Effects of adjuvant huaier granule therapy on survival rate of patients with hepatocellular carcinoma.

Objective: Clinical trials have reported that Huaier granule inhibits the recurrence of hepatocellular carcinoma (HCC) after resection. However, its efficacy in patients at different clinical stages of HCC remains unknown. We investigated the effects of Huaier granule on the 3-year overall survival (OS) rate of patients at different clinical stages. Design: This cohort study included 826 patients with HCC, screened between January 2015 and December 2019. The patients were divided into Huaier (n = 174) and control groups (n = 652), and the 3-year OS rates were compared between the two groups. To eliminate bias caused by confounding factors, propensity score matching (PSM) was performed. We used the Kaplan-Meier method to estimate OS rate and tested the difference using the log-rank test. Results: Multivariable regression analysis revealed that Huaier therapy was an independent protective factor for 3-year survival rate. After PSM (1:2), the Huaier and control groups comprised 170 and 340 patients, respectively. The 3-year OS rate was remarkably higher in the Huaier group than in the control group (adjusted hazard ratio [aHR]: 0.36; 95% confidence interval: 0.26-0.49; p < 0.001). The aHR for Huaier use for 3-12, 12-24, and >24 months was 0.48, 0.23, and 0.16, respectively, indicating a dose-response pattern. For the 3-12-, 12-24-, and >24-month groups, the 3-year OS rate was 54.1%, 68.6%, and 90.4%, respectively. Multivariate stratified analysis confirmed that the mortality risk in Huaier users was lower than that in non-Huaier users in most subgroups. Conclusion: Adjuvant Huaier therapy improved the OS rate in patients with HCC. However, these findings require further verification through prospective clinical studies.

Evaluation of LiangXue JieDu Therapy in Combination With Western Medicine for Acute-On-Chronic Liver Failure: A Systematic Review and meta-Analysis.

Objectives: To assess the efficacy of LiangXue JieDu (LXJD) therapy in combination with Western medicine (WM) for acute-on-chronic liver failure (ACLF). Methods: Articles on randomized controlled trials of LXJD therapy for ACLF were obtained from PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, VIP, Wanfang, and China Biology Medicine databases, with the search range from database inception to March 2022. We evaluated the quality of data from these articles using the Cochrane risk-of-bias tool. Evaluation indicators were total effective rate, mortality rate, complications, liver and coagulation function, and Traditional Chinese medicine (TCM) syndrome score. We then calculated the risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables with a 95% confidence interval (CI). Results: The meta-analysis included 18 studies with moderate quality and totaling 1,609 patients. Compared with WM alone, LXJD therapy plus WM improved total effective rate [RR = 1.34, 95% CI: (1.24, 1.45)], while reducing mortality rate [RR = 0.54, 95% CI: (0.42, 0.70)] and complications [RR = 0.43, 95% CI: (0.26, 0.71)]. The combined treatment also improved prothrombin activity [MD = 1.30, 95% CI: (1.02, 1.59)], prothrombin time [MD = -0.90, 95% CI: (-1.40, -0.39)], international normalized ratio [MD = -0.59, 95% CI: (-0.93, -0.25)], alanine aminotransferase [MD = -0.92, 95% CI: (-1.30, -0.55)], aspartate aminotransferase [MD = -0.57, 95% CI: (-0.93, -0.21)], total bilirubin [MD = -1.07, 95% CI: (-1.38, -0.76)], and TCM syndrome score [MD = -1.70; 95% CI: (-2.03, -1.37)]. Conclusions: This study suggests that LXJD therapy plus WM can significantly improves ACLF clinical symptoms and short-term outcomes. However, more high-quality trials are required to confirm the efficacy of LXJD therapy.

Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. Objective: This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. Methods: A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to ≥1 lg·IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. Results: The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg ≥1 lg·IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). Conclusion: The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836.

Effects of Traditional Chinese Medicine Adjuvant Therapy on the Survival of Patients with Primary Liver Cancer.

Aim: This study aims to evaluate whether adjuvant traditional Chinese medicine (TCM) can improve the survival of patients with primary liver cancer (PLC). Methods: A total of 1,859 patients with PLC at Beijing Ditan Hospital between August 2008 and September 2017 were included. The patients were divided into TCM and control groups according to whether the patients took TCM for ≥3 months. There were 1,111 patients in the TCM group and 748 in the control group. Univariate and multivariate Cox regression analyses were used to analyze the factors affecting the 3-year survival of patients with PLC. To reduce selection bias, 1 : 1 propensity score matching (PSM) was performed between the two groups. The overall survival outcomes were evaluated using the Kaplan-Meier (K-M) survival curve, and the log-rank test was used to compare the differences in survival curves. Results: After multivariate Cox regression analysis, TCM was an independent favorable factor for the 3-year survival of patients with PLC (adjusted hazard ratio (aHR) 0.359, 95% confidence interval (CI) 0.292-0.441, P < 0.001). Before and after PSM, the 3-year overall survival rates were 33.3% and 54% in the control group and 79.7% and 69.7% in the TCM group, respectively. The 3-year mortality risk in the TCM group was lower than that in the control group for different PLC subgroups. Conclusions: TCM adjuvant therapy increased the 3-year overall survival rate of patients with PLC.

Severe Type of COVID-19: Pathogenesis, Warning Indicators and Treatment.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is a major public health issue. The epidemic is unlikely to be contained until the global launch of safe and effective vaccines that could prevent serious illnesses and provide herd immunity. Although most patients have mild flu-like symptoms, some develop severe illnesses accompanied by multiple organ dysfunction. The identification of pathophysiology and early warning biomarkers of a severe type of COVID-19 contribute to the treatment and prevention of serious complications. Here, we review the pathophysiology, early warning indicators, and effective treatment of Chinese and Western Medicine for patients with a severe type of COVID-19.

Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. PURPOSE: To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. METHODS: We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. RESULTS: After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p < 0.0001), shorter time to negative conversion of viral nucleic acid (p < 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p < 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1ß, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation. CONCLUSION: YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway.

Integrating Chinese and western medicine for COVID-19: A living evidence-based guideline (version 1).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

Minimal Hepatic Encephalopathy and Biejia-Ruangan Are Associated with First Hospital Readmission in Nonalcoholic Cirrhosis Patients.

Introductionand Aim. Patients with cirrhosis are often hospitalized repeatedly for a variety of complications. This retrospective study aimed to assess the effects of minimal hepatic encephalopathy (MHE) and Biejia-Ruangan (BR) on first hospital readmission in nonalcoholic cirrhosis patients without previous overt hepatic encephalopathy (OHE) or hepatocellular carcinoma (HCC). Materials and Methods. A total of 176 hospitalized patients with nonalcoholic cirrhosis were included in this retrospective study. Patients who were first admitted to Beijing Ditan Hospital of Capital Medical University from January 2017 to September 2019 were enrolled. The primary endpoint was their first liver-related hospital readmission. The risk factors for readmission were analyzed by Cox proportional hazard regression analysis. Results. A total of 176 nonalcoholic cirrhosis patients without previous OHE or HCC were included; 57 patients (32.4%) were diagnosed with MHE, and 63 patients (35.8%) were administered BR (2 g, three times a day). Multivariate analysis revealed that nonalcoholic cirrhosis patients with MHE (HR, 5.805; 95% CI, 3.007-11.206; x, P < 0.001) and a higher Model for End-Stage Liver Disease (MELD) score (HR, 1.145; 95% CI, 1.068-1.227; P < 0.001) had an increased risk of first hospital readmission, and patients treated with BR (HR, 0.318; 95% CI, 0.151-0.670; P=0.003) had a decreased risk of first hospital readmission. Conclusion. MHE increased the risk of hospital readmission in nonalcoholic cirrhosis patients without previous OHE or HCC, and this risk was decreased by BR administration.

Fuzheng Jiedu Xiaoji formulation inhibits hepatocellular carcinoma progression in patients by targeting the AKT/CyclinD1/p21/p27 pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment options. Conventional antitumor therapy combined with traditional Chinese medicine (TCM) to limit tumor progression has gradually become the focus of complementary and alternative therapies for HCC treatment. The Fuzheng Jiedu Xiaoji formulation (FZJDXJ) alleviates the clinical symptoms of patients and inhibits tumor progression, but its curative effect still requires extensive clinical research and mechanistic analysis. PURPOSE: To explore the effectiveness of FZJDXJ in HCC patients and investigate its biological function and mechanism underlying anticancer therapy. METHODS: This randomized controlled clinical trial enrolled 291 HCC patients receiving transcatheter arterial chemoembolization (TACE) therapy; patients received either FZJDXJ combined with standard treatment, or standard treatment alone, for 48 weeks. Statistical analyses were performed according to survival time at the end of the trial. The main constituents of the FZJDXJ extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. The antitumor effects of FZJDXJ and its specific biological mechanism of action were studied. RESULTS: After 48 weeks of treatment, one-year overall survival (OS) and progression-free survival (PFS) were significantly different between the two groups. Co-administration of FZJDXJ and TACE prolonged the OS of HCC patients, especially in BCLC A or B stage. FZJDXJ and TACE treatment effectively extended the PFS of patients, especially in the BCLC B stage. HPLC-MS/MS identified 1619 active constituents of FZJDXJ, including formononetin, chlorogenic acid (CGA), caffeic acid, luteolin, gallic acid, diosgenin, ergosterol endoperoxide, and lupeol, which may function through the AKT/CyclinD1/p21/p27 pathways. Through molecular docking, CGA and gallic acid could effectively combine with Thr308, an important phosphorylation site of AKT1. FZJDXJ inhibited tumor growth in nude mice. In vitro, FZJDXJ-mediated serum inhibited the proliferation, migration, and invasion of liver cancer cells, and promoted cell apoptosis. CONCLUSION: Clinically, FZJDXJ combined with TACE therapy significantly prolonged OS and PFS and reduced the mortality rate of HCC patients. Mechanistically, FZJDXJ effectively inhibited the proliferation and migration of liver cancer cells through the modulation of the AKT/CyclinD1/p21/p27 pathways, and may be a promising TCM drug for anti-HCC therapy.

Effects of Adjuvant Chinese Patent Medicine Therapy on Prevention of Variceal Rebleeding: A Retrospective Cohort Study.

OBJECTIVE: To assess whether adjuvant Chinese patent medicines (CPMs) to standard treatment could reduce recurrent bleeding after variceal bleeding in cirrhotic patients. METHODS: This study retrospectively collected 555 consecutive patients who recovered from variceal bleeding. A population-based cohort study was established depending on if adjuvant CPMs were administered to prevent rebleeding. A total of 139 patients who had taken ⩾28 cumulative defined daily doses (cDDDs) of CPMs were included in the CPMs cohort, and 416 patients who used <28 cDDDs of CPMs were enrolled in the non-CPMs cohort. On evaluation of rebleeding incidence, 1:2 propensity score matched was used to estimate for reducing bias. Patients were followed for at least 12 months. The end-point of this study was clinically significant esophagogastric variceal rebleeding. RESULTS: Following multivariate analysis, CPMs therapy was an independent factor for variceal rebleeding [adjusted hazard ratio (AHR)=0.657; 95% confidence interval=0.497-0.868; P=0.003]. After the 1:2 propensity score matching, a significant reduction (23.5%) in the incidence of variceal rebleeding in patients was observed, from 58.3% in the non-CPMs cohort to 44.6% in the CPMs cohort (modified log-rank test, P=0.002) within a year. The AHRs for rebleeding were 0.928, 0.553, and 0.105, for 28-90 cDDDs, 91-180 cDDDs, and >180 cDDDs of CPMs, respectively. The median rebleeding interval in the CPMs cohort was significantly larger compared with the non-CPMs cohort (113.5 vs. 93.0 days; P=0.008). CONCLUSION: Adjuvant CPMs to standard therapy can significantly reduce the incidence of variceal rebleeding and delay the time to rebleeding.

Adjuvant Fuzheng Huayu Capsule Reduces the Incidence of Hepatocellular Carcinoma in Patients with Hepatitis B-Caused Cirrhosis.

AIM: Fuzhenghuayu (FZHY) capsule can inhibit the progression of cirrhosis. This study explored whether FZHY can reduce the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B-caused cirrhosis (HBC) undergoing antiviral therapy. METHODS: A retrospective review of 842 patients with HBC between 2011 and 2015 was performed, including 270 treated with FZHY combined with nucleos (t) ide analogues (NAs) and 572 with NAs alone. The incidence of HCC was compared between the FZHY (n = 259) and control (n = 259) groups using 1 : 1 propensity score (PS) matching. The incidence of HCC in patients with HBC with different Child-Turcotte-Pugh (CTP) classifications and Toronto HCC risk index (THRI) scores was analyzed using Kaplan-Meier curves. RESULTS: The 5-year cumulative incidence of HCC before and after PS matching was 151 (17.9%) and 86 (16.6%), respectively. In PS-matched samples, the multivariate Cox proportional-hazards model indicated that the FZHY group demonstrated a significantly lower risk for HCC than the control group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.19-0.53 P < 0.001). The risk of HCC diminished with increased duration of FZHY use. The stratified analysis revealed that the FZHY group, regardless of CTP classification, benefited significantly from FZHY therapy. Patients in the medium- and high-THRI risk groups were the dominant population for FZHY. CONCLUSIONS: FZHY combined with NAs was associated with a significantly lower risk of HCC than NAs alone in patients with HBC, which supports the integration of FZHY with antiviral treatment into clinical practice.

Entecavir combining Chinese herbal medicine for HBeAg-positive chronic hepatitis B patients: a randomized, controlled trial.

BACKGROUND AND AIM: Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. METHODS: 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. RESULTS: The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9-43.2%) in the experiment group and 27.21% (95% CI 22.0-32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4-12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. CONCLUSION: Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. CLINICAL TRIAL NUMBER: ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).

Fufang Banmao Capsule, a Traditional Chinese Medicinal Formulation, Enhances the Survival of Patients with Hepatocellular Carcinoma and Vp3-4 Portal Vein Tumor Thrombosis Undergoing Supportive Treatment.

Objectives: Fufang Banmao (FFBM) capsule, a type of Chinese medicinal formulation, has decades of history in treating hepatocellular carcinoma (HCC). This retrospective study aimed to observe the effect of FFBM capsules on the 6-month survival of patients with advanced HCC and Vp3-4 portal vein tumor thrombosis (PVTT) who received supportive therapy alone. Design: In total, 320 HCC/Vp3-4 PVTT patients underwent treatment with supportive therapy, of whom 95 took FFBM capsules and were treated with supportive therapy (FFBM group) and 225 received supportive therapy alone (control group). Comparisons of the 6-month overall survival (OS) rate of the two groups were performed. Propensity score matching (PSM) was used to match the characteristics between individuals in the two groups. A nomogram was built based on independent predictive factors for OS. Results: Cox multivariate analysis revealed that hepatic encephalopathy, aspartate transaminase (AST) and γ-glutamyl transpeptidase levels, Child-Pugh class, prothrombin time, α-fetoprotein level, largest tumor diameter, and use of FFBM capsules were independent predictive factors of OS. Variceal bleeding, alanine transaminase, AST, total bilirubin, and Barcelona Clinic for Liver Cancer stage were different at baseline in the FFBM and control groups. Analysis revealed no significant adverse effects or toxicities relevant to the medications. After PSM (1:1), 95 patient pairs were analyzed as FFBM versus control. The OS probability was remarkably higher for patients in the FFBM group than in those in the control group at 6 months (p < 0.0001). The median survival time was 4 months in the FFBM group and 2.2 months in the control group. Kaplan-Meier analysis showed significant statistical differences in the 6-month OS rates in the patients with total nomogram scores ≥84 (p < 0.0001). Conclusions: Given the satisfying survival outcomes, the results suggested that FFBM capsules should be administered to patients with HCC/Vp3-4 PVTT in the high-risk group (score ≥84). FFBM capsules have the potential for improving patient survival time in those with advanced HCC and Vp3-4 PVTT who receive supportive therapy alone, especially those in the high-risk group (score ≥84).

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

Culture-Positive Spontaneous Ascitic Infection in Patients with Acute Decompensated Cirrhosis: Multidrug-Resistant Pathogens and Antibiotic Strategies.

PURPOSE: This study investigated multidrug-resistant (MDR) pathogens and antibiotic strategies of culture-positive spontaneous ascitic infection (SAI) in patients with acute decompensated cirrhosis. MATERIALS AND METHODS: We retrospectively analyzed 432 acute decompensated cirrhotic patients with culture-positive SAI from 11 teaching hospitals in China (January 2012 to May 2018). A Cox proportional hazards model analysis was conducted to identify independent predictors of 28-day mortality. RESULTS: A total of 455 strains were isolated from 432 ascitic culture samples. Gram-negative bacteria (GNB), gram-positive bacteria (GPB), and fungi caused 52.3, 45.5, and 2.2% of all SAI episodes, respectively. Episodes were classified as nosocomial (41.2%), healthcare-related (34.7%), and community-acquired (24.1%). Escherichia coli (13.4%) and Klebsiella pneumoniae (2.4%) were extended-spectrum ß-lactamase producing isolates. The prevalence of methicillin-resistant Staphylococcus aureus was 1.1%. Ceftazidime, cefepime, aztreonam, and amikacin were recommended as first-line antibiotics agents for non-MDR GNB infections; piperacillin/tazobactam and carbapenems for MDR GNB in community-acquired and healthcare-related or nosocomial infections, respectively; and vancomycin or linezolid for GPB infections, regardless of drug-resistance status. Multivariate analysis revealed days of hospital stay before SAI, upper gastrointestinal bleeding, white blood cell count, alanine aminotransferase, serum creatinine concentration, total bilirubin, and international normalized ratio as key independent predictors of 28-day mortality. CONCLUSION: MDR pathogens and antibiotic strategies were identified in patients with acute decompensated cirrhosis with culture-positive SAI, which may help optimize therapy and improve clinical outcomes.

Yindan Jiedu Granules, a Traditional Chinese Medicinal Formulation, as a Potential Treatment for Coronavirus Disease 2019.

Background: Yindan Jiedu Granules (YDJDG) have been newly prescribed as a Chinese herbal formula. This study aimed to compare the efficacy of YDJDG and lopinavir-ritonavir in the treatment of coronavirus disease 2019 (COVID-19). Methods: Overall, 131 patients with COVID-19 were included in this study. In addition to standard care, 60 of these patients received YDJDG (YDJDG group) and 71 received lopinavir-ritonavir (lopinavir-ritonavir group). Propensity score matching (PSM) was used to match the characteristics of individuals in the two groups, while the Kaplan-Meier method was used to compare the proportion recovery observed. Results: Cox analysis revealed that YDJDG and CD4 ≥ 660 cells/µL were independent predictive factors of proportion recovery. At baseline, disease types differed between the YDJDG and lopinavir-ritonavir treatment groups. Furthermore, no significant adverse effects or toxicities relevant to YDJDG were observed. The median recovery time was 21 days in the YDJDG group and 27 days in the lopinavir-ritonavir group. After PSM (1:1), 50 patient pairs, YDJDG vs. lopinavir-ritonavir, were analyzed. In the YDJDG group, the proportion of recovered patients was remarkably higher than that observed in the lopinavir-ritonavir group (p = 0.0013), especially for those presenting mild/moderate disease type and CD4 < 660 cells/µL. In the YDJDG group, the mean duration of fever and pulmonary exudative lesions was significantly shorter than that observed in the lopinavir-ritonavir group (p = 0.0180 and p = 0.0028, respectively). Conclusion: YDJDG reveals the potential to hasten the recovery period in COVID-19 patients with mild/moderate disease type or CD4 < 660 cells/µL by shortening the mean duration of fever and pulmonary exudative lesions.

Effects of adjuvant traditional Chinese medicine therapy on long-term survival in patients with hepatocellular carcinoma.

BACKGROUND: Many patients with hepatocellular carcinoma (HCC) in Asian countries seek adjuvant therapy with traditional Chinese medicine (TCM). This study aims to explore the benefits of TCM therapy in the long-term survival of patients with hepatocellular carcinoma in China. PATIENTS AND METHODS: In total, 3483 patients with HCC admitted to the Beijing Ditan Hospital of Capital Medical University were enrolled in this study. We used 1:1 frequency matching by sex, age, diagnosis time, Barcelona Clinic Liver Cancer staging, and type of treatments to compare the TCM users (n = 526) and non-TCM users (n = 526). A Cox multivariate regression model was employed to evaluate the effects of TCM therapy on the HR value and Kaplan-Meier survival curve for mortality risk in HCC patients. A log-rank test was performed to analyze the effect of TCM therapy on the survival time of HCC patients. RESULTS: The Cox multivariate analysis indicated that TCM therapy was an independent protective factor for 5-year survival in patients with HCC (adjusted HR = 0.46, 95% CI 0.40-0.52, p < 0.0001). The Kaplan-Meier curve also showed that after PS matching, TCM users had a higher overall survival rate and a higher progression-free survival rate than non-TCM users. TCM users, regardless of the classification of etiology, tumor stage, liver function level, or type of treatment, all benefited significantly from TCM therapy. In addition, it was found that the most commonly used Chinese patent medications are Fufang Banmao Capsule, Huaier Granule, and Jinlong Capsule. CONCLUSION: Using traditional Chinese medications as adjuvant therapy can probably prolong median survival time and improve the overall survival among patients with HCC. Further scientific studies and clinical trials are needed to examine the efficiency and safety.

Comparative effectiveness and safety of traditional Chinese medicine supporting Qi and enriching blood for cancer related anemia in patients not receiving chemoradiotherapy: a meta-analysis and systematic review.

A systematic review and meta-analysis of previous randomized controlled trials of traditional Chinese medicine (TCM) supporting Qi and enriching blood in the treatment of cancer related anemia (CRA) in patients not receiving chemoradiotherapy were conducted. A total of 13 randomized controlled trials were included. Compared with the control group, better improvement was found for the level of hemoglobin (mean difference=4.57, 95% CI [1.38, 7.76], P=0.005) and overall therapeutic effect (risk ratio [RR]=1.31, 95% CI [1.18, 1.46], P<0.000) in the TCM groups. The incidence of related adverse events was not increased in the TCM groups (RR=0.54, 95% CI [0.29, 0.99], P=0.05). However, due to the relatively low quality and the small sample sizes of the included studies, the results should be interpreted with a degree of caution. Nevertheless, TCM with the role of supporting Qi and enriching blood may be a safe and effective treatment for CRA in patients not receiving chemoradiotherapy and might be considered as an alternative treatment to conventional western medicine including iron supplements and erythropoietin.

Xijiao Dihuang Decoction () and Rehmannia glutinosa Libosch. protect mice against lipopolysaccharide and tumor necrosis factor alpha-induced acute liver failure.

OBJECTIVE: To investigate the hepatoprotective effect of Xijiao Dihuang Decoction (, XJDHD) on lipopolysaccharide (LPS)- and tumor necrosis factor alpha (TNF-α)-induced acute liver failure (ALF) as well as the underlying mechanism of action, and to clarify the key herbs and components of XJDHD. METHODS: LPS/D-galactosamine (D-GalN) or TNF-α/D-GalN were intraperitoneally injected into C57BL/6J mice to induce ALF. Simultaneously, XJDHD or its individual herbs and components were orally administered. Survival rates, transaminase levels in serum, and hepatic histology were examined to evaluate the effects of XJDHD. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and real-time polymerase chain reaction were additionally performed to expound the mechanism underlying the anti-apoptotic activity of XJDHD. RESULTS: Oral administration of XJDHD protected mice from lethal liver failure induced by LPS and TNF-α, with notable amelioration of liver injury in histology and a significant decrease in transaminase levels in serum. XJDHD significantly inhibited apoptosis of hepatocytes and enhanced expression of the antiapoptosis genes, c-Flip, Iap1, Gadd45b and A20. In addition, Rehmannia glutinosa Libosch. was identified as the key herb of XJDHD and galactose as the effective component of Rehmannia glutinosa Libosch. that protects against ALF. CONCLUSIONS: XJDHD inhibits TNF-α-induced apoptosis of hepatocytes by promoting the expression of nuclear factor κ B-regulated anti-apoptotic genes. Rehmannia glutinosa Libosch. is the effective herb of XJDHD and galactose is an active component in this protection.

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial.

BACKGROUND: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. METHODS: The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. DISCUSSION: The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).