Interpretation on Consensus on drug-induced liver injury by CIOMS Working Group:liver injury attributed to herbal and dietary supplements / 中国中药杂志

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Relationship Between Traditional Chinese Medicine(TCM)Constitution and TCM Syndrome in the Diagnosis and Treatment of Chronic Diseases / 中国医学科学杂志(英文版)

Chronic diseases are global threats to human health. By applying the traditional Chinese medicine (TCM) theory of body constitution to the treatment of chronic diseases, and comprehensively identifying and differentiating the syndrome, disease, and constitution, TCM can be fully used in the diagnosis and treatment of chronic diseases. In this manner, population-based and evidence-based modern medicine can organically align with the individual-focused and speculation-based TCM, with subsequent benefits for the control of chronic diseases, reducing their burden on human health.

San-Cao Granule () Ameliorates Hepatic Fibrosis through High Mobility Group Box-1 Protein/Smad Signaling Pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis.</p><p><b>METHODS</b>A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor β1 (TGF-β1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase.</p><p><b>RESULTS</b>Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01).</p><p><b>CONCLUSION</b>SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-β1/Smad signaling pathway.</p>

Microcalorimetric investigation on the interaction of six alkaloids from rhizoma coptidis / 药学学报

How to identify active constituents of traditional Chinese medicines (TCMs) and study their interactions are key problems in the development of TCMs. The inhibitory effect of six alkaloids from Rhizoma Coptidis (RC) on Shigella dysenteriae (S. dysenteria) growth had been investigated by microcalorimetry in this study. Main active constituents of RC were confirmed by comparing their contributions to the bacteriostatic effect, and the interactions among active constituents were further researched. According to the result, in 0.8 mg-mL-1 extract of RC, the contributions of six active alkaloids including berberine, coptisine, epiberberine, palmatine and the combination of jatrorrhizine and columbamine were 52.83%, 36.31%, 2.49%, 4.27% and 3.21%, respectively. Therefore, berberine and coptisine were the main active constituents of RC that inhibited the growth of S. dysenteria. The study of interactions among the six alkaloids indicated that, 1 there were some contstituents antagonizing the inhibitory effect of RC, 2 there was a synergy effect between berberine and coptisine, 3 there were additive effects between other four alkaloids and the main active constituents. These results may provide some useful references for the establishment of the quality standard for RC and the development of multi-component TCMs.

Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The potential application of retinoic acid receptor activators, such as all trans-retinoic acid (ATRA), for treating various cancers have been studied both pre-clinically and clinically. Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown. We have explored the anticancer effect of ATRA in ESCC, and in this study, the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line, EC9706, in nude mice.</p><p><b>METHODS</b>The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues.</p><p><b>RESULTS</b>Compared to the control group, the tumor inhibition rates in the low dose ATRA, high dose ATRA, and 5-FU groups were 83.21%, 88.32%, 91.02%, respectively. The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P < 0.05). The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31, CD34, and CD105 (component of the TGF-β receptor) in ESCC xenograft tissues (P < 0.05).</p><p><b>CONCLUSIONS</b>ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice. These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction, which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.</p>