ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

[摘 要] 目的：探讨环指蛋白8（RNF8）对子宫内膜癌（EC）细胞顺铂（CDDP）敏感性的影响及可能机制。方法：基于在线数据库分析RNF8在EC组织中的表达及拷贝数变异；采用慢病毒介导shRNA稳定敲低Ishikawa细胞中RNF8表达并进行CDDP处理，按sh-NC+溶剂对照、sh-RNF8+溶剂对照、sh-NC + CDDP、sh-RNF8 + CDDP分组处理，并设置sh-RNF8 + CDDP + KU60019抑制实验。采用CCK-8、克隆形成、Annexin V-FITC/PI流式细胞术、Hoechst 33258/PI染色、WB及γ-H2AX免疫荧光检测细胞活力、克隆形成、凋亡、DNA损伤累积及ATM/CHK2通路相关蛋白表达。结果：RNF8在EC组织和细胞中表达升高。RNF8敲低降低细胞存活率和IC50，抑制克隆形成，并进一步增强CDDP诱导的凋亡；同时BAX、Cleaved-Caspase-3和γ-H2AX表达升高，BCL-2、p-ATM、p-CHK2和RAD21表达降低。KU60019处理进一步促进DNA损伤累积和细胞凋亡，并降低细胞活力。结论：RNF8可能通过ATM/CHK2轴促进DNA损伤应答并降低EC细胞对CDDP的敏感性；敲低RNF8可增加DNA损伤累积并增强CDDP敏感性。

Objective: To investigate the epidemiological and spatio-temporal characteristics of influenza in Jiaxing City, Zhejiang Province, so as to provide insights into perfecting the prevention and control strategies of influenza. Methods: Data of influenza in Jiaxing City from 2019 to 2023 were collected from the Chinese Disease Prevention and Control Information System. Population data of the same period were collected from the Zhejiang Health Information Network Reporting System. The epidemiological characteristics of influenza were analyzed using descriptive analysis. Vector map information was collected from the Open Street Map, and the spatio-temporal clustering characteristics of influenza were analyzed using spatial autocorrelation and spatio-temporal scanning. Results: A total of 181 501 cases of influenza were reported in Jiaxing City from 2019 to 2023, with an average annual reported incidence of 653.93/105. The majority of cases were aged 5 to <15 years (59 785 cases, 32.94%). The majority of the occupations were students (78 239 cases, 43.11%) and pre-school children (33 715 cases, 18.58%). The county (city, district) with the highest reported incidence was Haining City (1 451.70/105), and the town (street) with the highest reported incidence was Chang'an Town (1 932.78/105). Spatial autocorrelation analysis showed that the incidence of influenza in Jiaxing City from 2019 to 2023 had positive spatial correlations (all Moran's I>0, all P<0.05), with a high-high clustering in the southern region. Spatio-temporal scanning analysis showed that there was a spatio-temporal clustering of influenza in Jiaxing City from 2019 to 2023, with the southern region being the primary-type clustering area and the period between November and January of the following year being the clustering time. Conclusion There was a significant spatio-temporal clustering of influenza in Jiaxing City from 2019 to 2023, with winter being the peak season and the southern region being the primary area.

BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

Objective:To investigate the spatial and temporal distribution characteristics of brucellosis in Heilongjiang Province, Jilin Province and Inner Mongolia Autonomous Region (hereafter referred to as the Hei-Ji-Meng province and region), and study the influencing factors of brucellosis incidence.Methods:Using a retrospective analysis method, the data of brucellosis incidence in 22 prefecture-level cities in the Hei-Ji-Meng province and region from 2014 to 2018, as well as the data of natural environmental factors (precipitation, temperature, relative humidity, solar radiation, wind speed, vegetation index) and social environmental factors (livestock breeding, livestock and poultry meat production, cultivated land area) were collected and integrated. The spatial autocorrelation model and spatial Dubin model were used to analyze the spatial and temporal distribution rule of brucellosis and the impact of environmental factors on the incidence of brucellosis in prefecture-level cities.Results:From 2014 to 2018, the incidence of brucellosis in the Hei-Ji-Meng province and region was 18.77/100 000, among which the incidence in Inner Mongolia Autonomous Region was 33.45/100 000, followed by Heilongjiang Province (13.67/100 000) and Jilin Province (6.57/100 000). Among all prefecture-level cities, the brucellosis incidence was relatively higher in Hinggan League of Inner Mongolia Autonomous Region (69.10/100 000). Except 2016, the brucellosis incidence in other years had a positive spatial correlation (global Moran's I > 0, P < 0.05). The high-high concentration aggregation pattern was mainly concentrated in Ulanqab City, Xilingol League, Chifeng City, Tongliao City, Hinggan League, Hohhot City, and Hulunbuir City of Inner Mongolia Autonomous Region. Among the environmental factors related to brucellosis, cultivated land area and sheep breeding density had a positive effect on brucellosis incidence in the local area, with the effect intensity of 0.39 and 0.32, respectively ( P < 0.001). The average humidity from April to July had a negative effect on the brucellosis incidence in the local area, with the effect intensity of - 0.22 ( P = 0.023). The indirect effect of the number of pigs slaughtered on the brucellosis incidence in adjacent areas was the most significant, and the effect intensity was 2.15 ( P < 0.001). Conclusions:Among the Hei-Ji-Meng province and region, the annual average incidence rate of brucellosis in Inner Mongolia Autonomous Region is relatively higher, and the high-high concentration areas are mainly concentrated in this region. Among the environmental factors, the cultivated land area, sheep breeding density, the average humidity from April to July and the number of pigs slaughtered have an impact on brucellosis incidence.

Purpose To investigate the value of intratumoral and different ranges of peritumoral radiomics features of the primary lesion of breast cancer based on ultrasound images in predicting axillary lymph node metastasis(ALNM),and to explore the best peritumoral range.Materials and Methods A total of 312 cases confirmed by pathology in breast cancer patients with preoperative ultrasound images from June 2022 to February 2024 in Binzhou Medical University Hospital were retrospectively enrolled,and were randomly divided into training set and testing set according to the 7∶3 proportion.The tumor border of the ultrasound images was manually delineated as the intratumoral region of interest,and the peritumoral region of interest was obtained by conformal automatically extended different range(1,2,3,4 and 5 mm).The radiomics features were screened.Based on the selected optimal radiomics features,random forest classifier was used to construct three types of radiomics models(intratumoral model,5 peritumoral models,and 5 intratumoral+peritumoral models).The performance and clinical practicability of the models was assessed the area under the curve(AUC)and decision curve analysis.Results The AUCs of the intratumoral+peritumoral radiomics models for predicting ALNM in the training set and test set were 0.807-0.873,0.728-0.780,respectively,which were superior to those of the single intratumoral radiomics models(0.822,0.758)and peritumoral radiomics models(0.722-0.768,0.650-0.710).The intratumoral+peritumoral 3 mm radiomics model showed the best predictive performance,with AUC of 0.873 in the training set and 0.780 in the test set,respectively,and the decision curve showed that the model had a good clinical net benefit.Conclusion The combined intratumoral and peritumoral radiomics features of the primary lesion of breast cancer based on ultrasound images can effectively predict ALNM,and 3 mm peritumoral may be the best peritumoral range for predicting ALNM.

Objective:To explore the application effect of nurse-led navigation service in the economic toxicity management of prostate cancer patients, and to provide reference for the economic toxicity management of prostate cancer patients.Methods:By using the method of historical control study, 60 patients with prostate cancer admitted to Beijing Friendship Hospital, Capital Medical University were selected as the research subjects by convenience sampling from March to August 2023. According to the time sequence of admission, 30 patients admitted from March to May 2023 were included in the control group, and 30 patients admitted from June to August 2023 were included in the intervention group. The control group was given routine nursing, and the intervention group was given nurse-led navigation service. The patients were evaluated at admission, discharge and 3 months after discharge using the Comprehensive Scores for Financial Toxicity Based on the Patient-Reported Outcome Measures and the Compliance Behavior Questionnaire.Results:The age of the control group patients was ( 70.07 ± 5.76 ) years, and the age of the intervention group was ( 68.80 ± 7.22 ) years. The economic toxicity scores of the intervention group at discharge and 3 months after discharge were ( 35.13 ± 4.84 ) and ( 37.90 ± 4.89 ), respectively, which were higher than those of the control group ( 21.70 ± 2.52 ) and ( 21.33 ± 2.94 ), the differences were statistically significant ( t=-13.48, -15.89, both P<0.05 ). The complete compliance rate of the control group was 46.67 % (14/30), which was lower than 73.33% (22/30) of the intervention group, and the difference between the two groups was statistically significant ( χ2=4.44, P<0.05). Conclusions:Nurse-led navigation services can effectively monitor and evaluate the level of economic toxicity in patients with prostate cancer, reduce the degree of economic toxicity in patients with prostate cancer, help improve patients′ compliance behavior, and help patients cope with economic toxicity in a positive way.

Objective:To explore the effects of peripheral nerve injury(PNI)on neuropathic pain(NP)and memo-ry function in mice,as well as the activation of neurons in the paraventricular nucleus(PVT)of the thalamus,so as to provide a basis for studying the relationship between NP and memory impairment.Methods:Twenty one 8-week-old male C57 BL/6J mice were randomly divided into sham group and experimental group,and the routine spared nerve inju-ry(SNI)was constructed in the mice of experimental group.The pain behavior and memory impairment of mice after SNI were evaluated with hot plate and eight-arm maze behavioral tests.Pearson correlation analysis was performed to an-alyze the correlation between pain behavior and memory impairment.The c-FOS expression in PVT was detected with immuno-staining.Results:Compared with the sham group,the heat pain threshold of mice in the experimental group was significantly reduced(P＜0.001).The results of the eight-arm maze test showed that the total rest time was signifi-cantly increased(P＜0.001),and the working memory error was increased from 1 to 4 days after SNI(P＜0.01).Correlation analysis indicated that early working memory errors were negatively correlated with heat pain threshold after SNI(P＜0.001).The immunofluorescence revealed that the number of c-FOS positive cells in PVT increased signifi-cantly(P＜0.001).Conclusion:SNI can cause abnormal pain behavior and memory impairment in mice,and cause neuronal activation in PVT.This study provides a basis for neurons in PVT to participate in the regulation of memory impairment in the context of NP.

Objective Biomarkers associated with liver cancer CD8+T cells identified and prognostic models established by single-cell RNA sequencing and Bulk RNA sequencing.Methods Single-cell datasets of liver cancer were downloaded from the GEO database and differentially expressed genes in CD8+T cells between patients and controls were extracted by single-cell RNA sequencing.Gene expression profiling data and clinical data of liver cancer were downloaded from the TCGA database,and modular genes with relevance to CD8+T cells were screened using the CIBERSORT algorithm and WGCNA technology.Differential genes and modular genes were taken as intersecting genes and subjected to GO and KEGG analyses,and a prognostic model was established by applying univariate COX regression analysis and LASSO algorithm.The predictive effectiveness of the model in both internal and external datasets is validated by K-M and ROC curves.The effectiveness of the model's prediction in both internal and external datasets was validated by K-M and ROC curves.High-and low-risk groups were divided according to the median value of the risk score,and the distribution of infiltrating immune cells and tumor mutations between high-and low-risk groups were analyzed.Results A prognostic model with nine genes was constructed,and the K-M and ROC curves showed that the model had good predictive ability in both the internal and external datasets,and there were significant differences in the distribution of infiltrating immune cells and gene mutations in the high-and low-risk groups.Conclusion In this study,a novel prognostic model based on CD8+T cells was developed using bioinformatic method in combination with single-cell RNA sequencing and Bulk RNA sequencing technologies,which provides a reliable theoretical basis for prognostic improvement and survival prediction of liver cancer patients.

The Blow-Fill-Seal(BFS)technology is a highly automated aseptic manufacturing process that significantly reduces contamination risks by integrating container blowing,filling,and sealing operations.First,this article introduced the core technical features of BFS equipment and its advantages in aseptic production,followed by a comparative analysis of regulatory requirements for BFS technology across different jurisdictions.Finally,in light of pharmaceutical industry trends,it explored the future development prospects of BFS technology in intelligent manufacturing and high-barrier material applications,while examining its potential value in personalized medicine and specialized drug production.