Objective: To compare the predictive performance of the seasonal autoregressive integrated moving average (SARIMA) model, the Prophet model, and the Bayesian structural time series (BSTS) model in forecasting the incidence of hand, foot, and mouth disease (HFMD) , so as to provide a basis for optimizing the early warning system of this disease. Methods: Weekly incidence data of HFMD in Longgang District, Shenzhen City from 2014 to 2024 were collected. The HFMD incidence data from 2014-2019 and 2023 were used as the training set to construct SARIMA, Prophet, and BSTS models, while the data from 2024 were used as the test set to compare and evaluate the predictive performance of the three models. The technique for order preference by similarity to ideal solution (TOPSIS) method was employed to calculate the C-value. This approach integrates multiple evaluation metrics, such as the mean absolute error (MAE), mean squared error (MSE), root mean squared error (RMSE), and symmetric mean absolute percentage error (SMAPE), to comprehensively assess model performance. Results: A total of 150 111 cases of HFMD were reported in Longgang District from 2014 to 2024, with an average annual incidence of 400.72/105. The weekly incidence fluctuated between 0 and 63.78/105, exhibiting a bimodal seasonal pattern characterized by a primary peak from May to July and a secondary peak from September to October. In the training set, all three models demonstrated a good fit to the bimodal epidemic trend of HFMD, with the BSTS model achieving the best fit. The BSTS model yielded performance metrics as follows: MAE=0.124, MSE=0.050, RMSE=0.223, SMAPE=0.021, and a C-value of 1.000. In the test set, all three models, including SARIMA, Prophet, and BSTS, performed well for short-term predictions (≤16 weeks), with the Prophet model showing relatively superior predictive performance. However, the prediction accuracy of all models declined as the forecast horizon extended. During the primary peak period (May-July), the Prophet model exhibited better predictive performance, whereas the BSTS model performed relatively better during the secondary peak period (September-October). Conclusions For the short-term forecasting of weekly HFMD incidence, the Prophet model outperformed both the SARIMA and BSTS models. During the primary peak period, the Prophet model demonstrated superior predictive performance, whereas the BSTS model exhibited better accuracy in forecasting the secondary peak period.

Laboratory animal practitioners refer to various personnel engaged in work related to laboratory animals or animal experiments. Their development not only affects the occupational health and safety of practitioners but also directly impacts the development level of laboratory animal science and the accuracy of animal experiment results. This article reviews the training requirements for laboratory animal practitioners stipulated by national standards, regulations, normative documents, and management policies in Sichuan Province. It analyzes the scale and training status of laboratory animal practitioners in Sichuan Province, compiles statistics on the changes in the scale of laboratory animal practitioners in Sichuan Province from 2015 to 2024, and examines the number of practitioners in four categories (scientific researchers, management personnel, animal keepers, and other personnel) and three different educational levels (postgraduate degree, bachelor's degree, and below bachelor's degree). It summarizes the possible reasons for the changes in personnel structure from 2015 to 2024, namely the continuous refinement of the division of labor in laboratory animal-related work and the continuous development of disciplines such as life sciences, medicine, and pharmacy. The article analyzes the current training status of laboratory animal practitioners in Sichuan Province from three aspects, including training organizations, the training system, and training methods for laboratory animal practitioners in Sichuan Province. It provides a detailed analysis of the series of training sessions on laboratory animal-related topics organized by the Office of the Laboratory Animal Management Committee of Sichuan Province and the Sichuan Laboratory Animal Society since 2019. It concludes that there are advantages such as an increasing proportion of highly educated personnel and a relatively well-established training system, and discusses issues such as inadequate top-level design and insufficient attention from some units. Finally, it proposes corresponding countermeasures and suggestions, including strengthening the assessment of practitioner training, formulating training plans for laboratory animal practitioners, and compiling specialized training materials. This article can provide a reference for the development and training of laboratory animal practitioners.

Objective:To analyze the distribution of causes of death among residents in Chuzhou City of Anhui Province from 2019 to 2022,in order to provide evidence for formulating disease prevention and control strategies.Methods:The death data of residents in Chuzhou City from 2019 to 2022 were obtained from the cause of death surveillance system of Chuzhou Center for Disease Control and Prevention in Anhui Province.The crude death rate,composition ratio of cause of death and the rank of cause of death were analyzed.The annual percent change(APC)of mortality was calculated by using the Joinpoint regression model to describe the average annual change of mortality.Results:From 2019 to 2022,the average annual crude mortality of permanent residents in Chuzhou City was 668.80/100 000,and the crude mortality rate(/100 000)was 640.58,652.10,659.32,and 723.46,respectively(APC=3.10%,P=0.356).The annual crude mortality of males(735.93/100 000)was higher than that of females(598.52/100 000)(χ2=1 148.724,P＜0.01).The top three causes of death were malignant tumor,cerebrovascular disease,and cardiovascular disease.The mortality of malignant tumors showed a decreasing trend(APC=-1.51%,P＜0.01),and the top three causes of death of malignant tumors were lung cancer,gastric cancer and liver cancer.Among the age groups,congenital malformations and deformations,chromosomal abnormalities,and certain conditions originating in the perinatal period were the leading causes of death among residents aged 0 to 4 years old.Accidental injuries were the first cause of death among residents aged 5 to 14 years old.The leading cause of death among residents in the 15-44 and 45-64 age groups was malignant tumor.Cerebrovascular disease was the leading cause of death in≥65 years old.The mortality of accidental injuries showed an increasing trend(APC=1.64%,P＜0.01),and the specific types of death causes of accidental injuries were different among different age groups.Conclusion:Chronic non-communicable diseases,especially cancer and cardiovascular and cerebrovascular diseases,are the main health threats to the residents of Chuzhou City of Anhui Province,and feasible prevention and control measures should be formulated.

Objective To explore the underlying mechanisms by which time-restricted feeding(TRF)attenuates dextran sodium sulfate(DSS)-induced colitis in mice via modulation of regenerating islet-derived protein 3 gamma(Reg3γ)expression and gut microbiota.Methods Six-week-old C57BL/6 mice were stratified by body weight and randomized into ad libitum feeding(AL)and TRF groups(n=7).The AL mice were given unrestricted food access,whereas the TRF mice were allowed feeding only during 00:00 and 08:00 daily,for totally 4 weeks.Mouse colitis model was induced at the fourth week by adding 2.5%dextran sodium sulfate(DSS)in drinking water for 6 d.Disease severity and the effects of TRF were assessed with disease activity index(DAI)scoring,colon length measurement,HE staining and histopathological scoring,and mRNA expression levels of regenerating islet-derived 3 gamma(Reg3g)and inflammatory cytokines in colonic tissues.Another 14 mice were randomized into AL plus antibiotic cocktail(AL+ABX)and TRF plus antibiotic cocktail(TRF+ABX)groups,with 7 animals in each group.ABX was administered to deplete gut microbiota and evaluate the microbiota dependence of TRF in attenuating colitis.Fecal samples from AL and TRF mice were analyzed by 16S ribosomal RNA sequencing(16S rRNA-seq),and serum lipopolysaccharide(LPS)level was measured.The colonic epithelial cells were collected for RNA-seq.Results After modeling,the AL mice exhibited typical colitis symptoms,such as weight loss,diarrhea,and hematochezia.TRF intervention significantly attenuated these above symptoms,with lower DAI scores from day 4 post-modeling(P<0.001),reduced colon shortening(P<0.01),preserved tissue architecture,and decreased inflammation.RT-qPCR analysis showed that TRF down-regulated colonic mRNA expression levels of Reg3g and pro-inflammatory cytokines(IL-1 β,IL-6,TNF-α)(P<0.05)while up-regulated that of anti-inflammatory factor IL-10(P<0.000 1)when compared with the corresponding levels in AL mice.ABX treatment led no significant differences between the AL+ABX and TRF+ABX groups in term of DAI score,colon length,or histopathology.Obviously down-regulated Reg3g was observed in the TRF+ABX group than the AL+ABX group(P<0.05),whereas L-1β,IL-6,TNF-α and IL-10 showed no notable changes.16S rRNA-seq revealed that TRF markedly reshaped gut microbiota composition,with increased Gram-positive bacterial abundance,reduced Gram-negative bacteria,with concomitant lower serum LPS level(P<0.001).RNA-seq also indicated significant suppression of NF-κB and other inflammation-related signaling pathways in the TRF group.Conclusion TRF attenuates DSS-induced colitis in mice by downr-egulating Reg3γ expression,reshaping gut microbiota,and reducing serum LPS level,and thereby suppressing NF-κB-mediated inflammatory signaling pathways.

Non-clinical reproductive toxicity studies typically employ mammals like rats, rabbits, and cynomolgus monkeys, with animal pregnancy being a key challenge in such testing. This article focuses on the difficulties encountered in the animal pregnancy process and potential countermeasures. Rats can be used for fertility and early embryonic development toxicity studies (Segment Ⅰ), embryo-fetal development toxicity studies (Segment Ⅱ), and perinatal toxicity studies (Segment Ⅲ). The estrous cycle of female rats can be determined by vaginal smear, and mating behavior is confirmed through copulatory plug checks the following day after pairing one female with one male in the same cage. Rabbits are commonly used in embryo-fetal development toxicity studies (Segment Ⅱ). Mating behavior between male rabbits and estrous females is observed to determine the time of conception. However, challenges such as atypical estrus of female rabbits, large variations in estrus between batches, and mating failure often occur in reproductive toxicity testing, which may be addressed through prolonged light exposure, increased protein supplementation, optimized mating strategies, and environmental modifications like female and male rabbits are raised adjacent to each other. Non-human primates (NHPs) are typically employed in perinatal toxicity studies (Segment Ⅲ), where one of the key challenges lies in accurately determining sexual maturity in males - a critical factor for reproductive toxicity testing, which can be assessed through comprehensive evaluation of age, body weight, and testicular volume. Generally, male macaques are considered sexually mature when they meet the following criteria: age >4.5 years, body weight >4.5 kg, single testis volume >10 mL, and combined testicular volume >20 mL. For pregnancy confirmation, ultrasound examination demonstrating visible gestational sacs is required, though this necessitates experienced veterinary clinicians to establish standardized ultrasound examination protocols. In conclusion, reproductive toxicity studies should employ species-appropriate detection methods and evaluation criteria based on anatomical characteristics of the reproductive system to ensure successful mating and proper study execution.

OBJECTIVE To develop a prediction model for durable clinical benefit （DCB） in patients with advanced esophageal squamous cell carcinoma （ESCC） receiving programmed death-1 （PD-1） inhibitor. METHODS The clinical data of patients with advanced ESCC who received PD-1 inhibitor in Jieyang People’s Hospital were retrospectively collected between January 2020 to December 2023. Predictors were screened by least absolute shrinkage and selection operator （Lasso） regression， and a multivariable Logistic regression model was developed to predict DCB. A nomogram was constructed based on the model. Internal validation of the prediction model was performed by using the Bootstrap method， and the model was evaluated by the receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis. RESULTS A total of 91 patients with advanced ESCC were included. The results of Lasso regression combined with Logistic regression analysis indicated that the baseline lymphocyte monocyte ratio （LMR） [odds ratio （OR）＝1.97， 95% confidence interval （CI）： 1.15-3.36， P＝0.013]， albumin （ALB） content （OR＝1.35， 95%CI： 1.13-1.60， P＜0.001）， body mass index （BMI） category 1 [normal vs. low： OR＝ 0.28， 95%CI （0.09-0.96）， P＝0.042]， BMI category 2 [overweight-obesity vs. low： OR＝0.08， 95%CI （0.01-0.59）， P＝0.013]， and treatment regimen [monotherapy vs. monotherapy combination therapy： OR＝0.07， 95%CI （0.01-0.50）， P＝0.008] were predictive factors for patients with advanced ESCC to achieve DCB when treated with PD-1 inhibitor. A prediction model was constructed based on the above indicators. Internal validation of the model using the Bootstrap method showed an area under the curve of 0.831 （95%CI： 0.746-0.904）， with specificity of 74.4% and sensitivity of 75.0%. The Hosmer-Lemeshow test yielded χ2＝ 9.930， P＝0.270， and the calibration curve slope was close to 1. The decision curve analysis demonstrated that the model exhibited good clinical utility within a threshold range of 0.1 to 1.0. CONCLUSIONS The prediction model based on baseline LMR， ALB content， BMI， and treatment regimen demonstrates robust predictive performance and clinical utility for assessing therapeutic efficacy of PD-1 inhibitor in the treatment of advanced ESCC.

Objective:To analyze the distribution of causes of death among residents in Chuzhou City of Anhui Province from 2019 to 2022,in order to provide evidence for formulating disease prevention and control strategies.Methods:The death data of residents in Chuzhou City from 2019 to 2022 were obtained from the cause of death surveillance system of Chuzhou Center for Disease Control and Prevention in Anhui Province.The crude death rate,composition ratio of cause of death and the rank of cause of death were analyzed.The annual percent change(APC)of mortality was calculated by using the Joinpoint regression model to describe the average annual change of mortality.Results:From 2019 to 2022,the average annual crude mortality of permanent residents in Chuzhou City was 668.80/100 000,and the crude mortality rate(/100 000)was 640.58,652.10,659.32,and 723.46,respectively(APC=3.10%,P=0.356).The annual crude mortality of males(735.93/100 000)was higher than that of females(598.52/100 000)(χ2=1 148.724,P＜0.01).The top three causes of death were malignant tumor,cerebrovascular disease,and cardiovascular disease.The mortality of malignant tumors showed a decreasing trend(APC=-1.51%,P＜0.01),and the top three causes of death of malignant tumors were lung cancer,gastric cancer and liver cancer.Among the age groups,congenital malformations and deformations,chromosomal abnormalities,and certain conditions originating in the perinatal period were the leading causes of death among residents aged 0 to 4 years old.Accidental injuries were the first cause of death among residents aged 5 to 14 years old.The leading cause of death among residents in the 15-44 and 45-64 age groups was malignant tumor.Cerebrovascular disease was the leading cause of death in≥65 years old.The mortality of accidental injuries showed an increasing trend(APC=1.64%,P＜0.01),and the specific types of death causes of accidental injuries were different among different age groups.Conclusion:Chronic non-communicable diseases,especially cancer and cardiovascular and cerebrovascular diseases,are the main health threats to the residents of Chuzhou City of Anhui Province,and feasible prevention and control measures should be formulated.

Positron emission tomography (PET) now plays an important role in the research and development (R&D) of central nervous system (CNS) drugs. PET could characterize the biodistribution, pharmacokinetics, and receptor binding of CNS drugs quantitatively. The present review summarized the quantitative methods of PET used in the pharmacokinetics and receptor occupancy analysis of CNS drugs. Moreover, the present review listed various applications of PET supporting R&D of CNS drugs, which could provide a new direction for the R&D of CNS drugs.

Objective lo analyze the difference of peri-coronary tat attenuation index(pr Al)on different grades of hypertension(HT),and to explore the value of pFAI in evaluating the risk of HT patients.Methods Retrospective data on hospitalized patients who underwent coronary computed tomography angiography(CCTA)examination for chest pain were collected.A total of 415 clini-cally confirmed HT patients were selected as observation group(including 132 patients in grade 1 HT group,137 patients in grade 2 HT group,146 patients in grade 3 HT group),and 187 non-hypertension patients during the same period as control group.The differ-ence of fat attenuation index(FAI)in three main coronary arteries[left anterior descending artery(LAD),left circumflex artery(LCX),right coronary artery(RCA)]was compared,and the correlation between pF AI and HT patients was analyzed.Results RCA-FAI(-78.86 HU±7.66 HU)and LAD-FAI(-80.62 HU±7.50 HU)were higher in HT group than those in control group(-84.46 HU± 8.00 HU,-83.43 HU±7.51 HU,P＜0.05).pFAI value was higher in grade 3 HT group than that in grade 1 HT group and grade 2 HT group(P＜0.05),while there were no differences between grade 1 HT group and grade 2 HT group(P＞0.05).After adjusting the influence of traditional risk factors and coronaryartery disease,RCA-FAI had relatively closer relationship with HT grades(r=0.47,P＜0.001).Conclusion LAD-FAI,RCA-FAI in the HT group are higher than those in control group and RCA-FAI has relatively closer relationship with HT grades,suggesting that RCA-FAI may be an imaging indicator to evaluate the pro-gression of HT and predict the risk of HT.

Objective:To analyze the differentially expressed genes (DEGs) in visceral adipose tissue of patients with type 2 diabetes mellitus (T2DM) based on bioinformatics.Methods:The microarray dataset GSE78721 was downloaded from the Gene Expression Omnibus (GEO) database, including visceral fat samples data from 19 T2DM patients and 16 non-diabetic subjects. The analysis of transcriptomic profiling results from tissue samples was conducted, and a comparison between different groups of samples based on gender was performed. The online Xintao Academic Database was utilized for the analysis, employing the "limma" package in R language to filter DEGs. Subsequently, the DEGs were visualized, and Gene Ontology (GO) functional annotation along with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out and visualized. Based on the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, a protein-protein interaction network (PPI) of DEGs was constructed and key differentially expressed genes were identified and visualized using Cytoscape software.Results:Analysis of visceral adipose tissue gene expression profiles revealed 168 DEGs (|log 2FC|≥1, P<0.05). In females, 42 mRNAs were up-regulated, 3 were down-regulated; in males, 105 were up-regulated, 37 were down-regulated, 19 genes were shared by the two groups. GO analysis linked DEGs to insulin-like growth factor receptor signaling and regulation, nutrient response, and leukocyte migration. KEGG analysis implicated extracellular matrix receptor interactions and leukocyte transendothelial migration. The PPI network unveiled 10 key genes, including COL1A1, COL1A2, TGFB3, PCOLCE, TIMP1, COL6A2, COMP, COL14A1, VCAM1 and THY1. Conclusion:Bioinformatics technology can effectively analyze and screen DEGs in visceral adipose tissue of T2DM patients, providing useful clues for further exploring its molecular mechanism and finding therapeutic targets.