Diagnostic values of integrated evidence chain, Roussel Uclaf Causality Assessment Method, and Structured Expert Opinion Process method for drug-induced liver injury / 临床肝胆病杂志

Objective To investigate the clinical applicability and different characteristics of three commonly used diagnostic methods for drug-induced liver injury from the two aspects of liver injury induced by Western medicine and liver injury induced by traditional Chinese medicine. Methods A prospective cohort study was performed for 289 hospitalized patients with acute drug-induced liver injury who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2015 to December 2020 and did not receive integrated traditional Chinese and Western medicine therapy, among whom 187 patients had herb-induced liver injury and 102 had Western medicine-induced liver injury. The 289 patients were diagnosed by the integrated evidence chain (IEC), Roussel Uclaf Causality Assessment Method (RUCAM), and the Structured Expert Opinion Process (SEOP) method, and related data at acute onset were collected, including general information, latency period, detailed medication, and laboratory markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, alkaline phosphatase, and total bilirubin. A statistical analysis was performed to investigate the consistency between IEC, RUCAM, and SEOP in the diagnosis of Western medicine-induced liver injury and herb-induced liver injury and their own applicability. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data; the chi-square was used for comparison of categorical data. Results The hepatocellular type was the main type of clinical liver injury in both Western medicine-induced liver injury and herb-induced liver injury, accounting for 81.4% and 74.3%, respectively, and laboratory examination showed higher levels of ALT and AST. Western medicine-induced liver injury cases were diagnosed by IEC, RUCAM, and SEOP, with a clinical diagnosis rate of 65.7%, 100%, and 63.7%, respectively, and the constituent ratio of Western medicine-induced liver injury was 23.2%, 35.3%, and 22.5%, respectively. Herb-induced liver injury cases were diagnosed by these three methods, with a clinical diagnosis rate of 47.6%, 100%, and 29.9%, respectively, and the constituent ratio of herb-induced liver injury was 30.8%, 64.7%, and 19.4%, respectively. The consistency test of the three diagnostic methods showed that in the diagnosis of Western medicine-induced liver injury cases, there was good consistency between IEC and SEOP (Kappa=0.785, P 0.05) and between RUCAM and SEOP (Kappa=0.117, P > 0.05); in the diagnosis of herb-induced liver injury cases, there was poor consistency between RUCAM and SEOP (Kappa=0.066, P > 0.05), while there was good consistency between RUCAM and IEC (Kappa=0.026, P < 0.05) and between IEC and SEOP (Kappa=0.437, P < 0.05). Conclusion The IEC method shows good applicability for both Western medicine-induced liver injury and herb-induced liver injury, and there is good consistency between IEC and SEOP in the diagnosis of Western medicine-induced liver injury cases, while there is a relatively low level of consistency between IEC and SEOP in the diagnosis of herb-induced liver injury. There is poor consistency between RUCAM and the other two methods. In the clinical diagnosis of Western medicine-induced liver injury, IEC, RUCAM, and SEOP should be used in combination to accurately judge the causal relationship between drugs and liver injury.

The role of a disintegrin-like and metalloproteinase with throm bospondin typeⅠmotifs-8 in lung adenocarcinomaand its mechanism / 中国医师进修杂志

Objective:To explore the role of a disintegrin-like and metalloproteinase with throm bospondin typeⅠmotifs-8(ADAMTS8) gene in lung adenocarcinoma and its mechanism.Methods:Selected lung adenocarcinoma data sets GSE75037 and GSE116959 and lung adenocarcinoma transcriptome data and clinical information from the TCGA database; useed R software to analyze differential genes in lung adenocarcinoma tissues, and performed GO enrichment analysis and KEGG signal pathway enrichment for differential genes set analysis; analyzed the expression of ADAMTS8 gene in lung adenocarcinoma and its correlation with patient survival and prognosis; CCK-8 experiment detects the effect of ADAMTS8 overexpression or knockdown on the proliferation of A549 cells; Western blot detected ADAMTS8 overexpression or knockdown effect on Wnt/β-catenin signaling pathway. Results:The combined analysis found that 395 genes were up-regulated in lung adenocarcinoma samples, and 716 genes were down-regulated; ADAMTS8 was under-expressed in lung adenocarcinoma tissues, and its expression level was related to tumor stage; low-expression of ADAMTS8 was associated with shorter survival time, poor prognosis, Cox regression analysis showed that ADAMTS8 can be used as an independent prognostic marker for patients with lung adenocarcinoma; CCK-8 results showed that overexpression of ADAMTS8 can inhibit the proliferation of A549 cells, knocking down ADAMTS8 can promote the proliferation of A549 cells ( P<0.05); Western blot results showed that after overexpression of ADAMTS8, the protein levels of β-catenin, cyclin D1 and c-Myc in cells were significantly reduced ( P<0.05), while knocking down ADAMTS8 could cause the protein levels of β-catenin, cyclin D1 and c-Myc in cells increased significantly ( P<0.05). Conclusions:ADAMTS8 is under-expressed in lung adenocarcinoma and can be used as an independent prognostic marker for patients. Overexpression of ADAMTS8 may inhibit the proliferation of lung adenocarcinoma cells by inhibiting the activity of Wnt/β-catenin signaling pathway.

Clinical features of Caroli disease: An analysis of 41 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of patients with Caroli disease. MethodsThe clinical data were collected from 41 patients who were diagnosed with Caroli disease in The Fifth Medical Center of Chinese PLA General Hospital from April 2015 to January 2020, and the patients were divided into type I group with 16 patients and type Ⅱ group with 25 patients. A retrospective analysis was performed for general information, laboratory markers, and clinical features. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data; a Spearman correlation analysis was also performed. ResultsThe type Ⅰ group had a significantly higher level of albumin (Alb) than the type Ⅱ group (t=0.976, P=0.048), and the type Ⅱ group had a significantly higher prothrombin time (PT) than the type I group (Z=3.115, P=0.001). Compared with the type I group, the type Ⅱ group had significantly higher incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (χ2=6.077, 5.468, and 2.403, P=0.002, 0.019, and 0.028). In the patients with type Ⅱ Caroli disease, the level of cholinesterase was negatively correlated with the incidence rates of esophageal and gastric varices and portal hypertension (r=-0.468 and -0.436, P=0.018 and 0.029); Alb level was negatively correlated with the incidence rate of esophageal and gastric varices (r=-0.561, P=0.004); red blood cell count was negatively correlated with the incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (r=-0.662, -0.566, and -0.436, P＜0.001, P=0.003, and P=0.029); hemoglobin count was negatively correlated with the incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (r=-0.605, -0.590, and -0.510, P=0.001, 0.002, and 0.009); PT was positively correlated with the incidence rates of esophageal varices and portal hypertension (r=0.488 and 0.520, P=0.013 and 0.008). ConclusionCompared with the patients with type I Caroli disease, the patients with type Ⅱ Caroli disease have a higher incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension, with the changes in clinical indicators such as the decrease of Alb level and the increase of PT level, and they tend to have poor prognosis.

Clinical features and changing trend of elderly patients with drug-induced liver injury in The Fifth Medical Center of Chinese PLA General Hospital from 2009 to 2019 / 临床肝胆病杂志

ObjectiveTo investigate the features and changing trend of drug-induced liver injury (DILI) in the elderly from 2009 to 2019, and to provide a reference for clinical prevention and treatment of DILI in the elderly. MethodsA retrospective analysis was performed for the clinical data of 2107 elderly patients, aged ≥60 years, who were diagnosed with DILI in The Fifth Medical Center of Chinese PLA General Hospital from January 2009 to December 2019, and they were divided into groups according to age. Related clinical data were analyzed, including age, sex, clinical features, prognosis, and regional distribution. The Chi-square test was used for comparison of categorical data between groups. ResultsAmong the 2107 patients with DILI, there were 802 male patients and 1305 female patients, with a male/female ratio of 1∶1.63. Cholestasis type was the most common clinical type and was observed in 1439 patients (68.3%). There was the highest number of patients in the 60-64 years group (942 patients, 44.7%), among whom 618(65.6%) were female, 589(62.5%) had cholestasis type, 471(50.0%) had chronic DILI, 421(44.7%) had drug-induced liver cirrhosis, and 25(2.7%) had drug-induced liver failure. There were 187 patients in the 75-79 years group, among whom 110 (58.8%) patients were male, 137(73.3%) had cholestasis type, 114(60.9%) had liver cirrhosis, 4(2.1%) had drug-induced liver failure. The results showed that chronic DILI was more common in the 60-64 years group, and liver cirrhosis was more common in the 75-79 years group. As for prognosis, in the 60-64 years group, 27 patients (2.9%) were cured, 885 (93.9%) were improved, 30(32%) had no response or died; in the 65-69 years group, 16 (2.8%) were cured, 528 (92.0%) were improved, and 30(5.2%) had no response or died; in the 70-74 years group, 9(2.8%) were cured, 305(94.1%) were improved, and 10 (3.6%) had no response or died. The results showed that there was no significant difference in mortality rate between the different age groups (P＞0.05). The proportion of elderly DILI patients among hospitalized DILI patients increased from 15.90% in 2009 to 22.05% in 2013 and 27.51% in 2019, with a 1.73-fold increase in 11 years. As for regional distribution, the patients in North China accounted for the highest proportion of 47.08% (the patients from Hebei, Shanxi, and Inner Mongolia accounted for 24.92%, 10.96%, and 10.25%, respectively), followed by those in Northeast China who accounted for 17.85%. The patients in Beijing accounted for 11.53%. ConclusionThe proportion of elderly DILI patients among hospitalized DILI patients tends to increase in these years. Cholestasis type is the most common clinical type, and most of the patients with this clinical type progress to chronic DILI and drug-induced liver cirrhosis. Early diagnosis, early intervention, and standardized treatment of elderly DILI should be taken seriously.

Protection of Herbal Medicines to Tonify Qi and Strengthen the Spleen on Antituberculotic Liver Damage / 中医杂志

Objective To explore the protective effect of herbal medicine to tonify qi and strengthen the spleen on liver damage induced by antituberculotic according to the TCM theory "reinforce the earth to reduce the wood".Methods The 100 tuberculosis patients randomized into two groups,50 in each,all took antituberculosis drugs with the liver-protecting medicine,Tiopronin,and the herbal medicines to nourish qi and strengthen the spleen were administered to those in the treatment group.Incidence of liver damage and the changes of liver function including serum alanine aminotransferase(ALT),aspartate aminotransferase(AST) and total bilirubin(TBiL) were observed for four weeks.Results In the treatment group,the incidence of liver damage was significantly lower than that in the control group(P