Objective To explore the promoting effect of long-term administration of nicotiflorin on the recovery of neurological function in rats with cerebral ischemia-reperfusion injury （CIRI）. Methods The CIRI model was established and nicotiflorin was injected intraperitoneally after 1 hour of obstruction for 8 weeks. Tail suspension deflection experiment, balance beam experiment and water maze test were performed in the 2nd, 4th and 8th weeks. After 8 weeks, TTC staining was used to observe the volume of infarct atrophy, transcriptome sequencing was employed to screen differential expressed genes （DEGs） and highly enriched pathways were analyzed, Western-bloting and Elisa were used to assess proteins expression related to the pyroptosis pathway and inflammatory cytokines IL-1β and IL-18. Results By long-term administration of nicotiflorin, the contralateral deflection rate was significantly reduced and beam experiment score of CIRI rats was balanced, the number of crossing the platform in water maze test was increased （P<0.05）, the volume of cerebral infarction atrophy was decreased （P<0.01）, which significantly promoted the recovery of neurological function in rats. Transcriptome sequencing found that the expression of genes in the pyroptosis-related signaling pathways in the brain tissue of rats in the nicotiflorin group was significantly down-regulated （P<0.05）. Western-blot and Elisa experiments showed that nicotiflorin reduced the expression levels of Caspase-1 and GSDMD-N and other pyroptosis-related proteins, and at the same time, the release of inflammatory factors IL-1β and IL-18 was significantly reduced （P<0.05）, indicating that nicotiflorin could inhibit the inflammatory process of pyroptosis. Conclusion Nicotiflorin exhibited a significant long-term promotion effect on the recovery of neurological function in CIRI rats, which potentially attributed from its ability to inhibit pyroptosis.

Scientific research laboratory is the base of scientific research and talent training in the university.During the construction and development of"world-class universities and first-class disciplines",laboratory safety management has been facing urgent challenges.Based on the laboratory management methods of Zhongshan School of Medicine of Sun Yat-sen University,we analyzed the classification and characteristics of discipline laboratories,laboratory safety access training and assessment,and summarized the actual situation and construction of safety management system for basic medi-cal laboratories.This paper expounded on laboratory management,such as management system construction,safety man-agement,safety inspection and supervision,safety awareness of all staff and system execution,so as to provide a feasible and creative scientific guidance and basis for university laboratory biosafety management,and establish a healthy and safe experimental environment to ensure the safety of laboratory work.

Objective To investigate the correlation of neutrophil to high-density lipoprotein cho-lesterol ratio(NHR)and lipoprotein(a)[Lp(a)]with occurrence of acute ischemic stroke(AIS)in elderly patients with non-valvular atrial fibrillation(NVAF).Methods A total of 301 elderly NVAF patients admitted to Hefei First People's Hospital from May 2020 to May 2023 were en-rolled,and according to whether they were combined with AIS or not,they were divided into stroke group(143 cases)and non-stroke group(158 cases).Binary logistic regression analysis was used to screen risk factors,and ROC curve was plotted to assess their predictive values for AIS.Results Lp(a)and NHR in stroke group were significantly higher than those in non-stroke group,the difference was statistically significant(P＜0.01).Multivariate binary logistic regression analysis showed that NHR and Lp(a)were independent risk factors for death with NVAF com-bined AIS(OR=1.728,95％CI:1.367-2.186,P=0.000;OR=1.005,95％CI:1.002-1.007,P=0.000);ROC curve analysis indicated that the AUC value of NHR and Lp(a)in diagnosing AIS in NVAF patients was 0.668 and 0.735,respectively,and that of their combination was 0.789,which was significantly higher than that of NHR and Lp(a)alone(P＜0.01).Conclusion NHR and Lp(a)are independently related to AIS in NVAF patients,and their combination has certain diagnos-tic efficacy.

Background::Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.Methods::In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs).Results::In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years.Conclusion::These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

OBJECTIVE To investigate the components and metabolites of leaves of Cyclocarya paliurus in rats plasma. METHODS UHPLC-Q/TOF-MS method was applied to identify the components and metabolites of rat plasma. The prototype components and metabolites were analyzed in rats plasma of leaves of Cyclocarya paliurus water extract after intragastric administration by comparing the chromatograms of Cyclocarya paliurus, blank serum and drug-containing serum. RESULTS A total of 15 compounds including 6 prototype components and 9 metabolites were identified. The main prototype components in blood were caffeylquinic acid, flavonoids and saponins, and the metabolic pathways were methylation and hydroxylation. CONCLUSION This experiment showes that the prototype components absorbed into blood may be the potential bioactive components in leaves of Cyclocarya paliurus, providing a scientific basis for clarifying its material basis in pharmacodynamics.

Objective:To establish a long-term mortality rate prediction model for patients aged 60 years and over with atrial fibrillation and coronary heart disease using the machine learning method, and identify the corresponding risk factors of mortality.Methods:In this retrospective cohort study, a total of 329(11 cases lost of follow-up)patients with 183 males(55.6%)and 146 females(44.4%), aged(77.8±7.3)years, and 142 patients aged 80 years or older(43.2%)were selected in our hospitals from January 2013 to March 2015.And their clinical data on atrial fibrillation and coronary heart disease were analyzed.They were divided into the death group(151 cases)and the survival group(167 cases)according to the survival outcome.In addition, 60 patients aged 60 years and over admitted to our hospitals from April to July 2015 with atrial fibrillation and coronary heart disease were selected as external data validation set.The clinical data included age, gender, body mass index, diagnosis, co-morbidity, laboratory indicators, electrocardiogram, echocardiogram, treatment data.These patients were followed up for at least 6 years, and the main adverse cardiovascular and cerebrovascular events(MACCE), including death, were recorded.Finally, the data of the enrolled patients were randomly divided into the training set and the test set according to the ratio of 9∶1, Different models were established to predict the long-term mortality of patients with atrial fibrillation and coronary heart disease by machine learning algorithm.The optimal model was established by substituting external data(60 cases)into the model for verification and comparison.The top 20 risk factors for mortality were determined by Shapley additive explanation(SHAP)algorithm.Results:A total of 329 hospitalized patients were included in this study, the overall median follow-up time was 77.0 months(95% CI: 54.0~84.0), 11 cases lost during follow-up(3.3%), and 151 cases died(45.9%). The analysis found that the areas under the ROC curve for a support vector machine(SVM)model, k-Nearest Neighbor(KNN)model, decision tree model, random forest model, ADABoost model, XGBoost model and logistic regression model were 0.76, 0.75, 0.75, 0.91, 0.86, 0.85 and 0.81, respectively.The random forest model had the highest prediction efficiency, with the accuracy of 0.789 and F1 value of 0.806, which was better than the logistic regression model[the Area Under Receiver Operating Characteristic Curve(AUC): 0.91 vs.0.81, P<0.05]. D-dimer, age, number of MACCE, left ventricular ejection fraction, serum albumin level, anemia, New York Heart Association(NYHA)grade, history of old myocardial infarction, estimated glomerular filtration rate(eGFR)and resting heart rate were important risk factors for predicting long-term mortality. Conclusions:The random forest model based on machine learning method can predict the long-term mortality of patients with atrial fibrillation and coronary heart disease aged 60 years and over, have a good identification ability.Its accuracy is higher than that of the traditional Logistic regression model.Reducing the long-term mortality and improving the long-term outcomes can be achieved by intervening on D-dimer levels, correcting hypoproteinemia and anemia, improving cardiac function and controlling resting ventricular rates.

Human challenge trial (HCT) is a test in which human volunteers are intentionally infected with pathogens in order to evaluate the efficacy of candidate preventive or therapeutic drugs. During the COVID-19 pandemic, the HCT of vaccines has aroused people's attention due to its significant advantages over clinical trial. This paper introduces the concept, development and application of HCT, the advantages and limitations of HCT for vaccine evaluation, and the consideration of future HCT of COVID-19 vaccine in China.

Objective To evaluate the effect of exosomes from different sources on the growth, metastasis and immune microenvironment of hepatocellular carcinoma ( HCC ) in a mouse model of orthotopic transplanted hepatoma so as to provide new insight into the clinical immunotherapy of hepatocellular carcinoma. Methods The serum-derived exosomes were obtained by ultracentrifugation from Hepa1-6 cells and 3-week orthotopically tumor-bearing HCC mice. The morphology and size of exosomes were identified by transmission electron microscopy. One-week tumor-bearing HCC C57BL/6 mice were randomly divided into 3 groups ( 3 mice for each group ) , and respectively treated with tail vein injection of 120 μl PBS(control group), 120 μl Hepa1-6 cell-derived exosomes (1μg/μl, TEXcel group), and serum-derived exosomes (1μg/μl) (TEXserum group). The treatments were conduced once a week for 3 consecutive weeks. The mice were sacrificed on the 4th day after the treatments, and the liver tissue and lung tissues were dissected. The volumes of the liver cancer tissues were measured. The expression of PD-L1 protein and CD3+and FoxP3+T lymphocytes infiltration in the liver cancer tissues were respectively detected by Western Blot and immunohistochemical staining. The lung metastasis of the liver cancer was detected by hematoxylin-eosin staining. Results The diameters of the Hepa1-6 cell- and serum-derived exosomes both were about 100 nm, and were uniform vesicles with complete membrane structure. Compared with the control group, Hepa1-6 cell-derived exosomes had a certain inhibitory effect on the growth and lung metastasis of HCC, while there was no significant difference for the TEXserum group. Western Blot results showed that compared with the control group, PD-L1 protein expression was significantly up-regulated in both TEXcel group and TEXserum group. Immunohistochemical staining showed that compared with the control group, the infiltration number of Foxp3+-labeled regulatory T cells (Treg) had no significant changes in TEXcel group and the TEXserum group, and the differences were no statistically significant (all P>0.05). However, the infiltration number of CD3+-labeled T lymphocytes was significantly reduced in the two groups, and the differences were statistically significant (all P<0.05). Conclusion The Hepa1-6 cell-derived exosomes have a certain inhibitory effect on the growth and lung metastasis of HCC, and have no obvious regulation effects on the immune microenvironment of HCC. The serum-derived exosomes from orthotopically tumor-bearing HCC mice can promote the growth and lung metastasis of HCC and immunosuppress the microenvironment. The Hepa1-6 cell-derived exosomes are expected to be used for immunotherapy studies of liver cancer.

Objective To evaluate the relationship between macrophage migration inhibitory factor ( MIF) expression and obese-induced abolition of sevoflurane preconditioning-induced cardioprotection in mice. Methods Forty-eight male C57BL∕6J mice, aged 4 weeks, were divided into 2 groups ( n=24 each) using a random number table method: normal diet group ( Lean group ) and high-fat diet group ( Obese group) . Lean group were fed a normal diet ( 10％ kcal) for 12 weeks, while Obese group were fed a high-fat diet ( 60％ kcal) for 12 weeks. The weight of mice was measured. Blood samples were collected from the tail vein for determination of blood glucose concentrations, and plasma concentrations of total cho-lesterol, triglyceride, insulin and leptin. After measurement of the parameters mentioned above, Lean group and Obese group were divided into 3 subgroups ( n=8 each) using a random number table method:sham operation groups (L-Sham group, O-Sham group), myocardial ischemia-reperfusion groups (L-IR group, O-IR group) and sevoflurane preconditioning groups (L-IR+Sev group, O-IR+Sev group). The mice were anesthetized and their hearts were immediately removed and retrogradely perfused in a Langendorff apparatus with an oxygenated K-H solution at 37 ℃. Hearts were continuously perfused with K-H solution for 115 min in L-Sham and O-Sham groups. Hearts were subjected to global ischemia for 25 min, followed by 60-min reperfusion after being retrogradely perfused with K-H solution in L-IR and O-IR groups. In L-IR+Sev and O-IR+Sev groups, hearts were subjected to 3 cycles of 5-min perfusion with sevoflurane-contai-ning K-H solution ( final concentration 0. 6 mmol∕L) and 5-min washout, and then hearts were subjected to global ischemia for 25 min, followed by 60-min reperfusion. Left ventricular developed pressure ( LVDP ) , left ventricular end-diastolic pressure ( LVEDP ) , and the maximum rate of increase or decrease in left ventricular pressure ( ±dp∕dtmax) were recorded at the end of reperfusion. Hearts were obtained at the end of reperfusion for determination of myocardial infarct size and expression of MIF ( by Western blot) . Results Compared with Lean group, the weight, blood glucose, levels of plasma total cholesterol, tri-glyceride, insulin and leptin were significantly increased in Obese group (P<0. 05). Compared with L-Sham group, the LVDP and +dp∕dtmax were significantly decreased, LVEDP and -dp∕dtmax were in-creased, myocardial infarct size was increased, and the expression of myocardial MIF was up-regulated in L-IR and L-IR+Sev groups, and the expression of myocardial MIF was up-regulated in O-Sham group ( P<0. 05) . Compared with L-IR group, LVDP and +dp∕dtmax were significantly increased, LVEDP and-dp∕dtmax were decreased, myocardial infarct size was decreased, and the expression of myocardial MIF was up-regulated in group L-IR+Sev, and the expression of myocardial MIF was significantly up-regulated in group O-IR (P<0. 05). Compared with O-Sham group, LVDP and +dp∕dtmax were significantly de-creased, LVEDP and-dp∕dtmax were increased, and myocardial infarct size was increased, and no signif-icant change was found in the expression of MIF in O-IR and O-IR+Sev groups ( P>0. 05) . Conclusion The mechanism by which obese abolishes sevoflurane preconditioning-induced cardioprotection may be relat-ed to inducing MIF over-expression in mice.