[摘 要] 目的：探讨基于新型单载体SynNotch系统构建的局部分泌IL-2的CAR-T细胞（Syn.CD19.IL-2 CAR-T细胞）对传统CD19 CAR-T细胞功能的影响。方法：基于本课题组前期构建的单载体SynNotch系统，将CD19特异性FMC63抗体与IL-2表达模块整合，通过自失活逆转录病毒载体转导T细胞制备Syn.CD19.IL-2 CAR-T细胞。诱导验证实验分为Syn.CD19.IL-2 CAR-T细胞组和未转导T细胞组，通过ELISA检测抗原刺激后IL-2分泌水平。采用CFSE染色法检测在Syn.CD19.IL-2 CAR-T细胞存在时，CD19 CAR-T细胞与肿瘤Raji-Luc或SW620-CD19-Luc细胞共培养时，IL-2的分泌对CD19 CAR-T细胞增殖的影响。流式细胞术检测CD69表达，观察在Syn.CD19.IL-2 CAR-T细胞分泌IL-2的情况下，CD19 CAR-T细胞与Raji-Luc细胞共培养时的激活情况。结果：成功构建自失活逆转录病毒载体Syn.CD19.IL-2 CAR，制备出Syn.CD19.IL-2 CAR-T细胞，病毒滴度 > 1×107拷贝/mL，转导效率达37.1%。抗原刺激后，SynNotch CAR-T细胞IL-2分泌量显著高于未转导T细胞（P < 0.001）。在Syn.CD19.IL-2 CAR-T细胞分泌IL-2时，CD19 CAR-T细胞具有更强的增殖能力和更高的活化水平（均P < 0.001）。结论：成功构建的Syn.CD19.IL-2 CAR-T细胞能显著增强CD19 CAR-T细胞的增殖和活化能力。

Obstructive sleep apnea (OSA) is a global public health concern characterized by repeated upper airway collapse during sleep. Research indicates that OSA is a risk factor for the development of various diseases, including cardiovascular disease, metabolic disorders, respiratory diseases, neurodegenerative diseases, and cancer. Exosomes, extracellular vesicles released by most cell types, play a key role in intercellular communication by transporting their contents-such as microRNA, messenger RNA, DNA, proteins, and lipids-to target cells. Intermittent hypoxia associated with OSA alters circulating exosomes and promotes a range of cellular structural and functional disturbances involved in the pathogenesis of OSA-related diseases. This review discusses the potential roles of exosomes and exosome-derived molecules in the onset and progression of OSA-associated diseases, explores the possible underlying mechanisms, and highlights novel strategies for developing exosome-based therapies for these conditions.
Humans ; Exosomes/physiology* ; Sleep Apnea, Obstructive/metabolism* ; Animals ; MicroRNAs/metabolism*

OBJECTIVE: To investigate the surgical technique and effectiveness of tension band-assisted plate fixation combined with external fixator for volar marginal fractures of the distal radius. METHODS: A retrospective analysis was performed on the clinical data of 12 patients with volar marginal fractures of the distal radius treated by Kirschner wire tension band-assisted anatomical plate fixation combined with external fixator between October 2018 and July 2023. The cohort included 9 males and 3 females, aged from 20 to 52 years (mean, 35.5 years). The injury causes included traffic accidents in 6 cases, falls from height in 3 cases, and fall in 3 cases. According to AO/Orthopaedic Trauma Association (AO/OTA), there were 1 case of type B2, 4 cases of type B3, 2 cases of type C1, 3 cases of type C2, and 2 cases of type C3. According to Fernandez classification, there were 2 cases of type Ⅲ, 5 cases of type Ⅳ, and 5 cases of type Ⅴ. Associated injuries included radiocarpal joint dislocation or subluxation in 7 cases and median nerve injury in 2 cases. The time from injury to operation was 2-7 days (mean, 3.2 days). Postoperatively, functional outcomes were evaluated using the modified Mayo wrist score and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Grip strength was measured as the ratio to the unaffected side, and wrist range of motion (ROM) including dorsiflexion, palmar flexion, ulnar deviation, and radial deviation was assessed. RESULTS: All procedures were successfully completed, with an operation time of 55-110 minutes (mean, 65 minutes). All patients were followed up 6-36 months (mean, 13.7 months). Surgical incisions healed by first intention, without complications such as vascular-nerve injury or infection. Bony union and articular congruency were attained in all patients, with a healing time of 3-5 months (mean, 3.8 months). During follow-up, 1 case of Kirschner wire migration occurred with no instances of infections, radiocarpal dislocations, internal fixation failures, or extensor pollicis longus tendon ruptures. At last follow-up, the modified Mayo wrist score ranged from 65 to 92 (mean, 80.8), the DASH score ranged from 7 to 15 (mean, 11.6), the grip strength was 65%-90% (mean, 78.2%) of the unaffected side; and wrist ROM was palmar flexion 60°-85° (mean, 77.4°), dorsiflexion 55°-80° (mean, 74.8°), radial deviation 10°-25° (mean, 18.8°), and ulnar deviation 15°-30° (mean, 24.5°). CONCLUSION Kirschner wire tension band-assisted anatomical plate fixation combined with external fixator for volar marginal fractures of the distal radius is a simple method with reliable fixation, which can achieve satisfactory effectiveness.
Humans ; Male ; Adult ; Female ; Radius Fractures/diagnostic imaging* ; Retrospective Studies ; Middle Aged ; Bone Plates ; Bone Wires ; External Fixators ; Young Adult ; Fracture Fixation, Internal/instrumentation* ; Treatment Outcome ; Range of Motion, Articular ; Hand Strength ; Wrist Injuries/surgery*

OBJECTIVE: To investigate the feasibility and effectiveness of precise-guided temporary fixation assistive devices in assisting the main nail guide pin placement and precise temporary fixation in proximal femoral nail antirotation (PFNA) internal fixation of femoral intertrochanteric fractures. METHODS: A prospective randomized controlled study was conducted to analyze the clinical data of 60 patients with femoral intertrochanteric fractures over 65 years old who met the selection criteria between January 2020 and June 2022 and were treated with PFNA internal fixation. The patients were randomly divided into the trial group (auxiliary device guided main nail guide pin placement and temporary fixation) and the control group (conventional treatment), with 30 cases in each group. There was no significant difference in baseline data such as gender, age, cause of injury, time from injury to operation, fracture side, AO/Orthopaedic Trauma Association (AO/OTA) classification, and combined medical diseases between the two groups ( P>0.05). The operation time, times of main nail guide pin placement, intraoperative fluoroscopy frequency, intraoperative blood loss, and perioperative blood transfusion were recorded and compared between the two groups. The quality of fracture reduction was evaluated by CHANG Shimin et al criteria. Harris score was used to evaluate the hip function at 1 year after operation. RESULTS: In the trial group, 2 temporary fixation needles were successfully placed 2-5 times, including 2 times in 13 cases (43.3%), 3 times in 8 cases (26.7%), 4 times in 7 cases (23.3%), and 5 times in 2 cases (6.7%). The operation time, times of main nail guide pin placement, intraoperative fluoroscopy frequency, and intraoperative blood loss in the trial group were significantly less than those in the control group, and the reduction quality score was significantly better than that in the control group ( P<0.05). There was no significant difference in perioperative blood transfusion between the two groups ( P>0.05). All patients were followed up 12-19 months (mean, 15 months). There was no complication such as incision infection, deep vein thrombosis, or internal fixation loosening. At 1 year after operation, the Harris score of the affected hip joint in the trial group was significantly higher than that in the control group ( P<0.05). CONCLUSION The technique of main nail guide pin placement and temporary fixation under the guidance of auxiliary devices in PFNA internal fixation can achieve faster insertion of the main nail guide pin, accurate temporary fixation to maintain reduction, and avoid the subsequent operation space, so as to improve the effectiveness.
Humans ; Bone Nails ; Male ; Female ; Hip Fractures/surgery* ; Fracture Fixation, Intramedullary/instrumentation* ; Aged ; Prospective Studies ; Operative Time ; Treatment Outcome ; Fracture Fixation, Internal/instrumentation* ; Aged, 80 and over

Small cell lung cancer (SCLC) is the thoracic malignant tumor and accounts for about 15% of lung malignancies and transfer often occurs by the time of diagnosis. Extensive stage-small cell lung cancer (ES-SCLC) accounts for about 2/3 of all SCLC. For many years, radiotherapy has occupied an important position in the treatment of SCLC, especially in the treatment of ES-SCLC, because SCLC is more sensitive to radiotherapy. However, in recent years, immune checkpoint inhibitor has shown more excellent antitumor activity in the treatment of ES-SCLC and become the mainstream argument for the treatment of ES-SCLC. However, will radiotherapy be buried by the times among the therapeutic approaches for ES-SCLC? In this article, we will review the clinical progress of radiotherapy, immunotherapy and combination therapy for ES-SCLC.
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Humans ; Small Cell Lung Carcinoma/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy ; Neoplasm Staging ; Radiotherapy/methods* ; Combined Modality Therapy

BACKGROUND: There is growing evidence that the occurrence and severity of respiratory diseases in children are related to the concentration of air pollutants. Nonetheless, evidence regarding the association between short-term exposure to air pollution and outpatient visits for respiratory diseases in children remains limited. Outpatients cover a wide range of disease severity, including both severe and mild cases, some of which may need to be transferred to inpatient treatment. This study aimed to quantitatively evaluate the impact of short-term ambient air pollution exposure on outpatient visits for respiratory conditions in children. METHODS: This study employed data of the Second People's Hospital of Yichang from January 1, 2016 to December 31, 2023, to conduct a time series analysis. The DLNM approach was integrated with a generalized additive model to examine the daily outpatient visits of pediatric patients with respiratory illnesses in hospital, alongside air pollution data obtained from monitoring stations. Adjustments were made for long-term trends, meteorological variables, and other influencing factors. RESULTS: A nonlinear association was identified between PM_2.5, PM₁₀, O₃, NO₂, SO₂, CO levels and the daily outpatient visits for respiratory diseases among children. All six pollutants exhibit a hysteresis impact, with varying durations ranging from 4 to 6 days. The risks associated with air pollutants differ across various categories of children's respiratory diseases; notably, O₃ and CO do not show statistical significance concerning the risk of chronic respiratory conditions. Furthermore, the results of infectious respiratory diseases were similar with those of respiratory diseases. CONCLUSIONS Our results indicated that short-term exposure to air pollutants may contribute to an increased incidence of outpatient visits for respiratory illnesses among children, and controlling air pollution is important to protect children's health.
Humans ; China/epidemiology* ; Air Pollutants/analysis* ; Respiratory Tract Diseases/chemically induced* ; Child ; Child, Preschool ; Environmental Exposure/adverse effects* ; Air Pollution/analysis* ; Infant ; Male ; Particulate Matter/adverse effects* ; Female ; Ambulatory Care/statistics & numerical data* ; Outpatients/statistics & numerical data* ; Adolescent ; Infant, Newborn

To investigate the current status of sleep quality among nurses in tertiary hospitals in China, analyze the correlations of work stress and perceived organizational support with the risk of sleep problems, and further examine the mediating effect of perceived organizational support between work stress and sleep problems in nurses.

BACKGROUND/OBJECTIVES: The study examined the association between homocysteine and diabetes mellitus in patients with H-type hypertension and assessed the possible effect modifiers. SUBJECTS/METHODS: This cross-sectional study included 1,255 eligible participants in the ‘H-type Hypertension Management and Stroke Prevention Strategic International Science and Technology Innovation Cooperation Project’ among rural Chinese people with H-type hypertension. A multivariate logistic regression model was used to evaluate the relationship between homocysteine and diabetes mellitus. RESULTS: The mean level of total homocysteine (tHcy) in the diabetes mellitus population was 19.37 μmol/L, which was significantly higher than the non-diabetic patients (18.18 μmol/L). When tHcy was analyzed as a continuous variable, the odds ratio (OR) of diabetes was 1.17 (95% confidence interval [CI], 1.01–1.35; per interquartile range). When tHcy was stratified according to the quintile, the ORs for diabetes were 2.86 (95% CI, 1.22–6.69) in the highest quintile (tHcy ≥ 20.60 μmol/L) compared to the reference group (tHcy < 12.04 μmol/L). When tHcy was grouped by 15 μmol/L and 20 μmol/L, patients with tHcy ≥ 20 μmol/L had a significantly (P = 0.037) higher risk of diabetes (OR, 2.03; 95% CI, 1.04–3.96) than in those with tHcy < 15 μmol/L. Subgroup analysis showed that the tHcy-diabetes association was unaffected by other variables. CONCLUSION In this study of rural Chinese people with H-type hypertension, the tHcy levels showed a positive association with diabetes mellitus. This independent association is unaffected by other potential risk factors.

OBJECTIVE: To investigate the clinical effect the treatment of arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression in the treatment of the patients with intractable calcaneal pain. METHODS: The clinical data of 50 patients with intractable heel pain from January 2016 to January 2019 were retrospectively analyzed, including 20 males and 30 females;aged from 40 to 68 years old with an average of (50.12±7.35)years old, the medical history ranged from 1 to 4 years. All patients underwent arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression, and were followed up, the duration ranged from 24 to 60 months with an average of(42.00±3.28) months. All patients had obvious heel pain before surgery, and X-ray examinations often showed the presence of calcaneal spurs. In addition to the routine foot examination, the changes in the height and angle of the arch of the foot were also measured pre and post-operatively by X-ray, for the evaluation of clinical effect. The VAS system was used to evaluate the degree of foot pain;the AOFAS scoring system was used to comprehensively evaluate the foot pain, voluntary movement, gait and stability. RESULTS: The VAS decreased from (8.75±1.24) before surgery to (5.15±2.35) at 3 months after surgery, (4.07±2.53) at 6 months after surgery, and (3.95±2.44) at the last fllow-up(P<0.05). The AOFAS score increased from (53.46±4.17) before surgery to(92.46±2.53) at 3 months after surgery, (96.33±2.46) at 6 months after surgery, and (97.05±2.37) at the last follow-up(P<0.05). The arch height was (41.54±1.15) mm before operation and (41.49±1.09) mm after the operation, the difference was not statistically significant(P>0.05). The internal arch angle of the foot arch was (121±6)° before operation and (122±7)° after operation. The difference was not statistically significant(P>0.05). CONCLUSION Arthroscopy-assisted calcaneal bone spurs resection combined with plantar fascia release and calcaneal decompression exhibited great clinical effect for treating intractable heel.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Heel/surgery* ; Heel Spur/surgery* ; Retrospective Studies ; Calcaneus/surgery* ; Foot Diseases ; Pain ; Endoscopes ; Treatment Outcome

OBJECTIVE: To investigate the protective effects of total saponins from Panax japonicus (TSPJ) against high-fat dietinduced testicular Sertoli cell junction damage in mice. METHODS: Forty male C57BL/6J mice were randomized into normal diet group, high-fat diet group, and low-dose (25 mg/kg) and high-dose (75 mg/kg) TSPJ treatment groups (n=10). The mice in the normal diet group were fed a normal diet, while the mice in the other groups were fed a high-fat diet. After TSPJ treatment via intragastric administration for 5 months, the testes and epididymis of the mice were collected for measurement of weight, testicular and epididymal indices and sperm parameters. HE staining was used for histological evaluation of the testicular tissues and measurement of seminiferous tubule diameter and seminiferous epithelium height. The expression levels of ZO-1, occludin, claudin11, N-cadherin, E-cadherin and β-catenin in Sertoli cells were detected with Western blot, and the localization and expression levels of ZO-1 and β-catenin in the testicular tissues were detected with immunofluorescence assay. The protein expressions of LC3B, p-AKT and p-mTOR in testicular Sertoli cells were detected using double immunofluorescence assay. RESULTS: Treatment with TSPJ significantly improved high-fat diet-induced testicular dysfunction by reducing body weight (P < 0.001), increasing testicular and epididymal indices (P < 0.05), and improving sperm concentration and sperm viability (P < 0.05). TSPJ ameliorated testicular pathologies and increased seminiferous epithelium height of the mice with high-fat diet feeding (P < 0.05) without affecting the seminiferous tubule diameter. TSPJ significantly increased the expression levels of ZO-1, occludin, N-cadherin, E-cadherin and β-catenin (P < 0.05) but did not affect claudin11 expression in the testicular tissues. Immunofluorescence assay showed that TSPJ significantly increased ZO-1 and β-catenin expression in the testicular tissues (P < 0.001), downregulated LC3B expression and upregulated p-AKT and p-mTOR expressions in testicular Sertoli cells. CONCLUSION TSPJ alleviates high-fat diet-induced damages of testicular Sertoli cell junctions and spermatogenesis possibly by activating the AKT/mTOR signaling pathway and inhibiting autophagy of testicular Sertoli cells.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Testis ; Sertoli Cells ; beta Catenin ; Diet, High-Fat ; Occludin ; Proto-Oncogene Proteins c-akt ; Seeds ; Cadherins ; Intercellular Junctions