1.Comparative Analysis of Clinical Efficacy of Traditional Chinese Medicine Manipulative Reduction Combined with Small Splint Fixation Versus Surgical Treatment for Type A Distal Radius Fracture
Yang SHAO ; Zihan WANG ; Jianwei WANG ; Guoda DAI ; Hengyan CUI ; Zhen HUA ; Tingchen ZHU ; Shaoshuo LI ; Jun MAO ; Fenghua CHEN ; Shuai TAO ; Mao WU
Journal of Traditional Chinese Medicine 2026;67(10):1078-1085
ObjectiveTo compare the clinical efficacy of traditional Chinese medicine (TCM) manipulative reduction combined with small splint fixation versus surgical treatment for type A distal radius fracture (DRF) and to explore the factors influencing the choice of treatment. MethodsA multi-center retrospective study was conducted, collecting data from 1237 type A DRF patients treated in 11 hospitals in Jiangsu province from September, 2023 to April, 2025. Among them, 851 patients in the TCM group received manipulative reduction combined with small splint fixation, and 386 patients in the surgical group underwent open reduction and internal fixation. Visual analog scale (VAS) scores for pain and radiographic indicators including palmar tilt, ulnar deviation, and radial height were compared before treatment, 5-7 days after treatment, and 4-6 weeks after treatment. The wrist joint function scores including Dienst and Gartland-Werley scores at 12 weeks after treatment were recorded. Subgroup analysis was conducted for the excellent rate of Dienst and Gartland-Werley scores, stratified by age (<50, 50-59, 60-69, ≥70 years old) and AO subtypes (A1, A2, A3). A multivariate logistic regression model was used to identify independent factors influencing treatment choice. ResultsOn 5-7 days after treatment, the surgical group had lower VAS scores than the TCM group, while 4-6 weeks after treatment, the TCM group showed lower VAS scores than the surgical group (P<0.01). In terms of radiographic indicators, except for the palmar tilt before treatment being higher in the surgical group than in the TCM group (P<0.01), there were no significant differences in palmar tilt, ulnar deviation, and radial height at other timepoints (P>0.05). Twelve weeks after treatment, the surgical group had a higher average Gartland-Werley score and the excellent rate than the TCM group (P<0.01). Subgroup analysis showed that in patients with A2 type DRF aged 50-59 and 60-69 years old, the excellent rates of Dienst and Gartland-Werley scores in the TCM group were higher than those in the surgical group (P<0.05). Multivariate logistic regression analysis revealed that age, palmar tilt, ulnar deviation, and the degree of swelling on the affected side were independent factors influencing the choice of treatment (P<0.05). ConclusionBoth TCM manipulative reduction combined with small splint fixation and surgical treatment for type A DRF can achieve good therapeutic effects. TCM manipulative reduction combined with small splint fixation has certain advantages in medium- and long-term pain relief, especially in elderly patients, where wrist joint function recovery is more stable. Age, palmar tilt, ulnar deviation, and swelling degree are the main factors influencing the treatment choice.
2.Clinical Efficacy and Radiographic Outcomes of Manipulative Reduction Combined with Small Splint Fixation for Distal Radius Fractures:A Retrospective Multicenter Study with Propensity Score Matching
Mao WU ; Guoda DAI ; Yang SHAO ; Shaoshuo LI ; Zhen HUA ; Hengyan CUI ; Tingchen ZHU ; Dipeng LI ; Jintao LIU ; Ming ZHOU ; Peimin WANG ; Liyong ZHANG ; Jianwei WANG
Journal of Traditional Chinese Medicine 2026;67(10):1086-1092
ObjectiveTo observe the clinical efficacy and radiographic outcomes of manipulative reduction combined with small splint fixation in the treatment of distal radius fractures. MethodsThe clinical data of 1051 patients with distal radius fractures were retrospectively collected from five hospitals included in the Jiangsu Diagnosis and Treatment Data Platform for Traditional Chinese Medicine(TCM) Dominant Diseases. Propensity score matching at a 1∶4 ratio was applied, resulting in 580 cases selected for final analysis, which comprised 448 patients in the TCM group(manipulative reduction plus small splint fixation) and 132 in the surgical treatment group(open reduction and internal fixation). Each group was further stratified into type A, B, and C subgroups based on AO fracture classification. Radiographic indicators including palmar tilt, radial inclination, and radial height were compared between groups before treatment and 1 day, 1 week, and 4-6 weeks after treatment, and pain visual analog scale(VAS) scores before treatment and 1 week and 4-6 weeks after treatment were also compared. Wrist joint function was assessed 12 weeks after treatment, using the Dienst wrist function score and the Gartland and Werley(G-W) wrist function score. Additionally, the radiographic indicators at different timepoints and the 12-week wrist function levels were compared between groups across different fracture types. ResultsNo statistically significant difference was observed in radiographic indicators and VAS scores at all timepoints before and after treatment, as well as wrist joint function grades assessed by the Dienst score and the G-W score at 12 weeks after treatment (P>0.05). Compared to those before treatment, both groups showed increased palmar tilt, radial inclination, and radial height 1 week and 4-6 weeks after treatment, and decreased VAS scores (P<0.05). Compared to those 1 week after treatment, both groups showed a decrease in palmar tilt, an increase in radial inclination and radial height, and a reduction in VAS score 4-6 weeks after treatment(P<0.05). In type A and B subgroups, the surgical treatment group had a higher radial inclination than the TCM group 4-6 weeks after treatment, while in the type C subgroup, a higher radial height was shown in the surgical treatment group than in the TCM group 4-6 weeks after treatment(P<0.05). In type C subgroup, there was significant difference between groups in the wrist joint function by G-W scores 12 weeks after treatment(P<0.05). ConclusionManipulative reduction combined with small splint fixation can maintain fracture alignment and alleviate pain in treating distal radius fractures, which achieves therapeutic outcomes comparable to surgical treatment. It is particularly suitable for type A and B fractures and can be considered an effective treatment option for distal radius fractures.
3.Construction and Clinical Validation of a Deep Learning-Based Automatic Measurement Model for Palmar Tilt and Radial Inclination in Distal Radius Fractures
Guoda DAI ; Jianwei WANG ; Mao WU ; Bin KANG ; Yang SHAO ; Hengyan CUI ; Shaoshuo LI ; Tingchen ZHU ; Zhen HUA ; Zhongming SHEN ; Jintao LIU ; Ming ZHOU
Journal of Traditional Chinese Medicine 2026;67(10):1093-1100
ObjectiveTo construct an automatic measurement model for palmar tilt and radial inclination suitable for traditional Chinese medicine (TCM) clinical scenarios, and to validate its accuracy and efficiency in TCM manipulative reduction settings. MethodsData on anteroposterior (AP) and lateral X-rays of distal radius fractures were collected from patients admitted to 18 TCM/ integrated TCM and western medicine hospitals in Jiangsu province between September 1st, 2023, and September 1st, 2024, via the Jiangsu Diagnosis and Treatment Big Data Platform for TCM Dominant Diseases. A medical image segmentation framework based on multi-scale feature fusion and edge-awareness was employed, combined with anatomical knowledge specific to TCM orthopedics, to optimize the feature extraction strategy of an artificial intelligence (AI) model. This framework enabled automatic segmentation of fracture regions and measurement of distal radius palmar tilt and radial inclination. The accuracy of the AI model in measuring radial inclination and volar tilt was validated, and the measurement time and average time gain rate of the AI model were compared to those of manual measurement. ResultsA total of 15,444 AP and lateral X-ray images of distal radius fractures were collected, and were divided into a training set (11,144 images, 5066 AP and 6078 lateral), a validation set (3700 images, 1840 AP and 1860 lateral), and an independent test set (600 images, 300 AP and 300 lateral) after preprocessing. In the measurement of 300 AP X-rays in the independent test set for radial inclination, when the degree error between AI measurement and manual measurement was <3° and <5°, AI measurement accuracy was 83% and 93%, respectively. In 300 lateral X-rays in the test set for palmar tilt, when AI measurements had an error of <3° and <5° compared to manual measurements, corresponding accuracy rate was 78% and 90%, respectively. For 50 X-ray images, AI measurement time was (1.37±0.05) min for radial inclination while manual measurement time was (22.57±2.52) min (P<0.001); in terms of palmar tilt, the AI measurement time was (1.33±0.14) min, shorter than (23.70±2.80) min for manual measurement time (P<0.001). Average time gain rates for manual and AI measurements were 93.93% and 94.39% respectively. ConclusionAn automatic measurement model for palmar tilt and radial inclination in distal radius fractures has been established, enabling more accurate and efficient assessment as well as providing a tool to support the quantitative evaluation of the efficacy of TCM manipulative reduction and large-sample clinical research.
4.Single-cell sequencing reveals heterogeneity of B cells in osteoporosis patients and their interactions with osteoblasts
Zhi TANG ; Yang SHAO ; Shaoshuo LI ; Shubin QI ; Hengyang LU ; Mao WU ; Junfeng YANG ; Jianwei WANG
Chinese Journal of Tissue Engineering Research 2025;29(26):5501-5510
BACKGROUND:The pathogenesis of osteoporosis is closely related to the immune system.A comprehensive and in-depth study of the relationship between immunity and osteoporosis is crucial for understanding and treating the disease.OBJECTIVE:To investigate the role of immune cells in osteoporosis using single-cell sequencing technology.METHODS:Femoral head tissue samples from osteoporosis and non-osteoporosis patients were downloaded from GEO database and analyzed using single-cell sequencing.Data analysis,including cell clustering,functional enrichment,pseudotime trajectory,and cell interaction analyses,was performed using R4.3.0 and software packages such as Seurat v.4.3,monocle(2.28.0),and CellChat.The femoral head tissues of patients with femoral neck fracture who underwent artificial hip replacement surgery were obtained,including two cases of osteoporosis patients and two cases of non-osteoporosis patients.Immunohistochemical staining was used to detect the protein expression of CCL13 and CCL18.qPCR was used to detect the immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA expression.Western blot was used to detect the protein expression of receptor-type tyrosine protein phosphatase C,CD22,and CD99.RESULTS AND CONCLUSION:Transcriptomic analysis identified 10 cell clusters,including osteoclasts,myeloid cells,T cells,osteoblasts,macrophages,monocytes,erythrocytes,B cells,bone marrow mesenchymal stem cells,and mast cells.There was an increase in the ratio of osteoclasts to T cells and a decrease in the ratio of osteoblasts to B cells in the femoral head tissue of the osteoporosis group.Among the B-cell subpopulations,the proportion of B-cells of taxa 1,3(BC1,BC3)in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,and the proportion of B-cells of taxa 2(BC2)was less than that of the non-osteoporosis group.BC1 was enriched significantly for labels such as regulation of adaptive immune response,somatic recombination of immune receptors,and modulation of lymphocyte-mediated immunity,while BC3 was enriched significantly for labels such as regulation of immunoglobulin production,response to type Ⅱ interferon,apoptotic processes involving cysteine endopeptidases,and cytotoxicity.The communication intensity between B-cell subtype BC1 and osteoblasts in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,while the communication intensity between BC3 and BC1 was also increased.The communication between BC3 and BC1 was significantly enriched in the CD22-receptor-type tyrosine protein phosphatase C pathway;the communication between BC1 and osteoblasts was mainly enriched in the CD99-CD99 pathway;and the communication between BC3 and osteoblasts was also highly enriched in the CD99-CD99 pathway.Protein expression of CCL13,CCL18,receptor-type tyrosine protein phosphatase C,CD22,CD99,immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA were higher in femoral tissues of the osteoporosis group than those of the non-osteoporosis group(P<0.05).To conclude,specific B cell subpopulations can influence the differentiation and apoptosis of osteoblasts in the femoral tissue of osteoporosis patients.
5.Clinicopathological features and surgery-related outcomes of duodenal adenocarcinoma: a multicenter retrospective study
Qifeng XIAO ; Xin WU ; Chunhui YUAN ; Zongting GU ; Xiaolong TANG ; Fanbin MENG ; Dong WANG ; Ren LANG ; Gang ZHAI ; Xiaodong TIAN ; Yu ZHANG ; Enhong ZHAO ; Xiaodong ZHAO ; Feng CAO ; Jingyong XU ; Ying XING ; Jishu WEI ; Shanmiao GOU ; Chengfeng WANG ; Jianwei ZHANG
Chinese Journal of Oncology 2025;47(10):1026-1038
Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P>0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P<0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.
6.A retrospective cohort study on the risk of pulmonary tuberculosis incidence among individuals with latent tuberculosis infection in schools
Xiaowei DONG ; Jingwen LAI ; Shanshan HUANG ; Lanjun FANG ; Jianwei LI ; Huizhong WU ; Yuhui CHEN ; Wenpei WEN
Chinese Journal of Preventive Medicine 2025;59(10):1708-1715
Objective:To evaluate the risk of developing pulmonary tuberculosis (PTB) among individuals with latent tuberculosis infection (LTBI) in schools and the protective effect of tuberculosis preventive treatment (TPT).Methods:A retrospective cohort study was conducted to collect data on 15 school outbreaks that occurred in Guangdong Province from 2017 to 2021. Baseline information on tuberculin skin test (TST) or interferon-gamma release test (IGRA) was obtained during contact surveys, as well as baseline information such as TPT. The incidence of PTB between 2017 and 2022 was queried using the Chinese Center for Disease Control and Prevention Information System. Poisson regression analysis was used to compare the incidence risk of PTB in the LTBI population under different TST states at baseline. Current cases, new cases and all cases (the sum of the two) were used as dependent variables. Cox regression models were used to analyze various risk factors affecting the risk of PTB in the LTBI population and evaluate the protective effect of TPT.Results:A total of 6 550 contacts were included in this study, of which 409 received TPT. Within 0-3 months after baseline survey, 119 cases were diagnosed as current cases [19.4‰, 119/(6 550-409)]. A total of 17 221.65 person-years of follow-up were conducted, during which 71 new cases were diagnosed (4.1/1 000 person-years, 71/17 221.65). The incidence density of PTB was 47.7/1 000 person-years, 6.6/1 000 person-years, 1.4/1 000 person-years, and 0.9/1 000 person-years, respectively, in TST strong/IGRA positive, TST moderate positive, TST generally positive, and TST and IGRA negative populations. The difference in PTB incidence density was statistically significant [likelihood ratio test LRT=153.16, P<0.001]. TPT was performed for individuals with strong TST or IGRA positivity, and the protection rate could reach 93% ( HR=0.07, 95% CI: 0.02-0.23). Conclusion:After the outbreak of the school epidemic, individuals with strong TST/IGRA positivity have a higher risk of developing PTB in the future. Targeted implementation of TPT can achieve better protection effects. In addition, the risk of developing PTB in individuals with moderate TST positivity is also worth noting.
7.Development and validation of a nomogram for predicting postoperative prognosis in gallbladder cancer patients based on the HALP score
Shujie HE ; Zhelong JIANG ; Lili WU ; Xuanhua LIN ; Lizhi LYU ; Yang CHENG ; Baipo ZHOU ; Fang YANG ; Jianwei CHEN
Chinese Journal of Hepatobiliary Surgery 2025;31(9):666-670
Objective:To analyze the effects of hemoglobin, albumin, lymphocyte and platelet count (HALP) scores on the survival of gallbladder cancer patients after radical surgery, and to construct a prognostic prediction model and evaluate based on HALP scores.Methods:The clinical data of 95 patients with gallbladder cancer who underwent surgical treatment in Fuzong Clinical Medical College of Fujian Medical University (the 900th Hospital) from January 2010 to December 2022 were retrospectively analyzed, including 40 males and 55 females, with the age of (63.3±12.2) years. All patients were divided into a low HALP group (HALP score ≤35.4, n=45) and a high HALP group (HALP score >35.4, n=50) based on the optimal cut-off value of 35.4 for predicting postoperative survival as determined by the receiver operating characteristic (ROC) curve. Survival curves were plotted by the Kaplan-Meier method, and survival comparisons were performed using the log-rank test. Univariate and multivariate Cox regression were used to analyze the effect of HALP score on survival after radical surgery in patients with gallbladder cancer. Based on the multifactorial results, nomogram was constructed to predict the survival of gallbladder cancer patients after radical surgery, and ROC curves, consistency indexes were evaluated in the model. Results:A total of 95 patients were followed up for 1-150 months, with a median of 13 months. The 1-, 3-, and 5-year postoperative cumulative survival rates of patients in the low HALP group were 56.2%, 31.2%, and 11.1%, respectively, which were lower than those of the high HALP group, which were 82.9%, 59.6%, and 40.7%, and the difference was statistically significant ( χ2=12.50, P<0.001). Based on multifactorial Cox regression analysis, preoperative total bilirubin ≥23 μmol/L, with lymph node metastasis, tumor TNM stage Ⅲ-Ⅳ, and postoperative incision infection were the risk factors for survival after radical surgery in patients with gallbladder cancer, and a HALP score of >35.4 and Child-Pugh A were protective factors (all P<0.05). Based on the results of multivariate Cox regression analysis to construct a nomogram for predicting overall survival after radical surgery in patients with gallbladder cancer, the consistency index between the prediction of the nomogram and the actual situation was 0.801 (95% CI: 0.752-0.850), and the area under the ROC curve for predicting overall survival was 0.812 (95% CI: 0.704-0.902). Conclusion:The preoperative high HALP score (HALP > 35.4) is a protective factor for survival after radical surgery in gallbladder cancer patients, and the nomogram constructed based on the HALP score for survival prediction after radical surgery for gallbladder cancer has high accuracy and can be used for the assessment of postoperative survival.
8.Application of real-time virtual sonography combined with intraductal biliary contrast-enhanced ultrasound in percutaneous transhepatic cholangial drainage
Huajun WU ; Jianwei YI ; Zhigang HU ; Binghai ZHOU ; Jiafu GUAN ; Jinlong YAN ; Xin YU ; Rongfa YUAN ; Shubing ZOU ; Kai WANG
Chinese Journal of Surgery 2025;63(8):732-737
Objective:To explore the application value of real-time virtual sonography (RVS) combined with intraductal biliary contrast-enhanced ultrasound (IB-CEUS) in percutaneous transhepatic cholangial drainage (PTCD).Methods:This retrospective cohort study included data from 71 patients who underwent PTCD at the Department of Hepatobiliary and Pancreatic Surgery in the Second Affiliated Hospital of Nanchang University between May 2021 and August 2022. There were 36 male and 35 female patients,aged 35 to 94 years. Based on the guidance modality used,patients were divided into two groups: the RVS combined with IB-CEUS group ( n=36) and the digital subtraction angiography (DSA) group ( n=35). PTCD was performed under the guidance of RVS combined with IB-CEUS in the RVS+IB-CEUS group,and under conventional DSA fluoroscopic guidance in the DSA group. Two clinicians classified the biliary conditions as either simple or complex based on preoperative ultrasound and CT (or MRI) imaging. Statistical analyses were conducted using independent sample t-tests,rank-sum tests, χ2 tests,or Fisher′s exact tests,as appropriate. Results:Significant differences were observed between the RVS+IB-CEUS group and the DSA group in terms of the number of punctures (1.0±0.2 vs. 2.2±1.4, t=-5.148, P<0.01) and postoperative complication rate(2.8% (1/35) vs. 17.1% (6/36), P=0.049). There were 9 patients with complex biliary conditions in the DSA group and 12 in the RVS+IB-CEUS group. The number of punctures in both the simple and complex subgroups of the RVS+IB-CEUS group(1.0±0.2 and 1.0±0.0) remained lower than that in the corresponding DSA subgroups(2.2±1.6 and 2.4±0.4) ( t=-3.606, P<0.01; t=-3.959, P=0.002). Moreover,the complication rate in the simple biliary subgroup of the RVS+IB-CEUS group was significantly lower than that of the DSA group(0 (0/24) vs. 19.2% (5/26), P=0.031),whereas no significant difference was found in the complex biliary subgroup (1/12 vs. 1/9, P=0.686). Conclusion:Guided by RVS and IB-CEUS, PTCD can help reduce the number of punctures during surgery and postoperative complications, and patients with complex bile duct conditions can still benefit from PTCD.
9.Short-term efficacy of endoscopic submucosal dissection for early carcinoma in the remnant stomach
Ying ZHOU ; Qi JIANG ; Baisheng CHEN ; Xia WU ; Qiuli JIANG ; Nashan LI ; Xingyu WU ; Pinghong ZHOU ; Weifeng CHEN ; Jianwei HU
Chinese Journal of Clinical Medicine 2025;32(4):620-626
Objective To explore the short-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early carcinoma in the remnant stomach. Methods A retrospective study was conducted on 45 patients with early residual gastric cancer underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2014 to April 2024, with a total of 45 lesions. The patients were divided into an anastomotic group (n=15) and a non-anastomotic group (n=30) based on the location of tumor occurrence, and their clinical data, endoscopic diagnosis and treatment, and histopathological conditions were compared between the two groups. Results All 45 patients had lesions with redness and erosion. There were 9 cases of poor lifting of submucosal injection in the anastomotic group and 2 cases in the non-anastomotic group, respectively, and the difference was statistically significant (P<0.05). ESD surgery was performed on 13 lesions in the anastomotic group and 28 lesions in the non-anastomotic group, with surgery times of 80.00 (50.00, 100.00) min and 55.00 (43.75, 80.00) min, respectively. The difference in surgery time between the two groups was statistically significant (P=0.03). Among the 45 patients, ESD surgery achieved curative resection in 35 cases, including 11 cases in the anastomotic group and 24 cases in the non-anastomotic group, with no statistically significant difference. Conclusions Careful preoperative evaluation of early carcinoma in the remnant stomach is essential to prevent oversight. Lesions at anastomotic sites and suture lines present higher technical challenges for complete resection. ESD is safe and effective, with auxiliary traction technique available when necessary.
10.Increasing trends of hyperglycemia and diabetes in treatment-naive people living with HIV in Shenzhen from 2013 to 2019: An emerging health concern.
Liqin SUN ; Haipeng ZHU ; Man RAO ; Fang ZHAO ; Yang ZHOU ; Lukun ZHANG ; Xia SHI ; Jianwei WU ; Yun HE ; Hongzhou LU ; Jiaye LIU
Chinese Medical Journal 2025;138(16):2043-2045

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