Objective To explore the impact of the sialic acid binding lectin-E(Siglec-E)on the inhibitory properties of parthenolide(PTL)against lipopolysaccharide(LPS)-induced M1 polarization of microglia(BV2).Methods ①Single cell sequencing data of Siglece related mouse brain tissue was obtained from Gene Expression Omnibus(GEO)database and divided into the WT group(n=3)and the Siglece-/-group(n=4).The microglia cells were screened,and the enrichment analysis was performed to analyze related differential genes and pathways.BV2 cells were constructed by the shRNA interference technique and were divided into NC-shRNA and Siglece-shRNA to detect the expression level of Siglec-E(Siglece).② NC-shRNA and Siglece-shRNA cells were respectively divided into the Control group,LPS group,PTL group and PTL+LPS group(n=3).The mRNA levels of markers of M1 polarization in microglia,iNOS,IL-1 β and IL-6,were detected by RT-qPCR.Siglecefl/fl and Cx3cr1cre mice were mated to obtain microglia-specific Siglece deletion(Siglecefl/fl×Cx3cr1cre)mice,and LPS-induced neuroinflammation model was established.③ Nine WT and Siglecefl/fl×Cx3cr1cre male mice were assigned to the Control group,LPS group and PTL+LPS group(n=3).RT-qPCR,immunofluorescence assay and Western blotting were used to verify the knock-out effect and polarization-related pathways,and to investigate the mechanism of Siglec-E affecting PTL inhibition of M1 polarization of microglia.Results Compared with the NC-shRNA group,the expression of Siglec-E in the Siglece-shRNA group was significantly decreased(P<0.01),indicating that the Siglec-E knock-down cell model was successfully established.With the stimulation of LPS,mRNA levels ofiNOS,IL-1 β and IL-6 were significantly up-regulated compared with the Control group both in shRNA cells and Siglece-shRNA cells(P<0.01).With the influence of PTL and LPS,the markers of M1 polarization in NC-shRNA cells mentioned before were significantly decreased(P<0.05),while for Siglice-shRNA cells,there were no significant changes in the markers of M1 polarization.PTL inhibited the phosphorylation of JNK and IκB protein(P<0.01)and the nuclear translocation of NF-κB in BV2 cells,down-regulated Siglec-E,and weakened the inhibitory effect.Compared with mice in the WT group,the expression of Siglec-E in microglia of Siglecefl/fl×Cx3cr1cre mice was decreased significantly(P<0.01),and the inhibitory effect of PTL on the phosphorylation of NF-κB in microglia of Siglecefl/fl×Cx3cr1cre mice was also decreased.Conclusion The absence of Siglec-E in microglia attenuates the inhibition of M1 polarization by the MAPK/NF-κB pathway targeted by PTL.

Objective To compare the efficacy and safety of endoscopic ligation treatment and endoscopic tissue glue injection for secondary prevention of gastric variceal bleeding.Methods Patients with cirrhosis and esophagogastric variceal bleeding treated with gastric variceal ligation in Zhongshan Hospital,Fudan University,from January 2017 to December 2019 were screened(ligation group).And during the same period,patients underwent endoscopic cyanoacrylate treatment were also screened(tissue glue group).59 patients were included in the two groups after propensity score matching.Univariate and multivariate Cox proportional hazard regression models were used to anslyze risk factors for re-bleeding.Kaplan-Meier curves were plotted to analyze re-bleeding rate and mortality of the two treatment groups.Results There was no statistically significant difference in the eradication rate of esophagogastric varices between the ligation group and the tissue glue group(83.05％vs 79.66％,P=0.778);the ligation group required fewer median endoscopic treatments for variceal eradication(2 vs 3,P=0.017)and a lower average dosage of cyanoacrylate(0.70 mL vs 2.67 mL,P＜0.001).Multivariate Cox regression analysis showed that portal shunt was a risk factor for esophagogastric varices re-bleeding(HR=3.14,95％CI 1.02-9.68,P=0.046),endoscopic variceal ligation was a protective factor against re-bleeding(HR=0.25,95％CI 0.08-0.71,P=0.010).Compared with endoscopic cyanoacrylate injection,endoscopic ligation treatment did not significantly increase the 2-year risk of esophagogastric variceal re-bleeding(18.69％vs 36.29％,P=0.067)or risk of death(1.69％vs 3.39％,P=1.000);patients with GOV1 type had a significantly lower risk of re-bleeding after endoscopic ligation treatment(0 vs 40.27％,P=0.012)and there was a trend towards a lower re-bleeding risk in patients with GOV2 type after endoscopic ligation treatment(13.27％vs 34.16％,P=0.056).Conclusions Endoscopic ligation treatment has higher eradication rate for esophagogastric varices,and does not increase the risk of re-bleeding,death,or other adverse events.Therefore,it can be considered an effective secondary prevention way for patients with gastric varices.

Objective:This study investigates the influence of the apolipoprotein E ε4(APOE ε4)genotype on the relationship between glucose-lipid metabolism disorders and diabetes-related cognitive impairment(DCI).Methods:A case-control study was conducted involving 891 patients with type 2 diabetes mellitus(T2DM)with a mean age of(62.1±13.8)years, all of whom underwent elective surgery at the First Hospital of Shanxi Medical University between January 2017 and December 2022.Among these participants, 229 were diagnosed with DCI(case group), while 662 were cognitively normal(control group).Routine clinical information was collected, and peripheral venous blood samples were analyzed for glycated hemoglobin(HbA1c)and blood lipid levels.The single nucleotide polymorphisms rs429358 and rs7412 were analyzed to determine the presence of the APOE ε4 genotype.Stepwise Logistic regression was employed to identify independent risk factors for DCI, and subgroup analyses were performed to evaluate the effect of the APOE ε4 genotype on the relationship between HbA1c and blood lipid levels in relation to DCI risk. Results:Among all patients, female gender( OR=1.915, 95% CI: 1.393-2.631, P<0.001), longer duration of T2DM( OR=1.169, 95% CI: 1.087-1.257, P<0.001), elevated triglycerides( OR=1.161, 95% CI: 1.041-1.294, P=0.007), and being an APOE ε4 carrier( OR=1.638, 95% CI: 1.115-2.405, P=0.012)were identified as independent risk factors for developing DCI.High levels of low-density lipoprotein(LDL)were found to be independently associated with an increased risk of DCI specifically in APOE ε4 carriers( OR=1.408, 95% CI: 1.060-1.870, P=0.018), but not in non-APOE ε4 carriers( P>0.05).In contrast, elevated HbA1c was independently associated with a higher risk of DCI in non-APOE ε4 carriers( OR=1.220, 95% CI: 1.040-1.430, P=0.014), but not in APOE ε4 carriers( P>0.05).Additionally, elevated triglycerides were independently linked to an increased risk of DCI across the entire sample and within each APOE ε4 genotype subgroup. Conclusions:The APOE genotype plays a significant role in modulating the relationship between dyslipidemia and the risk of developing DCI.This highlights the critical importance of lipid metabolism disorders and APOE risk genes in both the development and progression of DCI.These findings offer valuable insights for future clinical and mechanistic studies focused on DCI.

Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Objective:To realize the optimization and upgradation of the detection method of you only look once(YOLO)algorithm model based on the improved YOLO network on the ultrasound image for breast tumor.Methods:A total of 659 images of breast tumor of the Kaggle database were selected as the initially dataset,and the image annotation tool Labelimg was used to conduct pre-labeling for the detection targets in the images.According to a ratio as 7:3,629 images of the 659 images were divided into the train set and validation set,and the other 30 images were used as the test set.The convolutional block attention module(CBAM)and bidirectional feature pyramid network(BiFPN)were introduced into the original YOLO algorithm to underwent structural improvement,which was named as YOLOv5-BiFPN-CBAM.Both the train set and validation set were placed in original YOLO algorithm model and YOLOv5-BiFPN-CBAM model to conduct train,which included 200 rounds of iterative training.The obtained optimal weight files were used in the final test of test set.Results:After 200 rounds of iterative train for two kinds of models,the test results of validation set indicated that the mean values of average precision of two kinds of models were respectively 72.1%and 80.5%for all ultrasound images of breast tumor.The result,that the optimal weight file of improved model was tested by test set,indicated the test ability of improved model was significantly enhanced than that of original model for small target in image.Conclusion:Compared with the original YOLO algorithm model,the improved YOLO algorithm model has higher recognition capability for image,which also enhances precision and sensitivity in identifying small targets of ultrasound images of breast tumor.This model is helpful to improve the diagnostic efficiency in clinical practice for breast tumor.

There are gradual increases in the incidence rates of metabolic associated fatty liver disease （MAFLD） and type 2 diabetes mellitus （T2DM）， with close relationship and mutual interaction between the two diseases， but the specific mechanism is still unclear. Studies have shown that T2DM and MAFLD may cause aggravation of each other through insulin resistance， inflammation， some hepatocyte factors， and cellular senescence and protect each other through some hepatocyte factors. Further research on the association between T2DM and MAFLD and the mechanism of comorbidity is of great significance for the clinical prevention and treatment of the two diseases.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death, and most patients with HCC are diagnosed at an advanced stage. Before 2017, tyrosine kinase inhibitors were the main drugs for the treatment of advanced hepatocellular carcinoma. With the emergence of immune checkpoint inhibitors (ICIs), immunotherapy has gradually brought new hope to such patients. At present, the combination of ICIs and other systemic or local treatments has become a potential strategy for the treatment of advanced hepatocellular carcinoma, and some of these combinations have been included in large-scale clinical trials. The main challenges of immunotherapy for advanced hepatocellular carcinoma include the exploration of predictive biomarkers, management of immune-related adverse events, and exploration of effective combination regimens. This article provides the latest research progress on the single or combined use of ICIs and other immunotherapy for hepatocellular carcinoma and discusses the limitations of current research and clinical application and the future development direction.

Objective:To investigate the application value of carbon nanoparticle tracer in lymph node dissection for Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 147 patients with Siewert type Ⅱ and Ⅲ AEG who were admitted to Shengli Petroleum Central Hospital from June 2015 to July 2020 were collected. There were 109 males and 38 females, aged (65±9)years. All the patients underwent laparoscopic-assisted radical resection of AEG via esophageal hiatus. Of 147 patients, 61 cases not injected with carbon nanoparticle tracer preoperatively were allocated into control group and 86 cases injected with carbon nanoparticle tracer preoperatively were allocated into experimental group. Observation indicators: (1) surgical and postoperative situations; (2) influencing factors analysis of No.10 lymph nodes metastasis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test. Univariate analysis was conducted by statistic methods based on data type, and multivariate analysis was conducted by the Logistic step-wise regression model. Results:(1) Surgical and postoperative situations. Patients of the experimental group and control group completed laparoscopic-assisted radical resection of AEG via esophageal hiatus successfully. There was no significant difference in the operation time, volume of intraoperative blood loss, the total number of lymph node dissection, the number of the first station, the second station and positive lymph nodes between the two groups ( P>0.05). For the experimental group, the black staining rate of lymph nodes was 57.937%(1 365/2 356), the black staining rate of the first station and second station lymph nodes was 77.989%(1 024/1 313) and 43.691%(232/531), the black staining rate of Siewert type Ⅱ and Ⅲ AEG patients was 56.855%(423/744) and 58.437%(942/1 612), respectively. The lymph node metastasis rate was 19.091%(815/4 269) of 147 patients, 18.573%(242/1 303)of Siewert type Ⅱ AEG patients and 19.319%(573/2 966) of Siewert type Ⅲ AEG patients. For Siewert type Ⅱ AEG patients, the metastasis rate of No.1, 2, 3, 4sa, 4sb, 7, 8a, 11p lymph nodes was more than 10%, the metastasis rate of No.4d, 5, 6, 9, 10, 11d, 12a lymph nodes was lower than 10%. For Siewert type Ⅲ AEG patients, the metastasis rate of No.1, 2, 3, 4sa, 4sb, 7, 8a, 10, 11p and lower mediastinal lymph nodes was more than 10%, the metastasis rate of No.4d, 5, 6, 9 11d, 12a and lower mediastinal lymph nodes was lower than 10%. There was no significant difference in the Clavien Dindo classification of postoperative complications between the two groups ( P>0.05). (2) Influencing factors analysis of No.10 lymph nodes metastasis. Results of multivariate analysis showed that tumor T staging and degree of tumor differention was an independent influencing factor for No.10 lymph nodes metastasis ( P<0.05). Conclusions:For Siewert type Ⅱ and Ⅲ AEG patients, the application of carbon nano-partide tracer can not increase the number of lymph node dissection. The second station lymph node dissection should be paid attention for Siewert type Ⅱ AEG. Tumor T staging and degree of tumor differentiation are independent influencing factors for No.10 lymph nodes metastasis.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.