OBJECTIVE To explore the effect and mechanism of Buyang huanwu decoction （BYHWD） on mitochondrial dynamics in rats with cerebral ischemia-reperfusion injury （CIRI）. METHODS CIRI rats were randomly divided into CIRI group， low-dose BYHWD （L-BYHWD， intragastric administration of 3.15 mg/kg BYHWD） group， high-dose BYHWD （H-BYHWD， intragastric administration of 12.60 mg/kg BYHWD） group， positive control （intraperitoneal administration of 150 mg/kg Extract of Ginkgo biloba leaves injection） group， H-BYHWD+solvent control （intragastric administration of 12.60 mg/kg BYHWD+ intraperitoneal injection of 20 mg/kg DMSO） group and H-BYHWD+Compound C （intragastric administration of 12.60 mg/kg BYHWD+intraperitoneal injection of 20 mg/kg Compound C） group， with 15 rats in each group. Additionally， 15 rats were assigned to the sham operation group. All rats received the corresponding medications or saline solution via intragastric administration or intraperitoneal injection once daily for 4 consecutive weeks. After the last administration， the cerebral infarct volume of rats was measured； the ultrastructure of mitochondria in endothelial cells in the ischemic penumbra （IP） region was observed； the mitochondrial membrane potential was evaluated； the fluorescence colocalization area ratio of optic atrophy 1 （OPA1） to cluster of differentiation 31 （CD31） in the IP region was detected； the expressions of mitofusin 2 （MFN2）， OPA1， mitochondrial fission 1 protein （Fis1）， and proteins related to the AMP-activated protein kinase （AMPK）/dynamin-related protein 1 （Drp1） pathway in the IP region were determined. RESULTS Compared with the sham operation group， mitochondria in endothelial cells of the IP region in brain tissue of rats in the CIRI group were swollen， mostly spherical， with fractured cristae and severe vacuolation； the percentage of cerebral infarct volume， Fis1 expression level and phosphorylation level of Drp1 were increased significantly （P＜0.05）， while mitochondrial membrane potential in the IP region， fluorescence colocalization area ratio of OPA1 to CD31， the expressions levels of MFN2 and OPA1， and phosphorylation level of AMPK were significantly decreased （P＜0.05）. These indicators were improved in the L-BYHWD group， H-BYHWD group， and positive control group， M025） compared with the CIRI group （P＜0.05）. Compared with the H-BYHWD group and H-BYHWD+solvent control group， the above indicators of rats in the H-BYHWD+Compound C group showed significant reversal（P＜0.05）. There was no statistically significant difference in the above indicators between the H-BYHWD+solvent control group and the H-BYHWD group （P＞0.05）. CONCLUSIONS BYHWD may improve CIRI by activating the AMPK/Drp1 pathway and ameliorating mitochondrial dynamic disorders.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective To investigate the efficacy of surface electromyography biofeedback combined with respiratory training on post-stroke dysphagia and its impacts on serum neuron specific enolase(NSE)and insulin-like growth factor 1(IGF-1)in patients.Methods Totally 120 patients with post-stroke dysphagia in our hospital were stochastically assigned into the control group and the combined group,with 60 patients in each group.Both groups were given conventional treatment first,while the control group received respiratory training treatment.The combined group received surface electromyography biofeedback treatment on the top of the control group.The efficacy,serum NSE,central nervous system specific protein(S100β),IGF-1,functional oral intake scale(FOIS)score,standard swallowing function assessment scale(SSA)score,respiratory function,pharyngeal contraction rate and duration of pharyngeal contraction were compared between the two groups.Results After treatment,the total effective rate was higher in the combined group(x2=4.876,P＜0.05).Compared with before treatment,NSE,S100β,SSA score and pharyngeal contraction rate decreased after treatment in both groups,and those were even lower in the combined group(t=5.193,9.000,8.976,10.614,P＜0.05).Compared with before treatment,IGF-1,FOIS score,force vital capacity(FVC),forced expiratory volume in one second(FEV1),peak expiratory flow rate(PEF)and duration of pharyngeal contraction increased after treatment in both groups,with even higher levels in the combined group(t=4.212,6.220,3.765,6.935,5.020,4.249,P＜0.05).Conclusion Surface electromyography biofeedback combined with respiratory training can improve neuronal damage in patients with dysphagia,enhance swallowing efficiency,reduce serum NSE,S100β levels and pharyngeal retention time,with significant curative effect.

Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG)instillation after transurethral resection of bladder tumor(TURBT)in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC),and to construct a prediction model for recurrence after BCG treatment.Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation.The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set,while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set.A total of 17 variables were included and analyzed.Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation,and nomograms were plotted to predict 1-year,3-year,and 5-year recurrence-free survival(RFS).Calibration curve,decision curve analysis(DCA),and receiver operating characteristic(ROC)curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model.Results In the training set,26 patients(23.64%)experienced recurrence during the follow-up period,with a median RFS of 32.00(18.00～50.50)months.Univariate Cox regression analysis suggested that platelet count,eosinophil to lymphocyte ratio(ELR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune inflammation(SII)index,and neutrophil-monocyte to lymphocyte ratio(NMLR),pathological T1 stage(pT1)tumor and hemoglobin,albumin,lymphocyte,and platelet(HALP)score were potential factors influencing recurrence after BCG instillation.Multivariate Cox regression analysis identified high HALP score(HR=0.185,95%CI:0.046～0.736,P=0.017)as an independent protective factor,while high ELR(HR=3.599,95%CI:1.505～8.608,P=0.004)and pT1 stage(HR=3.240,95%CI:1.191～8.818,P=0.021)were independent risk factors for recurrence.Based on this,a nomogram prediction model was constructed.The calibration curves demonstrated good agreement between predicted and actual 1-,3-,and 5-year recurrence risks.Decision curve analysis indicated clinical utility across a wide threshold probability range.In the training set,the model showed strong predictive performance for 1-(AUC=0.842),3-(AUC=0.847),and 5-year(AUC=0.887)recurrence risks,which was further validated in the external cohort.Conclusion Higher HALP score prior to BCG instillation therapy is a protective factor against tumor recurrence,while higher ELR and pT1 stage are risk factors.Our nomogram prediction model based on HALP score,ELR and pathological T stage,can identify individuals at high risk of recurrence after BCG instillation therapy.

Objective:To explore the clinical features of Brucellar myelitis and diagnosis and treatment of secondary neuromyelitis optica spectrum disorder (NMOSD), and enhance the awareness of clinicians about this disease.Methods:A retrospective study was performed; 13 patients with Brucellar myelitis admitted to Department of Neurology, Inner Mongolia Autonomous Region People's Hospital from January 2020 to December 2024 were chosen. Clinical data were collected, and MRI images and serological changes during the infection period were observed. Serum and cerebrospinal fluid demyelinating antibody markers and cerebrospinal fluid oligoclonal bands (OCBs) in the suspected secondary inflammatory demyelinating diseases of the central nervous system patients were detected. All patients received standard antibiotic treatment and/or individualized immunotherapy depending on disease severity. The patients were followed up for 24 (12, 42) months. At the last follow-up, the neurological outcomes were evaluated using modified Rankin scale (mRS, scores of 0-2: good prognosis; scores of 3-6: poor prognosis).Results:(1) Among the 13 patients, 12 had motor disorder, 9 had bladder/bowel dysfunction, 7 had sensory abnormality, and 4 had other symptoms such as dizziness, behavioral changes, or unsteady gait. (2) MRI results showed that 8 patients had spinal cord abnormalities, including 2 with long-segment intramedullary high signal at T2-weighted image and 6 with short-segment local intramedullary high signal at T2-weighted image. Enhanced MRI was performed in 11 patients, with 2 showing lesion enhancement, 3 showing meningeal enhancement, and 6 showing no enhancement. (3) Four patients had elevated cerebrospinal fluid pressure (>180 mmH 2O); 9 patients had elevated cerebrospinal fluid protein level (>0.45 g/L). Brucella-specific DNA was detected in the cerebrospinal fluid of 6 patients. One patient was positive for OCB type II. One patient was positive for aquaporin 4 antibody (AQP4-IgG) in both serum and cerebrospinal fluid, and one patient was double positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG) and AQP4-IgG in serum. (4) All 13 patients received standard antibiotic treatment; 12 patients received immunotherapy. (5) Among the 4 patients with poor prognosis, 3 died and the remaining 9 had a good prognosis. The mRS score decreasing from 4 (3, 4) at admission to 2 (2, 3) at the last follow-up, showing an overall improvement in neurological function. (6) Among the 13 patients, 2 were diagnosed as having Brucellar myelitis secondary NMOSD. On the basis of antibiotic treatment, one AQP4-IgG positive patient was treated with high-dose glucocorticoids only and later died; one MOG-IgG and AQP4-IgG double positive patient was treated with intravenous immunoglobulin combined with high-dose glucocorticoids and sequential rituximab, with mRS score decreasing from 5 at admission to 2 at the last follow-up and good neurological function recovery. Conclusions:The clinical manifestations of Brucellar myelitis are diverse and overlap with the clinical features of NMOSD. For patients with suspected Brucellar myelitis secondary NMOSD, combination of immunosuppressant (such as rituximab) with antibiotics may be an effective individualized treatment.

This article is to evaluate the clinical outcomes and health economics of minimally invasive surgery for hypertensive intracerebral hemorrhage(HICH).This review systematically compares clinical efficacy and economic value of three minimally invasive techniques:small bone window microsurgery,neuroendoscopic surgery and stereotactic drainage based on 12 randomized controlled trials(RCTs),7 cohort studies,and 8 economic evaluations 2019-2024.Cost-effectiveness analysis(CEA)and cost-utility analysis(CUA)were employed to assess resource utilization and health outcomes.Minimally invasive approaches overall outperform conventional craniotomy.Stereotactic surgery achieves the shortest hospitalization(5-8 days)and lowest direct costs;neuroendoscopy significantly improves quality of life(quality-adjusted life years(QALYs);and small bone window surgery offers the best postoperative stability.It is recommended to choose the surgical method based on patient characteristics and to optimize healthcare resource allocation through medical insurance payment reform and technology promotion.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To investigate the efficacy of surface electromyography biofeedback combined with respiratory training on post-stroke dysphagia and its impacts on serum neuron specific enolase(NSE)and insulin-like growth factor 1(IGF-1)in patients.Methods Totally 120 patients with post-stroke dysphagia in our hospital were stochastically assigned into the control group and the combined group,with 60 patients in each group.Both groups were given conventional treatment first,while the control group received respiratory training treatment.The combined group received surface electromyography biofeedback treatment on the top of the control group.The efficacy,serum NSE,central nervous system specific protein(S100β),IGF-1,functional oral intake scale(FOIS)score,standard swallowing function assessment scale(SSA)score,respiratory function,pharyngeal contraction rate and duration of pharyngeal contraction were compared between the two groups.Results After treatment,the total effective rate was higher in the combined group(x2=4.876,P＜0.05).Compared with before treatment,NSE,S100β,SSA score and pharyngeal contraction rate decreased after treatment in both groups,and those were even lower in the combined group(t=5.193,9.000,8.976,10.614,P＜0.05).Compared with before treatment,IGF-1,FOIS score,force vital capacity(FVC),forced expiratory volume in one second(FEV1),peak expiratory flow rate(PEF)and duration of pharyngeal contraction increased after treatment in both groups,with even higher levels in the combined group(t=4.212,6.220,3.765,6.935,5.020,4.249,P＜0.05).Conclusion Surface electromyography biofeedback combined with respiratory training can improve neuronal damage in patients with dysphagia,enhance swallowing efficiency,reduce serum NSE,S100β levels and pharyngeal retention time,with significant curative effect.