OBJECTIVES: To explore the mechanism by which Tougu Xiaotong Capsule (TXC) promotes chondrogenic differentiation and cartilage repair in mice with osteoarthritis (OA). METHODS: Fifty 8-week-old male C57BL mice were randomly divided into normal control group, cartilage damage (induced by subchondral ring-shaped drilling) model group and TXC treatment groups at low, moderate and high doses (184, 368 and 736 mg/kg, respectively). Saline (in normal control and model groups) and TXC were administered after modeling by daily gavage for 6 consecutive weeks. The changes of cartilage damage in the mice were assessed by measuring thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) and using micro-CT, modified safranine O and fast green staining, HE staining, and qPCR. Primary cultures of mouse synovial mesenchymal stem cells (SMSCs) with lentivirus vector transfection for interfering CXCL12, TXC treatment, or both for 24 h were examined for chondrogenic differentiation using immunofluorescence staining, scratch assay, immunocytochemistry, and Western blotting. RESULTS: In mouse models with cartilage damage, TXC treatment at the moderate dose significantly alleviated joint pain, promoted cartilage repair, and upregulated the mRNA expression levels of CXCL12, GDF5, collagen II, aggrecan, Comp and Sox9 in the cartilage tissue. In primary mouse SMSCs, CXCL12 knockdown resulted in significant reduction of GDF5 protein expression, migration ability and Sox9 protein expression, and these changes were obviously reversed by TXC treatment. CONCLUSIONS TXC promotes chondrogenic differentiation of mouse SMSCs to promote repair of cartilage damage in mice by activating the CXCL12/GDF5 pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Osteoarthritis/metabolism* ; Male ; Growth Differentiation Factor 5/metabolism* ; Mice, Inbred C57BL ; Mice ; Chemokine CXCL12/metabolism* ; Signal Transduction/drug effects* ; Cell Differentiation/drug effects* ; Cartilage, Articular/drug effects* ; Mesenchymal Stem Cells/cytology*

Managing cirrhosis complications is an important measure for improving patients' clinical outcomes. Therefore, in order to provide a complete disease assessment and comprehensive treatment, improve quality of life, and improve the prognosis for patients with cirrhosis, it is necessary to pay attention to complications such as thrombocytopenia and portal vein thrombosis in addition to common or severe complications such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. The relevant concept that an effective albumin concentration is more helpful in predicting the cirrhosis outcome is gradually being accepted; however, the detection method still needs further standardization and commercialization.

Objective:To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis.Methods:A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ2 test. The inter-group comparison was performed using continuous variables, a t-test, one-way analysis of variance (ANOVA), or a nonparametric test. Results:There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP ( OR=1.32, 95% CI: 1.12-1.56, P=0.001). Patients combined with EGV ( OR=3.09, 95% CI: 2.63-3.65, P<0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism ( P<0.001). Patients with PBC ( OR=0.64, 95% CI: 0.50-0.82, P<0.001) and PSC ( OR=0.23, 95% CI: 0.06-0.65, P=0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients ( P<0.001), and the lower proportion of hypersplenism in combined PSC patients ( P=0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures ( P<0.05), but a lower rate of liver biopsy ( P<0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without ( P=0.004). Conclusion:TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.

Hepatitis B virus (HBV) infection is a common cause of liver disease in China, and with the continuous progress in the research on antiviral therapy for chronic hepatitis B, the indications for antiviral therapy are constantly expanding. However, there are still controversies over the indications for antiviral therapy in patients with chronic hepatitis B (CHB), especially those with negative HBV. By analyzing the limitations of HBV DNA detection, the risk of HBV reactivation in HBV-negative CHB patients, the risk of disease progression in the DNA-negative population with compensated hepatitis B cirrhosis, antiviral response, and the economic benefits of antiviral therapy, this article proposes the necessity of antiviral therapy for HBV-negative HBsAg-positive patients with compensated hepatitis B cirrhosis.

Objective:To understand the clinical characteristics of hospitalized patients with liver cirrhosis, so as to provide theoretical basis for disease diagnosis and treatment, formulation of intervention measures, and improve the level of disease diagnosis and treatment.Methods:Hospitalized patients who were initially diagnosed with liver cirrhosis at Peking University First Hospital from August 2017 to December 2018 were selected retrospectively as the research objects. Liver cirrhosis demographic data, etiology, severity classification, incidence of complications, diagnosis and prognosis were recorded. Statistical analysis was performed using SPSS software.Results:Among all liver cirrhosis cases, there were 291 males and 209 females, with a male-to-female ratio of 1.4:1 and an age of 59.5±12.9 years as at August 2017 to December 2018. HBV infection, alcoholic liver disease, and autoimmune liver diseases were the most common etiology of liver cirrhosis. HBV infection alone, HBV infection combined with other factors, alcoholic liver disease alone, alcoholic liver disease combined with other factors, autoimmune liver disease alone, and autoimmune liver disease combined with other factors were presented in 163 (32.6%), 57 (11.4%), 47 (9.4%), 63 (12.6%), 85 (17.0%), and 22 (4.4.0%) cases, respectively. Ascites (221 cases, 44.2%), followed by esophagogastric varices (214 cases, 42.8%), and other including hypersplenism (137 cases), liver cancer (126 cases), upper digestive system tract hemorrhage (66 cases), hepatic encephalopathy (40 cases), infection (37 cases), portal vein thrombosis (23 cases), hepatorenal syndrome (20 cases) were the most common complications. The most common site of infection was the abdominal cavity (20 cases), accounting for 54.1%; followed by respiratory tract infection (8 cases), accounting for 21.6% in patients with liver cirrhosis with concurrent infection. Among them, there were 32 cases of bacterial infection alone, one case of bacterial infection combined with fungal infection, one case of bacterial infection combined with viral infection, and three cases of unknown pathogens. There were 69 cases in Child Pugh grade C, and the average hospitalization times were 12.6 days in terms of prognosis. There were total seven cases of death, of which five cases were due to upper gastrointestinal hemorrhage and two due to hepatic encephalopathy.Conclusion:HBV infection, ascites, and upper gastrointestinal bleeding were the most common etiologies, complications, and causes of death in patients with liver cirrhosis at our hospital.

Patients with chronic (hepatitis B virus,HBV) infection can be divided into immunotolerant, immunoclearance (HBeAg-positive, immune-active), immunocontrol (inactive), and reactivation (HBeAg-negative, immune-active) phases according to HBV serological markers, HBV DNA, alanine aminotransferase, and liver pathology results. Chronic HBV infection is considered indeterminate when the above four phasing criteria are not met. The Chinese "Guidelines" recommend antiviral B treatment for chronic HBV-infected patients with elevated alanine aminotransferase levels after excluding other potential causes. As a result, patients with chronic HBV infection in the immunoclearance and reactivation phases are included in the indication population for antiviral therapy, and the expanded indications are mainly for other infected individuals beyond these two phases: immunotolerant, immunocontrol, and indeterminate. Antiviral therapy may benefit individuals in an indeterminate phase, because they are at a relatively high risk of disease progression.

ObjectiveTo investigate the features of liver injury and related influencing factors in adolescents and adults with infectious mononucleosis (IM). MethodsA retrospective analysis was performed to investigate the features of liver injury in adolescents and adults with IM who were hospitalized in Peking University First Hospital from January 2005 to December 31 2018, and the patients were divided into subgroups based on age, Epstein-Barr virus (EBV) DNA level, and presence or absence of jaundice or infection with cytomegalovirus or hepatitis E virus (HEV). The t-test was used for comparison of continuous data meeting analytical conditions between two groups, and the Mann-Whitney U test was used for comparison of continuous data which did not meet analytical conditions between two groups; the chi-square test was used for comparison of categorical data between two groups, and the Fisher’s exact test was used for comparison of categorical data which did not meet the analytical conditions of the chi-square test. A logistic regression analysis was used for multivariate analysis. ResultsA total of 274 patients were enrolled, with 154 male patients (56.2%) and 120 female patients (43.8%), and the mean age of onset was 22.3±67 years. The incidence rate of liver injury ［defined as alanine aminotransferase (ALT) ＞50 U/L and/or aspartate aminotransferase (AST)＞40 U/L］ was 97.4% (267/274), and that of jaundice was 27.6% (74/268). The patients, aged ≥20 years, tended to have a higher level of gamma-glutamyl transpeptidase (GGT) (Z=2.070, P=0.038). Serum EBV DNA was measured for 167 patients, among whom 90 had positive results and 77 had negative results. The positive serum EBV DNA group had significantly higher levels of GGT (Z=3.005, P=0.003) and lactate dehydrogenase (Z=2.162, P=0.031) than the negative serum EBV DNA group. The patients with cytomegalovirus infection tended to have a higher level of alkaline phosphatase (Z=2.351, P=0.019), and the patients with HEV infection presented with a higher level of GGT (Z=1.988, P=0.047). AST (odds ratio ［OR］=1.006, 95% confidence interval ［CI］: 1.002-1.010, P=0.005) and ALP (OR=1.012, 95%CI: 1.005-1.020, P=0.001) were independent risk factors for jaundice. ConclusionThere is a high incidence rate of liver injury in adolescents and adults with IM, and the patients with an older age or positive serum EBV DNA tend to have more severe liver injury.

Objective:To analyze the effectiveness of antiviral therapy on adolescents and adults with infectious mononucleosis (IM).Methods:The clinical data of patients aged≥16 years old with IM who were hospitalized in Peking University First Hospital from January 1, 2005 to December 31, 2018 were analyzed retrospectively, and the patients were divided into antiviral treatment group and non-antiviral treatment group. The duration of hospitalization day, fever duration, ratio of lymphocytes and duration for normalization of Epstein-Barr virus (EBV) markers were compared between the two groups through single factor and propensity score matching analysis. Statistical analysis was conducted by independent sample t test, Mann-Whitney U test, chi-square test or Fisher exact probability method. Results:A total of 274 cases were enrolled and 176 cases (64.23%) were divided into antiviral treatment group and 98 cases (35.77%) into non-antiviral treatment group. The proportion of male (56.25%(99/176) vs 56.12%(55/98)), age (21.0(18.0, 26.0) years old vs 21.0(18.0, 27.0) years old), the ratio of fever (98.30%(173/176) vs 93.88%(92/98)), sore throat (90.34%(159/176) vs 88.78%(87/98)), lymphocyte ratio (0.648(0.568, 0.707) vs 0.663(0.581, 0.711)), atypical lymphocyte ratio (0.150(0.100, 0.235) vs 0.135(0.060, 0.250)) and serum EBV DNA level (2.71(2.70, 3.47) lg copies/mL vs 2.70(2.70, 3.28) lg copies/mL) were comparable between two groups at admission, and the differences were all not statistically significant(all P>0.05). The durations of hospitalization and fever in antiviral treatment group were 14.0(10.0, 18.0) d and (14.91±7.24) d, respectively, which were both significantly longer than those in non-antiviral treatment group (11.0(7.0, 15.0) d and (9.95±5.67) d, respectively). The differences were both statistically significant ( Z=-3.294 and t=-5.035, respectively, both P<0.01). Twenty-six patients each in the antiviral treatment group and non-antiviral treatment group were included in the propensity score matching assessment. The fever days of the two groups were 15.0(10.0, 18.0) d and 7.5(5.0, 12.5) d, respectively, and the hospitalization days were (15.4±5.5) d and (12.0±5.7) d, respectively. The differences were both statistically significant ( Z=-3.781 and t=-2.187, respectively, both P<0.05). However, there were no significant differences in the time required for the ratio of lymphocytes returning to normal, the time required for the ratio of atypical lymphocytes decreasing to <0.100, and the time required for serum EBV DNA becoming negative(all P>0.05). Conclusion:The antiviral treatment could not improve the prognosis of adolescent and adult IM patients.

Liver cirrhosis is the final stage of many chronic liver diseases, and is still a heavy disease burden. The proportion of liver cirrhosis caused by the hepatitis B virus is declining, while that caused by the non-alcoholic fatty liver disease (metabolic-associated fatty liver disease) is rising. Several predictive models and techniques such as transient elastography have been used for the early non-invasive evaluation of liver cirrhosis. Effective etiological treatment and complication management are the possible key to reverse and recompense liver function during liver cirrhosis treatment. In recent years, the effectiveness and availability of anti-hepatitis B and C virus drugs have been significantly improved, which provides the basis for effective etiological treatment of liver cirrhosis. However, there is still a lack of etiological treatment measures for non-alcoholic fatty liver disease. Therefore, in addition to focusing on common complications, we should also manage "rare" complications. This article reviews the changes in epidemiological characteristics, the update of the natural history concepts, diagnostic evaluation methods, and the treatment measures for liver cirrhosis.