BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is not yet fully understood.A deep comprehension of the pathology and molecular mechanisms of steroid-induced osteonecrosis of the femoral head,as well as the search for diagnostic markers with high specificity and sensitivity,are crucial for the prevention and treatment of this condition.OBJECTIVE:To identify immune diagnostic markers for steroid-induced osteonecrosis of the femoral head and predict potential drug targets through drug enrichment analysis and molecular docking techniques.METHODS:The study utilized gene expression profile data(GSE123568 and GSE74089)from the GEO databases(a public gene expression database built by the U.S.National Center for Biotechnology Information).R software was used for data normalization and differential gene screening,followed by weighted gene co-expression network analysis(WGCNA)to identify disease-related genes.Immune-related genes were obtained from the GeneCards database and intersected with the differential genes and WGCNA gene sets to select immune-related genes for steroid-induced osteonecrosis of the femoral head.Mendelian randomization was used to validate the potential causal relationship between these immune-related genes and steroid-induced osteonecrosis of the femoral head.Gene Set Enrichment Analysis was conducted to analyze the immune-related pathways involved,and protein-protein interaction networks were used to assess functional associations.Finally,drug enrichment analysis and molecular docking were performed to predict potential drugs targeting these immune-related genes.RESULTS AND CONCLUSION:Three key immune-related genes-RNASEL,SECTM1,and HSPA6-were identified.These genes were highly expressed in steroid-induced osteonecrosis of the femoral head and exhibited good diagnostic potential,which were involved in multiple immune-related signaling pathways.Mendelian randomization analysis confirmed their potential causal relationship with steroid-induced osteonecrosis of the femoral head.Drug enrichment analysis and molecular docking identified nine potential drugs,including β-ecdysterone,showing the possibility of intervening in the pathological process of steroid-induced osteonecrosis of the femoral head by regulating the HSPA6 protein.These findings provide new biomarkers and drug targets for the early diagnosis and personalized treatment of steroid-induced osteonecrosis of the femoral head.They also highlight the potential application of bioinformatics in Chinese biomedical research,facilitating the integration and translational use of international data in local disease studies.

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is not yet fully understood.A deep comprehension of the pathology and molecular mechanisms of steroid-induced osteonecrosis of the femoral head,as well as the search for diagnostic markers with high specificity and sensitivity,are crucial for the prevention and treatment of this condition.OBJECTIVE:To identify immune diagnostic markers for steroid-induced osteonecrosis of the femoral head and predict potential drug targets through drug enrichment analysis and molecular docking techniques.METHODS:The study utilized gene expression profile data(GSE123568 and GSE74089)from the GEO databases(a public gene expression database built by the U.S.National Center for Biotechnology Information).R software was used for data normalization and differential gene screening,followed by weighted gene co-expression network analysis(WGCNA)to identify disease-related genes.Immune-related genes were obtained from the GeneCards database and intersected with the differential genes and WGCNA gene sets to select immune-related genes for steroid-induced osteonecrosis of the femoral head.Mendelian randomization was used to validate the potential causal relationship between these immune-related genes and steroid-induced osteonecrosis of the femoral head.Gene Set Enrichment Analysis was conducted to analyze the immune-related pathways involved,and protein-protein interaction networks were used to assess functional associations.Finally,drug enrichment analysis and molecular docking were performed to predict potential drugs targeting these immune-related genes.RESULTS AND CONCLUSION:Three key immune-related genes-RNASEL,SECTM1,and HSPA6-were identified.These genes were highly expressed in steroid-induced osteonecrosis of the femoral head and exhibited good diagnostic potential,which were involved in multiple immune-related signaling pathways.Mendelian randomization analysis confirmed their potential causal relationship with steroid-induced osteonecrosis of the femoral head.Drug enrichment analysis and molecular docking identified nine potential drugs,including β-ecdysterone,showing the possibility of intervening in the pathological process of steroid-induced osteonecrosis of the femoral head by regulating the HSPA6 protein.These findings provide new biomarkers and drug targets for the early diagnosis and personalized treatment of steroid-induced osteonecrosis of the femoral head.They also highlight the potential application of bioinformatics in Chinese biomedical research,facilitating the integration and translational use of international data in local disease studies.

In laparoscopic and robot-assisted ultra-low sphincter-saving surgeries for rectal cancer, preserving sexual function, preventing anastomotic leakage, anastomotic stricture, and low anterior resection syndrome (LARS) is critical to ensuring a good postoperative quality of life. The primary strategy for preventing postoperative sexual dysfunction is the meticulous preservation of the autonomic nerves, particularly the neurovascular bundles in the prostate area, guided by precise anatomical dissection. Partial preservation of the Denonvilliers fascia during total mesorectal excision (TME) not only helps protect the anterior mesorectum but also safeguards the neurovascular bundles. To prevent anastomotic leakage, it is essential to achieve clear oncologic margins, ensure a robust blood supply to both the proximal and distal margins, maintain a tension-free anastomosis, and avoid thermal or radiation injury whenever possible. In elderly patients with metabolic diseases, persistent descending mesocolon, or those undergoing neoadjuvant chemoradiotherapy, selective preservation of the left colic artery may be considered. Additionally, reinforcing the anastomosis with sutures at the 'dog-ear' site, closing the pelvic peritoneum, and placing a transanal tube for drainage are beneficial strategies. Early identification of anastomotic leakage and timely intervention to ensure drainage can prevent delayed leakage, strictures, and the structural sequelae of anastomotic failure. To minimize fecal dysfunction, selective exemption from radiotherapy may be beneficial for mid-to-high rectal cancer, while for low rectal cancer, reconstruction of J-pouch reservoirs, end-to-side anastomosis, and transverse coloplasty can help reduce the incidence of severe low anterior resection syndrome. Additionally, for low rectal cancer following neoadjuvant therapy, a selective rectum-preserving strategy that avoids major surgery can effectively prevent these complications.

Total pelvic exenteration (TPE) is widely regarded as the most effective intervention for the management of primary locally advanced rectal cancer and locally recurrent rectal cancer. However, TPE presents several challenges, including the potential for failing to achieve R0 resection, high incidence of complication, decreased postoperative quality of life, and the possible overtreatment in patients without carcinomatous adhesions or with only inflammatory adhesions, as well as in those who achieve pathological complete response after neoadjuvant therapy. In the context of precision medicine, further investigation is necessary to enhance the accuracy of preoperative diagnoses of extrarectal cancer invasion and to explore the comprehensive application of genetic molecular typing methods alongside innovative neoadjuvant treatment strategies. Such research should aim to enhance the R0 resection rate of TPE, minimize surgical complications and mortality, improve postoperative quality of life, and achieve an optimal balance between radical resection and the preservation of organ function.

Left hemicolectomy is predominantly utilized for the management of carcinomas located at the splenic flexure, descending colon, and sigmoid colon. The incidence of carcinomas at the splenic flexure and descending colon is comparatively low. With advancements in therapeutic modalities, there has been a progressive improvement in the prognosis of left colon cancer. Presently, the oncological outcomes following radical resection for non-metastatic left colon carcinoma are marginally superior to those observed in right colon carcinoma. The vascular supply to the splenic flexure is subject to variability, encompassing arteries originating from both the superior mesenteric artery and the inferior mesenteric artery systems. Its distinctive anatomical location and intricate lymphatic drainage have sparked debates regarding the appropriate extent of surgical resection. Recent research has demonstrated that adherence to the "10 cm" principle for left hemicolectomy is justified, and a minimal resection of the splenic flexure is adequate. The scope of lymph node dissection can be ascertained based on the positive rate of each lymph node station, with station 253 not necessitating dissection. However, when the accessory middle colic artery is present, it should be regarded as the primary vascular supply for D3 dissection. Furthermore, advancements in the study of fascial anatomy related to the left colon have yielded new perspectives in the surgical management of carcinoma at the splenic flexure left colon carcinoma. The extra-omental sac dissection, which is grounded in the principles of fascial anatomy, facilitates the safe and efficient mobilization of the splenic flexure colon.

Objective: Patients with severe symptomatic aortic stenosis are assessed for coronary artery disease (CAD) prior to transcatheter aortic valve implantation (TAVI) with treatment implications. Invasive coronary angiography (ICA) is the recommended modality but is associated with peri-procedural complications. Integrating machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) into existing TAVI-planning CT protocol may aid exclusion of significant CAD and thus avoiding ICA in selected patients. Materials and Methods: A single-center, retrospective study was conducted, 41 TAVI candidates with both TAVI-planning CT and ICA performed were analyzed. CT datasets were evaluated by a ML-based CT-FFR software. Beta-blocker and nitroglycerin were not administered in these patients. The primary outcome was to identify significant CAD. The diagnostic performance of CT-FFR was compared against ICA. Results: On per-patient level, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were 89%, 94%, 80%, 97% and 93%, respectively. On per-vessel level, the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 75%, 94%, 67%, 96% and 92%, respectively. The area under the receiver operative characteristics curve per individual coronary vessels yielded overall 0.90 (95% confidence interval 85%–95%). ICA may be avoided in up to 80% of patients if CT-FFR results were negative. Conclusion ML-based CT-FFR can provide accurate screening capabilities for significant CAD thus avoiding ICA. Its integration to existing TAVI-planning CT is feasible with the potential of improving the safety and efficiency of pre-TAVI CAD assessment.

Objective:To investigate the effect of exosomes released from triple-negative breast cancer cells (TNBC) on immune cells after radiotherapy.Methods:When TNBC (3 types: MDA-MB-231, MDA-MB-453, MDA-MB-468) reached 70% confluence, cells were irradiated with a dose of 8 Gy in one group and no intervention was given in the control group. The supernatants were collected at 48 h after irradiation. Subsequently, these supernatants were co-cultured with lymphocytes in peripheral blood mononuclear cells, and the uptake of exosomes by T cells was confirmed by fluorescence microscopy. Meanwhile, the expression of regulatory T cells (Treg) in the cells was detected using flow cytometry. Differences in Treg cell differentiation between two groups were compared by t-test (expressed as Treg cell positivity rate). Results:Transmission electron microscopy scanning and nanoparticle analysis showed that the extracellular vesicles extracted in the experiment were exosomes. Lymphocytes phagocytosed the exosomes and the exosomes were mainly concentrated in the cytoplasm after phagocytosis. Following the co-culture of 3 kinds of lymphocytes with exosomes from TNBC, there was an increase in Treg cell differentiation compared to control group (1.07%, 0.60%, 0.63% vs. 0.30%, P<0.01). In addition, exosomes released from TNBC further increased the differentiation of Treg cells after radiotherapy (MDA-MB-231 cells: 1.07% vs. 1.81%, P<0.01; MDA-MB-453 cells: 0.60% vs. 0.93%, P<0.05). Conclusions:In summary, exosomes released from TNBC can promote the differentiation of Treg cells. In addition, radiotherapy-induced exosomes released by TNBC further exacerbate the differentiation of Treg cell.

Objective:To evaluate the efficacy and safety of anlotinib neoadjuvant therapy for newly diagnosed locally advanced thyroid cancer (LATC).Methods:Twenty-four newly diagnosed LATC patients (10 males and 14 females, age (47.1±3.3) years) admitted to Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University of Chinese Medicine were prospectively included from January 2023 to April 2024. Patients were given anlotinib neoadjuvant therapy (12mg/d, 2 weeks of medication, 1 week of discontinuation), and the efficacy of the treatment was evaluated by CT and multi-disciplinary treatment at the end of each treatment cycle. Patients assessed as suitable for surgery would be scheduled for surgery, while those who were not suitable for surgery would continue to receive neoadjuvant therapy and periodic evaluations. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the R0/1 resection rate and adverse events (AE) after neoadjuvant therapy were observed. Paired- t test was used to analyze the differences between groups, and the Clopper-Person accurate method was used to calculate the bilateral 95% CI of ORR and other indicators. Results:Twenty-four patients received 2(2, 3) cycles of neoadjuvant therapy with anlotinib, of which 23 underwent surgery after anlotinib therapy. After neoadjuvant therapy, the mean maximum diameter of target lesions decreased by 23.5%(95% CI: 2.8%-44.3%) compared with baseline ( t=9.22, P<0.001). The ORR and DCR were 37.5%(95% CI: 18.8%-59.4%) and 100%(95% CI: 85.8%-100%), respectively. About 91.7%(95% CI: 73.0%-99.0%) of patients eventually underwent R0/1 resection. Hand and foot skin reactions, hypertension, oral mucositis, and leukopenia were common AE; grade 4 and 5 AE were not observed. Conclusion:Anlotinib can be safely used as neoadjuvant therapy for newly diagnosed LATC patients with good antitumor effects, providing better surgical opportunities for R0/1 resection.

Objective:To explore the current implementation status and challenges of family doctor contract services (FDCS) from the perspective of contracted residents.Methods:This qualitative study used purposive sampling to select contracted residents from 11 primary healthcare institutions across five cities in China. Semi-structured interviews were conducted from March to December 2024, covering topics such as awareness of contracting, service experience, health needs, service continuity, and policy recommendations. Thematic framework analysis was applied to organize, code, and summarize the data.Results:A total of 25 contracted residents were interviewed (6 men, 19 women; 11 from central urban areas, 14 from suburban or rural towns; 8 with chronic diseases). Three main themes and ten sub-themes emerged: Theme Ⅰ: Pathways to improved service accessibility (optimized chronic disease management, more efficient referrals, and improved health education). Theme Ⅱ: Structural misalignment between supply and demand (limited specialty services despite patient needs, insufficient coverage and public awareness of home-based medical care, imbalanced human resources, and service disruption due to clinician turnover). Theme Ⅲ: Challenges in service awareness and communication mechanisms (information asymmetry and public misperception regarding FDCS, perverse incentives in administrative performance evaluation, and communication barriers in building patient-doctor trust).Conclusions:While FDCS has shown progress in chronic disease management, referral coordination, and health education, structural supply-demand gaps and communication challenges continue to hinder service quality. Improvements in resource allocation and service models are needed to support high-quality development.

Objective:To evaluate the efficacy and safety of anlotinib neoadjuvant therapy for newly diagnosed locally advanced thyroid cancer (LATC).Methods:Twenty-four newly diagnosed LATC patients (10 males and 14 females, age (47.1±3.3) years) admitted to Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University of Chinese Medicine were prospectively included from January 2023 to April 2024. Patients were given anlotinib neoadjuvant therapy (12mg/d, 2 weeks of medication, 1 week of discontinuation), and the efficacy of the treatment was evaluated by CT and multi-disciplinary treatment at the end of each treatment cycle. Patients assessed as suitable for surgery would be scheduled for surgery, while those who were not suitable for surgery would continue to receive neoadjuvant therapy and periodic evaluations. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the R0/1 resection rate and adverse events (AE) after neoadjuvant therapy were observed. Paired- t test was used to analyze the differences between groups, and the Clopper-Person accurate method was used to calculate the bilateral 95% CI of ORR and other indicators. Results:Twenty-four patients received 2(2, 3) cycles of neoadjuvant therapy with anlotinib, of which 23 underwent surgery after anlotinib therapy. After neoadjuvant therapy, the mean maximum diameter of target lesions decreased by 23.5%(95% CI: 2.8%-44.3%) compared with baseline ( t=9.22, P<0.001). The ORR and DCR were 37.5%(95% CI: 18.8%-59.4%) and 100%(95% CI: 85.8%-100%), respectively. About 91.7%(95% CI: 73.0%-99.0%) of patients eventually underwent R0/1 resection. Hand and foot skin reactions, hypertension, oral mucositis, and leukopenia were common AE; grade 4 and 5 AE were not observed. Conclusion:Anlotinib can be safely used as neoadjuvant therapy for newly diagnosed LATC patients with good antitumor effects, providing better surgical opportunities for R0/1 resection.