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.

Objective: To investigate the association between occupational stress and health-related quality of life (HRQoL) among grassroots medical personnels, so as to provide the reference for improving their physical and mental well-being. Methods: From March to May 2024, medical staff from nine street community health service centers in Liangxi District, Wuxi City, Jiangsu Province were selected by a convenient sampling method. Basic information was collected through questionnaire surveys. Occupational stress was assessed using the Core Occupational Stress Measurement Scale. Health utility value and the Visual Analog Scale (EQ-VAS) score were investigated using the European Quality of Life Five-Dimension Five-Level (EQ-5D-5L) questionnaire. The association between occupational stress and HRQoL was analyzed using multiple linear regression model. Results: A total of 909 individuals were surveyed, including 141 males (15.51%) and 768 females (84.49%). The average occupational stress score was (24.41±9.45) points. The average health utility value was (0.96±0.07), with 372 individuals (40.92%) experiencing health problems in at least one dimension. The primarily problems were pain/discomfort and anxiety/depression, with 249 (27.39%) and 265 (29.15%) individuals, respectively. The average EQ-VAS score was (86.62±13.84) points. Multiple linear regression analysis revealed that occupation (nurses, β'=0.101; pharmacists, β'=0.101; medical technicians, β'=0.090), professional title (intermediate, β'=-0.079; associate senior, β'=-0.081; senior, β'=-0.101), and occupational stress (β'=-0.288) were influencing factors for health utility value. Occupation (nurses, β'=0.087; pharmacists, β'=0.146; medical technicians, β'=0.073) and occupational stress (β'=-0.226) were influencing factors for EQ-VAS score. After adjusting for variables such as gender, age, educational level, occupation, professional title, work experience, and monthly income, grassroots medical personnels with higher occupational stress score had lower health utility values (β'=-0.296) and EQ-VAS score (β'=-0.237). Conclusions Occupational stress can reduce the HRQoL among grassroots medical personnels. It is recommended to regularly assess occupational stress levels and intervene early to address their psychological and physical health issues.

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.

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.

Objective To investigate the inhibitory effects of formononetin on sortase A(SrtA)of Staphylococcus epidermidis(S.epi-dermidis)and its biofilm formation.Methods Biofilm-producing S.epidermidis standard strain RP62A and biofilm-producing S.epider-midis clinical strains were collected.The minimal inhibitory concentration(MIC)of formononetin against S.epidermidis was investigated using the two-fold dilution method.The inhibitory effects of different concentrations of formononetin on the growth of S.epidermidis in vitro were studied by growth curve analysis using microplate reader.The cytotoxicity of formononetin was measured by cell culture.The biocompatibility of formononetin was studied by hemolysis assay.The inhibitory effect of formononetin on the activity of SrtA was deter-mined by fluorescence resonance energy transfer(FRET)assay.The effect of formononetin on the ability of S.epidermidis binding fi-bronectin was assessed by fibronectin binding assay.The effect of formononetin on the anchoring of serine-rich repeat proteins(SRRPs)in S.epidermidis was assessed by immunofluorescence staining.The effect of formononetin on the biofilm formation of S.epidermidis was measured by crystal violet staining.Results The MICs of formononetin against S.epidermidis were greater than 512 μg/mL.Compared with the control group,32 μg/mL of formononetin did not significantly affect the growth of S.epidermidis or reduce the viability of hu-man aortic endothelial cells.The hemolysis rate of human red blood cells was less than 5%.The inhibition rate of SrtA activity was ap-proximately 53.8%.The binding capacity of S.epidermidis to fibronectin was reduced by approximately 45.4%.Microscopic observation revealed a significant reduction in the anchoring of SRRP in S.epidermidis,and the formation of biofilm of S.epidermidis was inhibited by approximately 41.7%.Conclusion Formononetin inhibits the activity of SrtA in S.epidermidis,reduce its fibronectin-binding ca-pacity and biofilm formation,and thus represents a promising candidate for the prevention of S.epidermidis infections.

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.

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.