ObjectiveTo investigate the effect of Yiqi Yangyin Jiedu Huayu prescription on minimal hepatic encephalopathy in liver cirrhosis based on intestinal metabolomics. MethodsA total of 11 patients with liver cirrhosis who were hospitalized in Beijing Ditan Hospital， Capital Medical University， from March to May 2024， and were diagnosed with MHE based on psychometric hepatic encephalopathy score were enrolled as subjects， and 11 healthy family members of the patients were enrolled as control group. Fecal samples were collected for metabolomics analysis from the control group and the patients with MHE before and after treatment with Yiqi Yangyin Jiedu Huayu prescription， and a population cohort study was conducted to investigate the effect of Yiqi Yangyin Jiedu Huayu prescription on intestinal metabolism of patients with MHE. The Fisher’s exact test was used for categorical data between two groups； the independent samples t-test was used for comparison of normally distributed continuous data between two groups， the paired t-test was used for comparision before and after treatment within the same group， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsA total of 29 differentially expressed metabolites were detected between the MHE group and the control group， mainly amino acids， organic acids， organic amines， carbohydrates， fatty acids， and vitamins， and there were 12 upregulated metabolites and 17 downregulated metabolites in the MHE group， which were mainly enriched in the metabolic pathways of ornithine， branched-chain amino acid， and aromatic amino acid. After the treatment with Yiqi Yangyin Jiedu Huayu prescription， 80 differentially expressed metabolites were detected in the patients with MHE， mainly carbohydrates， organic acids， and amino acids， and there were 56 upregulated metabolites and 24 downregulated metabolites， which were mainly enriched in the metabolic pathways of ornithine， branched-chain amino acid， and aromatic amino acid. ConclusionYiqi Yangyin Jiedu Huayu prescription can exert a therapeutic effect on patients with MHE by regulating intestinal metabolism.

Objective To investigate the genetic association between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM)using bidirectional two-sample Mendelian randomization(MR),as well as the causal relationship between NAFLD and T2DM across different body mass index(BMI)categories.Methods The data were derived from genome-wide association studies conducted in European populations,with a sample size of 32 941 cases for NAFLD,312 646 cases for T2DM,and 681 275 cases for BMI.The univariate and multivariate MR methods were used to assess the bidirectional causal relationship between NAFLD and T2DM in the general population and across different BMI subtypes.The methods of inverse-variance weighting,MR-Egger regression,constrained maximum likelihood and model averaging,and weighted median were used to conduct the MR analysis,and MR-Pleiotropy Residual Sum and Outlier,radial MR,the MR-Egger intercept method,and the Cochrane Q test were used for sensitivity analysis.Results The univariate MR analysis revealed a bidirectional causal relationship between NAFLD and T2DM in the general population(forward analysis:odds ratio[OR]=9.75,95%confidence interval[CI]:2.57-37.00,P＜0.001;reverse analysis:OR=1.01,95%CI:1.00-1.01,P＜0.01).After adjustment for BMI,the multivariate MR analysis showed that the causal relationship between NAFLD and T2DM remained significant in the general population(OR=33.12,95%CI:7.57-144.95,P＜0.000 1).The subgroup analysis showed a causal relationship between NAFLD and T2DM across all BMI subtypes(lean subgroup:OR=12.19,95%CI:3.35-44.40,P＜0.001;overweight subgroup:OR=4.30,95%CI:1.69-10.92,P＜0.01;obese subgroup:OR=1.67,95%CI:1.14-2.44,P＜0.01).Conclusion This study reveals the causal relationship between NAFLD and T2DM in the general population of NAFLD and across different BMI subtypes from a genetic perspective.

Objective:To investigate the correlation between intraoperative red blood cell (RBC) transfusion and postoperative continuous renal replacement therapy (CRRT) in patients with acute type A aortic dissection (ATAAD).Methods:Clinical data of 302 patients undergoing emergency surgery for ATAAD in the Department of Cardiac Surgery at Beijing Anzhen Hospital from September 2015 to October 2020 were retrospectively analyzed. Among them, 238 were males with a nean age of(46.3±10.0) years old; 64 were females with a mean age of (52.0±11.7) years old. Patients were divided into the CRRT group and the non-CRRT group based on whether they received CRRT postoperatively. Logistic regression analysis was used to investigate the correlation between intraoperative RBC transfusion and postoperative CRRT. Results:Forty-two patients (13.9%) required CRRT postoperatively. Univariate logistic regression analysis showed that intraoperative RBC transfusion increased the risk of postoperative CRRT ( OR=2.499, 95% CI: 1.266-4.470, P=0.008). However, after adjusting for other variables, multivariate logistic regression analysis showed that the association was not statistically significant ( OR=1.777, 95% CI: 0.583-5.417, P=0.312). Conclusion:The increased risk of postoperative CRRT in ATAAD patients due to intraoperative RBC transfusion is caused by confounding factors, and they are actually not significantly correlated.

Objective:To investigate the correlation between intraoperative red blood cell (RBC) transfusion and postoperative continuous renal replacement therapy (CRRT) in patients with acute type A aortic dissection (ATAAD).Methods:Clinical data of 302 patients undergoing emergency surgery for ATAAD in the Department of Cardiac Surgery at Beijing Anzhen Hospital from September 2015 to October 2020 were retrospectively analyzed. Among them, 238 were males with a nean age of(46.3±10.0) years old; 64 were females with a mean age of (52.0±11.7) years old. Patients were divided into the CRRT group and the non-CRRT group based on whether they received CRRT postoperatively. Logistic regression analysis was used to investigate the correlation between intraoperative RBC transfusion and postoperative CRRT. Results:Forty-two patients (13.9%) required CRRT postoperatively. Univariate logistic regression analysis showed that intraoperative RBC transfusion increased the risk of postoperative CRRT ( OR=2.499, 95% CI: 1.266-4.470, P=0.008). However, after adjusting for other variables, multivariate logistic regression analysis showed that the association was not statistically significant ( OR=1.777, 95% CI: 0.583-5.417, P=0.312). Conclusion:The increased risk of postoperative CRRT in ATAAD patients due to intraoperative RBC transfusion is caused by confounding factors, and they are actually not significantly correlated.

Acute decompensated cirrhosis is a stage of end-stage liver disease during which patients often experience decompensated complications and rapid progression. Systemic inflammatory response is characterized by excessive secretion of inflammatory factors caused by bacterial infection of local tissue and rapid spread to the whole body, thereby affecting the physiological activities of the body and causing organ damage or disorder, and it is a relatively serious inflammatory state. This article elaborates on the occurrence of systemic inflammation, the factors affecting the severity of systemic inflammation, the manifestation of systemic inflammation in different stages of decompensated cirrhosis, and the role of systemic inflammation in complications, in order to gain a deeper understanding of systemic inflammation and apply it in the research and development of new therapies and drugs.

Objective:To analyze and evaluate the decrease of anticoagulant effect of warfarin by herbal and dietary supplements (HDS) based on case report literature.Methods:The case reports on decrease of anticoagulant effect of warfarin by HDS were selected by searching the relevant databases at home and abroad (up to June 24, 2023). The degree of decrease of anticoagulant effect of warfarin by HDS was evaluated according to the reduction degree of international normalized ratio and the occurrence of thrombotic events in patients in the case reports. The reliability scoring criteria of HDS-warfarin interaction was established according to the causality of the interaction between HDS and warfarin, the number of case reports, and the other evidences (warnings issued by relevant national institutions, clinical studies, pharmacokinetic/pharmacodynamic studies, animal studies, etc.). It was evaluated as highly, relatively, possibly, and suspiciously reliable if the total score was ≥9, 6-8, 3-5, and ≤2 points, respectively.Results:A total of 17 case reports were enrolled in the analysis, involving 25 patients and 11 kinds of HDS. Two kinds of HDS reduced the anticoagulant effect of warfarin severely, including ginseng ( Radix Ginseng)[(American ginseng ( Radix Panacis Quinquefolii), red ginseng, etc.] and Myrrh; 5 kinds of HDS reduced the anticoagulant effect of warfarin moderately, including St. John′s wort ( Hypericum perforatum L.), tea [green tea ( Camellia sinensis), black tea], peppermint ( Herba Menthae), coenzyme Q 10, and chitosan; 4 kinds of HDS reduced the anticoagulant effect of warfarin slightly, including milkvetch root ( Radix Astragali seu Hedysari), avocado, seaweed ( Sargassum), and soya ( Glycine max). The reliability of anticoagulant effect reduction of warfarin was evaluated as highly reliable in 1 kind of HDS, namely St. John′s wort (10 points), relatively reliable in 2 kinds of HDS, including ginseng and tea (8 and 6 points, respectively), possibly reliable in 7 kinds of HDS, including Myrrh, peppermint, coenzyme Q 10, chitosan, milkvetch root, avocado, and seaweed (5, 5, 5, 4, 4, 4, and 3 points, respectively), and suspiciously reliable in 1 kind of HDS, namely soya (2 points). Conclusion:The degree and reliability of anticoagulant effect reduction of warfarin by ginseng (American ginseng, red ginseng, etc.), St. John′s wort, and tea (green tea, black tea), are higher, which should be paid attention to by clinicians and clinical pharmacists.

Objective:To analyze and evaluate the decrease of anticoagulant effect of warfarin by herbal and dietary supplements (HDS) based on case report literature.Methods:The case reports on decrease of anticoagulant effect of warfarin by HDS were selected by searching the relevant databases at home and abroad (up to June 24, 2023). The degree of decrease of anticoagulant effect of warfarin by HDS was evaluated according to the reduction degree of international normalized ratio and the occurrence of thrombotic events in patients in the case reports. The reliability scoring criteria of HDS-warfarin interaction was established according to the causality of the interaction between HDS and warfarin, the number of case reports, and the other evidences (warnings issued by relevant national institutions, clinical studies, pharmacokinetic/pharmacodynamic studies, animal studies, etc.). It was evaluated as highly, relatively, possibly, and suspiciously reliable if the total score was ≥9, 6-8, 3-5, and ≤2 points, respectively.Results:A total of 17 case reports were enrolled in the analysis, involving 25 patients and 11 kinds of HDS. Two kinds of HDS reduced the anticoagulant effect of warfarin severely, including ginseng ( Radix Ginseng)[(American ginseng ( Radix Panacis Quinquefolii), red ginseng, etc.] and Myrrh; 5 kinds of HDS reduced the anticoagulant effect of warfarin moderately, including St. John′s wort ( Hypericum perforatum L.), tea [green tea ( Camellia sinensis), black tea], peppermint ( Herba Menthae), coenzyme Q 10, and chitosan; 4 kinds of HDS reduced the anticoagulant effect of warfarin slightly, including milkvetch root ( Radix Astragali seu Hedysari), avocado, seaweed ( Sargassum), and soya ( Glycine max). The reliability of anticoagulant effect reduction of warfarin was evaluated as highly reliable in 1 kind of HDS, namely St. John′s wort (10 points), relatively reliable in 2 kinds of HDS, including ginseng and tea (8 and 6 points, respectively), possibly reliable in 7 kinds of HDS, including Myrrh, peppermint, coenzyme Q 10, chitosan, milkvetch root, avocado, and seaweed (5, 5, 5, 4, 4, 4, and 3 points, respectively), and suspiciously reliable in 1 kind of HDS, namely soya (2 points). Conclusion:The degree and reliability of anticoagulant effect reduction of warfarin by ginseng (American ginseng, red ginseng, etc.), St. John′s wort, and tea (green tea, black tea), are higher, which should be paid attention to by clinicians and clinical pharmacists.

Objective To investigate the effect of Liangxue Jiedu decoction on intestinal flora in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods The patients who were hospitalized and diagnosed with HBV-ACLF in Beijing Ditan Hospital from October 2018 to October 2019 were enrolled, and healthy individuals were enrolled as HP group. High-throughput sequencing was used to screen for the differences in bacterial diversity and species between HBV-ACLF patients and healthy individuals, and differentially expressed bacteria between the two groups were screened out at the phylum and genus levels. With the help of in vitro simulated fermentation experiment, fecal samples were collected from the patients with HBV-ACLF and were then cultured in the medium containing different concentrations of Liangxue Jiedu decoction (0, 10%, 50%, and 100%) for 24 hours, and the changes in intestinal flora were analyzed and compared between the HBV-ACLF treatment group, the HBV-ACLF non-treatment group, and the HP group at the genus level. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. Results A total of 10 HBV-ACLF patients were enrolled, with 5 in the HBV-ACLF treatment group and 5 in the HBV-ACLF non-treatment group, and there were 15 individuals in the HP group. Compared with the HP group, the HBV-ACLF non-treatment group had significant reductions in the diversity and abundance of intestinal flora. At the phylum level, Bacteroidetes and Firmicutes were mainly observed in the samples of the HP group, while the HBV-ACLF non-treatment group had a significant reduction in Bacteroidetes and significant increases in Fusobacteria , Proteobacteria , and Fibrobacteres. At the genus level, compared with the HP group, the HBV-ACLF non-treatment group had significant reductions in Ruminococcus, Blautia , and Eubacterium and significant increases in Parabacteroides, Lactobacillus, Fusobacterium , and Streptococcus . The in vitro fermentation experiment showed that compared with the HBV-ACLF non-treatment group, the HBV-ACLF treatment group had significant increases in Ruminococcus, Lachnospira, Bacteroides , and Genusgenus and significant reductions in Fusobacterium and Proteobacteria (all P < 0.05). Conclusion Liangxue Jiedu decoction can regulate intestinal flora disturbance, restore the diversity of intestinal flora, increase dominant bacteria, and reduce pathogenic bacteria, which may be one of its important mechanisms of action in the treatment of HBV-ACLF.

Three patients (patient 1, a 27-years-old male with chronic hepatitis C; patient 2, a 71-years-old male with hepatitis C complicated by hepatocellular carcinoma; patient 3, a 60-years-old male with hepatitis C decompensated cirrhosis) were treated with daclatasvir-based regimens and developed drug resistance or treatment failure. Patient 1 and patient 2 received daclatasvir combined with asunaprevir. No resistance variants in the non-structural protein (NS) 5A region of HCV were detected in the 2 patients before treatment. In patient 1, HCV RNA levels were both <15 IU/ml at 4 weeks of treatment and when the drug was stopped at 24 weeks of treatment. Ten days after the drug withdrawal, virological breakthrough occurred and HCV sequence analysis showed variants at 4 sites, including S122G, L31V, Y93H, and C316N. In patient 2, HCV RNA was <15 IU/ml at 8 weeks of treatment and virological breakthrough occurred at 12 weeks of treatment. Both patients were given sofosbuvir/velpatasvir combined with ribavirin for 12 weeks and achieved sustained virologic response (SVR). Patient 3 received sofosbuvir combined with daclatasvir for 24 weeks. His HCV RNA levels were all <15 IU/ml at 4 and 12 weeks of treatment and when the drugs were stopped at 24 weeks of treatment. Virological breakthrough appeared at 12 weeks of drug withdrawal. Sofosbuvir/velpatasvir combined with ribavirin were given for 24 weeks and SVR was achieved.

Objective:To explore the effects of tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF) on blood lipid.Methods:The relevant databases (up to August 31, 2021) were searched. The data of dyslipidemia in treatment of hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection with TAF (trial group) and TDF (control group) in randomized controlled trials (RCTs) were collected. Methodological quality was evaluated by bias risk assessment tool of Cochrane collaborative network, and the meta-analysis was conducted using RevMan 5.3 software. The effect value was the risk ratio ( RR) and its 95% confidence interval ( CI). Results:A total of 11 RCTs were enrolled in the analysis, including 4 on the treatment of hepatitis B (HBV subgroup) and 7 on the treatment of AIDS (HIV subgroup), and the methodological quality evaluation results showed low risk of bias for all. Eleven thousand eight hundred and eighty-eight patients were involved in the 11 RCTs, of which 6 273 were in the trial group and 5 615 in the control group. The results of meta-analysis showed that the incidences of increased low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) with the severity of ≥3 grade were higher in the trial group than those in the control group and the differences of incidences in LDL-C and TC increase were significant between the 2 groups [LDL-C: 2.9% (157/5 347) vs. 0.8% (37/4 727), RR=3.39, 95 %CI: 2.35-4.89, P=0.001; TC: 0.7% (36/4 880) vs. 0.1% (6/4 397), RR=4.25, 95 %CI: 1.91-9.45, P<0.001; TG: 0.5% (16/3 157) vs. 0.3% (8/3 102) , RR=1.83, 95 %CI: 0.81-4.15, P=0.140]. The changes of blood lipid after treatment were compared and the results showed that the increase of LDL-C was higher in the trial group (14.00 mg/dl) than that in the control group (4.00 mg/dl), and the difference was statistically significant ( P=0.004). Conclusion:TAF can significantly increase the levels of LDL-C and TC in patients.