[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 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.

Transdiaphragmatic intercostal hernia (TDIH) is a rare condition involving simultaneous disruption of the diaphragm and intercostal muscles, allowing abdominal organs to herniate into the chest wall. It is usually traumatic and spontaneous cases are uncommon and can be easily overlooked. We report the case of a man in his late 60s with six years of progressive right chest wall swelling and recent vomiting and breathlessness. Initial imaging was misinterpreted as pleural effusion, but a computed tomography confirmed a five cm diaphragmatic defect with bowel herniation through the 7th –8th intercostal space. Prompt recognition is vital, as delayed diagnosis may lead to bowel obstruction, strangulation, and life -threatening complications

Transdiaphragmatic intercostal hernia (TDIH) is a rare condition involving simultaneous disruption of the diaphragm and intercostal muscles, allowing abdominal organs to herniate into the chest wall. It is usually traumatic and spontaneous cases are uncommon and can be easily overlooked. We report the case of a man in his late 60s with six years of progressive right chest wall swelling and recent vomiting and breathlessness. Initial imaging was misinterpreted as pleural effusion, but a computed tomography confirmed a five cm diaphragmatic defect with bowel herniation through the 7th –8th intercostal space. Prompt recognition is vital, as delayed diagnosis may lead to bowel obstruction, strangulation, and life -threatening complications

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

OBJECTIVES: This study aimed to analyze the correlations and proportional relationships between maxillary anterior teeth (MAT) and facial measurements in Han Chinese individuals with the most attractive smiles, as evaluated by dental professionals. METHODS: Ten dentists with more than 5 years of clinical experience from different professional directions in a tertiary stomatological hospital were selected to evaluate the smile attractiveness of volunteers by visual analogue scale (VAS). Eighty-eight Han volunteers with the most attractive smile were selected. The perceived width of the MAT, the dimensions (height and width) of the maxillary central incisors (MCI), and the facial dimensions (intercanthal distance, interzygomatic distance, interalar distance, facial height and lower facial height) of the volunteers were measured on the frontal photos of the smile, digital oral model, and 3D face model. Pearson correlation analysis was performed to analyze linear correlations, and regression analysis was carried out to explore the proportional relationships. Reliability analysis using the intraclass correlation coefficient verified the stability of these proportional relationships. In addition, the correlations between MAT perceived width and the proportional relationships of (MCI) height to width ratio, with facial dimensions were explored and their reliability was verified. RESULTS: In Han Chinese individuals with the most attractive smiles, as evaluated by dental professionals, the Pearson correlation coefficients among MAT perceived widths were 0.813, 0.389, and 0.560. A proportional relationship existed between the lateral incisor and central incisor, and the ratio was 0.729. No significant correlations were found between MCI and the inner canthal distance, zygomatic distance, interalar distance, facial height, or the lower one-third facial height except for a negative correlation (r=-0.357) between MCI height and facial height in males and a positive correlation (r=0.249) between MCI width and interalar width when genders were combined. CONCLUSIONS Correlations exist among MAT perceived widths in Han Chinese individuals with the most attractive smiles, as evaluated by dental professionals. Partial correlations are observed between MCI height and width and facial measurements. The perceived width of the lateral incisor can serve as a reference indicator for predicting the perceived width of the central incisor, providing a reference for the aesthetic restoration of MAT in the Han ethnicity population.
Adult ; Female ; Humans ; Male ; China ; Esthetics, Dental ; Face/anatomy & histology* ; Incisor/anatomy & histology* ; Maxilla/anatomy & histology* ; Smiling ; East Asian People

OBJECTIVE: To compare the effects of piriformis muscle release versus preservation in total hip arthroplasty (THA) via supercapsular percutaneously-assisted total hip (SuperPATH) approach on muscle injury. METHODS: Forty-nine patients undergoing initial THA via SuperPATH approach between June 2022 and June 2023 were randomly divided into two groups, with 24 patients in trial group and 25 patients in control group. The trial group received piriformis muscle release intraoperatively, whereas the control group underwent muscle preservation. There was no significant difference in baseline data such as gender, age, body mass index, disease type, American Society of Anesthesiologists (ASA) grading, and preoperative muscle infiltration, muscle atrophy, muscle injury serological indicators, Harris score, etc. ( P>0.05). The incision length, operation time, intraoperative blood loss, total blood loss, hospital stay, preoperative and postoperative 1-day muscle injury serological indicators [including creatine kinase (CK) and lactic dehydrogenase (LDH)], and incidence of complications between two groups were recorded. Harris score was used to evaluate the recovery of hip joint function. MRI was used to evaluate the extent of hip muscle injuries (gluteus minimus, gluteus medius, piriformis, obturator internus, quadratus femoris), including tendon integrity, degree of muscle fat infiltration, and degree of muscle atrophy preoperative and 1 year postoperatively. RESULTS: The operation time, intraoperative blood loss, and total blood loss in the trial group were significantly shorter than those in the control group ( P<0.05). There was no significant difference in the incision length and length of hospital stay between the two groups ( P>0.05). Both groups showed a significant increase in serum CK and LDH levels on postoperative day 1 compared to preoperative levels ( P<0.05), but there was no significant difference between the two groups ( P>0.05). All patients were followed up, the follow-up time for the trial group and the control group was (14.8±2.8) and (15.1±3.0) months, respectively, with no significant difference ( t=-0.400, P=0.691). Incisions healed by first intention in both groups, with 1 case in the trial group and 2 cases in the control group experiencing venous thrombosis in the calf muscle space. There was no complication such as deep vein thrombosis, pulmonary embolism, hip dislocation, prosthesis loosening, or periprosthetic infection in the lower limbs. There was no significant difference in the incidence of complications between the two groups ( P>0.05). At 1 year after operation, both groups of patients showed a significant increase in Harris scores compared to preoperative levels ( P<0.05), but there was no significant difference between the two groups ( P>0.05). Compared with preoperative results, both groups showed significant fat infiltration in the piriformis and obturator muscles at 1 year after operation ( P<0.05), while there was no significant fat infiltration in the gluteus minimus, gluteus medius, and quadratus femoris muscles ( P>0.05). At 1 year after operation, except for the higher incidence of piriformis muscle fat infiltration in the control group compared to the trial group ( P<0.05), there was no significant difference in the incidence of other muscle infiltrations between the two groups ( P>0.05). At 1 year after operation, both groups of piriformis and obturator muscles showed significant muscle atrophy compared to preoperative levels ( P<0.05). The gluteus minimus and gluteus medius showed mild atrophy compared to preoperative levels, while the maximum transverse diameter of the quadriceps muscle slightly increased, but the differences were not significant ( P>0.05). There was no significant difference in the maximum cross-sectional diameter or cross-sectional area changes of each muscle between the two groups ( P>0.05). At 1 year after operation, the continuity of the gluteus medius and quadratus femoris muscles in both groups was intact. Both groups had some patients with incomplete continuity of the piriformis muscle, obturator internus, and gluteus minimus, but the difference was not significant ( P>0.05). CONCLUSION The SuperPATH approach THA may cause injury to the piriformis, gluteus minimus, and obturator internus. The piriformis muscle release does not increase muscle injury, but it can shorten the operation time and reduce bleeding.
Humans ; Arthroplasty, Replacement, Hip/adverse effects* ; Male ; Female ; Muscle, Skeletal/surgery* ; Middle Aged ; Aged ; Postoperative Complications/epidemiology* ; Adult ; Operative Time ; Muscular Atrophy ; Creatine Kinase/blood* ; Length of Stay ; Treatment Outcome

Objective: To investigate the application effect of bovine pericardium in horizontal bone augmentation surgery in the aesthetic area and to assess its clinical feasibility in guided bone regeneration (GBR). Methods: This study was approved by the Ethics Committee. A total of 29 patients with anterior tooth loss accompanied by labial bone defects were selected, and horizontal bone augmentation was performed using a bovine pericardium membrane combined with particulate or block bone grafts. Centered on the virtual implant in the preoperative design, labial bone thickness at the implant neck and 1-5 mm below it was measured at different time points: preoperatively (T0), immediately postoperatively (T1), and 6 months postoperatively (T2). The results were used to assess bone regeneration outcomes. Additionally, the visual analog scales (VASs) of postoperative pain and swelling were recorded, and whether any complications such as infection or wound dehiscence occurred were monitored. Results: Immediately after surgery, labial bone thickness of all implants significantly increased, with an average increase more than 3 mm. Six months after surgery, the bone augmentation was well maintained. Specifically, labial bone thickness 3-5 mm below the shoulder of the implant was greater than 3 mm. The VAS scores showed that postoperative pain and swelling peaked on the third day and then gradually decreased, with good recovery 10 days after surgery. No complications such as infection or wound dehiscence occurred during the follow-up period. Conclusion Bovine pericardium shows good bone augmentation effect and biocompatibility in horizontal bone augmentation in the anterior aesthetic area, and it is suitable for various horizontal bone augmentation surgeries in the aesthetic area.

Objective:To investigate the characteristics of hand dysfunction and its associated factors in patients with rheumatoid arthritis (RA).Methods:A cross-sectional study. Patients with RA were recruited from January 2019 to April 2024 at the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Demographic and clinical data were collected, including age, gender, active smoking, disease duration, time of morning stiffness, rheumatoid factor and anti-cyclic citrullinated peptide antibody, disease activity, radiographic indicators, and hand function assessment. Hand function was assessed by grip strength measures and self-reported items related to hand function in the Stanford Health Assessment Questionnaire. Factors related to hand function were analyzed by logistic regression analyses.Results:A total of 1 079 RA patients were recruited [mean age: (53.0±12.6) years]. Overall, 72.6% (783/1 079) patients experienced a decrease in grip strength, 57.2% (617/1 079) patients experienced a decreased grip strength in both hands, with the average grip strength of the left and right hands decreasing by 16.3% and 14.1%, respectively, compared to normal values; 39.9% (430/1 079) patients had self-reported hand dysfunction. There were 185 (17.1%) older RA patients (age ≥65 years). The proportion of older RA patients with decreased grip strength [89.7% (166/185) vs. 69.0% (617/894)] and degree of decrease in grip strength compared to normal values (left hand:-35.3%±30.6% vs. -12.3%±38.6%; right hand:-32.6%±32.3% vs. -10.3%±42.1%) were significantly higher than that in young patients, and the proportion of older patients with self-reported hand dysfunction was also significantly higher [53.0% (98/185) vs. 37.1% (332/894), all P<0.001]. Multivariate logistic regression analysis showed that pain visual analogue scale ( OR=1.375, 95% CI 1.020-1.854) was independently associated with grip strength decrease in older RA patients, while the 28-joint tender joint count ( OR=1.151, 95% CI 1.063-1.246) and provider global assessment of disease activity ( OR=1.381, 95% CI 1.171-1.628) were associated with self-reported hand dysfunction. Conclusions:Hand dysfunction is common in RA patients, especially among older RA patients, which is related to pain, joint tenderness and provider global assessment of disease activity. This result implies the importance of pain management in RA patients.