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.

Meta-analysis of efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs in treatment of liver fibrosis and cirrhosis in chronic hepatitis B / 中国中药杂志

The present study evaluated the clinical efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs for the treatment of liver fibrosis and cirrhosis in chronic hepatitis B. CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched for the relevant randomized controlled trials(RCTs) published from database inception to February 2021. All the retrieved papers were independently screened, extracted and evaluated by two researchers, followed by Meta-analysis by Review Manager 5.4. Finally, 18 RCTs were included, involving 2 168 patients(1 106 in the treatment group and 1 062 in the control group). The Meta-analysis results showed that compared with conventional drugs alone, Liuwei Wuling Tablets combined with conventional drugs could increase the effective rate of clinical treatment by reducing serum hyaluronic acid(HA), laminin(LN), procollagen type Ⅲ(PCⅢ), and type Ⅳ collagen(Ⅳ-C) to improve liver function, decreasing the levels of total bilirubin(TBiL), alanine amino-transferase(ALT), and aspartate aminotransferase(AST), and improving the negative conversion ratio of hepatitis B virus(HBV) DNA. In terms of safety, there were no serious adverse reactions in the treatment group and the control group. The results showed that Liuwei Wuling Tablets combined with antiviral or other conventional liver-protecting drugs could improve liver function, treat liver cirrhosis, and reduce liver fibrosis with high safety. However, due to the influence of literature quality and quantity, multi-center and high-quality RCTs with large sample size are needed for verification.

Impact of “Elaphurus davidianus return home project” on the transmission of schistosomiasis in Poyang Lake areas / 中国血吸虫病防治杂志

Objective To investigate the prevalence of Schistosoma japonicum infections in Elaphurus davidianus released to Poyang Lake areas and evaluate the impact of the project of “E. davidianus released to wild environments for natural reproduction and growth” “(E. davidianus return home project”) on the transmission of schistosomiasis in Poyang Lake areas. Methods During the period from April 2018 to December 2019, the population distribution, inhabiting activity and natural reproduction of E. davidianus released to Poyang Lake areas were investigated by means of GPS and artificial observations. The S. japonicum infection was identified in animal feces in E. davidianus inhabitats using a hatching test, and snail distribution was surveyed in E. davidianus inhabiting grass islands using a systematic sampling method. Results A total of 51 E. davidianus were released to the Poyang Lake areas in 2018, which subsequently produced 5 E. davidianus habitats in Yinlong Lake, Longkou, Nanchi Lake, Lianzi Lake and Zhu Lake. E. davidianus was found to predominantly inhibit in grass islands, farmlands and forest lands in hilly regions around the Poyang Lake areas. The natural reproduction rate of E. davidianus was 25% in the habitats in 2019, and the mean density of snails was 0.009 to 0.039 snails/0.1 m2 in E. davidianus inhabitats; however, no S. japonicum infection was identified in snails. In addition, the mean densities of wild E. davidianus and bovine feces were 4.6 samples/hm2 and 2.1 samples/hm2, Conclusions The E. davidianus released to Poyang Lake areas may get infections with S. japonicum, and cause schistosomiasis transmission through fecal contamination in grass islands. The impact on and the prevalence of S. japonicum infection was 4.35% and 13.16% (P = 0.236), respectively; however, the intensities of S. japonicum infections were “+++” and “+”, respectively. Conclusions The E. davidianus released to Poyang Lake areas may get infections with S. japonicum, and cause schistosomiasis transmission through fecal contamination in grass islands. The impact on local schistosomiasis transmission and the response strategy requires to be investigated following the release of E. davidianus to lake regions, to ensure the achievement of the goal of schistosomiasis elimination and the successful implementation of the “E. davidianus return home project” in Poyang Lake areas.

A 4-year follow-up study on sexual orientation, sexual behavior and AIDS related knowledge of undergraduate students in a medical university / 中华疾病控制杂志

Objective To explore the characteristics of medical sexual orientation, sexual behavior and acquired immunodeficiency syndrome(AIDS) related knowledge changing with grade. Methods A group of 876 undergraduate students of 2015 in a medical university were selected to conduct an anonymous survey once a year and a total of four times using self-compiled questionnaires on AIDS-related knowledge, sexual orientation and behavior of college students. Descriptive epidemiological methods were adopted for statistical description. Results The distribution of sexual orientation among medical students with different survey batches was statistically significant ( 2=26.223, P=0.036). The proportion of openly gay people in the total number of homosexuals showed an increasing trend ( 2trend=4.150, P=0.042). Follow-up study of Chinese medicine students on AIDS related knowledge of the overall rate of increased ( 2trend=23.462, P<0.001). The incidence of general sexual behavior and male homosexual sex among medical students in the past six months showed an increasing trend with grade growth ( 2trend=4.450, P=0.035; 2trend=6.738，P=0.009). At the second and third follow-ups, the proportion of men who used condoms occasionally and never used condoms increased, and the difference was statistically significant ( 2=7.935, P=0.047). Conclusions Due to the weak awareness of medical sexual safety protection, the school should continue to strengthen the AIDS publicity and prevention education of medical students in all grades, and improve the school sexual health education mechanism.

Guidelines for clinical diagnosis and treatment of herb-induced liver injury / 中国中药杂志

In recent years, the issues related to herb-induced liver injury (HILI) have received much concern. Its clinical diagnosis is much difficult than that of Western medicine-induced liver injury due to its complicated drug combination and multiple constituents. Moreover, it is also correlated with physiques, inheritance and basic diseases. China Association of Chinese Medicine has released the first standards for HILI diagnosis and treatment technology in 2016, namely Guidelines for clinical diagnosis of herb-induced liver injury (hereinafter referred to as the Guidelines). The diagnostic processes with different diagnostic results were explained in this paper to help clinicians, particularly liver specialists, in diagnosing liver diseases by applying the operation of the Guidelines.

Clinical analysis of two diagnosis methods for herb-induced liver injury / 中国中药杂志

To compare the consistency and difference of herb-induced liver injury between two methods in guidelines for clinical diagnosis and treatment of liver injury related to Chinese herbal medicine in China (2016) and guidelines for the diagnosis and treatment of drug-induced liver injury in China(2015). This retrospective analysis included 390 patients with herb-induced liver injury who had a history of suspicious Chinese herbal medicines or patent medicines; the patients with integrative Chinese and western medicines were excluded from this study. The results indicated that there were 14(4%) extremely probable patients (>8 points), 185(47%) highly probable patients (6-8 points) and 191(49%) probable patients(3-5 points) in 390 cases with guidelines for diagnosis and treatment of drug-induced liver injury of China (2015). While when guidelines for clinical diagnosis and treatment of liver injury related to Chinese herbal medicine in China (2016) was used for 390 patients, the results indicated that there were 5 (1%) cases with proven diagnosis, 163(42%) cases with clinical diagnosis, and 222(57%) cases with suspected diagnosis. Statistics showed that two methods had a consistency of 43% and difference of 14%. The research results showed that Guidelines for clinical diagnosis and treatment of liver injury related to Chinese herbal medicine in China(2016) was more suitable for the diagnosis of herb-induced liver injury. Due to the limitations of retrospective case study, further more prospective studies would be needed.

Clinical Analysis of Drug-induced Liver Injury Caused by Polygonum multiflorum and its Preparations / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To analyze hepatotoxicity of Polygonum multiflorum and clinical character- istics of drug-induced liver injury (DILI) caused by Polygonum multiflorum and its preparations.</p><p><b>METHODS</b>A retrospective study was performed in 158 patients treated at 302 Military Hospital between January 2009 and January 2014. All of them had used Polygonum multiflorum and its preparations before the onset of DILI, and their clinical characteristics and prognoses were analyzed.</p><p><b>RESULTS</b>Of the 158 DILI patients who used Polygonum multiflorum or its preparations, 92 (58.2%) combined with Western medicine or Chinese herbal preparations without Polygonum multiflorum; 66 patients (41.8%) used Polygonum mult florum and its preparations alone. In 66 DILI patients induced by Polygonum multiflorum or its preparations alone, 51 cases (77.3%) were induced by Polygonum multiflorum compounds and 22.7% by single Po- lygonum multiflorum; 4 cases (6.1%) were caused by crude Polygonum multiflorum and 62 (93.9%) by processed Polygonum multiflorum and its preparations. Clinical injury patterns were hepatocellular 92.4% (61 cases), cholestatic 1.5% (1 case), and mixed 6.1% (4 cases). Pathological examination was per- formed by liver biopsy in 32 cases (48.15%), manifested as hepatocellular degeneration and necrosis, fibroplasia, Kupffer cells with pigment granule, and a large number of eosinophil infiltration, were ob- served. Four patients were developed into liver failure, 4 into cirrhosis, and 1 died.</p><p><b>CONCLUSION</b>Polygo- num multiflorum and its preparations could induce DILI, but clinical diagnosis of Polygonum multiflorum induced hepatotoxicity should be cautious.</p>

A study on genetic characteristics of Enterovirus type 71 of hand-foot-mouth disease in Shaoxing city / 预防医学

Objective To undersyand the genetic characteristics of Enterovirus Type 71 (EV 71 )isolated from clinical specimens of children with hand-foot-mouth disease (HFMD)in Shaoxing city from 2012 to 2013.Methods RNA was extracted from specimens collected from stool,throat swab and vesicle from children with HFMD,and EV 71 were identified by reverse transcriptase polymerase chain reaction (RT-PCR).Ten positive samples were isolated and were amplified by segmented PCR,then,they were spliced into a full-length after sequenced according to the reference strains. Homology analysis on region VP1 and phylogenetic tree were carried out based on nucleotide sequence and amino acid sequence.Results The results indicated that the ten isolated strains were all EV 71 positive.Sequence alignment of VP1 showed that the nucleotide and amino acid homogeneity of these 10 strains were related to C4a genotypes,with 95.06%-97.87% and 93.60%-98.99% respectively.Phylogenetic tree based on VP1 indicated that these 10 strains all belonged to C4a genotype.Conclusion The identified EV 71 strains isolated from HFMD children in Shaoxing city belong to genotype C4a.

Integration of metabolism images into multimodal neuronavigation for frameless stereotaxy / 中华外科杂志

<p><b>OBJECTIVES</b>To evaluate the efficacy of integration of metabolism images into multimodal neuronavigation for frameless stereotactic biopsy.</p><p><b>METHODS</b>From January to December 2012, 32 patients with brain lesions underwent frameless stereotactic biopsy guided by positron emission tomograph (PET) and proton magnetic resonance spectroscopy ((1)H-MRS)-based multimodal neuronavigation and intraoperative magnetic resonance imaging (iMRI). The cohort consisted of 16 male and 16 female patients, with a mean age of 45 years (range: 7 - 62 years). Biopsy targets were identified according to PET and (1)H-MRS. Biopsy was performed with Varioguide frameless biopsy system. Diagnostic yield and complications were assessed.</p><p><b>RESULTS</b>Metabolism images-based multimodal neuronavigation and iMRI were successfully implemented in all cases. iMRI confirmed accuracy of biopsy targets. All the specimens obtained pathological diagnosis, the diagnostic yield was 100%. In 1 patient, iMRI found small hematoma (< 5 ml), surgical evacuation wasn't needed with intraoperative complication rate 3.1%. With the help of multimodal neuronavigation, no patients had new or worsened neurologic deficits.</p><p><b>CONCLUSIONS</b>Integration of metabolism images into multimodal neuronavigation provide not only anatomical, but also metabolic and functional information for frameless stereotaxy, increasing diagnostic yield and avoiding postoperative neurologic deficits.</p>

Application of positron emission tomography molecular probes in hepatocellular carcinoma biological imaging / 中国医学科学杂志(英文版)

Biological behavior is a hot issue in hepatocellular carcinoma (HCC) study. Positron emission tomography (PET), a biological imaging technique, has been widely applied in many types of tumors. It is capable of noninvasive detection of biological behavior. Different radiotracers provide different information of HCC, including glucose/lipid metabolism, DNA synthesis, and apoptosis. In addition, radiotracer uptake relates to biological and clinical prognostic markers. In this article we review the application of several existing and novel radiotracers in PET in HCC study.

Down-regulation of peroxisome proliferator-activated receptor γ coactivator-1α expression in fatty acid-induced pancreatic beta-cell apoptosis involves nuclear factor-κB pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pancreatic beta-cell apoptosis induced by lipotoxicity, to a large extent, contributes to the progression of type 2 diabetes. To investigate the mechanism of free fatty acid induced apoptosis, we aimed to study the effects of palmitic acid (PA) on the apoptosis and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression in βTC3 cells as well as the possible role of nuclear factor-κB (NF-κB) in this process.</p><p><b>METHODS</b>Hoechst 33258 was used to detect βTC3 cell apoptosis, which was induced by PA stimulation for 12 hours. PGC-1α expression was analyzed by reverse transcription polymerase chain reaction, IκB kinase β (IKKβ), IκBα, NF-κB-inducing kinase (NIK) and Rel-B expressions were analyzed by Western blotting. MG132 was employed to block the endogenous IκBα degradation before PA administration, and then its effect on PA-inducing cell apoptosis and PGC-1α mRNA expression was analyzed.</p><p><b>RESULTS</b>Significant increased cell apoptosis was found at the concentration of 0.5 mmol/L and 1.0 mmol/L PA administration. PA (0.5 mmol/L) could extensively reduced the expression of PGC-1α mRNA. After exposing βTC3 cells to 0.5 mmol/L PA for different time periods (0, 4, 6, 8, 10 and 12 hours), IKKβ protein expression increased while IκBα, NIK and Rel-B protein expression declined in a time-dependent manner. Pretreatment with MG132 to inhibit the degradation of IκBα, partially prevented the down-regulation of PGC-1α mRNA expression after 12-hour PA treatment in accordance with the decrease of PA induced apoptosis.</p><p><b>CONCLUSIONS</b>NF-κB canonical pathway was activated in PA-mediated βTC3 cell apoptosis, whereas non-canonical pathway was inhibited. Reduced PGC-1α expression by PA in βTC3 cells could involve the activation of canonical NF-κB pathway, so as to deteriorate the PA induced apoptosis.</p>

Positron emission tomography imaging of cell transplantation in a rat model of Alzheimer's disease / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the value of positron emission tomography (PET) in the Alzheimer's disease (AD) rat model verification and in monitoring the therapeutic effectiveness of cell transplantation.</p><p><b>METHODS</b>A beta(1-40) hippocampus injected rat model was successfully established and neural stem cells were injected into hippocampus. Results of behavior tests and histological examinations were compared between model group and graft group, and then the N-methyl-[(11)C]2-(4 methylaminophenyl)-6-hydroxybenzothiazole ((11)C-PIB) and (18)F-fluorodeoxyglucose ((18)F-FDG) imaging were performed to observe whether the result of imaging was matched with behavior test and histological examination.</p><p><b>RESULTS</b>The Morris water maze showed that the latent period of the escape was significantly longer in model group than in control group (P<0.01). In histological examinations, the neuron loss and A beta deposition were found in hippocampus CA1 and dentate gyrus of rat model. (11)C-PIB imaging showed increased uptake in model rat hippocampus district (P<0.05), while (18)F-FDG imaging showed that the uptake in the injected side of hippocampus in model group was significantly lower than that in the same side in control group (P<0.001). After cell transplantation, the latent period of the escape was significantly shorter in graft group than in model group (P<0.01). Histological examinations showed that there was no obvious changes in A beta deposition; in addition, the neural stem cells differentiated and expressed neuronal nuclei-positive cells, and continuously expressed 5-bromodeoxyuridine-positive cells for six weeks. (11)C-PIB imaging and (18)F-FDG imaging showed the uptakes were not significantly different between between model group and transplantation group(P>0.05).</p><p><b>CONCLUSION</b>(11)C-PIB imaging is useful in diagnosing AD and monitoring the pathological change of AD model in vivo, while (18)F-FDG imaging provides useful visual information for monitoring short-term therapeutic effectiveness of stem cell transplantation.</p>

Comparison of the Golgi proteome of hepatocellular carcinoma with that of the adjacent non-tumor tissues / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the Golgi proteome of hepatocellular carcinoma (HCC) with that of the adjacent non-tumor tissues.</p><p><b>METHODS</b>Hepatocellular carcinoma and adjacent non-tumor tissues were obtained from HCC patients. The protein expression maps in Golgi were obtained by two-dimensional gel electrophoresis (2-DE), and the differentially expressed protein spots were analyzed by PD-Quest software. Peptide mass fingerprint (PMF) of differential protein spots was obtained with MALD-TOT-MS.</p><p><b>RESULTS</b>According to 2-DE maps, the average numbers of protein spots were (1153+/-49) and (1086+/-37) in hepatocellular carcinoma and the adjacent non-tumor tissues. Compared to the adjacent non-tumor tissues, 27 proteins were upregulated, and 20 proteins were downregulated in HCC Golgi.</p><p><b>CONCLUSIONS</b>The Golgi proteome in HCC tissues is different from that in the adjacent non-tumor tissues, and the differential expression proteins are involved in energy metabolism, tumor metastasis, and cell cycle regulation.</p>