Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

ObjectiveTo investigate the inhibitory effect of gingerol， an active component of ginger， on Staphylococcus aureus （S. aureus） infection， and to preliminarily explore its mechanism related to extracellular vesicles （EVs）. MethodsS.aureus infection models were established in human umbilical vein endothelial cell （HUVECs）， Vero E6 cells， and C57BL/6 mice. Experimental groups included control， infection， and gingerol-treated groups. Bacterial load and VE-cadherin protein expression were detected using immunofluorescence and Western blot. EVs were isolated by size exclusion chromatography and characterized by transmission electron microscopy and nanoparticle tracking analysis. miRNA sequencing was performed on EVs. ResultsGingerol treatment significantly reduced the bacterial load in both in vitro and in vivo infection models and upregulated VE-cadherin expression. miRNA sequencing of EVs revealed that S. aureus infection upregulated the expression of hsa-miR-320c， while gingerol treatment reversed this abnormal expression. Bioinformatic analysis further predicted that the target genes of hsa-miR-320c were significantly enriched in cell junction-related pathways. ConclusionGingerol exhibits clear antibacterial and host-protective effects， by regulating hsa-miR-320c in EVs to maintain endothelial barrier integrity.

PURPOSE: Lateral patellar compression syndrome (LPCS) is characterized by a persistent abnormally high stress exerted on the lateral articular surface of the patella due to lateral patellar tilt without dislocation and lateral retinaculum contracture, leading to anterior knee pain. The purpose of this study is to evaluate the efficacy and prognosis of lateral retinaculum release (LRR) combined with chondroplasty in the treatment of LPCS. METHODS: This retrospective study evaluated 40 patients who underwent LRR combined with chondroplasty for LPCS between 2020 and 2021. The assessment included improvement in postoperative tenderness and knee joint function. Patients were evaluated using the Lysholm, Tegner, and International Knee Documentation Committee 2000 scoring systems, as well as the visual analog scale, both preoperatively and postoperatively, with the paired comparisons analyzed using a t-test. Additionally, intraoperative observations were made regarding knee joint lesions, including cartilage damage and osteophyte formation, with analysis by the Chi-square test. RESULTS: The visual analog scale score for tenderness showed a significant decrease after surgery (p < 0.001). Evaluation of knee joint function also indicated significant improvements, as demonstrated by increased Lysholm, Tegner, and International Knee Documentation Committee 2000 scores postoperatively (p < 0.001, p = 0.011, p < 0.001, respectively). Furthermore, all LPCS patients included in the study presented with cartilage injuries and osteophyte formation. Significant differences were noted in the incidence of cartilage damage and osteophyte formation at different locations within the knee among patients with LPCS. CONCLUSION LRR combined with chondroplasty is an effective surgical approach for treating patients with LPCS, with satisfactory recovery observed at the 1-year follow-up. Additionally, the incidence of cartilage damage and osteophyte formation in LPCS patients varies significantly depending on the specific location within the knee joint.
Humans ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Patella/surgery* ; Knee Joint/physiopathology* ; Recovery of Function ; Young Adult ; Treatment Outcome ; Cartilage, Articular/surgery* ; Adolescent

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective To explore the feasibility and safety of ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer.Methods Totally 84 patients who underwent ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer were enrolled,and the technical success rate,complete ablation rate,complication rate,pain relief rate and survival time,etc.were observed.Results The median age of 84 cases was 61.5 years.Totally 86 tumors,including 44.19％(38/86)at the head/neck and 55.81％(48/86)at the body/tail of pancreas were detected,and a total of 85 ablation sessions were performed with the median ablation energy applied per tumor of 9.90(1.08,21.60)kJ and the complete ablation rate of 42.86％(36/84).The technical success rate was 100％(85/85).Thirty-nine complication events occurred in 25 cases,no ablation-related death.Among 34 patients underwent ablation mainly for pain symptoms,the pain score decreased from(6.22±1.12)points before treatment to(1.94±1.64)points after treatment(P＜0.001).During 6.8(3.3,12.9)months' follow-up,the mean survival time was(8.5±6.7)months,and all 47 patients died due to tumor progression.Conclusion Ultrasound-guided percutaneous microwave ablation was safe and feasible for unresectable pancreatic cancer.

Objective To explore the effects of evidence-based nursing combined with multi-dimensional health education on negative emotions and postoperative rehabilitation of patients undergoing elective surgery for cholecystolithiasis.Methods A total of 100 patients with cholecystolithiasis who underwent elective surgery in Yixing Traditional Chinese Hospital Medicine from September 2023 to August 2024 were selected.The patients were assigned to control group and observation group by PEMS3.1 for Windows completely random(two groups and multiple groups)program,with 50 cases in each group.The control group received routine nursing,and the observation group received evidence-based nursing combined with multidimensional health education on the basis of routine nursing.The intervention duration of the two groups was 7 days.Visual analogue scale(VAS)scores,negative emotions(self-rating anxiety scale[SAS]and self-rating depression scale[SDS]),postoperative complications,and postoperative rehabilitation were compared between the two groups.Results The VAS scores at 24 h and 72 h after surgery were lower than those at 6 h after surgery in both groups,especially in the observation group(P<0.05).The scores of SAS and SDS in both groups after intervention were significantly decreased compared with those before intervention,and the scores of negative emotions in the observation group after intervention were significantly lower than those in the control group(P<0.05).The total incidence of gastrointestinal discomfort,biliary fistula and wound infection/bleeding in the observation group was significantly lower than that in the control group(4.00%vs.18.00%,P<0.05).The time of getting out of bed,the time of anal exhaust,the time of resuming normal diet and the time of hospitalization in the observation group were significantly lower than those in the control group(P<0.05).Conclusion The combination of evidence-based nursing and multi-dimensional health education during perioperative period of cholecystolithiasis surgery can reduce postoperative pain,improve the positive attitude of treatment,reduce complications,and promote the recovery of the disease.

Objective To discuss the effect of different particle activities and tumor shrinkage speed on the dosimetric parameters of the target area at the same prescription dose after 125I particle implantation.Methods A 6cm-sized cube tumor model was outlined by using a computerized three-dimensional treatment planning system(3D-TPS)with a prescription dose(PD)of 100 Gy,and 125I particle activities of 0.4 mCi and 0.8 mCi were selected.Assuming that the tumor shrinks centripetally after seed implantation and that the 125I particles were uniformly and centripetally concentrated without shedding or wandering,the tumor volume shrank at different rates every month after implantation(0,5％,10％,15％,20％,25％,30％,35％,40％,45％and 50％),according to the different activities of 125I particles,the experiments were divided into A1-K1 group(0.4 mCi)and A2-K2 group(0.8 mCi).Based on the 125I particle decay law,the validation program(using TPS simulation of the A1-K1 group and A2-K2 group at postoperative 1,2,3,4,5 and 6 months)obtained the dose received by 90％of the target volume(D90)in the two groups with different 125I particle activities at different postoperative time points,the percentages of the target volume covered by the 100％,150％and 90％prescription dose(V100,V150,V90),and the mean dose(Dmean).By comparing the differences in D90,V100,V150,V90 and Dmean after tumor implantation of 125I particles with different activities,the dosimetric impact of the tumor target area shrinking at a rate of 0～50％after implantation of 125I particles with different activities into tumor tissues was analyzed.Results When the monthly shrinkage rate of the tumor target area was≤30％,there was no obvious difference in D90 between the 0.4 mCi group and 0.8 mCi group in 1～6 months after surgery.When the monthly shrinkage rate of the tumor target area was＞30％,the D90 of 0.8 mCi group was higher than that of 0.4 mCi group;when the monthly shrinkage rate of the tumor target area was＜25％,the V90 of 0.4 mCi group was higher than that of 0.8 mCi group,and the changes of V90 of the two groups tended to be the same in the 5th～6th month after surgery.When the monthly shrinkage rate of the tumor target area was ≥30％,the V90 of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more significant,the results of V100 were consistent with those of V90.When the monthly shrinkage rate of tumor target area＜35％,V150 of 0.4 mCi group was higher than that of 0.8 mCi group,when the monthly shrinkage rate of tumor target area ≥35％,V150 of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more prominent.When the monthly shrinkage rate of tumor target area＜25％,Dmean of 0.4 mCi group was higher than that of 0.8 mCi group,when the monthly shrinkage rate of tumor target area ≥25％,Dmean of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more obvious.Conclusion With the same prescription dose,when the tumor target area shrinks at a rate of＜30％per month,the activity of 125I particles has little effect on D90,and all V90,V100,V150 and Dmean in the low activity group are higher than those in the high activity group,meanwhile the homogeneity of the target area is relatively good;when the monthly shrinkage rate of tumor target area ≥35％,all D90,V90,V100,V150 and Dmean in the high activity group are higher than those in the low activity group,and the duration of the presence of high-dose area is long.This difference becomes more obvious with the increasing of the monthly shrinkage rate of the target area.