Objective To investigate the causal relationship between immune cells and various molecular subtypes of breast cancer (BC) by using two-sample Mendelian randomization (MR). Methods This study employed a two-sample MR analysis, with 731 immune cell types from the GWAS catalog as the exposure factors and four BC molecular subtypes (HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−) from the BCAC Consortium as the outcome variables. For causal inference, inverse variance weighting (IVW) was employed as the primary analytical method, alongside multiple consistency validation approaches, including MR-Egger, weighted median, weighted mode, simple mode, and Bayesian weighted Mendelian randomization. Reverse MR and sensitivity analyses were employed to effectively evaluate and exclude potential biases and interference from reverse causality. Results Significant causal associations were identified for specific immune cell phenotypes across subtypes. In HR+ BC, the HER2+ subtype was associated with seven immunophenotypes (five protective and two risk increasing), whereas the HER2− subtype was associated with eight immunophenotypes (four protective and four risk increasing). In HR− BC, the HER2+ subtype was associated with five immunophenotypes (one protective and four risk increasing), and the HER2− subtype (triple-negative BC) was associated with seven immunophenotypes (six protective and one risk-increasing). CD28+CD45RA−CD8+ T cells and naive CD8+ T cells have a bidirectional causal relationship with HR+/HER2+ breast cancer, Whereas the expression of CD8 on CD39+CD8+ cells also has a bidirectional relationship with HR+/HER2− breast cancer. Furthermore, CD4−CD8− NKT cells exhibited opposing effect directions in HER2+ versus HER2− subtypes. Conclusion From a genetic perspective, this study confirms the existence of subtype-specific causal associations between immune cell phenotypes and distinct molecular subtypes of BC, revealing heterogeneity in immune regulation.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To investigate the methodology,technical considerations,and precautions of transcatheter arterial emboliza-tion(TAE)using medical adhesive as the primary embolic agent for visceral artery aneurysm(VAA).Methods A total of 14 patients with VAA treated with medical adhesive-based TAE were retrospectively analyzed.Among the 14 patients,6 cases were hepatic artery pseudoaneurysms,4 cases were true gastroduodenal aneurysms,3 cases were gastroduodenal pseudoaneurysms,and 1 case was renal artery pseudoaneurysm.Among the 14 patients,medical adhesive alone was used in 12 cases,while the other 2 cases were employed medical adhesive combined with supplemental coil embolization.Follow-up assessments including abdominal computed tomography angiography(CTA)and laboratory tests were conducted at 3,6,and 12 months post-procedure.Results Technical success was achieved in all cases with mean procedure duration of(60.4±8.2)min and average hospital stay of(8.9±2.1)d.No recanalization,aneurysm enlargement,or non-target embolization were observed during follow-up.Conclusion Medical adhesive-based TAE demonstrates high technical success when performed by experienced interventionists,with low complication rate,low recurrence rate,and low pro-cedure-related mortality,representing a cost-effective preferred treatment for VAA.

Objective:To investigate the influencing factors of secondary type 2 diabetes in young obesity patients, and construct and validate a risk prediction model.Methods:The retrospective cohort study was conducted. The clinical data of 847 young obesity patients who were admitted to The First Affiliated Hospital of Nanjing Medical University from January 2022 to July 2024 were collected. There were 382 males and 465 females, aged (29.4±3.8)years. Patients were randomly divided into a training set of 593 cases and a validation set of 254 cases based on a random number table method of 7∶3 ratio. The training set was used to construct the prediction model, and the validation set was used to validate prediction model. Observation indicators: (1) analysis of influencing factors of secondary type 2 diabetes in young obesity patients; (2) construc-tion and validation of a prediction model for secondary type 2 diabetes in young obesity patients. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic regression model, and the area under the curve (AUC) of receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow test, the calibration curve and decision curve were used to evaluate the predictive performance of the model. Results:(1) Analysis of influencing factors of secondary type 2 diabetes in young obesity patients. Of the 847 young obesity patients, there were 238 patients with secondary type 2 diabetes, including 161 cases in the training set and 77 cases in the validation set, 609 patients of simple obesity, including 432 cases in the training set and 177 cases in the validation set. Results of multivariate analysis showed that family history of diabetes, hypertension, high-sugar diet, exercise habits, triglyceride (TG), homeostasis model assessment of insulin resistance (HOMA-IR) and neutrophil-to-lymphocyte ratio (NLR) were independent factors influencing secondary type 2 diabetes in young obesity patients [ odds ratio=9.476, 2.420, 3.219, 0.272, 2.137, 26.759, 41.535, 95% confidence interval ( CI) as 3.242-27.696, 1.159-5.052, 1.525-6.796, 0.117-0.632, 1.019-4.481, 12.907-55.476, 16.085-107.251, P<0.05]. (2) Construction and validation of a prediction model for secondary type 2 diabetes in young obesity patients. A nomogram prediction model for secondary type 2 diabetes in young obesity patients was constructed based on the results of multivariate analysis. Results of ROC curve analysis showed that the AUC of prediction model for the training set was 0.963(95% CI as 0.946-0.980), with sensitivity of 89.6% and specificity of 93.2%, respectively, and the AUC of prediction model for the validation set was 0.966(95% CI as 0.944-0.988), with sensitivity of 92.7% and specificity of 88.3%, respectively. Results of Hosmer-Lemeshow test showed that the P-values for both the training set and validation set were >0.05, indicating good model fit. The calibration curves for both the training set and validation set closely matched the actual curve, demonstrating the prediction model with a good fit. The decision curve analysis showed high practical value of the model. Conclusions:Family history of diabetes, hypertension, high-sugar diet, exercise habits, TG, HOMA-IR and NLR are independent factors influencing secondary type 2 diabetes in young obesity patients. The prediction model constructed based on these factors demons-trates good predictive performance.

Approximately 300 million tons of plastic are produced globally each year,which has a serious impact on human health,marine life and the livestock industry.Microplastics have also been detected in meat and milk samples.Research has shown that nanoplastics(NP)(＜1 μm)and mi-croplastics(MP)(1 μm-5 mm)can affect the digestive,immune and reproductive systems of ani-mals.This experiment aims to investigate whether NP and MP regulate autophagy and damage the nervous system and spatial memory of animals.This experiment was divided into control group,nanoplastic group(PS-NP group,0.1 μm)and microplastic group(PS-MP group,1 μm),with 20 mice in each group.The mice were given 0.5 mL of PS-NP and PS-MP every day for 35 consecutive days,followed by neck amputation and brain analysis.The results showed that NPs and MPs of dif-ferent diameters caused varying degrees of damage to the brains of mice.In the behavioral tests of new object recognition,barnes maze and Y-shaped maze spatial memory,compared with the control group,the PS-NP group and PS-MP group showed a significant decrease in spatial memory ability of mice.HE staining results showed that neuronal cells in the PS-NP and PS-MP groups of mice exhibited shrinkage,decreased cell volume and deepened staining.The number of Nissl bodies de-creased,leading to dissolution and disappearance.RT-PCR and Western blot results showed that compared with the control group,the expression of glutamate receptors NR1,NR2A and NR2B in-creased in mice administered NP and MP orally,while the expression of autophagy related proteins Parkin,LC3B and Beclin1 was inhibited.In summary,this study suggests that nanoplastics and mi-croplastics stimulate glutamate receptors in mice by inhibiting the autophagy pathway,leading to impaired spatial memory.

The success of"New Medical Sciences"in higher education requires effective tools in evalua-ting students'performance in courses.Previously,we reported a teamwork(T),critique(C)and ap-preciation(A)(TCA)ideological and political model,a teaching model widely applied in Basic Medical courses.TCA is an abbreviation derived from Tricarboxylic Acid Cycle in Biochemistry as an analogy for nurturing the abilities of thinking and teamwork(T),critique(C)and appreciation(A),which hope-fully could provide students with moral norms for cognition,science and life.This paper further explores the tools to assess the educational outcomes of the TCA model,by which teachers can collect feedback and reflect on teaching quality and effectiveness.Addressing the challenges of individual differences in large classes,fragmented learning feedback,and the difficulty of measuring meta-cognition in educational evaluation,this study employs strategies of value-added assessment,matrix assessment and norm-transfer-able assessment to evaluate the TCA abilities from the aspects of thinking quality,thinking creativity,co-operation ability,iterative thinking,dialectical thinking and job responsibility.By modifying/using 18 e-valuation tools in Education and Psychology,we have established a rubric system composed of 30 primary indicators(with 11 newly designed,10 partly modified and 9 directly adopted),along with 49 secondary indicators and 98 tertiary indicators to enhance the feasibility of the evaluation process.This rubric sys-tem was applied to Biochemistry teaching among the five-year-program undergraduates at Air Force Medi-cal University.Specifically,thinking and teamwork are evaluated by creative works from"the magic bio-chemical-circle",while critiques are assessed in large classes under the guidance of basic and clinical teachers,coupled with appreciation measured by job responsibility in a task-driven virtual reality(VR)project.The results indicate that Biochemistry teaching not only accumulates knowledge in students,but also achieves the goals in nurturing values and cognition.The inclusion of creative performance evalua-tion,cooperative learning and clinical case studies,can enhance students'interpersonal skills,coopera-tion,quality of thinking,creative thinking,iterative thinking and dialectical thinking to varying degrees.TCA-based Biochemistry teaching has a long-lasting impact on character education,and is capable of in-ducing positive long-term changes in students'cognition and lifestyle.Taken together,with the help of this rubric system,teachers can promptly acknowledge the effectiveness of their teaching,thereby facilita-ting their teaching strategies.

Objective To investigate the methodology,technical considerations,and precautions of transcatheter arterial emboliza-tion(TAE)using medical adhesive as the primary embolic agent for visceral artery aneurysm(VAA).Methods A total of 14 patients with VAA treated with medical adhesive-based TAE were retrospectively analyzed.Among the 14 patients,6 cases were hepatic artery pseudoaneurysms,4 cases were true gastroduodenal aneurysms,3 cases were gastroduodenal pseudoaneurysms,and 1 case was renal artery pseudoaneurysm.Among the 14 patients,medical adhesive alone was used in 12 cases,while the other 2 cases were employed medical adhesive combined with supplemental coil embolization.Follow-up assessments including abdominal computed tomography angiography(CTA)and laboratory tests were conducted at 3,6,and 12 months post-procedure.Results Technical success was achieved in all cases with mean procedure duration of(60.4±8.2)min and average hospital stay of(8.9±2.1)d.No recanalization,aneurysm enlargement,or non-target embolization were observed during follow-up.Conclusion Medical adhesive-based TAE demonstrates high technical success when performed by experienced interventionists,with low complication rate,low recurrence rate,and low pro-cedure-related mortality,representing a cost-effective preferred treatment for VAA.

Objective To addresses the challenges arising from the rapid expansion of pharmaceutical clinical trials and the growing demands for quality management,this paper investigates the application of low-code technology in project management.Its goals are to enhance the operational efficiency and execution capabilities of clinical trial institutions,ensure trial quality and safety,and accelerate the translation of pharmaceutical scientific achievements.Methods A brainstorming session was conducted to analyze the technical and functional requirements for managing pharmaceutical clinical trial projects.Utilizing the ＂template design＂ and ＂decision analysis＂ functionalities of low-code technology,the study adopted a modular and visually driven data management approach to develop a system compliant with Good Clinical Practice(GCP)standards.This system integrates key functionalities,including project progress management,funding management,drug inventory management,and quality control.Its effectiveness was evaluated through real-world operation and performance validation.Results The system had demonstrated stable operation with substantial improvements in practical application.Compared with conventional management approaches,it significantly enhanced project management efficiency:the time required for project schedule management was reduced by 80%,the efficiency of financial processing increased by 95%,drug inventory management efficiency improved by 75%,and the time spent on quality control was shortened by 60%.Conclusion The pharmaceutical clinical trial project management system developed using low-code technology offers substantial advantages and promising application potential.It represents a critical practice in applying digital and intelligent tools to advance pharmaceutical productivity in the medical and healthcare sectors.

Objective To evaluate the efficacy of combining surgical treatment with biological agents for perianal fistulizing Crohn's disease(pfCD).Methods Sixty patients with perianal fistulizing Crohn's disease(pfCD)admitted to our hospital from May 2021 to December 2023 were randomly allocated into two groups:Treatment Group A(n=30)and Treatment Group B(n=30).Treatment Group A received pfCD surgery combined with inflix-imab(IFX)and azathioprine(AZA),while Treatment Group B underwent pfCD surgery along with ustekinumab(UST)and AZA.The CDAI score,PDAI score,and Assche score were monitored for both groups,and postoperative MRI examinations were conducted to evaluate the healing of pfCD.Results There were statistically significant differences in CDAI,PDAI,and Assche scores between pre-treatment and post-treatment comparisons within treat-ment groups A and B(P<0.05),as well as in the magnitude of change at each time point.Comparisons of CDAI,PDAI,and Assche scores at 8,16,24,and 32 weeks,and PDAI scores at 40 weeks between groups A and B using independent samples t-tests did not yield statistically significant results(P>0.05).However,significant differences were observed for CDAI and Assche scores at 40 weeks(P<0.05).Significant changes in CDAI,PDAI,and Assche scores were noted at 8,16,24,32,and 40 weeks post-treatment within both groups A and B(P<0.05).Multiple comparisons using the LSD method revealed that the changes in these scores at each time point were statistically significant(P<0.05).The data indicate a temporal trend in the changes of CDAI,PDAI,and Assche scores,with group B showing a more rapid decline compared to group A.In terms of fistula response rates,both groups A and B achieved 100%(30/30).However,the clinical healing rate of fistulas was higher in group B at 86.7%(26/30)compared to 76.7%(23/30)in group A.Conclusion The combination of surgical treatment with IFX/UST plus AZA is safe and effective for treating pfCD.However,the long-term efficacy of combining surgical treatment with UST appears to be superior.

The detection rate of thyroid nodules has gradually increased in recent years.Comprehensive and accurate preoperative evaluation and early identification of risk factors help doctors to choose treatment options and improve prognosis.Radiomics extracts quantitative features from medical images for evaluation of thyroid nodules through high-throughput mining of invisible image features,which has been widely used and has excellent performance in the identification of benign and malignant thyroid nodules,lymph node metastasis,extrathyroidal extension,molecular biological changes,recurrence and prognosis of thyroid cancer.However,there are also shortcomings such as large differences in performance among models from different institutions.This article reviews the application value,limitations and future development prospects of radiomics in the thyroid nodules,so as to provide new ideas for clinical practice and research.