Objective:To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely.Methods:A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI.Results:Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T 0.5ALP and T 0.5ALT) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC)?=?0.787, 95%CI: 0.697~0.878, P ?

BACKGROUND: Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment. METHODS: Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature. RESULTS: There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib. CONCLUSIONS At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.
Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mice ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins B-raf/genetics*

Indirect drug-induced liver toxicity (IDLT) refers to the condition that the use of some therapeutic drugs may induce new liver diseases or exacerbate the original liver disease, with the phenotype of underlying or predisposed liver diseases. IDLT may induce persistent liver injury or even acute liver failure and affect the pharmacotherapy for tumor or other comorbidities, leading to the suspension or termination of ongoing chemotherapy, immunotherapy, and targeted therapy, and therefore, it should be taken seriously in clinical practice. This article elaborates on the mechanisms and prevention strategies of several types of IDLT.

Objective:To understand the oral health and frailty status of the elderly in the community in Beijing and analyze the correlation between the two, so as to provide a reference for the frailty management of the elderly in the community.Methods:This study was a cross-sectional study. Using the multi-stage stratified sampling method, a total of 241 community elderly people in 9 communities in Beijing from July to December 2021 were selected as the research objects. They were investigated using the general information questionnaire, Mini-Nutritional Assessment (MNA) and the Fried Frailty Phenotype. Univariate analysis and ordinal logistic regression analysis were used to explore the influencing factors of frailty among the elderly in the community. A total of 260 questionnaires were distributed in this study and 241 valid questionnaires were recovered, with an effective recovery rate of 92.6%.Results:Among the 241 community elders, 115 (47.7%) were not frail, 92 (38.2%) were pre-frail and 34 (14.1%) were frail. Ordinal Logistic regression analysis showed that the number of teeth of 0-9, 10-19, dry mouth and incomplete or unrepaired restoration of missing teeth were risk factors for frailty among the elderly in the community ( P<0.05) . Conclusions:From the perspective of oral health, this study further analyzes the risk factors of frailty in the elderly in the community. Medical institutions and elderly care institutions at all levels can use oral health status as a screening item for the frailty risk of the elderly in the community, providing new ideas for the prevention and intervention of frailty in the community.

0bjective To study the angular dependence of optically stimulated luminescent dosimeter (OSLD) with solid phantoms under SSDL radiation level ⁶⁰Co radiation field, and to discuss the possibility of OSLD in volumetric modulated arc therapy (VMAT) and other rotating irradiation dose audit. Methods OSLDs were embedded in the two phantoms with the same size and material, respectively. The phantom 1 was set to make the first OSLD perpendicular to the beam, and the phantom 2 was set to make the second OSLD parallel to the beam. The OSLDs were irradiated at 8 angles: 0°, 45°, 90°, 135°, 180°, −45°, −90, −135°. The counts of the OSLSs were read and the response of each angle which normalized to 0° were calculated. Results When the OSLDs are perpendicular to the beam, the angular response is between −6.76% ～ +1.5%, with the maximum angular dependence at 90° and −90°. When the OSLDs are parallel to the beam, the angular response is between −1.74%～+1.67%, below 2%. Conclusion It is better to correct the sensitivity of dosimeters by Element Correction Factors (ECF) for dose audit. Under the condition of rotating irradiation, OSLD shoud be set parallel to the beam, which can better reduce the influence of angular dependence and facilitate further application research of VMAT dose audit.

Objective:To estimate the induced radioactive 56Mn and its level of iron in heavy concrete shielding wall due to neutron activation during tumor proton therapy. Methods:A Geant4 program was adopted to build the model of a heavy concrete shielding wall in a proton therapy room, simulate secondary neutrons generated by 245 MeV proton beam irradiating water phantom. The statistical distribution of radionuclide 56Mn in shielding wall was calculated. The shielding wall was layered every 10 cm thickness, the dose equivalent rate of radionuclide 56Mn in the first three shielding walls was calculated. Results:Under the maximum beam irradiation conditions (1.872 × 10 10), the number of radionuclide 56Mn in the first three layers of shielding walls are 3.10×10 8, 1.60×10 8, 9.33×10 8. The ambient dose equivalent rate at a distance of 1 m from the treatment room are 2.13×10 -3, 8.82×10 -4, 9.10×10 -4 μSv/h, and the total ambient dose equivalent rate for the first three layers was 3.92× 10 -3 μSv/h. Conclusions:During proton therapy, the shielded walls near the central axis of the beam produce more induced radioactivity. The induced radioactivity produced by the neutron-activated iron element at the ahead of the shielding wall is the strongest, and decreases exponentially as the thickness of the shield wall increases.The induced radioactivity in front of the shielding wall of proton therapy room should be concerned.

The application of modern bioinformatics, 'omics’ and molecular biology to research of fibrotic liver diseases holds promise to accelerate the development of new therapeutic targets and therapies for hepatic fibrosis. Specifically, progress is anticipated in delineating pathways of fibrosis reversal and functional compensation, and defining key determinants and presenting factors associated with fibrosis progression and reversion. These efforts will also lead to develop accurate biomarkers and methods for early noninvasive diagnosis, and to accelerate the testing of anti-fibrotic drugs.

Liver fibrosis is a pathophysiological process characterized by abnormal accumulation of connective tissues in the liver caused by chronic liver injuries, in which the activation and migration of hepatic stellate cells (HSCs) play a central role. Extracellular vesicles (EVs) are a class of nanoscale, bilayer lipid enveloped vesicles secreted by almost all cells. EVs are of great interest in liver pathology because they have been found to mediate the communication between cells and regulate cellular microenvironment via horizontal transfer of their cargoes. EVs carry bioactive cargoes including proteins, lipids and RNA molecules, and are involved in the activation of HSCs during liver fibrogenesis.

Portal hypertension is the major cause of complications in decompensated liver cirrhosis. Research results showed that non-selective β-blockers, angiotensin receptor antagonists, and statins can improve portal hypertension by reducing portal vein blood flow and intrahepatic resistance, and have certain prevention and treatment effect on hemodynamic disorders and portal hypertensive complications in chronic liver diseases. Herein, we review the mechanism of action, clinical effects and limitations of these three types of drugs on portal hypertension of cirrhosis.

Liver fibrosis is the scar repairing reaction in response to chronic liver injury due to various etiologies. It has been considered as the early and reversible stage of liver cirrhosis. This article points out the distinction between liver fibrosis and cirrhosis, introduces the current staging system of chronic liver diseases, and recent progress in diagnosing and evaluating liver fibrosis, as well as the medical treatment.The critical importance of diagnosing and treating liver fibrosis in preventing liver diseases progression into decompensated liver cirrhosis is emphasized.