OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

Objective:To explore the chain mediating role of professional identity and positive coping between leadership empowerment and work engagement of clinical research nurses (CRNs) .Methods:Convenience sampling was used to select 250 CRNs working in Beijing Friendship Hospital, Capital Medical University from August to September 2024 for the study. The survey was conducted with the General Information Questionnaire, Utrecht Work Engagement Scale, Empowering Leadership Behavior Scale, Professional Identification Scale for Nurse, and Simplified Coping Style Questionnaire. The chain mediating effects were tested using Model 6 of the SPSS PROCESS program.Results:A total of 250 questionnaires were distributed, 236 questionnaires were recovered, and 223 valid questionnaires were recovered after excluding the regularly answered questionnaires, with an effective recovery rate of 89.20% (223/250). Mediating effect analysis revealed that leadership empowerment directly and positively predicted work engagement of CRNs, with a direct effect value of 0.194, accounting for 67.60% of the total effect. Leadership empowerment also had an impact on work engagement of CRNs through three mediating paths. Mediating path 1: leadership empowerment→professional identity→ work engagement, with an effect value of 0.036, accounting for 12.54% of the total effect. Mediating path 2: leadership empowerment → positive coping → work engagement, with an effect value of 0.049, accounting for 17.07% of the total effect. Mediating path 3: leadership empowerment → professional identity → positive coping → work engagement, with an effect value of 0.008, accounting for 2.79% of the total effect. The total mediating effect was 0.093, accounting for 32.40% of the total effect.Conclusions:Leadership empowerment can not only directly affect work engagement of CRNs, but also indirectly affect it through the mediating role of professional identity and positive coping.

Objective To retrospective analysis summarized the effectiveness and safety of the"triple"conversion therapy regimen combining immune,targeted and local therapy.Methods From February 2019 to June 2023,52 patients with advanced liver cancer from February 2019 to June 2023 in XI,an Jiao Tong university medicine college affiliated 3201 hospital were admitted and received conversion treatment regimens combining sintilimab with bevacizumab and combined with local treatment,analyzed the surgical resection rate and pathological complete response rate(pCR),complete response rate(CR),partial response rate(PR),progression of disease(PD),stable disease(SD),objective response rate(ORR)and disease control rate(DCR).To evaluated the effect of conversion therapy and adverse reactions.Results 21 cases had recived operative resection in the 52 patients with primary liver cancer receiving sintilimab and bevacizumab.The postoperative resection rate was 40.4％(21/52),pCR 42.9％(9/21).The other 31 cases have complete response 5.8％(3/52),PR 25.0％(13/52),PD 11.5％(6/52),SD 17.3％(9/52).The overall objective response rate(ORR)was71.2％(37/52),and the disease control rate(DCR)was 88.5％(46/52).Adverse reactions manifest as Grade 1-2 skin-related damage primarily affecting the epidermis.Conclusions For patients with potentially resectable primary liver cancer in middle and advanced stage,the"triple"conversion therapy with sintilimab combined with bevacizumab as systematic treatment and combined with local therapy can achieve good conversion treatment effect with controllable safety.

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective:To evaluate the levels and source of cadmium exposure by dietary pathway among middle-aged and elderly people ≥40 in cadmium-contaminated areas of China.Methods:A total of 7 193 people aged 40-89 years from four typical cadmium-contaminated areas in China were selected as the study subjects. Food Frequency Questionnaire (FFQ), Total Diet Study (TDS) and a 3-day-24-hour dietary recall survey were conducted. Dietary cadmium intake and food sources through dietary pathways were assessed based on cadmium content in foods, consumption amounts and intake frequencies.Results:The mean age of the participants was 63.39±12.21 years, with 50.05% being males. The average monthly dietary cadmium intake was 7.39 μg/(kg·BW). Staple foods and vegetables were the primary sources of dietary cadmium intake, accounting for 57.51% and 32.48%, respectively. The monthly dietary cadmium intake in all surveyed regions did not exceed the Provisional Tolerable Monthly Intake (PTMI) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).Conclusion:The monthly dietary cadmium intake among middle-aged and elderly people in cadmium-contaminated areas of China is relatively low, with the risk remaining at an acceptable level. Staple foods and vegetables are the most significant contributors to dietary cadmium intake.

Objective To compare the short-term outcomes and long-term prognosis between laparoscopic and open surgery for large gastric gastrointestinal stromal tumors(GISTs).Methods A retrospective cohort study was conducted on 110 patients with large gastric GISTs who underwent surgical treatment in the medical department of general surgery,Chinese People's Liberation Army General Hospital,from January 2015 to December 2020.Among them,47 were males(42.73%)and 63 were females(57.28%),with a median age of 55 years.Patients were divided into the open surgery group(n=57)and the laparoscopic surgery group(n=53)based on the surgical approach.Pro-pensity score matching(PSM)was performed using a 1∶1 nearest-neighbor matching method,resulting in 34 patients in each group after matching.Short-term outcomes and long-term prognosis were compared between the two groups.Results After matching,the laparoscop-ic surgery group showed significantly better outcomes than the open surgery group in terms of drainage tube removal time,operative time,intraoperative blood loss,and postoperative hospital stay(all P<0.05).No significant differences were observed in nasogastric tube removal time,time to first flatus,or time to resuming oral intake(all P>0.05).The open surgery group had lower hospitalization cost compared to the laparoscopic surgery group(P<0.05).Regarding long-term survival,the 1-,3-,and 5-year disease-free survival(DFS)rates in the lapa-roscopic surgery group were 100%,88.1%,and 88.1%,respectively,while those in the open surgery group were 100%,94.1%,and 94.1%.The 1-,3-,and 5-year overall survival(OS)rates in the laparoscopic surgery group were 100%,100%,and 88.8%,respectively,compared to 100%,97.1%,and 94.7%in the open surgery group.No statistically significant differences were found in DFS and OS between the two groups(both P>0.05).Conclusions Laparoscopic resection of large gastric GISTs is safe and feasible,without increasing the risk of tumor recurrence,and achieves comparable efficacy to open surgery.However,its application should still be approached with caution.

Objective To retrospective analysis summarized the effectiveness and safety of the"triple"conversion therapy regimen combining immune,targeted and local therapy.Methods From February 2019 to June 2023,52 patients with advanced liver cancer from February 2019 to June 2023 in XI,an Jiao Tong university medicine college affiliated 3201 hospital were admitted and received conversion treatment regimens combining sintilimab with bevacizumab and combined with local treatment,analyzed the surgical resection rate and pathological complete response rate(pCR),complete response rate(CR),partial response rate(PR),progression of disease(PD),stable disease(SD),objective response rate(ORR)and disease control rate(DCR).To evaluated the effect of conversion therapy and adverse reactions.Results 21 cases had recived operative resection in the 52 patients with primary liver cancer receiving sintilimab and bevacizumab.The postoperative resection rate was 40.4％(21/52),pCR 42.9％(9/21).The other 31 cases have complete response 5.8％(3/52),PR 25.0％(13/52),PD 11.5％(6/52),SD 17.3％(9/52).The overall objective response rate(ORR)was71.2％(37/52),and the disease control rate(DCR)was 88.5％(46/52).Adverse reactions manifest as Grade 1-2 skin-related damage primarily affecting the epidermis.Conclusions For patients with potentially resectable primary liver cancer in middle and advanced stage,the"triple"conversion therapy with sintilimab combined with bevacizumab as systematic treatment and combined with local therapy can achieve good conversion treatment effect with controllable safety.

Objective To compare the short-term outcomes and long-term prognosis between laparoscopic and open surgery for large gastric gastrointestinal stromal tumors(GISTs).Methods A retrospective cohort study was conducted on 110 patients with large gastric GISTs who underwent surgical treatment in the medical department of general surgery,Chinese People's Liberation Army General Hospital,from January 2015 to December 2020.Among them,47 were males(42.73%)and 63 were females(57.28%),with a median age of 55 years.Patients were divided into the open surgery group(n=57)and the laparoscopic surgery group(n=53)based on the surgical approach.Pro-pensity score matching(PSM)was performed using a 1∶1 nearest-neighbor matching method,resulting in 34 patients in each group after matching.Short-term outcomes and long-term prognosis were compared between the two groups.Results After matching,the laparoscop-ic surgery group showed significantly better outcomes than the open surgery group in terms of drainage tube removal time,operative time,intraoperative blood loss,and postoperative hospital stay(all P<0.05).No significant differences were observed in nasogastric tube removal time,time to first flatus,or time to resuming oral intake(all P>0.05).The open surgery group had lower hospitalization cost compared to the laparoscopic surgery group(P<0.05).Regarding long-term survival,the 1-,3-,and 5-year disease-free survival(DFS)rates in the lapa-roscopic surgery group were 100%,88.1%,and 88.1%,respectively,while those in the open surgery group were 100%,94.1%,and 94.1%.The 1-,3-,and 5-year overall survival(OS)rates in the laparoscopic surgery group were 100%,100%,and 88.8%,respectively,compared to 100%,97.1%,and 94.7%in the open surgery group.No statistically significant differences were found in DFS and OS between the two groups(both P>0.05).Conclusions Laparoscopic resection of large gastric GISTs is safe and feasible,without increasing the risk of tumor recurrence,and achieves comparable efficacy to open surgery.However,its application should still be approached with caution.

Objective:To analyze the efficacy of combination of peginterferon α-2b（Peg-IFN α-2b）with nucleos（t）ide analogues（NAs）on antiviral therapy in children with chronic hepatitis B（CHB）and to provide an optimized clinical treatment strategies for CHB children.Methods:A retrospective analysis was conducted on 30 CHB children treated in The First Affiliated Hospital of the Army Medical University（Southwest Hospital）from January 2022 to January 2025 with treatment duration at least 48 weeks. The enrolled children were aged between 2 and 17 years and divided into the NAs combined with Peg-IFN α-2b（NPI）group（n=13）and NAs group（n=17）by their therapy regimens. The characteristics of baseline，week 12，week 24，week 48 and week 96 were compared between groups，as well as the differences in response to biochemical，immune and viral indicators at each observation point. Logistic regression analysis and receiver operating characteristic（ROC）curve analysis were performed to identify factors influencing the HBsAg seroclearance. Results:At baseline of treatment，the proportion of HBeAg positivity in the NPI group and the NAs group was high（76.9% vs 86.6%， χ2=0.679， P=0.628），and the alanine aminotransferase（ALT）and aspartate aminotransferase（AST）in the NPI group were significantly lower than those in the NAs group（ P<0.001）. At 24 weeks，the decrease in HBsAg in the NPI group was also significantly higher than that in the NAs group（ Z=-3.161， P=0.002）. Finally，the cumulative seroclearance rate of HBsAg at 96 weeks in the NPI group was significantly higher than that in the NAs group（46.15% vs 5.88%， χ2=0.679， P=0.025）. Mulitivariate Logistic regression analysis showed that treatment regimen and gender were risk factors affecting the outcome of HBsAg（ P<0.05）. ROC curve analysis showed that the increase in ALT at 12 weeks compared with baseline（AUC=0.857，Cutoff value=3.615 IU/L），the decrease in ALT at 24 weeks（AUC=0.870，Cutoff value=47.85 IU/L），and the decrease in HBsAg at 12 weeks and especially at 24 weeks（AUC=0.885，Cutoff value=0.97log IU/ml）were effective predictors of HBsAg prognosis at 96 weeks. Conclusion:In CHB children，antiviral regimen Peg-IFN α-2b combined with NAs was more effective than NAs alone in improving the HBsAg seroclearance rate of CHB，and the effects in female were better than in male. The decline of HBsAg and the fluctuation of ALT in the early treatment period are valid predictors of HBsAg clearance.

Identifying drug-drug interactions(DDIs)is essential to prevent adverse effects from polypharmacy.Although deep learning has advanced DDI identification,the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits.Here,we developed a Multi-Dimensional Feature Fusion model named MDFF,which integrates one-dimensional simplified molec-ular input line entry system sequence features,two-dimensional molecular graph features,and three-dimensional geometric features to enhance drug representations for predicting DDIs.MDFF was trained and validated on two DDI datasets,evaluated across three distinct scenarios,and compared with advanced DDI prediction models using accuracy,precision,recall,area under the curve,and F1 score metrics.MDFF achieved state-of-the-art performance across all metrics.Ablation experiments showed that integrating multi-dimensional drug features yielded the best results.More importantly,we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs.Among 12 real-world adverse drug reaction reports,the predictions of 9 reports were supported by relevant evidence.Additionally,MDFF demon-strated the ability to explain adverse DDI mechanisms,providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.