This experiment was designed to investigate the expression profile of miRNAs (microRNA) in human gastric cancer tissues.Methods The expression profiles of miRNAs were compared between 3 pairs of GC and adjacent normal tissues using an Exiqon miRNA array,following which quantitative PCR (qPCR) was employed to confirm the results of the miRNA array,and 10 miRNAs were selected.Bioinformatics was used to analyze the biological function of the differentially expressed miRNAs and its target genes in gastric cancer.Results Compared with adjacent mucosal tissues,95 miRNAs were up-regulated and 16 miRNAs were down-regulated in GC (＞ 2 folds,P ＜ 0.05).The qPCR results were consistent with microarray-based expression analysis (P =0.049).Furthermore,the online GO and pathway analysis revealed that miRNAs might involve RNA transcription,RNA metabolism,gene expression,gene silencing,and other biological functions in GC.Conclusion There is abnormal expression of miRNAs in gastric cancer,and the abnormal expression of miRNAs may be related to GC tumorigenesis.

AIM:To detect the changes of cardiac functions of septic mice in the early stage of sepsis. METHODS:Health male Kunming mice were used in the study. The techniques of 2D,Mmode and Doppler echocardiography were applied to evaluate the cardiac functions before cecal ligation and puncture(CLP) as baseline and at time points of 12 h,24 h,36 h,48 h and 168 h after CLP. The mice survived for 168 h(7 d) were considered as survivals. RESULTS:Compared to the baseline at the time point of 24 h after CLP,the blood volumes of heart return decreased significantly in the early stage of sepsis induced by CLP. LVEDV reduced by 46%. Notable compensatory responses of the hearts in septic mice were observed,especially the systolic functions,in which LVEF and LVFS increased by 27% and 39% ,respectively. However,the compensatory responses of diastolic function were weaker than the systoles. E/A ratio and EDT decreased by 30% and 25% respectively at the time point of 24 h. CONCLUSION:The strong compensatory cardiac functions are one of the factors for supporting the septic animal to survive. Protection of the cardiac functions especially the diastoles is important in the treatment of septic patients.

Objective To investigate the risk factors of lower extremity deep venous thrombosis(DVT)after internal fixation in patients with type C pelvic fracture,and to establish a relevent nomogram model.Methods Atotal of 217 patients with type C pelvic fractures who were admitted to the Orthopedic Center of the hospital from January 2018 to January 2022 were included in the study.All patients underwent internal fixation.According to whether DVT of the lower extremities was formed after operation,they were divided into the DVT group and the non-DVT group(N-DVT).The general clinical data and preoperative in-flammatory factor expression levels of the two groups was compared.Multivariate analysis was used to obtain independent predictors of DVT formation after internal fixation in patients with type C pelvic fractures.The correlation between preoperative inflammatory factors and DVT formation after internal fixation in patients with type C pelvic fractures was analyzed.The relevant nomograph model was constructed,and the Bootstrap method and calibration curve were used to verify the nomograph model internally.The ROC curve and deci-sion curve for predicting DVT formation after internal fixation in patients with type C pelvic fracture were drawn,and the predictive efficiency and net rate of return of independent prediction and combined prediction were an-alyzed.Results Multivariate analysis showed that age,diabetes,preoperative tumor necrosis factor-α(TNF-α),traction and braking,and bed rest time were independent predictors of DVT formation after internal fixa-tion in patients with type C pelvic fractures(P＜0.05).A nomograph model was constructed based on inde-pendent predictors to predict the formation of DVT after internal fixation in patients with type C pelvic frac-ture,and the C index of the distinguishing evaluation index of the nomogram model was 0.834(95％CI:0.812-0.924),the results of goodness of fit(H-L)test showed that the predicted value of DVT formation probability after internal fixation in patients with type C pelvic fracture was in good agreement with the actual observed value(P＞0.05).ROC curve analysis and decision curve analysis showed that age,diabetes,TNF-α,traction and braking,bed rest time and combined prediction model had good predictive performance and net yield in predicting DVT formation after internal fixation in patients with type C pelvic fracture.Conclusion Age,diabetes,TNF-α,traction braking and bed rest time are independent predictors of DVT formation after internal fixation in pa-tients with type C pelvic fracture.The nomogram model based on the above independent predictors has a high value in predicting DVT formation after internal fixation in patients with type C pelvic fracture.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Objective: To understand the epidemiologic characteristics and pathogen spectrum of hand, foot and mouth disease (HFMD) in Hunan Province during 2008—2017 and provide the basis for the prevention and control strategy of hand, foot and mouth disease. Methods: Collecting data from national disease reporting information system throughout 2008—2017, the descriptive epidemiological method were used to analyze the data of HFMD monitoring and the result of pathogenic agent detection. Results: A total of 1, 255, 530 HFMD cases were reported throughout 2008—2017, including 10097 severe cases and 394 deaths. The average annual attack rate is 190.38/100, 000. The peak incidence of HFMD occurred in summer and fall. The reported incidence is on the rise. The number of critically ill and the number of deaths is declining. Proportion of male cases was higher than that of females. The majority of the children were those under 5 years of age. Enterovirus (EV)-A71, coxsackievirus (CV)-A16 and other other EV positive cases accounted for 33.29%, 20.04% and 46.67% of laboratory diagnosed cases. Conclusions The epidemic of hand, foot and mouth disease in Hunan has obvious seasonal and population characteristics. There are different dominant pathogens causing HFMD in different years.