Humans ; Liver Diseases ; Practice Guidelines as Topic ; Prognosis

Objective: To explore the hot issues and developing trend of the research of campus bulling,and to provide a reference for the research on campus bullying. Methods: The power of research, high-impact authors, highly cited journals, high-frequency keywords, and burst terms related to school bullying from the Web of Science database were analyzed using CiteSpace software. The data collection time was May 9, 2018. Results: A total of 3 561 literature data were obtained. The results showed that the country with the highest number of publications was the United States; England had the highest centrality and was in a critical position in the research. The University of Turku in Finland was the core research institution. Salmivalli C was the author of the highest publication, Olweus D was the most frequent cited author. The high-impact journal was Aggressive Behavior. In terms of high-frequency keywords, the core vocabulary such as bully, adolescence, and victim were listed. Middle school students were the most frequently studied; in the form of bullying, the frequency of violence, aggression, and cyberbully was more common; depression, mental health and health appeared more frequently in terms of bullying outcomes. Mutant words including school children, bullying, victimization, relational aggression were more common. Conclusion The research hotspots on campus bullying during the past decade include violence, gender, social support, and mental health. Bullying among college students will be a hot research topic in the future. Continued efforts should be carried out in the field of campus bullying in China.

Based on the national policies, regulations and documents on residency training, this paper sorts out the historical evolution of the standardized residency training system in China, and divides its development into four stages: preliminary exploration, local pilot, national trials, and implementation. It also puts forward some practical thoughts on its development law and future trend, such aspects as that the system reform follows the top-down administrative order and indicative plan, the system pays attention to the gradual implementation on the basis of summing up practical experience, and the system needs continuous implementation and improvement from the overall perspective.

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

OBJECTIVE: To investigate the effects of brazilin on the proliferation, apoptosis and autophagy of human tongue squamous cell carcinoma Tca8113 cells in vitro and explore its molecular mechanism. METHODS: The changes in the proliferation, morphology and apoptosis of Tca8113 cells in response to brazilin treatment were detected using MTT assay, Hoechst33342 staining, and Annexin V/PI double staining, respectively. The expressions of apoptosis-related protein Bax, Bcl-2, cleaved caspase-3 and autophagy-related proteins p-AMPK, p-mTOR, LC3B, and p62 in the treated cells were detected using Western blotting. The effect of treatment with both the AMPK pathway inhibitor and brazilin on the expressions of the pathway-related proteins p-AMPK, p-mTOR, and LC3B was assessed. RESULTS: MTT assay showed that brazilin significantly inhibited the proliferation of Tca8113 cells with an IC50 of 31.17 μmol/L at 24 h. Hoechst33342 staining showed that brazilin induced apoptotic morphological changes in Tca8113 cells in a concentration-dependent manner. Treatment with different concentrations of brazilin resulted in increased apoptosis in the cells. Brazilin obviously inhibited the expression of Bcl-2, p62 and p-mTOR and enhanced the expressions of Bax, cleaved caspase-3, LC3B and p-AMPK. The AMPK pathway inhibitor significantly inhibited the increase in p-AMPK and LC3B expressions and the decrease in p-mTOR expression induced by brazilin. CONCLUSIONS Brazilin can inhibit the proliferation and promote apoptosis in Tca8113 cells and at the same time induces autophagy in the cells through the AMPK/mTOR pathway.
Apoptosis ; Autophagy ; Benzopyrans ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Tongue Neoplasms

【Objective】 To investigate the expression of optineurin (OPTN) in multiple myeloma (MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM. 【Methods】 In this study, three gene expression omnibus (GEO) data sets were used to analyze the expression level of OPTN in MM. Clinical bone marrow samples of MM patients were collected. qRT-PCR was used to further verify the expression of OPTN in MM patients. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM. At the same time, MM transcriptome data were downloaded from the Cancer Genome Atlas (TCGA) database. According to the median boundary of OPTN mRNA expression level, the MM patients were divided into OPTN high- and low-expression groups. In order to investigate the possible molecular mechanisms of OPTN in MM, gene set enrichment analysis (GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language. 【Results】 The expression level of OPTN was significantly lower in MM tissues than in normal tissues (P<0.05). OPTN expression level was significantly correlated with International Staging System (ISS) in MM patients (P<0.05). ROC results showed that the expression level of OPTN could distinguish between normal and MM patients. Survival analysis showed that the overall survival (OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression (P<0.05). GO, KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy, and regulate cellular immune response by regulating Nod-like receptors, NF-κB, TNF and RAS/MAPK pathways. 【Conclusion】 Low expression of OPTN in MM is associated with poor prognosis of patients, and thus may be an important potential biomarker for the diagnosis and treatment of MM.

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.