[摘 要] 目的：制备低亲和力的CD117 CAR-T细胞，探讨其对急性髓系白血病（AML）细胞Kasumi-1的体外杀伤效应。方法：调取CD117低亲和力抗体巴佐利单抗（barzolvolimab）和Fab-79D VH和VL序列，设计VH-(G4S)3-VL结构的单链抗体，分别构建带4-1BB共刺激分子的经典二代CAR分子，经基因合成后分别亚克隆至pMFG逆转录病毒载体，获得CD117-79D CAR和CD117-0159 CAR质粒。将两种CAR质粒分别包装制备逆转录病毒，检测其滴度合格后转导活化后的T细胞，构建CD117-79D CAR-T和CD117-0159 CAR-T细胞，采用流式细胞术检测两种CAR-T细胞的阳性率。将未转导T细胞与两种CAR-T细胞分别与CD117+ Kasumi-1细胞共培养，通过流式细胞术检测Kasumi-1细胞凋亡率，以评估两种CAR-T细胞的抗肿瘤活性。结果：成功构建CD117-79D CAR-T和CD117-0159 CAR-T细胞，其阳性率分别为（59.4 ± 2.6）%、（62.5 ± 1.2）%。未转导T细胞、CD117-79D CAR-T和CD117-0159 CAR-T细胞体外培养均能稳定增殖，且三者的增殖能力均无显著差异（均P > 0.05）。体外杀伤Kasumi-1细胞结果显示，不同效靶比条件下，CD117-79D CAR-T和 CD117-0159 CAR-T细胞较未转导T细胞展现出显著增强的杀伤能力（P < 0.05或P < 0.01），但两种CAR-T细胞的杀伤效率无显著差异（P > 0.05）。结论：成功构建低亲和力的CD117-79 CAR-T和CD117-0159 CAR-T细胞，体外实验证实其可有效杀伤CD117+ Kasumi-1细胞，为AML的靶向治疗提供了实验依据。

AIM:To evaluate visual outcomes and visual function in nonamblyopic adults with myopic anisometropia treated with small incision lenticule extraction(SMILE).METHODS:Prospective comparative cohort study. The consecutive patients who underwent SMILE for the treatment of myopia or myopic astigmatism at Zhongshan Ophthalmic Center(Guangzhou, China)between October 2015 and January 2016 were included. They were divided into two groups based on the bilateral difference of a spherical equivalent(SE)refraction ≥1.50 D: the anisometropic myopia group(interocular SE difference ≥1.50 D)and non-anisometropic myopia group(interocular SE difference<1.50 D). Refractive status, uncorrected and corrected distance visual acuity(UDVA and CDVA), and visual function parameters including fusional vergence amplitude, stereoacuity and horizontal phoria were measured preoperatively and at 1 wk,1,3 and 6 mo after surgery.RESULTS:A total of 49 cases(98 eyes)were included in the study, and 19 cases(38 eyes)in the anisometropic group, including 11 males and 8 females, with a mean age of 25.4±6.2 y, and 30 cases(60 eyes)in the non-anisometropic myopia group, including 19 males and 11 females, with a mean age of 26.8±4.6 y. The CDVA of the non-anisometropia group was significantly better than that of the anisometropia group 6 mo postoperatively(P=0.036). However, the safety and efficacy indexes of the two groups did not show significant differences. The fusional vergence(break point and recovery point)of the anisometropia group decreased(P=0.005 and P=0.03)and was significantly lower than that in the non-anisometropia group at 6 mo post operatively(P=0.029 and P=0.046). Both groups showed a significant improvement in distance and near stereopsis at 1, 3 and 6 mo in comparison with the preoperative baseline and 1 wk postoperatively(all P<0.05). No clinically significant change in the amount of ocular alignment in terms of distance and near deviation postoperatively in either groups.CONCLUSION: SMILE is a predictable, effective, and safe method for correcting myopic anisometropia in adults without amblyopia. Although the fusional vergence amplitudes changed, stereopsis can be improved after surgery.

Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Objective To explore the prognostic factors for patients with descending duodenum gastrointestinal stromal tumors (GIST), analyze the impact of different surgical approaches on prognosis, and develop a predictive model for surgical approach selection. Methods This single-center retrospective cohort study included patients with primary descending duodenum GIST treated in Zhongshan Hospital, Fudan University from January 2010 to January 2015, with follow-up until August 2025. The primary outcomes were incidence of postoperative complications, disease-free survival (DFS) rate, and overall survival (OS) rate. Cox regression and logistic regression were used to identify factors influencing prognosis and surgical approach selection, respectively. A nomogram model for selecting the surgical approach was constructed. Results A total of 78 patients with descending duodenum GIST were included, with age of (56.14±11.76) years. The 1-, 5-, and 10-year OS rates were 100%, 98.7%, and 85.7%, respectively, and the corresponding DFS rates were 100%, 90.9%, and 82.3%. Intraoperative blood loss, postoperative gastroparesis, mucosal ulceration, maximum tumor diameter, and Ki-67-positive cell ratio were independent risk factors for DFS, while maximum tumor diameter and mitotic figure were independent risk factors for OS (P＜0.05). The 10-year DFS rate was higher in the local resection group than in the pancreaticoduodenectomy group (89.45% vs 74.24%; HR＝0.300, P＝0.013), but there was no statistical difference in OS between the two groups. The incidence of postoperative complications in the pancreaticoduodenectomy group was higher than that in the local resection group (P＜0.001). Maximum tumor diameter and distance from tumor to the duodenal papilla were independent factors influencing surgical approach selection. The nomogram model based on these two indices demonstrated good discrimination and accuracy upon internal validation. Conclusions The long-term prognosis of patients with descending duodenal GIST is favorable, and surgical treatment achieves satisfactory outcomes. The nomogram model developed in this study can effectively guide individualized surgical approach selection and provide a reference for clinical decision-making.

Objective To explore the effects of different serum potassium levels on the 28-day prognosis of elderly patients with sepsis. Methods A retrospective analysis was conducted on the clinical data and laboratory indicators within 24 hours after the diagnosis in 204 elderly patients with sepsis admitted to the Department of Critical Care Medicine, Zhongshan Hospital, Fudan University from January 2018 to January 2022. According to the potassium concentrations in the blood of the patients within 24 hours after admission to intensive care unit (ICU), the patients were divided into the hyperkalemia group (K^＋≥5.3 mmol/L), normokalemia group (K^＋ 3.5–＜5.3 mmol/L), and hypokalemia group (K^＋＜3.5 mmol/L). According to 28-day outcomes, the patients were divided into the death group and survival group. The acute physiological and chronic health evaluation (APACHE) Ⅱ score, sequential organ failure assessment (SOFA) score and laboratory indicators were analyzed. Multivariate logistic regression analysis was used to analyze the risk factors for 28-day mortality in elderly patients with sepsis. Results Compared with the normokalemia group (n＝99), patients in both the hyperkalemia (n＝61) and hypokalemia (n＝44) groups had significantly higher levels of C-reactive protein (CRP) and procalcitonin (PCT), longer duration of mechanical ventilation, longer length of hospital stay and ICU stay, and higher mortality (P ＜ 0.05). The death group (n＝49) had significantly higher APACHE Ⅱ score, SOFA score, white blood cell (WBC) counts, CRP level, and PCT level than the survival group (n＝155, P＜0.05). Multivariate logistic regression analysis showed that increased or decreased serum potassium level, higher SOFA score, and increased WBC counts were independent risk factors for 28-day mortality in elderly patients with sepsis (P＜0.05). Quadratic fitted curve showed a U-shaped association between serum potassium levels and 28-day mortality risk in elderly patients with sepsis, with the lowest mortality risk observed within the intermediate (normal) range, and both hypokalemia and hyperkalemia were associated with an increased mortality risk (P＝0.182). Conclusion Both increased and decreased serum potassium levels are independent risk factors for 28-day mortality in elderly patients with sepsis, which should be given particular attention in clinical management.

Objective To explore the number of peripheral blood regulatory T cells (Treg) in patients with chronic kidney disease (CKD) and its correlation with vascular calcification. Methods This was a single-center, cross-sectional, and observational study. Non-dialysis patients with CKD treated at Zhongshan Hospital, Fudan University from March 2021 to March 2022 were enrolled. Abdominal aortic calcification (AAC) was assessed using lateral abdominal X-ray. Number of Treg and cytokine levels were measured by flow cytometry. Logistic regression analysis was performed to evaluate the related factors for AAC in CKD patients. Results A total of 83 patients were included, aged 17–86 years, with 57 males (68.7%). The distribution of CKD stages was as follows: stage G1 in 7 patients (8.4%), stage G2 in 17 patients (20.5%), stage G3 in 21 patients (25.3%), stage G4 in 19 patients (22.9%), and stage G5 in 19 patients (22.9%). No AAC was observed in patients with stages G1 and G2, while the prevalence of AAC in patients with stages G3, G4, and G5 was 23.8%, 21.1%, and 26.3%, respectively. Compared with stage G1 patients, those with stages G3–5 showed decreased number of peripheral blood Treg and elevated levels of interleukin (IL)-6 and IL-17F (P＜0.05). The area under the receiver operating characteristic curve for number of peripheral blood Treg in predicting AAC in CKD patients was 0.766 (95%CI 0.652–0.879, P＝0.002). Logistic regression analysis showed that decreased number of Treg was related factor for AAC in CKD patients (OR＝0.957, 95%CI 0.922–0.992, P＝0.018). Conclusion As CKD progresses, number of peripheral blood Treg significantly decreases, which is correlated with AAC in CKD patients.

Objective To explore the correlation between changes in spleen volume and stiffness before and after transjugular intrahepatic portosystemic shunt (TIPS) and the occurrence of hepatic encephalopathy. Methods A retrospective study was conducted on 104 patients who underwent TIPS in the Department of Interventional Therapy, Zhongshan Hospital, Fudan University, from January 1, 2023 to July 30, 2024. Spleen volume and stiffness were measured before and after surgery. Patients were divided into the overt hepatic encephalopathy (OHE) group and the non-OHE group. Univariate and multivariate logistic regression analyses were used to identify factors correlated with OHE after TIPS. The predictive values of the related factors of OHE were evaluated using receiver operating characteristic (ROC) curves. Results OHE occurred in 34 patients (32.69%). Compared with the non-OHE group, the OHE group had a smaller percentage reduction in spleen volume after TIPS (P＜0.001), but there was no statistically significant difference in the percentage reduction in spleen stiffness between the two groups. Multivariate logistic regression analysis revealed that the percentage reduction in spleen volume was correlated with postoperative OHE (OR＝0.90, P＜0.001). ROC analysis showed that the area under the curve (AUC) for spleen volume reduction percentage in predicting postoperative OHE was 0.773, superior to spontaneous portosystemic shunt (SPSS; Z＝2.088, P＝0.037). Conclusions Reduction in spleen volume after TIPS may be a protective factor against hepatic encephalopathy, while changes in spleen stiffness were not found to be correlated with its occurrence.

High myopia has become a major public health concern worldwide, particularly in China and Southeast Asia. It is associated not only with a variety of fundus diseases but also with earlier onset and greater severity of cataracts, resulting in significant visual impairment. Phacoemulsification is currently the main surgical treatment for cataracts. However, intraoperative fluctuations in perfusion pressure and exposure to ultrasonic energy may affect the vitreoretinal structures, potentially accelerating the progression of fundus pathology after surgery in highly myopic eyes. This article summarizes current evidence on the progression of posterior scleral staphyloma, myopic maculopathy, and retinal detachment following phacoemulsification in highly myopic eyes.

OBJECTIVE To explore the influencing factors for successful detoxification in patients undergoing methadone maintenance therapy. METHODS A retrospective selection of 161 methadone maintenance therapy patients from the South Branch of Zhongshan Second People’s Hospital （including methadone maintenance treatment sites in Shiqi District， Xiqu District， Development Zone of Zhongshan City） from January 1， 2012， to January 1， 2025， was conducted as the study object. Data collected included patients’ sociodemographic information， drug abuse history， laboratory test results， medication records， etc. Patients were divided into the unsuccessful detoxification group and the successful detoxification group based on whether methadone detoxification was achieved. Univariate， univariate Cox regression， and multivariate Cox proportional hazards regression were used for influencing factor analysis， and the Kaplan-Meier method was employed for survival analysis. RESULTS Among the 161 methadone maintenance therapy patients， 96 were in the successful detoxification group and 65 in the unsuccessful detoxification group， yielding a successful detoxification rate of 59.63%. Multivariate Cox proportional hazards regression analysis revealed that age， registered residence status， age at first drug use， and duration of drug abuse were key influencing factors for successful detoxification in methadone maintenance therapy patients （P＜0.05）. Specifically， the successful detoxification rate for patients with Zhongshan local registered residence was 8.364 times higher than that for patients with non-local registered residence； for every 1-year increase in patient age， the successful detoxification rate decreased by 22.7%； for every 1-year increase in age at first drug use， the successful detoxification rate rose by 33.4%； and for every 1-year increase in duration of drug abuse， the successful detoxification rate increased by 33.5%. Survival analysis showed that the successful detoxification rate in the methadone low-dose group （≤30.8 mg） was significantly higher than that in the methadone high-dose group （＞30.8 mg） （P＝0.015）， and the successful detoxification rate in the population with Zhongshan local registered residence was significantly higher than that in those with non-local registered residence （P＜0.001）. CONCLUSIONS Age， registered residence status， age at first drug use， and duration of drug abuse are key influencing factors for successful detoxification in patients undergoing methadone maintenance therapy， and the last methadone dose may be associated with successful detoxification.