Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

BACKGROUND:Osteoporosis is a significant contributor to the global burden of disease and disability.Plasma proteins are involved in complex biological processes and play a crucial role in uncovering disease mechanisms and identifying potential therapeutic targets.Although existing studies have suggested an association between plasma proteins and osteoporosis,the causal nature of these associations is not fully clarified.Therefore,it is imperative to identify the causal proteins associated with osteoporosis and potential therapeutic targets for the amelioration and management of this condition using large-scale plasma protein data.OBJECTIVE:To evaluate the causal relationship between plasma proteins and osteoporosis based on the UK Biobank database as source information using the two-sample Mendelian randomization.METHODS:A total of 1 001 plasma protein-related genome-wide significant quantitative trait loci(P<5×10-8)were obtained from the UK Biobank database and used as instrumental variables,with linkage disequilibrium excluded.Summary data on osteoporosis were collected from the FinnGen database,which included 438 872 individuals of European descent.The study was analyzed using inverse variance weighting,MR-Egger regression,weighted median,and several sensitivity analyses to ensure the robustness of the results.Further,a protein-protein interaction network was constructed,and Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to explore the functional relevance and potential mechanisms of plasma proteins.RESULTS AND CONCLUSION:(1)The Mendelian randomization analysis using the inverse variance weighted method identified 50 plasma proteins that have causal associations with osteoporosis(P<0.05).Among them,20 plasma proteins,including chromosome 19 open reading frame 12(odds ratio[OR]=0.610;95%confidence interval[CI]:0.483-0.769,P=2.967×10-5)and epidermal growth factor(EGF;OR=0.877;95%CI:0.770-0.999,P=0.049),might be associated with a reduced risk of osteoporosis.In contrast,30 plasma proteins,such as C-C motif chemokine ligand(CCL)18(OR=1.091;95%CI:1.037-1.147,P=0.001)and CD209(OR=1.036;95%CI:1.003-1.070,P=0.034),might be associated with an increased risk of osteoporosis.After Bonferroni correction,only chromosome 19 open reading frame 12 showed a significant causal association with osteoporosis.(2)Multiple sensitivity analyses revealed no evidence of pleiotropy or heterogeneity,indicating the robustness of the results.(3)The construction of the PPI network identified core proteins such as EGF,CCL5,C-X-C motif chemokine ligand(CXCL)13,CXCL5,vascular endothelial growth factor C,CCL17,CCL18,TEK receptor tyrosine kinase,tyrosine kinase with immunoglobulin like and EGF like domains 1,and CCL23.(4)Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that these plasma proteins play essential roles in the immune system,influencing osteoporosis through processes such as signal transduction,cell migration,and chemotaxis.(5)This study reveals the potential causal associations between 1 001 plasma proteins and osteoporosis,highlighting the utility of a large-scale,data-driven approach to identify new biomarkers and drug targets in diverse populations.Additionally,our findings suggest that processes such as immune signaling,cell migration,and chemotaxis play significant roles in the pathogenesis of osteoporosis,offering new directions for research under specific genetic backgrounds and environmental factors.Finally,the core proteins identified in this study(e.g.,EGF,CCL5,and CXCL13)may serve as novel biomarkers or therapeutic targets,providing a new basis for the precise prevention and treatment of osteoporosis.

Objective:To formulate the Guidelines for the Construction of Community Health Service Centers in Pudong New Area, Shanghai. Methods:This was a qualitative study. This study was divided into 2 stages. The first stage of the study was conducted from June to August 2023 and involved the heads of the General Affairs Departments of the 47 community health service centers in Pudong New Area. These individuals completed online questionnaires to compile a database on the current status of matching supply and demand resources in community health service centers in Pudong New Area. The second stage of the study run from September 2023 to August 2024. Firstly, the functional modules of China′s community health service centers would be clarified through a literature review. The construction scale and design requirements of similar institutions at home and abroad would be benchmarked, as well as practical experience. The results of Phase 1 research would then be combined to form the " Community Health Service Center Infrastructure Configuration Requirements and Design Suggestions (Draft)". Then, relevant experts were brought together to discuss the draft and form the " Community Health Service Center Infrastructure Configuration Requirements and Design Recommendations (Revised Version)". The experts involved in the discussion specialized in the study of infrastructure resource allocation for medical institutions. Finally, the medical and healthcare system managers, community health service center users, and relevant commissions and bureaus of Pudong New Area were consulted to further revise and finalize the Guidelines for the Construction of Community Health Service Centers in Pudong New Area, Shanghai. Results:The total floor area of community health service centers in Pudong New Area was 57% (31/55), the number of beds per 1 000 people was 14% (8/55), and the total number of beds was 10% (6/60). These figures showed that urgent upgrades and construction in accordance with the new standards were required. The final " Guidelines for the Construction of Community Health Service Centers" of Shanghai Pudong New Area comprised 15 chapters, covering topics from the macro construction scale, site selection and general plan to architectural design, structural design, water supply and sewage treatment, ventilation and air conditioning, electrical systems, informatics, medical gas supply, indoor design, signage, marking and fire protection, etc. The guidelines have been revised to incorporate the functional design of the 5 basic rooms, with a particular focus on the creating humanistic spaces and promoting digitalization. Particular attention was paid to creating humanistic spaces and improving ageing with digital applications. Conclusions:The Guidelines for the Construction of Community Health Service Centers in Pudong New Area of Shanghai have been successfully formulated. These guidelines can be used to guide the subsequent high-quality and standardized development of community health service centers.

Objective With the development of manned space missions to the moon and space exploration,extravehicular activities become more frequent and extravehicular mission become more complex,which puts forward higher requirements for the extravehicular spacesuit.In order to ensure the ergonomics of spacesuit,the flexible joints are usually adopted in the limbs of spacesuit.The structural design of large angle of movement and low resistance joints is the basic for ensuring the ergonomics of spacesuit.Methods This study established a method of spacesuit joint structure to analysis the motion characteristic of typical joints.Firstly,the structure and activity characteristics of the spacesuit and lunar space suits were comprehensively analyzed,and the activity characteristics of different typical structure are qualitatively analyzed based on existing empirical method.Then,the dynamics of typical structure was analyzed by finite element model.By studying the change trend of motion of spacesuit joint with motion angle,and the motion characteristic curve was obtained.Finally,the model was studied according to different structural size parameters.The influence of structural parameters on the motion characteristics was analyzed,and the curves was obtained to provide a basis for design of spacesuit motion joint structure.Results Through the above analysis,the motion characteristics of different typical structure are obtained qualitatively.And the influence of different structure parameters on the motion characteristics was analyzed.This establishes the method basis for structure design.Conclusion The study was carried out a method based on finite element model for joint motion analysis,which is suitable for the design of typical joint structure of spacesuit.

Objective The effect of lunar dust adhesion performance by fiber surface characteristics were investigated for the lunar dust adhesion mitigation of spacesuits.Methods In this research,an adhesion test method under ultraviolet ray radiation in vacuum was developed to measure the adhesion quantity of simulated lunar dust on fiber materials.Based on the microscopic image of the fiber sample after test,the influence of conductive and surface energy characteristics of the fiber materials on the lunar dust adhesion performance was studied.Results The simulated lunar dust were activated under ultraviolet ray radiation,which induced an increase of the adhesion quantity of simulated lunar dust on fiber materials;Lower surface energy or higher conductive characteristics of the fiber was both beneficial to reduce the adhesion quantity of simulated lunar dust.Conclusion The static electric forces were likely to be the major forces between the fiber and the lunar dust under ultraviolet ray radiation in vacuum.In addition to reducing surface energy,improving conductive characteristics of the fiber was more beneficial to reduce the adhesion quantity of simulated lunar dust.

Objective: To examine the associations between peer bullying and parental phubbing with executive function and their combined effect among primary and secondary school students, so as to provide scientific evidence for promoting healthy development of executive function among primary and secondary school students. Methods: In November 2024, a combining convenience with clustering method was used to select 3 547 primary and secondary school students in Shenzhen City. The Chinese versions of the Delaware Bullying Victimization Scale-Student (DBVS-S), the Parental Phubbing Scale (PPS), and the Teenage Executive Functioning Inventory (TEXI) were used to assess peer bullying, parental phubbing, and executive function, respectively. Generalized linear regression models were applied to analyze the associations of peer bullying and parental phubbing with executive function, and to assess their joint effects. Subgroup analyses were performed by ages and genders, and multiplicative interaction terms were used to test for interactions. Results: The score for peer bullying among primary and secondary school students was (15.27± 5.67 ), with verbal bullying, physical bullying, and relational bullying scores being (5.64±2.77) (4.70±1.62) (4.93±2.07), respectively. The score for parental phubbing was (13.98±5.00). Executive function score was (47.35±15.89), while inhibitory control and working memory scores were (26.44±9.00) (20.91±7.49), respectively. After adjusting for confounding factors such as age, gender, self reported family relationship, self reported family economic status, parental education level, both peer bullying ( β= 0.75, 95%CI =0.67-0.84), verbal bullying( β=1.41, 95%CI =1.23-1.58), physical bullying ( β=2.18, 95%CI =1.87- 2.49 ), relational bullying ( β=1.78, 95%CI =1.54-2.01) and parental phubbing ( β=0.88, 95%CI =0.79-0.98) were significantly positively associated with the degree of executive function impairment (all P <0.01). Joint effect analysis showed that, compared with the "no bullying low phubbing" group, the total executive function scores in other combined exposure groups were all higher ( β = 6.78-15.96, all P <0.01). Among them, the "bullying high phubbing" group exhibited the highest level of executive function impairment ( β=14.17, 95%CI=12.61-15.73, P <0.01). Subgroup analysis indicated significant interactions between verbal bullying and age on total executive function, inhibitory control, and working memory (all P interaction <0.01). The association of verbal bullying with executive function was slightly higher in primary and secondary school students younger than 13 years ( β=1.80, 95%CI = 1.45-2.16) than in those aged 13 years or older ( β=1.25, 95%CI =1.05-1.45) (both P <0.01). Other types of bullying and parental phone neglect showed no statistically significant interaction with age or gender in executive function, inhibitory control, and working memory(all P interaction >0.05). Conclusion Both peer bullying and parental phubbing are significantly associated with impaired executive function among primary and secondary school students, and there is a combined effect between them; among these, the association between verbal bullying and executive function impairment in younger primary and secondary school students is more pronounced.

Glioblastoma multiforme(GBM)is a grade 4 glioma with the highest malignancy and invasiveness in the central nervous system,accounting for approximately 30％of all tumors in the central nervous system.Due to the unclear pathogenesis of GBM,there is currently no specific target for the treatment of GBM.Temozolomide(TMZ)is the only first-line chemotherapeutic drug for the treatment of GBM,but suffers from a low drug response rate and high susceptibility to drug resistance.Therefore,the development of new targets and novel GBM therapeutic agents is an urgent clinical problem.Pentraxin 3(PTX3),a member of the pentameric protein superfamily,has been shown to have a promotive effect on a variety of tumors.Increasing evidences showed that PTX3 played a crucial role in the progression of GBM.PTX3 can promote the proliferation,migration and invasion ability of GBM cells,increase the angiogenesis ability in the GBM microenvironment and malignant progression of GBM.In the article,the structure,physiological function,expression regulation,role and mechanism of PTX3 in GBM were mainly reviewed,with a view to provide guidance for PTX3 as a potential drug target for the treatment of GBM.

BACKGROUND:Osteoporosis is a significant contributor to the global burden of disease and disability.Plasma proteins are involved in complex biological processes and play a crucial role in uncovering disease mechanisms and identifying potential therapeutic targets.Although existing studies have suggested an association between plasma proteins and osteoporosis,the causal nature of these associations is not fully clarified.Therefore,it is imperative to identify the causal proteins associated with osteoporosis and potential therapeutic targets for the amelioration and management of this condition using large-scale plasma protein data.OBJECTIVE:To evaluate the causal relationship between plasma proteins and osteoporosis based on the UK Biobank database as source information using the two-sample Mendelian randomization.METHODS:A total of 1 001 plasma protein-related genome-wide significant quantitative trait loci(P<5×10-8)were obtained from the UK Biobank database and used as instrumental variables,with linkage disequilibrium excluded.Summary data on osteoporosis were collected from the FinnGen database,which included 438 872 individuals of European descent.The study was analyzed using inverse variance weighting,MR-Egger regression,weighted median,and several sensitivity analyses to ensure the robustness of the results.Further,a protein-protein interaction network was constructed,and Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to explore the functional relevance and potential mechanisms of plasma proteins.RESULTS AND CONCLUSION:(1)The Mendelian randomization analysis using the inverse variance weighted method identified 50 plasma proteins that have causal associations with osteoporosis(P<0.05).Among them,20 plasma proteins,including chromosome 19 open reading frame 12(odds ratio[OR]=0.610;95%confidence interval[CI]:0.483-0.769,P=2.967×10-5)and epidermal growth factor(EGF;OR=0.877;95%CI:0.770-0.999,P=0.049),might be associated with a reduced risk of osteoporosis.In contrast,30 plasma proteins,such as C-C motif chemokine ligand(CCL)18(OR=1.091;95%CI:1.037-1.147,P=0.001)and CD209(OR=1.036;95%CI:1.003-1.070,P=0.034),might be associated with an increased risk of osteoporosis.After Bonferroni correction,only chromosome 19 open reading frame 12 showed a significant causal association with osteoporosis.(2)Multiple sensitivity analyses revealed no evidence of pleiotropy or heterogeneity,indicating the robustness of the results.(3)The construction of the PPI network identified core proteins such as EGF,CCL5,C-X-C motif chemokine ligand(CXCL)13,CXCL5,vascular endothelial growth factor C,CCL17,CCL18,TEK receptor tyrosine kinase,tyrosine kinase with immunoglobulin like and EGF like domains 1,and CCL23.(4)Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that these plasma proteins play essential roles in the immune system,influencing osteoporosis through processes such as signal transduction,cell migration,and chemotaxis.(5)This study reveals the potential causal associations between 1 001 plasma proteins and osteoporosis,highlighting the utility of a large-scale,data-driven approach to identify new biomarkers and drug targets in diverse populations.Additionally,our findings suggest that processes such as immune signaling,cell migration,and chemotaxis play significant roles in the pathogenesis of osteoporosis,offering new directions for research under specific genetic backgrounds and environmental factors.Finally,the core proteins identified in this study(e.g.,EGF,CCL5,and CXCL13)may serve as novel biomarkers or therapeutic targets,providing a new basis for the precise prevention and treatment of osteoporosis.

Glioblastoma multiforme(GBM)is a grade 4 glioma with the highest malignancy and invasiveness in the central nervous system,accounting for approximately 30％of all tumors in the central nervous system.Due to the unclear pathogenesis of GBM,there is currently no specific target for the treatment of GBM.Temozolomide(TMZ)is the only first-line chemotherapeutic drug for the treatment of GBM,but suffers from a low drug response rate and high susceptibility to drug resistance.Therefore,the development of new targets and novel GBM therapeutic agents is an urgent clinical problem.Pentraxin 3(PTX3),a member of the pentameric protein superfamily,has been shown to have a promotive effect on a variety of tumors.Increasing evidences showed that PTX3 played a crucial role in the progression of GBM.PTX3 can promote the proliferation,migration and invasion ability of GBM cells,increase the angiogenesis ability in the GBM microenvironment and malignant progression of GBM.In the article,the structure,physiological function,expression regulation,role and mechanism of PTX3 in GBM were mainly reviewed,with a view to provide guidance for PTX3 as a potential drug target for the treatment of GBM.

Objective:To formulate the Guidelines for the Construction of Community Health Service Centers in Pudong New Area, Shanghai. Methods:This was a qualitative study. This study was divided into 2 stages. The first stage of the study was conducted from June to August 2023 and involved the heads of the General Affairs Departments of the 47 community health service centers in Pudong New Area. These individuals completed online questionnaires to compile a database on the current status of matching supply and demand resources in community health service centers in Pudong New Area. The second stage of the study run from September 2023 to August 2024. Firstly, the functional modules of China′s community health service centers would be clarified through a literature review. The construction scale and design requirements of similar institutions at home and abroad would be benchmarked, as well as practical experience. The results of Phase 1 research would then be combined to form the " Community Health Service Center Infrastructure Configuration Requirements and Design Suggestions (Draft)". Then, relevant experts were brought together to discuss the draft and form the " Community Health Service Center Infrastructure Configuration Requirements and Design Recommendations (Revised Version)". The experts involved in the discussion specialized in the study of infrastructure resource allocation for medical institutions. Finally, the medical and healthcare system managers, community health service center users, and relevant commissions and bureaus of Pudong New Area were consulted to further revise and finalize the Guidelines for the Construction of Community Health Service Centers in Pudong New Area, Shanghai. Results:The total floor area of community health service centers in Pudong New Area was 57% (31/55), the number of beds per 1 000 people was 14% (8/55), and the total number of beds was 10% (6/60). These figures showed that urgent upgrades and construction in accordance with the new standards were required. The final " Guidelines for the Construction of Community Health Service Centers" of Shanghai Pudong New Area comprised 15 chapters, covering topics from the macro construction scale, site selection and general plan to architectural design, structural design, water supply and sewage treatment, ventilation and air conditioning, electrical systems, informatics, medical gas supply, indoor design, signage, marking and fire protection, etc. The guidelines have been revised to incorporate the functional design of the 5 basic rooms, with a particular focus on the creating humanistic spaces and promoting digitalization. Particular attention was paid to creating humanistic spaces and improving ageing with digital applications. Conclusions:The Guidelines for the Construction of Community Health Service Centers in Pudong New Area of Shanghai have been successfully formulated. These guidelines can be used to guide the subsequent high-quality and standardized development of community health service centers.