Objective: To explore the metabolic molecular mechanism of regulatory T cells (Tregs) resisting ferroptosis under a hypoxic stress microenvironment, and to provide scientific support for finding intervention targets to improve the immune microenvironment of oral squamous cell carcinoma (OSCC). Methods: This study was approved by the Institutional Medical Ethics Committee. Multiplex immunofluorescence was used to detect the distribution of Tregs and the localization of hypoxic regions in clinical pathological specimens from patients with OSCC tissues. Animal experiments were approved by the Laboratory Animal Ethics Committee. A tumor-bearing model was established in C57BL/6 mice. The submandibular, subscapular, inguinal, and popliteal lymph nodes were collected along with the spleen, and were homogenized to prepare single cell suspensions. C57BL/6 mouse naive CD4⁺ T cells were induced to differentiate into Tregs in vitro, and a 1% hypoxic culture model was established. Normoxia and hypoxia groups were established, and Treg viability under hypoxic conditions was assessed by flow cytometry. Transcriptomics and metabolomics were applied to analyze differentially expressed genes, metabolic pathways, and changes in cholesterol metabolites. Western blot was performed to detect the expression of emopamil-binding protein (EBP), glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1), and acyl-CoA synthetase long-chain family member 4 (ACSL4). The safe concentration of the EBP inhibitor TASIN-30 was determined by the CCK-8 assay. On this basis, four groups were established: normoxia control, hypoxia, hypoxia+TASIN-30, and hypoxia+TASIN-30+7-dehydrocholesterol (7-DHC). Treg viability in each group was measured by flow cytometry; intracellular Fe2+ content, lipid peroxidation level, and reactive oxygen species (ROS) accumulation were detected by cellular immunofluorescence and flow cytometry; the reduced/oxidized glutathione (GSH/GSSG) ratio was measured using a microplate reader; and mitochondrial morphology was observed by transmission electron microscopy. In vivo tumor-inhibition experiments in C3H/HeJ mice were performed to validate the in vivo effects of EBP inhibition, and clinical prognostic survival analysis based on the TCGA-HNSC cohort was performed to evaluate the clinical prognostic value of ferroptosis resistance in Tregs. Results: Tregs were highly enriched in OSCC tissue, preferentially accumulated in hypoxic areas, and could maintain cell survival under hypoxia. The cholesterol metabolism pathway was upregulated in the hypoxic group, with increased EBP mRNA expression (P < 0.001) and 7-DHC accumulation. Compared with the hypoxic group alone, the hypoxic + TASIN-30 group showed decreased GPX4 and FSP1 expression (P < 0.001, P = 0.003); increased ACSL4 expression (P < 0.001); a decreased viable cell ratio (P < 0.001); increased Fe2+, lipid peroxidation, and ROS levels (P < 0.001); a decreased GSH/GSSG ratio (P < 0.001); and mitochondrial shrinkage. Exogenous supplementation of 7-DHC reversed the effects of EBP inhibition. In vivo inhibition of EBP significantly inhibited tumor growth (P < 0.001). Conclusion Tregs upregulate EBP and promote 7-DHC accumulation in hypoxic microenvironments, thereby inhibiting Treg ferroptosis and maintaining their survival and immunosuppressive function. Inhibition of EBP can weaken the resistance of Tregs to ferroptosis under hypoxia.

Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.

Objective:To evaluate the clinical outcomesof primary reverse total shoulder arthroplasty (RTSA) and revision procedure with RTSA after treatment failure of complex proximal humeral fractures in the elderly.Methods:A retrospective analysis was conductedon 24 elderly patients with Neer three- or four-part proximal humeral fractures who underwent RTSA revision after treatment failure (RTSA revision group) from January 2017 to June 2022. There were 7 males and 17 females included, with a mean age of 78.23±5.78 years (range, 67-86 years). Forty-eight patients who underwent primary RTSA (primary RTSA group) during the same time period were selected by propensity score matchingin a 1∶2 ratio as controls, based on age, dominanthand, etiology, Neer typing, glenohumeral joint dislocation, rotator cuff integrity, and osteoporosis T-score. The primary RTSA group included 12 males and 36 females, with a mean age of 76.38±6.15 years (range, 65-87 years). Clinical indicators including demographic characteristics, healing rate of the greater tuberosity, visual analogue score (VAS), Constant-Murley score, American Shoulder and Elbow Surgeons (ASES), shoulder range of motion (ROM), patient satisfaction, and complication rate were collected and analyzed.Results:The mean follow-up duration was 40(32, 60) months (range, 25-72 months) in the primary RTSA group and 38(30, 61) months (range, 24-68 months) in RTSA revision group. There was no significant difference (χ 2=5.058, P=0.168) in the healing rate of the greater tuberosity between the primary RTSA group (41/48, 85.4%) and the RTSA revision group (15/24, 62.5%). Compared with preoperative status, the ROM of anterior elevation, abduction supination, external rotation, VAS score, Constant-Murley score, and ASES score were significantly improved at the last follow-up (all P<0.05) in the RTSA revision group. The anterior elevation (123.74°± 16.57°), abduction supination (113.73°±16.42°), and external rotation (36.45°±10.36°) in the primary RTSA group were superior to those in the RTSA revision group (109.43°±18.75°, 98.64°±15.47°, 30.47°±10.64°, respectively), the difference was statistically significant ( P<0.05). No statistical difference of ROM of internal rotation between the two groups was found (χ 2=4.034, P=0.133). At the last follow-up, the Constant-Murley scores (75.47±11.66) and ASES scores (73.58±15.72) of the primary RTSA group were higher than those in the RTSA revision group (60.43±10.24 and 63.28±18.77, respectively), and the differences were statistically significant ( P<0.05). In terms of VAS (1.66±0.93 vs. 2.02±1.15) and patient satisfaction [83%(40/48) vs. 88%(21/24)], no statistical difference was identified ( P>0.05). The complication rate were 10.4% (5/48) in the primary RTSA group and 20.8% (5/24) in the RTSA revision group (χ 2=1.452, P=0.285), with no serious complications requiring revision surgery in either group. Conclusions:For elderly patients with proximal humeral fractures after failed operation, RTSA revision might effectively improve the limb function and alleviatepain. However, compared with RTSA revision, primary RTSA demonstrated superiorearly clinical outcomes in shoulder ROM and functional recovery.

Objective To develop a hypoxia endurance testing system for aviation physiological training of pilots.Methods The hypoxia endurance testing system comprised a low-oxygen mixed gas generator,a pressurization system for low-oxygen mixed gas and a personal breathing apparatus.The low-oxygen mixed gas generator consisted of a main unit composed of an air compressor,a filter,a buffer tank,polymer membrane,a control module,sensors and regulators,wire cables,supporting hoses,etc.;the pressurization system for low-oxygen mixed gas was made up of a protective box,a cooling fan,a motor and a driver,a control module,a solenoid valve,a convergence block,a pressure gauge,etc.;the personal breating apparatus was composed of a gas cylinder,a pressure reducer,an oxygen supply regulator,etc.Forty-eight subjects were selected for hypoxia exposure tests to verify the effectiveness of the system.Results The system developed had the functions of low-oxygen gas preparation,pressurized filling and hypoxia experiment,and the experimental results indicated the acute hypoxia exposure by the system significantly caused signs and symptoms of hypoxia and weakened physiological functions.Conclusion The system developed gains advantages in high accuracy of gas volume fraction control,safety and remarkable effect of simulated hypoxia,and can be an effective tool for acute high-altitude hypoxia testing and training of pilots.[Chinese Medical Equipment Journal,2025,46(10):23-28]

Objective To observe the therapeutic effects of different doses of methylprednisolone(MP)on smoke inhalation-induced acute lung injury(SI-ALI)in rats,and to explore the changes in the expression of aquaporins(AQPs)and the underlying mechanisms for alleviating lung injury.Methods A total of 86 healthy adult male Sprague-Dawley(SD)rats were randomly divided into five groups:control group(n=6),smoke inhalation injury(SI)group(n=20),low-dose MP group(LMP,SI+0.4 mg/kg MP,n=20),medium-dose MP group(MMP,SI+4 mg/kg MP,n=20),and high-dose MP group(HMP,SI+40 mg/kg MP,n=20).A model of smoke inhalation-induced lung injury was established.The survival status of the rats in each group was monitored.Lung tissues were collected 24 hours after injury to determine the wet-to-dry(W/D)ratio of the lung tissues,arterial oxygen partial pressure(PaO2),and the expression levels of inflammatory cytokines TNF-α and IL-6.The degree of lung injury was evaluated using HE staining,and the mRNA and protein expression levels of AQP1 and AQP5 in the lung tissues were detected.Results Compared with control group,the survival rate of the rats in SI group was significantly decreased(P<0.05);compared with SI group,the survival rates of the rats in MMP and HMP groups were significantly increased(P<0.05).Compared with control group,the PaO2 of the Rats in SI group was significantly decreased(P<0.05),and the wet-to-dry(W/D)ratio and lung injury scores were significantly increased(P<0.05).Compared with SI group,the PaO2 of the rats in LMP,MMP,and HMP groups(P<0.05)was significantly increased(P<0.05),and the lung W/D ratio and injury scores in MMP and HMP groups were significantly decreased(P<0.05).ELISA results showed that compared with control group,the serum concentrations of TNF-α and IL-6 in SI group were significantly increased(P<0.05);compared with SI group,the concentrations of TNF-α and IL-6 in MMP and HMP groups were significantly decreased(P<0.05).HE staining revealed that the alveolar structure of the rats in SI group was severely damaged;compared with SI group,the damage to the alveolar structure in MMP and HMP groups was alleviated.Real-time PCR and Western blotting analysis results showed that compared with control group,the mRNA and protein expression levels of AQP1 and AQP5 in lung tissues in SI group were significantly decreased(P<0.05);however,compared with SI group,these levels in LMP,MMP,and HMP groups were significantly increased(P<0.05).Conclusions Smoke inhalation can induce acute lung injury in rats and down-regulate the expression levels of AQP1 and AQP5 in the lung tissues.Methylprednisolone can alleviate pulmonary edema and tissue damage in rats caused by smoke inhalation,and induce the up-regulation of the expression of AQP1 and AQP5.

Objective To analyze the characteristics and risk factors associated with postoperative deep vein thrombosis(DVT)of the lower extremities in patients undergoing surgery for lumbar degenerative diseases.Methods A retrospective analysis was conducted on clinical data from 298 patients who were hospitalized for lumbar degenerative diseases and underwent lumbar spine surgery treatment in the First Affiliated Hospital of Nanchang University from October 1,2022 to April 15,2023.Patients were divided into DVT group(n=71)and non-DVT group(n=227)according to whether DVT of the lower limbs occurred within 1 week postoperatively.The incidence and distribution characteristics of postoperative DVT were analyzed.Univariate and binary logistic regression analyses were performed to identify risk factors for DVT,and receiver operating characteristic(ROC)curves were used to determine cut-off values for relevant risk factors.Results A total of 298 patients were included,among whom 159 were males(53.4%)and 139 were females(46.6%),with an average age of(64.5±9.8)years.DVT occurred in 71 patients,and the incidence of lower extremity DVT was 23.8%.In the DVT group,there were 49 cases(69.0%)of intermuscular vein thrombosis,and 22 cases of other types of thrombosis(7 cases of peroneal vein thrombosis,4 cases of posterior tibial vein thrombosis,3 cases of common femoral vein thrombosis,1 case of anterior tibial vein thrombosis,and 7 cases of multiple thrombosis);58 cases(81.7%)had DVT in one lower extremity,and 13 cases(18.3%)had DVT in both lower extremities.Univariate analysis results showed that age,body mass index(BMI),length of hospital stay,history of hypertension,operative time,and intraoperative blood loss were associated with the occurrence of lower extremity DVT after surgery for lumbar degenerative diseases(P<0.05).Binary logistic regression analysis results indicated that older age(OR=1.079,P<0.01),higher BMI(OR=1.130,P=0.01),history of hypertension(OR=2.992,P<0.01),and larger intraoperative blood loss(OR=1.002,P=0.03)were independent risk factors for the occurrence of lower extremity DVT.ROC curve analysis demonstrated that patients with age>58.5 years,BMI>24.01 kg/m2,history of hypertension,and intraoperative blood loss>550 ml had a significantly increased risk of postoperative lower limb DVT.Conclusions The incidence of lower extremity DVT after surgery for lumbar degenerative disease is high,and intermuscular venous thrombosis is more common.Older age,higher BMI,history of hypertension,and larger intraoperative blood loss are independent risk factors for the occurrence of lower extremity DVT after surgery.

Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.