group, and normal saline was injected in the control group. After transplantation 24, 120, 168 hours, serum samples and liver tissues were col ected. RESULTS AND CONCLUSION:After transplantation 120 and 168 hours, the serum alanine transaminase and aspartate aminotransferase activities of the transplantation were significantly lower than those of the control group (P<0.05). In the transplantation group the apoptotic index was stil lower compared with the control group, and the difference was significant (P<0.05). The levels of CD163 and interleukin-10 in the serum and liver tissue in the transplantation group were decreased significantly compared with the control group (P<0.05). The results suggested that there were highly significant correlations between CD163 and interleukin-10 (P<0.01). Bone marrow mesenchymal stem celltransplantation has a therapeutic effect on acute liver failure rats. CDl63 and interleukin-10 play a very important role in the pathogenesis of acute liver failure, which can be used as sensitive serum marker proteins for diagnosis and prognosis of acute liver failure.