Association between proton pump inhibitors and risk of hepatic encephalopathy in patients undergoing transjugular intrahepatic portosystemic shunt: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Hepatic encephalopathy (HE) is a major complication of acute liver failure, cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS) placement. Its clinical manifestations range from mild cognitive deficits to coma. Furthermore, HE is a financial burden to a patient's family and significantly affects the patient's quality of life. In clinical practice, proton pump inhibitors (PPIs) are widely used for the treatment of HE. The use of PPIs is associated with an increased risk of post-TIPS HE; however, findings on the risk relationship between PPIs and post-TIPS HE are inconsistent. Therefore, a systematic evaluation of the relationship is needed to further provide valid evidence for the rational use of PPIs in patients who undergo TIPS. METHODS AND ANALYSIS: PubMed, Web of Science, Cochrane Library and Embase will be searched extensively for relevant information. Information from 1 July 2023 to 31 July 2023 in these databases will be included. Primary outcomes will be the use of PPIs and incidence of HE after TIPS; secondary outcomes will be survival, dose dependence and adverse events. This meta-analysis will be reported in accordance with the 50 Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The risk of bias, heterogeneity and quality of evidence of the included studies will be evaluated prior to the data analysis. All data will be analysed using Review Manager (V.5.4.1) and Stata (V.17.0) statistical software. ETHICS AND DISSEMINATION: Ethical approval will not be necessary for this review and meta-analysis. The results of the study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022359208.

The relationship between non-alcoholic fatty liver disease and incidence of chronic kidney disease for diabetic and non-diabetic subjects: A meta-analysis.

INTRODUCTION: The prevalence of chronic kidney disease (CKD) rises with age and co-morbid diseases such as liver diseases. OBJECTIVES: The main aim of the current meta-analysis is to assess the relationship between Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease incidence in both diabetic and non-diabetic subjects compared with control. MATERIAL AND METHODS: A systematic literature search of papers published from January 1, 2005, till April 30, 2022, found 19 studies including 1,111,046 subjects; 310,804 were diagnosed with NAFLD, and 800,242 were non-NAFLD. The measured outcome was the incidence of CKD among NAFLD subjects compared to non-NAFLD subjects in diabetic and non-diabetic subjects. Dichotomous analysis methods were used within the random effects model to calculate the odds ratio (OR) with 95% confidence intervals (95% CIs). RESULTS: The incidence of CKD is highly significant in NAFLD subjects compared with controls (OR: 1.95; 95% CI: 1.65-2.31). The diabetic non-NAFLD subjects showed a significantly increased incidence of CKD compared to the non-diabetic subjects with NAFLD (OR: 1.79; 95% CI: 1.35-2.38).. In addition, the incidence of CKD was significantly higher in the NAFLD group compared with the non-NAFLD non-diabetic subjects (OR: 2.52; 95% CI: 1.91-3.32). Diabetes acts as an independent risk factor for CKD, as proven by a significant increase in incidence of diabetic subjects compared to non-diabetic NAFLD subjects (OR: 1.82; 95% CI: 1.15-2.88). CONCLUSION: Non-alcoholic fatty liver disease is significantly related to an increased incidence of CKD, which is significantly higher in diabetic subjects.

Association between living arrangements and cognitive decline in older adults: A nationally representative longitudinal study in China.

BACKGROUND: Living arrangements are critical to the survival and well-being of older people, especially in China where the filial piety culture demands adult children care for and serve their parents. The study aimed to explore the association between living arrangements and cognitive decline among older people in China. METHODS: Participants included 6,074 older adults over 60 years old (49.65% male, mean age 67.2 years [range 60-98]) from four waves (2011-2018) of the China Health and Retirement Longitudinal Study. Two to four assessments were conducted over a follow-up of an average of 5.3 years (range, 2-7). Cognitive function was assessed using an adapted Chinese version of Mini-Mental State Examination (MMSE). Living arrangements were classified as follows: living alone, living with spouse, living with adult children, living with spouse and adult children and living with others. Multilevel models were used to investigate the relationship between living arrangements and cognitive decline, as well as the gender difference. RESULTS: As the main type of living arrangements of the study participants (44.91%), living with spouse was taken as the reference group. Compared to the reference group, living alone (ß=-0.126, P < 0.001), living with adult children (ß=-0.136, P < 0.001), living with spouse and adult children (ß=-0.040, P < 0.05) and living with others (ß=-0.155, P < 0.05) were all related to a faster rate of cognitive decline. Further, the association between living arrangements and cognitive decline varied by gender. Living alone (ß=-0.192, P < 0.001) was associated with a faster cognitive decline only in older men. Living with spouse and adult children (ß=-0.053, P < 0.05) and living with others (ß=-0.179, P < 0.05) were associated with faster cognitive decline only in older women. CONCLUSION: This study suggests that living arrangements in older people in China were associated with cognitive decline, and these associations varied by gender. Greater attention to living arrangements might yield practical implications for preserving the cognitive function of the older population.

Chinese Herb Jiedu Huayu Granules Inhibiting Immune and Inflammatory Response of Rats with Acute Liver Failure by Regulating the NF-κB Signaling Pathway.

Objective: To research the influence of Chinese medicine Jiedu Huayu granules (JDHY) on the immune response and inflammatory response of rats with acute liver failure (ALF) and investigate its related mechanism. Methods: Rats were randomly divided into 4 groups: control group (n = 6) were injected with the same amount of normal saline; ALF group (n = 10) were injected intraperitoneally with D-GaIN (700 mg/kg) and LPS (10 µg/kg); ALF+JDHY group (n = 10) were given JDHY 57.55 g/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose; and ALF+BAY group (n = 10) were given BAY 10 mg/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose. Changes in liver function and coagulation function were examined in rat serum; the pathological varieties of liver tissues were verified by HE staining; immunohistochemistry was utilized to determine the ratio of PCNA and F4/80 in liver tissues; the flow cytometry was applied to determine the ratio of CD4+/CD8+ cells in peripheral blood mononuclear cells (PBMCs); ELISA and qRT-PCR were utilized to check the level of IL-10, IL-6, IL-13, IL-1ß, TNF-α, IFN-γ, and CD163 in serum and liver cells. Western blot was adopted to check the expression of apoptotic protein and expression and NF-κB pathway-related protein expression. Results: JDHY and BAY could decline the expression of AST, ALT, ALP, and TBiL in ALF rat serum significantly (P < 0.01), increase PTA and PLT (P < 0.01), and mitigate liver tissue damage. Besides, JDHY and BAY could reduce the apoptosis and improve the proliferation of the liver cells in rats with ALF; meanwhile, the ratio of CD4+ cells and F4/80 cells was reduced while CD8+ cells were increased (P < 0.01). Further, JDHY and BAY could reduce the level of IFN-γ, IL-6, IL-1ß, and TNF-α while increasing the level of IL-10 and IL-13 (P < 0.01). Additionally, the expression of sCD163 in serum and CD163 expression in liver tissues increased (P < 0.01). The result of western blot confirmed that JDHY could inhibit the phosphorylated expression of NF-κB, IKßα, and IKKß in the ALF rat tissues. Conclusions: JDHY can upregulate the level of CD163/sCD163 by the NF-κB signaling pathway, thereby regulating immune response, inhibiting inflammatory response, and ultimately improving ALF in the rats.

Novel physical performance-based models for activities of daily living disability prediction among Chinese older community population: a nationally representative survey in China.

BACKGROUND: Physical performances including upper and lower limb functions have predictive roles in activities of daily living (ADL) disability, but they have rarely been incorporated into prediction models. This study primarily aimed to develop and validate novel physical performance-based models for ADL disability among Chinese older adults. Comparisons of predictive performance across multiple models were performed, and model simplification was further explored. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study in the 2011 and 2015 waves, containing 2192 older adults over 60 years old. Our models were constructed by logistic regression analysis, using a backward stepwise selection. Model performance was internally validated by discrimination, calibration, and clinical utility. Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) were used to assess the incremental benefit of the extended models. Moreover, nomograms were built for visualization. RESULTS: We selected gender, age, smoking, self-report health condition, BMI, depressive symptoms, and cognitive function into the fundamental model (Model 1). Based on Model 1, five novel prediction models were constructed by adding handgrip strength (Model 2), Short Physical Performance Battery (SPPB) (Model 3), gait speed (Model 4), handgrip strength plus SPPB (Model 5), and handgrip strength plus gait speed (Model 6), respectively. Significant improvement in predictive values were observed for all five novel models compared with Model 1 (C-index = 0.693). The lower limb model (Model 3 SPPB model: C-index = 0.731) may play a key role in the prediction of ADL disability, reflecting a comparable predictive value to the comprehensive models combining both upper and lower limbs (Model 5 handgrip strength + SPPB model: C-index = 0.732). When we simplified the lower limb models by replacing SPPB with gait speed, the predictive values attenuated slightly (C-index: Model 3 vs Model 4: 0.731 vs 0.714; Model 5 vs Model 6: 0.732 vs 0.718), but still better than the upper limb model (Model 2 handgrip strength model: C-index = 0.701). CONCLUSIONS: Physical performance-based models, especially lower limb model, provided improved prediction for ADL disability among Chinese older adults, which may help guide the targeted intervention.

Wenyang Huazhuo Tuihuang Formula Inhibits the Th17/Treg Cell Imbalance and Protects against Acute-on-Chronic Liver Failure.

Objective: Acute-on-chronic liver failure (ACLF) is a group of chronic liver diseases and caused by acute internal and external liver injury. Wenyang Huazhuo Tuihuang (WYHZTH) formula had a good clinical effect on promoting the resolution of jaundice. The aim of this study is to further investigate the mechanism of the WYHZTH formula in the ACLF rat model. Methods: The ACLF rat model was constructed by combining human serum albumin with LPS and D-gal. WYHZTH was used to intervene and treat. The cytokines IL-17, IL-23, IL-10, and TGF-ß were detected by ELISA and fluorescence-quantitative PCR. Flow cytometry was used to detect the percentage of Th17 and Treg cells in the peripheral blood and liver tissues of each group of rats. The pathological changes in the liver tissue were detected by hematoxylin-eosin staining, immunohistochemistry, and electron microscopy. Results: Compared with the ACLF group, the WYHZTH formula and Thy significantly decreased the levels of ALT, AST, and CHE in the ACLF group. After drug intervention, apoptosis was significantly reduced. The PCNA expression decreased in the ACLF model group but increased in the WYHZTH or Thy group. Under transmission electron microscope, hepatocytes in the ACLF group showed obvious necrosis. After drug intervention, hepatocyte necrosis was reduced with most of the structure returning to normal. Conclusion: This present study demonstrated that WYHZTH formula may protect against acute-on-chronic liver failure, which may be related to the inhibition of Th17/Treg cell imbalance.

Detoxification II Prescription Suppresses the Th-17/IL-17 Inflammatory Axis to Improve the Liver Function of ACLF-Rats via Inactivating the P38MAPK Pathway.

Hepatitis is a metabolic system disease which is a serious challenge to the medical and healthcare system of the world. This study attempted to investigate the therapeutic effect and illustrate the regulation pharmacological mechanism of Detoxification II Prescription on ACLF. In this study, the rats were injected with D-galactosamine to establish ACLF-rat models, and the levels of cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBiL) were measured with the related kits to reflect the liver functions of the rats. The levels of IL-17, IL-6, and IFN-γ in the serums of the rats were detected by qRT-PCR, and the percentages of Th-17 cells in CD4+ cells of the rats were measured by flow cytometry assay. In the results, the increased ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ and decreased ALB and CHE were found in the serums of the ACLF-rats, while Detoxification II Prescription could partly reverse those indexes of the ACLF-rats. Moreover, it was also found that Detoxification II Prescription could inhibit the expression of P38MAPK, and P38MAPK downregulation obviously improved the liver function indexes of the ACLF-rats including the levels of ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ cells. In conclusion, this study suggested that Detoxification II Prescription could suppress the Th-17/IL-17 inflammatory axis to improve the liver function of ACLF-rats via inhibiting the activity of the P38MAPK pathway.

Traditional Chinese medicine enema for acute chronic liver failure: A protocol of systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Acute chronic liver failure (ACLF) is the most common type of liver failure. The clinical symptoms are complex and changeable, the treatment is difficult and the fatality rate is high. It has become an urgent problem to actively seek effective treatment means and improve the clinical efficacy of ACLF patients. Studies have shown that decreased intestinal barrier function and bacterial endotoxin translocation in ACLF patients are considered to be the key causes of enterogenic endotoxemia, and traditional Chinese medicine enema has certain advantages in adjuvant treatment of this disease. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on Traditional Chinese medicine enema for ACLF and provide effective evidence for further research. METHODS: We will search the following electronic databases from their inception to July 2020: Electronic database includes PubMed, Embase, Cochrane Library, Chinese Biomedical Database WangFang, VIP medicine information, and China National Knowledge Infrastructure. Primary outcomes: survival rates, TCM syndrome score. SECONDARY OUTCOMES: liver function (alanine aminotransferase, aspartic acid amino transferase, total bilirubin), blood coagulation function (prothrombin activity), adverse events. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of Traditional Chinese medicine enema for ACLF. CONCLUSION: The systematic review of this study will summarize the currently published evidence of Traditional Chinese medicine enema for ACLF to further guide its promotion and application.

The underlying mechanisms of Jie-Du-Hua-Yu granule for protecting rat liver failure.

OBJECTIVES: Jie-Du-Hua-Yu (JDHY) granule is a combination of six traditional Chinese medicines with known therapeutic effect in treating acute liver failure (ALF). The aim of this study was to investigate the amelioration efficacy of JDHY in lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF in rat and explore the possible molecular mechanism underlying the therapeutic efficacy. MATERIALS AND METHODS: The efficacy of JDHY was determined by assessing hepatic pathology and function in LPS and D-GalN challenged Wistar rat. We also evaluated the effect of JDHY on LPS-induced Kupffer cells by measuring inflammatory cytokines and determining the phenotypic function. By means of bioinformatics analysis of liver tissue and validation in Kupffer cells, we identified possible pathways involved in the pharmacologic action of mechanism of JDHY. RESULTS: JDHY could attenuate LPS-induced liver injury in rat by inhibiting apoptosis and increasing hepatic activity. In vitro study showed that JDHY could decrease the production of proinflammatory cytokines (tumor necrosis factor-α, IL6, and interferon-γ), increase anti-inflammatory cytokines (IL10, IL13), and promote cell survival and proliferation, possibly due to inhibition of IκB/nuclear factor-κB (NF-κB) signaling pathway and expression of CD14 and CXCL2, which was consistent with the findings from bioinformatics analysis. CONCLUSION: Our results revealed that JDHY protected against LPS-induced liver damage both in vitro and in vivo, by inhibiting the NF-κB-mediated inflammatory pathway, indicating its potential function to treat liver diseases.