Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

ObjectiveWe conducted a drug resistance and homology analysis of diarrheagenic Escherichia coli （DEC） in Fengxian District of Shanghai in order to provide a basis for clinical rational drug use， risk monitoring and early warning. MethodsDEC were isolated from diarrheal patients in Fengxian District， Shanghai from 2019 to 2022. The minimum inhibitory concentrations （MIC） of 21 drugs to the DEC were determined. Genotyping and homology analysis were conducted with pulsed-field gel electrophoresis （PFGE）. ResultsThe DEC detection rate of diarrhea cases was 18.99% （131/690）， including enteroaggregative E.coli （EAEC） 64.89% （85/131）， enterotoxigenic E.coli （ETEC） 22.14% （29/131）， enteropathogenic E.coli （EPEC） 12.21% （16/131）， and enterohemorrhagic E.coli （EHEC） 0.76%（1/131）. The DEC detection showed obvious seasonal characteristics with a high incidence in summer. The DEC multidrug resistance rate was 66.41% with a total of 65 drug resistance profiles. The five antimicrobial drugs with the highest resistance rate were ampicillin （60.31%）， nalidixic acid （51.91%）， cefazolin （50.38%）， tetracycline （44.27%）， and cotrimoxazole （35.11%）. The rate of DEC resistance to levofloxacin was significantly increased from 2019 to 2022. Cluster analysis showed that the similarity of 85 EAEC cluster was 58.4%‒100.0%， and 69 band patterns were obtained. The similarity of 29 ETEC cluster was 58.5%‒100.0%， and 13 band patterns were obtained， including 2 dominant band types. The similarity of 16 EAEC clusters was 53.9%‒100.0%， and 15 band patterns were obtained. Five groups of homologous strains were found， consistent with the resistance phenotypes. ConclusionAmong the diarrhea cases， the DEC epidemic intensity is high， the drug resistance situation is severe， and the risk of outbreak infection is high in Fengxian District， Shanghai. Therefore， health monitoring and prevention need to be strengthened.

Non-muscle myosin heavy chain 9-related disease (MYH9-RD) is an autosomal dominant disease caused by the mutations of the MYH9 gene encoding the non-muscle mysoin heavy chain ⅡA and leads to abnormal accumulation of myosin in cells. These further causes functional disorders of the blood, eye, ear, kidney, and liver systems. MYH9-RD displays heterogeneous kidney involvement and outcomes, but doctors still lack understandings of the mechanism and treatment strategies, owing to difficulty of conducting renal biopsies. Here, we report a case of MYH9-RD with tail fragments heterozygous mutation, which renal pathology is presented as glomerular minor lesion. Moreover, we reviewed related relevant to strengthen clinical diagnosis and understanding of MYH9-RD.

Objective To investigate the health education needs and available resources in schistosomiasis-endemic areas based on integration of community resources, and to explore the operation pathways for health education and promotion during the stage of schistosomiasis elimination. Methods A community was selected from Nanji Township, Xinjian District, Nanchang City, Jiangxi Province around the Poyang Lake areas as the study site, and a questionnaire survey on health education needs for schistosomiasis control was conducted among permanent residents at ages of 20 years in the community during the period between June and July, 2022 using face-to-face interviews. In addition, the resources available for the community-based schistosomiasis control health education were investigated among workers in township-level specialized institutions, members of civil society organizations, villagers, teachers and high and primary school students through field observations, field surveys and thematic interviews. Results A total of 304 individuals participated in the questionnaire survey on community-based health education needs for schistosomiasis control, and 94.41% (287/304) and 93.42% (284/304) of the respondents were most interested in knowing/understanding knowledge of the morphology of schistosomes and knowledge associated with the transmission route of schistosomiasis. The four most popular patterns for disseminating schistosomiasis control knowledge included live broadcasting of schistosomiasis control videos (94.41%, 287/304), printed brochures (89.80%, 273/304), special lectures by doctors (62.50%, 190/304) and physical health education materials for schistosomiasis control (61.51%, 187/304). There were 96.71% (294/304) and 77.63% (236/304) of respondents that accepted the participation of township healthcare center and township government/village committees in dissemination of schistosomiasis control knowledge, and there were 95.72% (291/304) and 80.59% (245/304) of respondents that mainly acquired schistosomiasis control knowledge through village allocation of leaflets and volunteer schistosomiasis control activities, respectively. There was 96.71% (294/304) of respondents participating in the dissemination activities of schistosomiasis control knowledge held by village committees, township healthcare centers, and high and primary schools/kinder-gartens, and 61.25% (177/289) of respondents were willing to participate in volunteer schistosomiasis control activities. A total of 115 individuals participated in the survey of available resources for community-based schistosomiasis control health education, and there were a large number of organizational, human and cultural resources in the community that were useful for health communication services. Conclusions The abundant human and material resources from rural communities in schistosomiasis-endemic areas may be integrated into schistosomiasis control health education to generate a rural health education pathway with the joint participation of schistosomiasis control institutions, township governments, community departments and community residents, which may provide insights into the future development of schistosomiasis control health education.

Objective:To evaluate the safety and effectiveness for the treatment of totally robotic fundoplication.Methods:A retrospective analysis was conducted on the clinical data of 21 patients with gastroesophageal reflux disease (GERD) who underwent unassisted totally robotic fundoplication at the Second Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University from Aug 2023 to Jan 2024. The postoperative outcomes were evaluated using SF-36, GERD-Q, and NRS scoring indicators.Results:All 21 patients successfully underwent the surgery. The robotic surgery time was (99±41) minutes, with precise intraoperative anatomy and insignificant blood loss of (1.7±1.4) ml. There were no intraoperative or postoperative complications, and no conversions to open surgery . Postoperative recovery of bowel function was rapid (11.71±3.33) hours, with minimal postoperative pain (NRS score of 1.67±0.48).The postoperative hospital stay was short (3.86±2.90) days, and patient satisfaction was high, SF-36 score of (80.90±1.14);The symptoms of reflux after surgery was significantly reduced.Postoperative GERD-Q score of (4.38±1.69) significantly lower than the preoperative score of (13.90±2.07).Conclusion:Totally robotic fundoplication provides clear view of intraoperative anatomical structures, rapid postoperative recovery, minimal pain, and effective anti-reflux outcomes.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Objective:To explore the effect of teaching based on task-driven joint feedback mechanism on improving the quality and satisfaction of teaching practical nursing students in department of gynaecology and obstetrics.Methods:A total of 203 practical nursing students who had internship in the Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Hainan Medical University from June 2019 to June 2020 were selected as the research objects. They were divided into a control group ( n=96) and a study group ( n=107) according to the order of admission. The control group used traditional teaching, and the study group used task-driven joint feedback mechanism-based teaching. After the teaching, the teaching effect of the two groups of practical nursing students was evaluated through theoretical assessment, skill operation assessment and teaching satisfaction. SPSS 22.0 was used for t test and non-parametric rank sum test. Results:The theoretical assessment scores [(93.51±4.22) vs. (89.62±4.08)] and the total scores of the skill operation assessment [(93.20±4.14) vs. (82.06±3.82)] of the practical nursing students in the study group were better than those of the control group, and the difference was statistically significant ( P<0.05). The results of teaching satisfaction evaluation (teacher's ability and execution ability, teaching content and task design, teaching task completion, feedback mechanism execution and improvement after feedback) of the study group were better those of the control group, and the difference was statistically significant ( P<0.05). Conclusion:The teaching based on the task-driven joint feedback mechanism can effectively improve the teaching quality and teaching satisfaction of the practical nursing students in the department of obstetrics and gynecology.

Objective:To develop a neural network model for the evaluation of glomerular filtration rate (GFR) based on multilayer perceptual neural network, and to compare with the improved Chinese based creatinine GFR evaluation formula (C-GFR cr) and the evaluation formula (EPI-GFR cr) of the American Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for the clinical applicability of multilayer perceptual neural network model in evaluating GFR. Methods:A total of 684 chronic kidney disease (CKD) patients used for developing a modified version of China′s based creatinine GFR evaluation formula were taken as the research object. The data of 454 patients were randomly selected as the development group and the data of the other 230 patients were as the verification group. The multilayer perceptual neural network GFR evaluation model (M-GFR cr) was established. With the double plasma GFR as the reference value (rGFR), the correlation, mean difference, mean absolute difference, precision and accuracy of C-GFR cr, EPI-GFR cr and M-GFR cr were compared. Results:Among the 684 CKD patients, there were 352 males and 332 females, with age of (49.9±15.8) years. The correlation between M-GFR cr and rGFR was the highest (Pearson correlation =0.93, P<0.001). The mean difference of M-GFR cr was lower than that of C-GFR cr ( Z=9.929, P<0.001) and EPI-GFR cr ( Z=10.573, P<0.001). The mean absolute difference of M-GFR cr was also lower than that of C-GFR cr ( Z=3.953, P<0.001) and EPI-GFR cr ( Z=4.210, P<0.001). The accuracy of ±15% of M-GFR cr was higher than that of C-GFR cr ( χ2=26.068, P<0.001) and EPI-GFR cr ( χ2=23.154, P<0.001). The accuracy of ±30% of M-GFR cr was also higher than that of C-GFR cr ( χ2=8.264, P=0.001) and EPI-GFR cr ( χ2=11.963, P=0.001). The results of different stages of CKD showed that in the early stage of CKD (CKD 1-2), the mean difference of M-GFR cr was lower than that of C-GFR cr ( Z=7.401, P<0.001) and EPI-GFR cr ( Z=8.096, P<0.001); the mean absolute difference of M-GFR cr was also lower than that of C-GFR cr ( Z=4.723, P<0.001) and EPI-GFR cr ( Z=4.946, P<0.001); the accuracy of ±15% of M-GFR cr was higher than that of C-GFR cr ( χ2=23.547, P<0.001) and EPI-GFR cr ( χ2=26.421, P<0.001); the accuracy of ±30% of M-GFR cr was also higher than that of C-GFR cr ( χ2=12.089, P=0.001) and EPI-GFR cr ( χ2=16.168, P<0.001). But there was no significant difference in the applicability among C-GFR cr, EPI-GFR cr and M-GFR cr in the advanced stages of CKD (CKD 3-5). Conclusion:Compared with the improved Chinese based creatinine GFR evaluation formula C-GFR cr and CKD-EPI evaluation formula EPI-GFR cr, the accuracy of multilayer perceptual neural network model to evaluate GFR in CKD patients has been significantly improved, especially in CKD 1-2 stage.

Objective:To investigate the effect of electroporation-mediated local gene therapy on the expression of Wnt3a and β-catenin in callus of distraction gap during mandibular distraction osteogenesis of rabbits.Methods:The experiments were conducted in the laboratory of the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University from September 2019 to December 2019. Forty eight New-Zealand rabbits were randomly divided into control group (group A), gene therapy group (group B) and normal saline group (group C), with 16 rabbits in each group. After bilateral mandible osteotomy and distractors were implanted, the distractors were activated at a speed of 0.8 mm/d on 4th day, postoperatively, and lasted for 7 days, followed by consolidation period. Group A distracted only, group B was subject to local injection of recombinant plasmid pIRES-hBMP2-hVEGF165 in the distraction gap and electroporation stimulation at the beginning of activation distractors; and group C local injection of the same dose of normal saline in the distraction gap and electroporation stimulation at the beginning of activation distractors. Four animals in each group were sacrificed on the day at the end of distraction, 7th, 14th, 28th days of consolidation period, respectively. The callus in the distraction gap was taken for immunohistochemical staining and RT-PCR to detect the expression of Wnt3a and β-catenin, and image analysis was performed. SPSS 22.0 statistical software was used for data analysis.Results:Immunohistochemical staining showed that Wnt3a and β-catenin were mainly located in the cytoplasm and nuclei of fibroblasts, chondrocytes and osteoblasts in callus tissue. Immunohistochemistry and RT-PCR showed that the expression of Wnt3a and β-catenin reached a peak at the end of distraction. With the disappearance of distraction tension, the expression of Wnt3a and β-catenin gradually decreased. After gene therapy intervention, the expression of Wnt3a and β-catenin was significantly increased, and the expression of Wnt3a and β-catenin in group B was the highest at each time point, with statistically significant difference compared with groups A and C ( F=96.3, P<0.01). Conclusions:Gene therapy promotes the expression of Wnt3a and β-catenin in the callus of distraction gap, regulating the balance of the bone reconstruction system and thus promoting the formation of new bone in the distraction gap.

ObjectiveTo determine the drug resistance， main virulence genes and molecular typing of Vibrio parahaemolyticus from multiple sources in Fengxian District， Shanghai. MethodsA total of 210 strains of Vibrio parahaemolyticus were isolated in Fengxian District， Shanghai， from 2018 to 2020. Then drug susceptibility tests of 17 antibiotics， virulence gene detection of thermolabilehemolysin （tlh）， thermostable direct hemolysin （tdh） and thermostable direct hemolysin-relatedhemolysin （trh）， and pulsed-field gel electrophoresis （PFGE） were conducted. ResultsA total of 147 drug-resistant strains were detected， with the drug resistance of 70.00%. Among them， 126 strains were resistant to single antibiotic， mainly resistant to CFZ； 15 strains were resistant to two antibiotics， mainly resistant to CFZ and AMP； and 6 strains of MDR， mainly resistant to AMP， SXT， CFZ， CTX， CAZ and FEP. The AMP resistance of food-borne strains was higher than that of human-derived strains （P<0.05）. All 210 strains of Vibrio parahaemolyticus carried the virulence gene tlh. Furthermore， 84 human-derived strains carried tdh （89.29%） and trh （7.14%）. In contrast， 126 food-borne strains carried trh （1.59%）， while did not carry tdh. In additionally， 173 band patterns were determined by PFGE， sharing the similarity of 48.80%‒100.00%， among which major clones were prevalent. ConclusionVibrio parahaemolyticus in Fengxian District has multi-drug resistance， especially the resistance to β-lactam antibiotics. The prevalence of virulence gene remains high in human-derived strains. Furthermore， major clones are prevalent in human-derived strains， though the PFGE banding patterns are generally diverse. Due to high risk of food-borne diseases， this study warrants strengthening the prevention and control against Vibrio parahaemolyticus.