Objective:To explore the differences in clinical phenotype characteristics and auxiliary test results of Gerstmann-Str?ussler-Scheinker syndrome (GSS) patients in the same family with GSS carrying a P102L mutation in the PRNP gene. Methods:A family with GSS carrying a P102L mutation in the PRNP gene, which was identified and treated at the Department of Neurology, Xuanwu Hospital, Capital Medical University in January 2024 was collected. A comprehensive evaluation was conducted on the proband, including neuropsychological examination, imaging studies, electroencephalogram, cerebrospinal fluid (CSF) analysis, real-time quaking-induced conversion (RT-QuIC) assay of skin biopsy samples, and genetic testing. At the same time, a survey and analysis were conducted on the family members. Skin RT-QuIC, genetic testing and neuropsychological evaluation were performed on some of the family members. Results:Among the 4-generation members of the GSS family, there were 5 GSS patients, including the proband′s father, younger brother, uncle and cousin. The proband, her younger brother and cousin all carried the P102L mutation in the PRNP gene, and her son was a carrier of the P102L mutation in the PRNP gene. The proband was a 53 years old female, and had a typical GSS phenotype, with the initial symptom of ataxia. The CSF 14-3-3 protein was negative and there were no abnormalities observed on her brain magnetic resonance imaging. The skin and CSF RT-QuIC test results of the proband were both negative. The cousin of the proband had a typical GSS phenotype, and his skin RT-QuIC test result was negative. The younger brother of the proband had a GSS phenotype of Creutzfeldt-Jakob disease type, with the initial symptom of rapidly progressing dementia and a positive skin RT-QuIC test result. The first symptoms of the proband′s father and uncle were both ataxia, and they had passed away without undergoing genetic testing. The son of the proband was a carrier of the P102L mutation in the PRNP gene and had no clinical symptoms. Conclusion:Different family members in the same GSS family may exhibit different clinical phenotypes, and GSS with different phenotypes have differences in RT-QuIC results.

Objective:To explore the differences in clinical phenotype characteristics and auxiliary test results of Gerstmann-Str?ussler-Scheinker syndrome (GSS) patients in the same family with GSS carrying a P102L mutation in the PRNP gene. Methods:A family with GSS carrying a P102L mutation in the PRNP gene, which was identified and treated at the Department of Neurology, Xuanwu Hospital, Capital Medical University in January 2024 was collected. A comprehensive evaluation was conducted on the proband, including neuropsychological examination, imaging studies, electroencephalogram, cerebrospinal fluid (CSF) analysis, real-time quaking-induced conversion (RT-QuIC) assay of skin biopsy samples, and genetic testing. At the same time, a survey and analysis were conducted on the family members. Skin RT-QuIC, genetic testing and neuropsychological evaluation were performed on some of the family members. Results:Among the 4-generation members of the GSS family, there were 5 GSS patients, including the proband′s father, younger brother, uncle and cousin. The proband, her younger brother and cousin all carried the P102L mutation in the PRNP gene, and her son was a carrier of the P102L mutation in the PRNP gene. The proband was a 53 years old female, and had a typical GSS phenotype, with the initial symptom of ataxia. The CSF 14-3-3 protein was negative and there were no abnormalities observed on her brain magnetic resonance imaging. The skin and CSF RT-QuIC test results of the proband were both negative. The cousin of the proband had a typical GSS phenotype, and his skin RT-QuIC test result was negative. The younger brother of the proband had a GSS phenotype of Creutzfeldt-Jakob disease type, with the initial symptom of rapidly progressing dementia and a positive skin RT-QuIC test result. The first symptoms of the proband′s father and uncle were both ataxia, and they had passed away without undergoing genetic testing. The son of the proband was a carrier of the P102L mutation in the PRNP gene and had no clinical symptoms. Conclusion:Different family members in the same GSS family may exhibit different clinical phenotypes, and GSS with different phenotypes have differences in RT-QuIC results.

The study was aimed to assess the impact of Brucea javanica oil emulsion(BJOE)on the responsiveness of programmed death receptor-1(PD-1)monoclonal antibody to lung adenocarcinoma in mice.The experimental approach involved subcutaneously inoculating Lewis's lung adenocarcinoma(LLC)cells into C57BL/6 mice,which were then divided into four groups:model group,25 ml·kg-1 BJOE group,10 mg·kg-1 PD-1 group,and combination group(25 ml·kg-1 BJOE and 10 mg·kg-1 PD-1).Tumor volume,mass,and inhibition rate were evaluated;the apoptosis within tumor tissue was detected by TUNEL staining;CD4+and CD8+T cell proportions within tumor tissues were analyzed by flow cytometry;the levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and granzyme B in tumor tissue were measured by enzyme-linked immunosorbent assay(ELISA).Additionally,LLC cells were categorized into a control group and three BJOE treatment groups(10,30,50 μl·ml-1),and programmed death ligand 1(PD-L1)expression in tumor tissues and LLC cells were assessed by Western blotting.Data showed that as compared with the model group,PD-1 monoclonal antibody alone did not significantly alter tumor volume,tumor mass,CD4+and CD8+T cell proportions,cytokine levels(IFN-γ,TNF-α,Granzyme B),or apoptosis in lung cancer-bearing mice.However,BJOE treatment reduced tumor volume and mass,enhanced CD4+and CD8+T cell proportions,increased cytokine levels,and augmented apoptosis(all P<0.05).Furthermore,the combination therapy of BJOE and PD-1 monoclonal antibody yielded significantly greater reductions in tumor volume and mass,with heightened CD4+and CD8+T cell proportions,cytokine levels,and apoptosis compared to either treatment alone(all P<0.05).Both BJOE treatment and the combination therapy significantly upregulated PD-L1 protein expression in tumor tissues compared to the model or PD-1 monoclonal antibody groups(P<0.05).Similarly,BJOE treatment at all tested concentrations significantly increased PD-L1 protein expression in LLC cells as compared to the control group(P<0.05).In conclusion,BJOE could upregulate PD-L1 expression in LLC cells and enhance the sensitivity of lung adenocarcinoma-bearing mice to PD-1 monoclonal antibodies.

Objective:To explore the influencing factors of postoperative recurrence in patients with complex anal fistula, and to construct a nomogram model to predict the risk of postoperative recurrence and verify it.Methods:Clinical data of 310 patients with complex anal fistula who underwent fistulectomy in the hospital from Aug. 2019 to Mar. 2023 were retrospectively selected and divided into modeling group (93 cases) and validation group (217 cases) in a 3∶7 ratio according to system randomization method. Hospital electronic medical record system was used to collect patient baseline data and calculate the recurrence rate of patients 6 months after surgery. According to the data of the modeling group, multivariate Logistic regression was used to analyze the influencing factors of postoperative recurrence in patients with complex anal fistula. Based on the influencing factors, a nomogram model was established to predict the risk of postoperative recurrence, and external verification was performed based on the data of the validation group.Results:The recurrence rate at 6 months after operation was 20.43% (19/93) in the modeling group and 17.51% (38/217) in the validation group. There was no significant difference in recurrence rate between the two groups ( χ2=0.370, P=0.543) . The proportion of male, smoking history, diabetes mellitus, high anal fistula and unclear position of internal orifice in the recurrence group was higher than that in the non-recurrence group, and the body mass index and course of disease were higher than those in the non-recurrence group ( P<0.05) . Based on the above seven influencing factors, a nomogram model of the risk of recurrence of complex anal fistula after surgery was established. C index of the modeling group and the validation group was 0.984 and 0.798 respectively, the calibration curve was close to the ideal curve, and the Receiver operating characteristic AUC of the nomogram prediction model was>0.70, indicating that model consistency, prediction efficiency and differentiation were good. Conclusion:The nomogram prediction model based on gender, body mass index, smoking history, diabetes mellitus, course of disease, high anal fistula and internal orifice position can effectively predict the risk of postoperative recurrence in patients with complex anal fistula.

Objective:To investigate the current situation of cardiopulmonary bypass(CPB) in China and analyze the causes, to guide the formulation and implementation of technology standard.Methods:The survey task force sent out a nationwide survey to obtain up-to-date information on perfusion practice by ChSECC(Chinese Society of Extracorporeal Circulation). The unit of analysis for the survey was the medical center performs CPB. The survey consisted 48 questions covering four topics of qualifications, including certification and education, policies and practices, device and equipment, techniques used.Results:There were 540 of the 714 centers for an overall response rate of 76%. According to the annual number of CPB, they were divided into 4 groups: group A(≤50 cases/year), group B(50-100 cases/year), group C(100-500 cases/year) and group D(≥500 cases/year). The response rate of center with more than group D last year was 100%. Most of the perfusionists had certification issued by ChSECC. Although there were more than 80% of group D performed regular training and assessment of perfusionist, the result was still not ideal enough. Low utilization of safety equipment was not depend on the annual operation volume in most of responding centers. Ultrafiltration and blood protection technology had high application rate in group D compared with group A and B.Conclusion:The certification rate of perfusionists are high. Lower the number of annual CPB cases, lower the proportion of regular evaluation and training, and lower rate of standards performance. No matter the amount of CPB, the application rate of safety equipment is not ideal. Higher the number of CPB cases, higher the utilization rate of CPB related technologies.

Objective To evaluate the toxicity of the intra-articular injection of bevacizumab in the knee of the rabbit.Methods Thirty-two rabbits were divided into 3 experimental groups and normal control group.Three experimental groups were received intra-articular injection of bevacizumab (1, 2, 4 mg respectively) once every three weeks for two times and the normal control group was received the same amount of 0.9% sodium chloride solution.The animals were sacrificed after 6 weeks.Blood test was examined before and after treatment.Pathologic examinations of liver, kidney and artiluar tissue were taken after the sacrifice.The hematoxylin and eosin stain for synovium and cartilage were performed.The AB-PAS stain and Mankin's scale for cartilage were performed.Results All the rabbits kept normal physiological activity.There was no significant difference of major organs and articular tissue between experimental groups and normal control group.There was no significant difference for WBC, RBC, PLT, ALT, BUN and Mankin's scale among all groups.Conclusion No systemic toxicity effects were found for the intra-articular injection of bevacizumab in the knee of the rabbit.

Objective To compare the clinical efficacy of two surgical methods for the treatment of anal fissures in elderly patients.Methods A total of 138 elderly patients with anal fissures treated at our hospital from January to December 2016 were randomly divided into the conventional method group(69 cases) and the modified method group (69 cases).Patients in the conventional method group were treated with lateral sphincterotomy,while patients in the modified method group were treated with modified longitudinal sphincterotomy with transverse suture.Outcomes of treatment,VAS scores,incision wound infection rates,postoperative voiding dysfunction rates and recurrence rates were compared.Results There was no significant difference in overall effectiveness between the modified method group (98.6％)and the conventional method group(94.2％) (x2=1.8677,P=0.1717).The rates of incision wound infection,moderate postoperative urinary retention and recurrence in the conventional method group(8.7％,42.0％ and 10.1 ％,respectively)were significantly higher than those in the modified methods group(0.0 ％,15.9 ％ and 0.0％,respectively) (x2 =4.3561,11.4061 and 5.4177,respectively,P =0.0369,0.0007 and 0.0199,respectively).At 12 hours after operation,favorable VAS scores and incision healing times were observed in the modified method group,compared with the conventional method group,and the differences were statistically significant(each P＜0.05).Conclusions Modified longitudinal sphincterotomy with transverse suture produces about the same overall effectiveness as does lateral sphincterotomy in the treatment of elderly patients with anal fissures,but it is superior in reducing incision wound infection,moderate postoperative voiding dysfunction,recurrence and pain intensity,and in promoting incision healing.

Objective:To evaluate the effects of intraarticular injection of bevacizumab、sodium hyalu-ronate (SH)and 0.9% sodium chloride injection in the treatment of osteoarthritis (OA)in a rabbit model.Methods:Twenty-four male rabbits were randomly divided into bevacizumab group,SH group and control group after the model of OA had been made.The bevacizumab group and control group received intraarticular bevacizumab (4 mg)and 0.9% saline injection respectively once per three weeks for 2 times.The SH group received intraarticular SH once a week for 6 weeks.After 6 weeks,the histological examinations of cartilage and synovium,electron microscopy and expression of vasculan endothelial growth factorl (VEGF),for the synovium,expression of MMP-1 ,Mankin’s scale,macroscopic observation for cartilage were performed.Results:The histological observation of the bevacizumab group and the SH group showed that bevacizumab could decrease the synoviocytes and inhibit fibrous hyperplasia in synovial underlayer compard with the control group.Reduced apoptosis of chondrocytes and more integrated struc-ture of matrix and more glycosaminoglycan were also found in the bevacizumab group and the SH group compared with control group.The expression of VEGF and MMP-1 ,Mankin’s scale,macroscopic obser-vation were significantly decreased in the bevacizumab group compared with the SH group and the control group (P<0.05).Conclusion:Intraarticular injection of bevacizumab and SH can relieve inflammation of OA and alleviate the pathologic process of OA.The Bevacizumab was better than the SH in therapeutic effect,which maybe implicate a better choice for the treatment of OA.

Objective To investigate the effecof arthroscopiminimally invasion fothe local excision of benign bone tumo.MethodEighpatientwith benign bone tumofrom Augus2011 to Decembe2012 were treated by arthroscopimini-mally invasive operation ,including 3 caseof osteochondrom,2 caseof bone cys,1 case of non-ossifying fibromand 2 caseof osteoid osteom.The lesion location wadetermined by the preoperative imaging dat,the arthroscope and plane cuttewere placed into the lesion arethe tumowaperformed the local lesion resection undethearthroscopimonitoring ,then the plasmwaadopt-ed to treathe resected wound surface of tumo,the bone defectwere implanted by allogeneibone .ResultEighcasewere re-covered well afteoperation .No postoperative complicationwere found .The approach incision ＜3 and the wound length ＜1 .5 cm .Two casewere filled with allogeneibone .There were no recurrence ,fracture odyfunction during the average follow up peri-odof 8-12 month.The postoperative X-ray showed thathe lesion wacompletely resected and the bone defeclesion wacom-pletely filled with allogeneibone .Conclusion The resection of deep benign bone tumoundethe arthroscopimonitoring can maximize to retain the local anatomistructure .

10.3969/j.issn.1007-3969.2013.04.008