Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.

Purpose/Significance To investigate the status quo and influencing factors of self-management level of elderly diabetic mellitus patients in Dongcheng District of Beijing,and to provide references for further development of community diabetes health educa-tion and health management.Method/Process The survey is conducted on 1 962 cases of elderly patients with type 2 diabetes mellitus who are randomly selected from community-level health service institutions in Dongcheng District of Beijing and are investigated by self-made questionnaires and the summary of diabetes self-care activities.Multiple stepwise regression and logistic regression are used to analyze the influencing factors of patients'self-management level.Result/Conclusion The self-management level of elderly diabetic mellitus patients is affected by many factors,among which the awareness of disease-related knowledge,the form of medical security and the use of health-related software to manage chronic diseases are the main influencing factors(P＜0.05).Local management depart-ments can take targeted health interventions to further improve the self-management ability of elderly diabetic mellitus patients.

Purpose/Significance The paper systematically reviews relevant research on infectious disease prediction models based on internet data,helps to realize the advancement of infectious disease surveillance,and provides references for the construction of intelli-gent three-dimensional prevention and treatment system of infectious diseases.Method/Process The development history and research direction of infectious disease surveillance and early warning based on internet data collected in the core database of Web of Science and CNKI in the past 20 years are reviewed,major existing problems and challenges are analyzed,and common prediction models and their optimization directions are summarized.Result/Conclusion The study on internet infectious disease surveillance shows the trend of diver-sification of monitoring diseases,refinement and specialization of data sources.Due to the complexity and uncertainty of internet data,most of the existing models are only suitable for short-term or real-time prediction.By constructing a combination model,strengthening multi-source data fusion,improving the selection of keywords and influencing factors,the model can be further optimized and the fitting effect and prediction capacity can be strengthened.

Objective To discuss the clinical application of coronary CT angiography(CCTA)-derived fractional flow reserve(CT-FFR)in evaluating the risk stratification of the coronary artery stenosis and atherosclerotic plaque quantitative parameters.Methods A total of 122 patients,who received CCTA examination at the Xuzhou Municipal Central Hospital of China,were enrolled in this study.The patients were divided into non-ischemia group(CT-FFR＞0.8,n=66)and ischemia group(CT-FFR0.8,n=56).The characteristics of atherosclerotic plaque were compared between the two groups.Logistic regression analysis was used to analyze the correlation between plaque characteristics and ischemic lesions.Results There were 218 vessels having a CT-FFR＞0.8 and 174 vessels having a CT-FFR ≤0.8.Statistically significant differences in the total plaque volume,calcified plaque volume,plaque length,and stenosis ratio＞50％existed between the two groups(all P＜0.05).Logistic regression analysis indicated that the total plaque volume,calcified plaque volume,plaque length,and stenosis ratio＞50％were the risk factors for myocardial ischemia.Conclusion CT-FFR can be used for the risk stratification of coronary stenosis and atherosclerotic plaque characteristics,which can evaluate the local myocardial blood supply condition from the anatomical stenosis and functional level so as to optimize the diagnosis and treatment measures.

"Toxicity Testing in the 21st Century—A Vision and Strategy"proposed by the National Research Council of US has brought innovative directives and objectives for toxicity evaluation and risk assessment,pushing forward the next generation of toxicity testing and risk assessment.In this initiative,the concept of adverse outcome pathways(AOPs)has emerged as a prominent methodology,capturing the attention of toxicologists and researchers due to its promising applications in recent years.The quantitative AOP(qAOP)is an extension of the adverse outcome pathway,which is built upon the foundational qualitative adverse outcome pathway model and leverages mathematical frame-works to depict dose-response and/or response-response relationships.This article reviews the princi-ples and advancement surrounding qAOP,introduceds two prevalent methodologies for constructing qAOP,Bayesian network models and regression models,and demonstrates diverse applications of qAOP.Actual cases are used to underscore the transformative role of qAOP in contemporary toxicology and risk assessment practices.

OBJECTIVE To study the pharmacokinetics and pharmacodynamics of oral colon targeted pH-sensitive hydrogel of hydrocortisone sodium succinate(HSS-GEL). METHODS The plasma concentration changes of HSS-GEL and HSS in the mice were investigated; 2, 4, 6-trinitrobenzene sulfonic acid(TNBS)-induced mouse model of ulcerative colitis(UC) was established, disease activity index(DAI), colon length, myeloperoxidase(MPO) and organ index were used as indicators to investigate the therapeutic effect of HSS-GEL on colitis. RESULTS The results showed that the Tmax, Cmax and AUC of HSS-GEL were significantly different from those of HSS(P<0.01). The Tmax of HSS-GEL was significantly longer than that of HSS, and the time of drug absorption into the blood was significantly delayed. The Cmax of HSS-GEL group was significantly lower than that of HSS. The AUC of the HSS-GEL group was 39.38% of the same dose of HSS, indicating that the amount of the drug absorbed into blood was significantly reduced after the HSS was made into HSS-GEL orally. After modeling, DAI, MPO activity and organ index were increased, while the colon was shortened due to the inflammatory reaction, with the treatment of HSS-GEL, DAI, MPO activity and some organ index of mice were significantly decreased comparing with TNBS group(P<0.05 or P<0.01). The degree of reduction of MPO activity and some organ indexes of the mice in the TNBS+HSS-GEL group were significantly greater than those in the TNBS+HSS group, indicating that HSS-GEL had good therapeutic effect on TNBS-induced ulcerative colitis, and the effect was better than that of HSS. CONCLUSION The HSS-GEL prepared has good colon targeting characteristic and colitis treatment effect.

Phagosomes undergo the fusion of early endosomes, late endosomes and lysosomes, and then degrade antigens and kill pathogenic microorganisms, which is called phagosome maturation. The functional differences of phagosomes after maturation in different immune cells lead to distinct characteristics on their processing of phagocytic antigens. It has been found that the antigen degradation ability of immune cells is opposite to their antigen presentation capacity through comparing the functional differences of phagosomes from neutrophils, macrophages and dendritic cells after antigens uptake. Among them, dendritic cells have the strongest antigen presentation capacity, followed by macrophages and neutrophils. The in-depth study of immune cell phagosome maturation and antigen presentation will provide new strategies for vaccine development and immunotherapy.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a pathological subtype of lung neuroendocrine cancer, which accounts for 2.4%-3.1% in surgical specimens of lung cancer. It is characterized by high invasiveness and poor prognosis, and highly correlated with smoking. There are few relevant studies due to the low incidence and small sample size. Therefore, it is relatively difficult to diagnosis and treatment in clinical practice. In this review, we described molecular subtype, diagnostic and prognostic-related markers about large cell neuroendocrine carcinoma of lung based on the recent progress in genomic sequencing and molecular markers, to find the direction for the next research.
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Objective To determine the correlation between phosphorylation extracellular signal-regulated kinase (p-Erk) and monopolar spindle 1 (Mps1) in colorectal cancer patients with the BRAF V600E mutation or not, and to explore the relationship between the expression of p-Erk and Mps1 with the clinicopathological features and prognosis of colorectal cancer patients. Methods Two hundred and eighty-eight paraffin-embedded tissue sections containing both the carcinoma and its adjacent non-neoplastic colorectal tissue were collected from January 2009 to June 2015 in the First Hospital of Shanxi Medical University. BRAF mutation was detected by Sanger sequencing. Kaplan-Meier survival analysis was used to analyze the correlation between BRAF V600E and prognosis. Immunohistochemistry was used to detect the expression level of p-Erk and Mps1 in colorectal cancer with wild type or BRAF V600E mutation. The correlation between p-ERK and Mps1 expression was analyzed by using linear regression analysis. Results The BRAF V600E mutation rate was 5.2 % in colorectal carcinomas. In addition, the poorly differentiated tumours and mucinous tumours had higher incidence of BRAF mutations than well differentiated tumours and non-mucinous tumours respectively [14.3 % (9/63) vs. 2.7 % (6/225),χ 2= 11.208,P = 0.001; 25.0 % (6/24) vs. 3.4 %(9/264),χ 2=16.630,P <0.001). The positive rate of p-Erk and Mps1 in colorectal carcinomas with BRAF V600E was significantly higher than that in colorectal carcinomas with BRAF WT (14/15 vs. 3/15, P <0.05; 15/15 vs. 3/15, P < 0.05]. It was found that the p-Erk expression correlated positively to the Mps1 expression (R2= 0.419,P < 0.001). The expressions of p-Erk protein in poorly differentiated adenocarcinoma was significantly higher and mucinous adenocarcinoma than those in high differentiated adenocarcinoma and non-mucinous adenocarcinoma (χ 2= 6.679, P = 0.01; χ 2= 5.735, P = 0.017), as well as in the group with lymph node metastasis than without lymph node metastasis (χ 2=5.436, P =0.02). Positive rate of Mps1 in poorly differentiated carcinoma was higher than that in well differentiated adenocarcinoma of colorectal carcinomas (χ 2=7.950, P =0.009). The Kaplan-Meier survival analysis indicated that patients with BRAF V600E had a worse survival rate than BRAF WT patients. Conclusions BRAF V600E may play an important role in specific pathological kinds of colorectal carcinomas, which is expected to be an independent prognostic factor. The expression of p-Erk is significantly correlated with Mps1 in colorectal carcinomas, suggesting that Mps1 may become a new potential target for targeted therapy.

Objective The aim of this study was to determine the content of phthalate in disposable plastic tableware sold on Chengdu market,and to provide primary data for safety evaluation.Methods Sample selection was based on stratified sampling.Sixteen phthalate compounds were investigated in 60 disposable plastic tableware,divided into seven groups.The analysis was performed by gas chromatography-mass spectrometry (GC-MS).Results In this survey,diethyl phthalate,diisobutyl phthalate,dibutyl phthalate and diethylhexyl phthalate were detected,while the other 12 phthalate compound were not.The positive rates of the four detected phthalate were 6.7％ (4/60),10.0％ (6/60),46.7％ (28/60) and 28.3％ (17/60) respectively,and the highest concentrations were 10.3,6.4,7.2 and 65.6 mg/kg,respectively.Conclusion The observed level of detection rates and maximum concentrations were relatively high in this survey.In addition,some subgroups of PAEs that were not allowed to use in food contact materials were detected.Therefore,the migration in different food simulant would be analyzed in the next step for further health outcome assessment.