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.

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.

Objective To investigate the practical effects of pediatric rapid sequence intubation(RSI)nursing coordination training based on the LSPPDM(learn,see,practice,prove,do,maintain)framework in order to provide evidence for optimizing pediatric RSI nursing training programs.Methods Nurses from the intensive care unit(ICU)of Children's Hospital,Fudan University during Feb 2023 and Jan 2024 were divided into the experimental group(n=35)and the control group(n=35)by block randomization.The experimental group received LSPPDM framework-based training,while the control group underwent conventional training with theoretical lectures and procedural demonstrations.Outcomes included training satisfaction,theoretical knowledge and procedural skill assessment scores,team collaboration compliance and RSI procedure time were compared between the two groups.Results The experimental group demonstrated significantly higher training satisfaction(123.80±2.04 vs.117.26±9.82,P<0.05),superior post-training theoretical knowledge and procedural skills(P<0.05),enhanced team collaboration compliance(P<0.05),and shorter RSI completion time(P<0.05)compared with the control group.Conclusion Pediatric RSI nursing coordination training based on the LSPPDM framework can effectively increase training satisfaction,promote theoretical and procedural skills and reduce completion time in nurses.

Healthy female rabbits aged 3.5 to 4.0 months were randomly divided into four groups:the white light group(control group A),the green light group(treatment group B),the red light group(treatment group C)and the blue light group(treatment group D)with 3 replicates in each group,and 12 rabbits in each replicate.The light intensity was set to 80 lx,and the light was 16 h per day for 6 days before artificial insemination.Three reproductive cycles were carried out to de-termine the reproductive performance of female rabbits under different light colors,such as the number of fetuses,total litter size,weaning litter weight and serum reproductive hormone content.The results showed that,according to the comprehensive statistics of three breeding cycles:(1)the melatonin levels in the green group and red group were significantly lower than those in white group(P＜0.01),and the green group was significantly lower than the blue group(P＜0.05);the levels of luteinizing hormone in green group and red group were significantly higher than those in white group(P＜0.01);the follicle stimulating hormone in the green group was significantly high-er than in white group(P＜0.05);the estradiol content in the green group was significantly higher than that in the white group and blue group(P＜0.01),and significantly higher than that in the red group(P＜0.05).(2)the conception rate of the group was significantly higher than that of the white group(P＜0.01),and significantly higher than that of the red group and blue group(P＜0.05).(3)the number of rabbits in the green group at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.05),and the litter weight at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.01),and significantly higher than that in the white group(P＜0.05).In conclusion,the LED light belt is controlled by a dynamic light control system,the light intensity is set to 80 lx,and the light is 16 h a day for 6 d before artificial insemination.Green light can reduce the serum melatonin of Fujian white rabbits,which has the best comprehensive effect on the same period of conception rate and reproductive performance of Fujian white rabbits.

Aim To study whether intravenous injec-tion of miR-129-3p mimetic(agomir)can resist bone loss caused by hind limb disuse,and to provide new i-deas for preventing bone loss in microgravity environ-ment.Methods Forty-eight C57BL/6J male mice were randomly divided into the control group(CON),tail suspension model group(TS),tail suspension+miR-129-3p agomir administration group(miRNA)and tail suspension+miR-129-3p negative sequence agomir control group(NC).The miRNA group was given 4 mg·kg-1 miR-129-3p agomir by intravenous injection into the medial canthus twice a week.The NC agomir group were consistent with those in the miR-129-3p agomir group,and the CON and TS groups were given only equal volumes of normal saline.After four weeks,all mice were sacrificed and samples were collected.Micro-CT scan of femur,three-point femur bending test,serum bone metabolism index detection,oxidative stress index detection and osteogenesis-related protein expression analysis in bone tissue were per-formed.Results After four weeks,the number of tra-becular bone in the TS group was significantly re-duced,and Tb.BMD,Tb.Th,Tb.N,Tb.BS/TV and Tb.BV/TV were significantly lower than those in the CON group(P＜0.01).While Tb.Sp TS group was significantly higher than the CON group(P＜0.05),the maximum load and flexural strength of the femur significantly decreased(P＜0.01),the content of ser-um bone formation index PINP was significantly lower than that of the CON group(P＜0.01),and the con-tent of bone resorption index CTX-I was significantly higher than that of the CON group(P＜0.01),the content of serum oxidative damage indexes 8-iso-PGF2α and 8-OHdG significantly increased(P＜0.01),and the expression of osteogenesis-related pro-teins in bone tissue markedly decreased(P＜0.01).However,the increase or decrease of all indexes in miRNA group was significantly lower than that in TS group.Conclusions miR-129-3p mimetic can signifi-cantly reduce bone loss caused by hind limb disuse.This experiment provides a new idea and method for preventing bone loss in microgravity environment.

Objective:To evaluate the clinical process of fragment reattachment in crown-root fractures (CRF) of teeth that the fracture occurred between sub-gingival and supra-alveolar ridge (sub-gingival & supra-alveolar ridge) in the esthetic zone, and to analyze the feasibility of this minimally invasive technique for sub-gingival & supra-alveolar ridge CRF involving anterior teeth.Methods:Fourteen sub-gingival & supra-alveolar ridge CRF involving anterior teeth in 12 patients received fragment reattachment in the Department of Prosthodontics, School of Stomatology, the Fourth Military Medical University from January 2016 to August 2024. The success rate of the fractured teeth 3 years after reattachment and the complications during the follow-up period were retrospectively analyzed. The 3-year success rate and complications during follow-up were evaluated to assess the clinical efficacy of this technique.Results:The 14 treated teeth were followed for an average of (36.0±33.7) months (range: 4-99 months). Complications occurred in 2 teeth: one was extracted due to debonding and replaced with a removable partial denture, while the other developed a palatal sinus post-reattachment, which healed after local saline irrigation and medication (followed for 12 months without recurrence). The remaining 12 teeth exhibited no complications, resulting in a success rate of 13/14.Conclusions:Fragment reattachment is a minimally invasive, rapid, and cost-effective treatment option for sub-gingival & supra-alveolar ridge CRF in the anterior esthetic zone. With strict case selection, it delivers favorable outcomes and extends the clinical lifespan of affected teeth.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To investigate the safety and effectiveness of the clinical application of minimally invasive transcatheter patent foramen ovale occlusion.Methods:A total of 123 patients who underwent transcatheter patent foramen ovale (PFO) occlusion at the Department of Cardiac Surgery of Beijing Anzhen Hospital from January 1, 2023, to December 31, 2023, were retrospectively analyzed. According to the surgical protocol, this study divided the patients into the conventional occlusion group (Group A, 53 cases) and the minimal invasive occlusion group (Group B, 70 cases). The patients were followed up for at least six months after surgery to evaluate the safety and effectiveness of the new method.Results:The surgical success rate was 100% in both groups. Intraoperative fluoroscopy time decreased by over 50% (7 min in group A and 3 min in group B, P<0.001). At the six-month postoperative follow-up, contrast-enhanced transcranial Doppler ultrasound sonography revealed seven positive results, two of which indicated large shunts. It was further reviewed for combined pulmonary arteriovenous fistula. One patient experienced a recurrence of stroke after the surgery. The patients' overall migraine and transient ischemia attack (TIA) were significantly relieved, and their overall VAS scores decreased significantly compared to the previous ones. Conclusion:The minimally invasive transcatheter PFO occlusion procedure is safe, reliable, and cost-effective. It warrants further follow-up and promotion. Meanwhile, transcatheter PFO occlusion is an effective treatment for preventing recurrent stroke and relieving symptoms like migraine and TIA in patients.