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.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

[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。

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.

The morphological changes and functions of mitochondria are closely associated with the development and progression of non-alcoholic fatty liver disease （NAFLD）. Dynamin-related protein 1 （Drp1） is one of the primary proteins determining mitochondrial fission， and its activity is strictly controlled to ensure the balance of mitochondrial dynamics according to cellular needs. Drp1 can enhance mitochondrial interactions and mitochondrial fission by promoting the formation of endoplasmic reticulum tubules， and the phosphorylation state and deacetylation of Drp1 can also affect the morphological changes of mitochondria， thereby affecting the status of NAFLD. This article elaborates on the role and mechanism of action of Drp1 in the progression of NAFLD， in order to provide ideas for targeted therapy for NAFLD.

Objective To explore the valve regurgitation status of left heart after the implantation of left ventricular assist device (LVAD) and its effect on prognosis of patients with LVAD implantation. Methods A total of 35 patients with cardiomyopathy who underwent magnetic levitation LVAD implantation at Zhongshan Hospital, Fudan University from February 2021 to July 2024 were retrospectively selected. Clinical data during hospitalization were collected, including preoperative basic data and postoperative valve regurgitation status. Telephone follow-ups were conducted to monitor patients’ survival status and transthoracic echocardiography was used to assess left valve function. Kaplan-Meier survival curves and log-rank test were employed to compare the survival rate of patients with different levels of valve regurgitation. Results The 35 patients had a mean age of (53.9±11.1) years, with 85.7% male, and 3 patients (8.6%) died during hospitalization. Preoperatively, 17 patients (48.6%) had moderate or greater mitral regurgitation, while all 35 patients had less than moderate aortic regurgitation. One month postoperatively, thirty patients were followed up, among which 24 patients (80%) had less than moderate mitral regurgitation, including 11 cases with alleviated regurgitation compared to pre-surgery; 6 patients (20%) had moderate or greater mitral regurgitation, including 4 cases with stable regurgitation and 2 cases with progression of regurgitation compared to pre-surgery; 2 patients (6.7%) had progression of aortic regurgitation to moderate or greater. The follow-up time was 1.2 (1.0, 2.1) years, with 1-year survival rate of 91.4% and 3-year survival rate of 71.1%. Survival analysis showed that the 3-year survival rate of patients with moderate or greater mitral regurgitation one month postoperatively was significantly lower than that of patients with less than moderate regurgitation (66.7% vs 83.3%, P＝0.046). Conclusions After the implantation of magnetic levitation LVAD, most patients showed improvement in mitral regurgitation, while aortic regurgitation remained unchanged. The degree of mitral regurgitation one month postoperatively is associated with prognosis.

Objective To analyze the effect of the activation rate of peripheral blood monocytes on the recovery of patients after liver transplantation and to initially explore the possible influencing factors for differences in monocyte activation rates. Methods A total of 139 patients who underwent orthotopic liver transplantation from September 2020 to June 2023 at Department of Liver Surgery and Transplantation of Zhongshan Hospital, Fudan University were selected. The proportion of CD14^＋HLA-DR^＋ monocytes in peripheral blood was defined as the monocyte activation rate. The difference in monocyte activation rates between postoperative day 7 (POD7) and postoperative day 1 (POD1) was calculated as Δ, and patients were divided into Δ＞0 group (n＝73) and Δ＜0 group (n＝66). The two groups were compared in terms of complete blood count, liver and kidney function, coagulation indicators, infection indicators, ICU length of stay, total length of hospitalization, and 90-day mortality. Changes in the proportions of different monocytes subsets (Mo0, Mo1, Mo2, and Mo3) and HLA-DR expression in peripheral blood on POD1 and POD7 were detected using flow cytometry. Results The ICU length of stay in the Δ＜0 group was significantly longer than that in the Δ＞0 group (18[12, 26] days vs 14[10, 20.5] days, P＝0.018). On POD1, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.05); on POD7, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.001), while the proportions of Mo1, Mo2, and Mo3 were significantly higher than those in the Δ＜0 group (P＜0.001). Compared to POD1, the HLA-DR expression level of Mo0 in peripheral blood of patients with liver transplantation significantly decreased on POD7 (P＜0.01), while there was no significant difference in HLA-DR expression levels of Mo1, Mo2, and Mo3. Conclusions Increased proportion of Mo0 (CD14^lowCD16⁻HLA-DR^low) among peripheral blood monocyte subsets may be one of the influencing factors for the differences in monocyte activation rates in patients with liver transplantation. The difference in monocyte activation rate can serve as a new clinical indicator for assessing changes in the immune status and postoperative recovery of patients with liver transplantation.

BACKGROUND:Changes in skeletal muscle mass have been indicated in studies addressing the effects of low-frequency pulsed magnetic fields on the structure and morphology of the skeletal muscle,but no relevant studies have been conducted on the morphologic changes that occur after chronic exposure to the low-frequency pulsed magnetic field. OBJECTIVE:To observe the effects of chronic exposure to low-frequency pulsed magnetic fields on the maximal voluntary contraction and morphologic indicators of the quadriceps muscle of the leg,thereby providing a reference of muscle morphologic changes for the use of this technique as a strategy for muscle function improvement. METHODS:Seventy healthy subjects were recruited and randomly divided into a test group that received magnetic field stimulation and a control group that underwent sham treatment,with 35 subjects in each group,and the total duration of the trial was 4 weeks.The test group underwent low-frequency pulsed magnetic stimulation for 15 minutes every 48 hours,while the control group underwent sham treatment,with the same intervention interval and duration as the test group.After 4 weeks of intervention,changes in the maximum voluntary contraction value of the quadriceps muscle in different groups were observed,and B-mode ultrasonography was utilized as a means of assessment to observe changes in muscle thickness,muscle cross-sectional area,and pinnation angle indexes. RESULTS AND CONCLUSION:After 4 weeks of chronic exposure to low-frequency pulsed magnetic fields,68 subjects completed the test.The maximum voluntary contraction value of the quadriceps muscle in the test group increased significantly(P=0.000),and the increment was significantly higher than that of the control group(P=0.008).Three indexes related to muscle morphology in the test group were significantly higher than the pre-test values(P=0.000),while in the control group,muscle thickness showed a significant reduction(P=0.020),there was no significant change in the pinnation angle,but a significant increase in the cross-sectional area(P=0.000).Intergroup comparisons revealed that the three indicators related to muscle morphology,including muscle thickness(P=0.012),pinnation angle(P=0.003),and cross-sectional area(P=0.049),were significantly higher in the test group than in the control group.The above data confirmed that the maximum voluntary contraction of the quadriceps muscle was significantly increased in healthy adults after 4 weeks of chronic exposure to the low-frequency pulsed magnetic field,and significant increases in the three muscle morphometric indices of muscle thickness,cross-sectional area,and pinnation angle were observed in the test group,providing a basis of muscle tissue morphology for the use of this technique as an exercise alternative and medical treatment strategy for muscle improvement.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.