The hepatotoxicity of some Chinese herbs has been a cause for concern in recent years. However, some herbs, such as rhubarb, have been documented as having both therapeutic and toxic effects on the liver, leading to the complex problem of distinguishing the benefits from the risks of using this herb. To comparatively analyze the dose-response relationship between rhubarb and hepatic health, we administrated total rhubarb extract(RE) to normal and carbon tetrachloride(CCl₄)-treated rats for 12 weeks at 4 dosage levels(2.00, 5.40, 14.69 and 40.00 g·kg⁻¹, measured as the quantity of crude material), followed by biochemical and histopathological tests of the rats' livers. A composite pattern was extracted by factor analysis, using all the biochemical indices as variables, into a visual representation of two mathematically obtained factors, which could be interpreted as the fibrosis factor and the cellular injury factor, according to the values of the variable loadings. The curative effect of administering the two lowest dosages of RE to CCl₄-treated rats was mainly expressed as a decrease in the extent of cellular injury. The hepatoprotective mechanism of RE might be related to its antioxidant effect, the antagonism of the free radical damage to hepatocytes caused by CCl₄. By contrast, the RE-induced liver damage was mainly expressed as a significant increase in the amount of fibrosis in both normal rats at all dosage levels and CCl₄-treated rats at the two highest dosage levels. Therefore, the hepatotoxic potential of RE could be attributable to the liver cell fibrosis induced by high doses of the herb. This study illustrates the bidirectional potential of rhubarb and demonstrates the feasibility of using factor analysis to study the dose-response relationships between herbal medicines and hepatotoxicity or the healing effects of these herbs by extracting the underlying interrelationships among a number of functional bio-indices in a holistic manner.

The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl₄-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1α/ERK pathway in rat liver fibrosis induced by CCl₄. In this study, liver fibrosis was induced by CCl₄ in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and α-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1α and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1α partly through the ERK pathway.

Doxorubicin (Dox), one of the most effective chemotherapy drug for cancer treatment, is limited by its severe side effects and chemoresistance. Dox induces DNA damage and leads to significant proteomic changes in the cancer cells, which makes the ubiquitin-proteasome system a potential target to enhance the efficacy of Dox therapy. The unsuccessful clinical trials of proteasome inhibitor PS-341 (bortezomib) in solid tumors led to the invention of MLN9708 (ixazomib), an orally bioavailable next-generation proteasome inhibitor with improved pharmacokinetic and pharmacodynamic features. In this preclinical study, we used eight human breast cancer cell lines, which represent the major molecular subtypes of breast cancer, to validate the cytotoxic effects of MLN9708, alone and in combination with Dox. We found that MLN9708 had cytotoxic effects, induced autophagy and MKP-1 expression, and enhanced Dox-induced apoptosis in these cell lines. MLN9708 also enhanced Dox-induced JNK and p38 phosphorylation and inhibited Dox-induced IκBα degradation. Our in vitro results suggest that MLN9708 has antitumor effects in breast cancer and can sensitize breast cancer cells to Dox treatment. This promising combination may be an effective and feasible therapeutic option for treating breast cancer and warrants clinical validation.

Objective. The systematic review was designed to evaluate the safety and efficacy of Qishen Yiqi dropping pill combined with conventional Western medicine in the treatment of chronic heart failure (CHF). Methods. Relevant randomized controlled trials (RCTs) investigating the clinical efficacy of Qishen Yiqi dropping pill combined with conventional Western medicine in treating CHF were widely searched in electronic databases, including PubMed, Cochrane Library, EMBASE, CBM, CNKI, Read-show database, VIP database, and WanFang up to December 26, 2020. The methodological quality of each trial was assessed according to the Cochrane Reviewers Handbook 5.0. Meta-analysis was performed by using Review Manager 5.3. Results. Twenty-one RCTs (N=2162) that met the criteria were included in the review for the assessment of methodological quality. Meta-analysis showed that compared with the conventional Western medicine (control group), Qishen Yiqi dropping pill combined with conventional Western medicine (experience group) significantly improved clinical efficiency, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), brain natriuretic peptide level (BNP), 6 min-walk distance (6-MWD), and adverse reactions. Conclusion. Qishen Yiqi dropping pill combined with conventional Western medicine are better than conventional Western medicine alone to improve the indicators of patients with CHF, which provides a certain basis for the treatment of CHF.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Yuan Dong1, *, Weiwei Yan2, *, Shi-Long Zhang1, Mu-Zi-He Zhang1, Yan-Ping Zhou1, Hai-Hui Ling1, Meng Ning1, Yanling Zhao1, Ang Huang3 and Ping Zhang4 1Department of Pharmacy, 302 Hospital of People’s Liberation Army, Beijing, People’s Republic of China 2Liver Cancer Center, 302 Hospital of People’s Liberation Army, Beijing 100039, People’s Republic of China 3Non-infectious Liver Disease Center, 302 Hospital of People’s Liberation Army, Beijing 100039, People’s Republic of China 4Chinese Medicine Pharmacy of Intergrative Medicine Center, 302 Hospital of People’s Liberation Army, Beijing 100039, People’s Republic of China *These authors have contributed equally to this work Correspondence to: Yanling Zhao, email: zhaoyl2855@126.com Ang Huang, email: hanjpla@163.com Ping Zhang, email: zhp1231@126.com Keywords: MIR22HG; prognosis; hepatocellular carcinoma Received: October 12, 2017 Accepted: November 22, 2017 Published: December 11, 2017 ABSTRACT Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer worldwide and the second most frequent cause of cancer death. The aim of this study is to identify the association between the expression of long non-coding RNA (lncRNA) MIR22HG and the clinical and tumor characteristics of patients with HCC, and to explore the prognostic significance of lncRNA MIR22HG on patients with HCC. We retrospectively reviewed 127 patients with HCC(42 female, 85 male) who were managed in our hospital between May 1^st 2010 and June 30^th 2016. The expressions of lncRNA MIR22HG were detected by real-time PCR. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models. For the entire cohort of 127 patients, the normalized real-time PCR showed that the expression of lncRNA MIR22HG was lower in HCC tissues compared with corresponding nontumorous tissues. MTT assay showed that si-MIR22HG remarkably inhibited the proliferation tumor cells in three HCC cell lines including SMMC-7721, Huh-7 and Hep3B. Moreover, under-expression of MIR22HG was closely related to tumor encapsulation, microvascular invasion (MVI), and TNM stage. Cox proportional hazards analysis demonstrated that lncRNA MIR22HG under-expression was an independent risk factor associated with the prognosis of patients with HCC. In conclusion, we found that lncRNA MIR22HG expressed significantly lower in HCC tissues compared with non-tumorous tissues. Under-expression of lncRNAMIR22HG was an independent risk factor associated with the prognosis of patients with HCC.

Background. Traditional Chinese medicine (TCM) is used as an adjuvant drug for the treatment of chronic hepatitis B liver fibrosis and is used frequently. We still do not know which TCM has the best curative effect as an adjuvant drug. Therefore, we decided to use network meta‐analysis to solve this problem. Methods. We used the RevMan software (5.3) and Stata software (13.0) to achieve this network meta‐analysis (NMA). The primary outcomes of this study were HA, LN, PCIII, and IV‐C; the secondary outcomes of this study were AST, ALT, and HBV‐DNA negative conversion rate, and the Cochrane risk‐of‐bias tool was used to assess the quality of the included studies. For all outcomes, the scissors funnel plot, Egger test, and Begg test were used to detect publication bias, and sensitivity analysis was used to investigate the stability of the results. And the meta‐regression was used to explore the source of heterogeneity. Results. A total of 34 articles were included in this study. The study involved a total of 3199 patients, of which 1578 were assigned to the control group and 1621 patients were assigned to the experimental group. The number of men and women is roughly equal, and the average age is about 43 years old. In addition, nine treatment strategies were involved in this study. The combination of TCM and entecavir can significantly improve the patients’ HA, LN, PCIII, IV‐C, AST, ALT, and HBV‐DNA negative conversion rates. The comprehensive evaluation results showed that FHC combined with entecavir has more advantages than other treatment strategies. Conclusion. For improving the HBV‐DNA negative conversion rates, adding TCM to the therapeutic strategies does not seem to show absolute superiority. Finally, FHC combined with entecavir is the best therapeutic strategy.