BACKGROUND:Rheumatoid arthritis is influenced by complex genetic and environmental factors.Although observational studies have found some correlation between plasma proteins and rheumatoid arthritis,the susceptibility to confounding and reverse causation makes it difficult to clarify whether these proteins are pathogenic factors of rheumatoid arthritis.OBJECTIVE:To explore the potential of plasma proteins as biomarkers and therapeutic targets in rheumatoid arthritis through Mendelian randomization analysis of plasma proteins in the onset and progression of rheumatoid arthritis.METHODS:A large-scale two-sample Mendelian randomization analysis was conducted to comprehensively assess the causal relationships between 1 553 circulating proteins and rheumatoid arthritis based on the Decode database(developed by Decode Genetics in Iceland,which contains genomic data from the Icelandic population),the MR-Base platform(developed by a team of researchers at the University of Oxford in the United Kingdom,specifically designed to provide genetic and phenotypic data for Mendelian randomization analyses),and the GWAS Catalog platform(developed by the European Institute of Bioinformatics,which provides data for genome wide association studies worldwide).The causal effects were estimated using the Wald ratio and inverse variance weighting methods,with Bonferroni correction applied to control for false positives caused by multiple testing.To ensure the robustness of the results,sensitivity analyses were performed to validate the positive causal relationship between circulating proteins and rheumatoid arthritis,and Bayesian colocalization and phenome scanning were used to exclude confounding effects and horizontal pleiotropy.Additionally,external validation was carried out using new plasma protein datasets to reduce the likelihood of false discoveries.Finally,small-molecule compounds associated with candidate proteins were identified using the Drug Signatures Database(DsigDB),and molecular docking was performed to predict the binding patterns and energies between proteins and compounds,identifying the most stable and likely binding molecules and mechanisms.RESULTS AND CONCLUSION:(1)Sensitivity analyses,including Bayesian colocalization and phenome scanning,identified four plasma proteins with reliable causal relationships with rheumatoid arthritis:FCRL3,IL6R,ICOSLG,and TNFAIP3.Their genetic effects were estimated as follows:FCRL3[odds ratio(OR)=1.12,95％confidence interval(CI):1.07-1.17],IL6R(OR=0.94,95％CI:0.91-0.96),ICOSLG(OR=2.42,95％CI:1.67-3.52),and TNFAIP3(OR=2.19,95％CI:1.88-2.56).Furthermore,molecular docking analysis revealed that the small-molecule compound benzo[a]pyrene exhibited favorable binding with these candidate proteins,suggesting its potential as a therapeutic agent for rheumatoid arthritis.(2)This study provides a comprehensive analysis of the genetic causal relationships of FCRL3,IL6R,ICOSLG,and TNFAIP3 in rheumatoid arthritis.These proteins not only serve as potential molecular biomarkers for rheumatoid arthritis risk screening and disease prevention,but also offer key candidate targets for further understanding the pathogenic mechanisms of rheumatoid arthritis and developing targeted therapies.Although the study is based on European populations,its findings offer important insights for biomedical research in China.By incorporating Mendelian randomization methods to analyze genetic causality,future research on rheumatoid arthritis in the Chinese population could provide more accurate causal inferences,offering theoretical support for localized risk assessment and treatment strategies.

BACKGROUND:The long-term patency rate of synthetic blood vessels remains a significant challenge that requires urgent attention.Enhancing the anticoagulant performance of small-caliber artificial blood vessels is crucial in ensuring their long-term efficacy.OBJECTIVE:To investigate the anticoagulation activity of polycaprolactone/low molecular weight fucoidan nanofibers with shell core structure and determine the effect on the activity of human umbilical vein endothelial cells.METHODS:Polycaprolactone nanofiber membranes and polycaprolactone/low molecular weight fucoidan nanofiber membranes with polycaprolactone as shell layer and low molecular weight fucoidan as core layer were prepared by emulsion electrospinning method(the mass ratio of low molecular weight fucoidan to polycaprolactone was 10％,25％,40％,and 55％,respectively).The morphology and structure of the fibers were characterized by scanning electron microscopy,fluorescence microscopy,and infrared spectroscopy.The mechanical strength of the fiber membranes was detected by tensile test.The loading rate and sustained release rate of low molecular weight fucoidan in the nanofibers were detected by 1,9-dimethylmethylene blue dye.The anticoagulant properties of the fiber membranes were verified by hemolysis test,dynamic coagulation test,plasma recalcification test,and platelet adhesion test.The five fiber membranes were co-cultured with human umbilical vein endothelial cells.The cell proliferation was detected by CCK-8 assay and the cell morphology was observed by fluorescence microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscope showed that the surface of polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane was smooth,the fiber diameter was uniform,and there was no obvious beaded structure.With the increase of low molecular weight brown algae polysaccharide content in the fiber membrane,the diameter of the fiber membrane increased and the maximum tensile stress decreased,but it still met the mechanical properties requirements of small-caliber artificial blood vessels.Fluorescence images and infrared spectra confirmed that low molecular weight brown algae polysaccharide was successfully loaded into polycaprolactone nanofiber membrane,and the low molecular weight brown algae polysaccharide loaded in each group of fiber membranes was released suddenly within 12 hours and released at a relatively low rate after 48 hours.(2)Compared with polycaprolactone nanofiber membrane,polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane had better anticoagulant activity,among which the group with a mass ratio of low molecular weight brown algae polysaccharide to polycaprolactone of 25％had the best anticoagulant effect.All five fiber membranes supported the growth and proliferation of human umbilical vein endothelial cells without affecting cell morphology and had no obvious cytotoxicity.(3)The results show that the polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane has good anticoagulant function,blood compatibility,and cell compatibility.

BACKGROUND:Epidemiological studies indicate that individuals with neurodegenerative diseases exhibit a comparatively lower risk of developing the majority of cancers.Although the precise mechanisms underlying this inverse correlation remain unclear,it is noteworthy that aberrant glucose metabolism,a pathological factor common to both conditions,may significantly contribute to this association.OBJECTIVE:To review the potential relationship between cancers and neurodegenerative diseases in glucose metabolism.METHODS:PubMed was searched for relevant literature using the search terms of"cancer,neurodegenerative diseases,Alzheimer's disease,Parkinson's disease,metabolic reprogramming,glucose metabolism,aerobic glycolysis,neuroprotection,aging,"and 136 articles were finally included for analysis.RESULTS AND CONCLUSION:Cancer and neurodegenerative diseases exhibit a profound pathological correlation at the level of glucose metabolism imbalance associated with aging.Cancer cells promote uncontrolled proliferation,invasion,and metastasis through the persistent activation of aerobic glycolysis,whereas neurodegenerative diseases are characterized by a reduction in aerobic glycolysis.Restoring aerobic glycolysis may confer neuroprotective effects and delay disease progression.The key nodes of glucose metabolism demonstrate a bidirectional regulatory pattern:metabolic regulators,which are significantly upregulated or aberrantly activated in cancer,are inhibited or functionally inactivated in neurodegenerative diseases.Mitochondria play a crucial role in mediating the aging process through the regulation of reactive oxygen species homeostasis and mitochondrial autophagy.They establish regulatory networks that connect cancer and neurodegenerative diseases,and maintaining their functional homeostasis is of paramount importance for disease prevention and treatment.

BACKGROUND:Rheumatoid arthritis is influenced by complex genetic and environmental factors.Although observational studies have found some correlation between plasma proteins and rheumatoid arthritis,the susceptibility to confounding and reverse causation makes it difficult to clarify whether these proteins are pathogenic factors of rheumatoid arthritis.OBJECTIVE:To explore the potential of plasma proteins as biomarkers and therapeutic targets in rheumatoid arthritis through Mendelian randomization analysis of plasma proteins in the onset and progression of rheumatoid arthritis.METHODS:A large-scale two-sample Mendelian randomization analysis was conducted to comprehensively assess the causal relationships between 1 553 circulating proteins and rheumatoid arthritis based on the Decode database(developed by Decode Genetics in Iceland,which contains genomic data from the Icelandic population),the MR-Base platform(developed by a team of researchers at the University of Oxford in the United Kingdom,specifically designed to provide genetic and phenotypic data for Mendelian randomization analyses),and the GWAS Catalog platform(developed by the European Institute of Bioinformatics,which provides data for genome wide association studies worldwide).The causal effects were estimated using the Wald ratio and inverse variance weighting methods,with Bonferroni correction applied to control for false positives caused by multiple testing.To ensure the robustness of the results,sensitivity analyses were performed to validate the positive causal relationship between circulating proteins and rheumatoid arthritis,and Bayesian colocalization and phenome scanning were used to exclude confounding effects and horizontal pleiotropy.Additionally,external validation was carried out using new plasma protein datasets to reduce the likelihood of false discoveries.Finally,small-molecule compounds associated with candidate proteins were identified using the Drug Signatures Database(DsigDB),and molecular docking was performed to predict the binding patterns and energies between proteins and compounds,identifying the most stable and likely binding molecules and mechanisms.RESULTS AND CONCLUSION:(1)Sensitivity analyses,including Bayesian colocalization and phenome scanning,identified four plasma proteins with reliable causal relationships with rheumatoid arthritis:FCRL3,IL6R,ICOSLG,and TNFAIP3.Their genetic effects were estimated as follows:FCRL3[odds ratio(OR)=1.12,95％confidence interval(CI):1.07-1.17],IL6R(OR=0.94,95％CI:0.91-0.96),ICOSLG(OR=2.42,95％CI:1.67-3.52),and TNFAIP3(OR=2.19,95％CI:1.88-2.56).Furthermore,molecular docking analysis revealed that the small-molecule compound benzo[a]pyrene exhibited favorable binding with these candidate proteins,suggesting its potential as a therapeutic agent for rheumatoid arthritis.(2)This study provides a comprehensive analysis of the genetic causal relationships of FCRL3,IL6R,ICOSLG,and TNFAIP3 in rheumatoid arthritis.These proteins not only serve as potential molecular biomarkers for rheumatoid arthritis risk screening and disease prevention,but also offer key candidate targets for further understanding the pathogenic mechanisms of rheumatoid arthritis and developing targeted therapies.Although the study is based on European populations,its findings offer important insights for biomedical research in China.By incorporating Mendelian randomization methods to analyze genetic causality,future research on rheumatoid arthritis in the Chinese population could provide more accurate causal inferences,offering theoretical support for localized risk assessment and treatment strategies.

BACKGROUND:The long-term patency rate of synthetic blood vessels remains a significant challenge that requires urgent attention.Enhancing the anticoagulant performance of small-caliber artificial blood vessels is crucial in ensuring their long-term efficacy.OBJECTIVE:To investigate the anticoagulation activity of polycaprolactone/low molecular weight fucoidan nanofibers with shell core structure and determine the effect on the activity of human umbilical vein endothelial cells.METHODS:Polycaprolactone nanofiber membranes and polycaprolactone/low molecular weight fucoidan nanofiber membranes with polycaprolactone as shell layer and low molecular weight fucoidan as core layer were prepared by emulsion electrospinning method(the mass ratio of low molecular weight fucoidan to polycaprolactone was 10％,25％,40％,and 55％,respectively).The morphology and structure of the fibers were characterized by scanning electron microscopy,fluorescence microscopy,and infrared spectroscopy.The mechanical strength of the fiber membranes was detected by tensile test.The loading rate and sustained release rate of low molecular weight fucoidan in the nanofibers were detected by 1,9-dimethylmethylene blue dye.The anticoagulant properties of the fiber membranes were verified by hemolysis test,dynamic coagulation test,plasma recalcification test,and platelet adhesion test.The five fiber membranes were co-cultured with human umbilical vein endothelial cells.The cell proliferation was detected by CCK-8 assay and the cell morphology was observed by fluorescence microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscope showed that the surface of polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane was smooth,the fiber diameter was uniform,and there was no obvious beaded structure.With the increase of low molecular weight brown algae polysaccharide content in the fiber membrane,the diameter of the fiber membrane increased and the maximum tensile stress decreased,but it still met the mechanical properties requirements of small-caliber artificial blood vessels.Fluorescence images and infrared spectra confirmed that low molecular weight brown algae polysaccharide was successfully loaded into polycaprolactone nanofiber membrane,and the low molecular weight brown algae polysaccharide loaded in each group of fiber membranes was released suddenly within 12 hours and released at a relatively low rate after 48 hours.(2)Compared with polycaprolactone nanofiber membrane,polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane had better anticoagulant activity,among which the group with a mass ratio of low molecular weight brown algae polysaccharide to polycaprolactone of 25％had the best anticoagulant effect.All five fiber membranes supported the growth and proliferation of human umbilical vein endothelial cells without affecting cell morphology and had no obvious cytotoxicity.(3)The results show that the polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane has good anticoagulant function,blood compatibility,and cell compatibility.

BACKGROUND:Epidemiological studies indicate that individuals with neurodegenerative diseases exhibit a comparatively lower risk of developing the majority of cancers.Although the precise mechanisms underlying this inverse correlation remain unclear,it is noteworthy that aberrant glucose metabolism,a pathological factor common to both conditions,may significantly contribute to this association.OBJECTIVE:To review the potential relationship between cancers and neurodegenerative diseases in glucose metabolism.METHODS:PubMed was searched for relevant literature using the search terms of"cancer,neurodegenerative diseases,Alzheimer's disease,Parkinson's disease,metabolic reprogramming,glucose metabolism,aerobic glycolysis,neuroprotection,aging,"and 136 articles were finally included for analysis.RESULTS AND CONCLUSION:Cancer and neurodegenerative diseases exhibit a profound pathological correlation at the level of glucose metabolism imbalance associated with aging.Cancer cells promote uncontrolled proliferation,invasion,and metastasis through the persistent activation of aerobic glycolysis,whereas neurodegenerative diseases are characterized by a reduction in aerobic glycolysis.Restoring aerobic glycolysis may confer neuroprotective effects and delay disease progression.The key nodes of glucose metabolism demonstrate a bidirectional regulatory pattern:metabolic regulators,which are significantly upregulated or aberrantly activated in cancer,are inhibited or functionally inactivated in neurodegenerative diseases.Mitochondria play a crucial role in mediating the aging process through the regulation of reactive oxygen species homeostasis and mitochondrial autophagy.They establish regulatory networks that connect cancer and neurodegenerative diseases,and maintaining their functional homeostasis is of paramount importance for disease prevention and treatment.

Objective: To explore the effects of intergenerational parent-child separation on internalizing and externalizing behavioral problems among rural preschoolers aged 3-6 years, so as to provide empirical evidence for formulating targeted intervention strategies and blocking the intergenerational transmission of parent-child separation. Methods: From March to June, 2024, ten kindergartens were selected from rural areas of Nanling County, Wuhu City, Anhui Province, and 2 279 preschool children aged 3- 6 years, along with their fathers, mothers and primary caregivers, were recruited for survey by cluster convenient sampling method. Children s fathers and mothers reported their own childhood parent-child separation information separately. Information on the children s history of psychological and behavioral problems was reported by the primary caregivers. Information of internalizing and externalizing behavioral problems in preschool children was reported with Strengths and Difficulties Questionnaire (SDQ).The Chi square test was used to compare the differences in the detection rates of psychological and behavioral problems among children with different intergenerational continuity of parent-child separation. Binary Logistic regression model was applied to analyze the association between intergenerational continuity of parent-child separation and internalizing and externalizing behavioral problems in preschool children. Results: The detection rate of internalizing behavioral problems was 27.5% and externalizing behavioral problems was 19.1% among rural preschool children. There were significant differences in internalization behavior, externalization behavior, hyperactivity impulse and peer communication problems among preschool children in different types of parent-child separation groups( χ 2=14.29, 8.80, 17.26, 13.84, all P <0.05). Binary Logistic regression analysis showed that after adjusting for covariates such as children s gender, birth weight, and delivery mode, compared with children without separation, intergenerational continuity of parent-child separation group( OR =1.95), only child separation( OR =1.74) were associated with significant higher risk of conduct problems(both P ＜0.05). Parent-child separation intergenerational continuation groups( OR =1.68), only child separation( OR = 1.47) were associated with significant higher risk of peer problems(both P ＜0.05). Both types of parent-child separation experiences significantly increased the risk of children s prosocial behavior problems，among them, the intergenerational continuation group was 1.99 times that of the control group ( OR =1.99), and the childhood only separation group was 2.09 times that of the control group ( OR =2.09)(both P ＜0.05). Compared with children whose parents and children had no experience of parent-child separation, children in the intergenerational continuation group of parent-child separation had increased risks of both internalizing and externalizing behavior problems ( OR =1.53, 1.65, both P <0.05). Conclusion All types of parent-child separation are associated with internalizing and externalizing behavioral problems among rural children aged 3 to 6 years.

Objective: To explore the association between daytime outdoor physical activity (OPA) and oral health indicators among primary school students, aiming to provide evidence for developing oral health intervention strategies based on natural exposure. Methods: In October 2023, based on the "Tianchang Children s Light Exposure and Growth Development Cohort", 799 second and third grades children were recruited from two primary schools in Tianchang, Chuzhou City, Anhui Province. Physical activity intensity and light exposure were objectively monitored for 24 hours over 5 consecutive days using triaxial accelerometers synchronized with portable illuminance meters. Standardized oral examinations were performed to record dental caries, gingivitis, and malocclusion. Demographics, lifestyle variables, and household socioeconomic data were collected via questionnaires. Multiple linear regression (for the number of carious teeth) and Logistic regression (for gingivitis risk) were used to analyze the relationship between daytime outdoor moderate to vigorous physical activity (MVPA) and oral health outcomes. Results: The average daytime outdoor MVPA was (0.76±0.35)h, with (0.95±0.40)h on weekdays and (0.49±0.47)h on weekends. The detection rates for dental caries, gingivitis, and malocclusion were 31.0%, 4.6%, and 59.7%, respectively. Compared with children with good oral health, the duration of outdoor MVPA on school days was reduced in children with caries or gingivitis ( Z =-11.4, -5.01, both P <0.01). Multiple regression analysis showed that after adjusting for factors such as gender, age, body mass index, oral hygiene behaviors, an increase in daytime outdoor MVPA duration was associated with a decrease in the number of dental caries ( β=-0.64, 95%CI =-0.93 to -0.35) and a reduced risk of gingivitis ( OR= 0.58 , 95%CI =0.34-0.98) in primary school students (both P <0.05). The association was primarily observed on school days ( β=-0.72, 95%CI = -1.07 to -0.37; OR=0.42, 95%CI =0.21-0.85) (both P < 0.05). Conclusions Daytime outdoor MVPA on weekdays is significantly associated with a lower number of carious teeth and a reduced risk of gingivitis in primary school students. Increasing daytime outdoor activities on weekdays may serve as a promising and potential strategy for promoting children s oral health.

Objective: To analyze the epidemiological characteristics of varicella among nursery children in Shenzhen from 2015 to 2024, and to evaluate the impact of optimizing varicella vaccine (VarV) immunization strategies on varicella incidence. Methods: Varicella incidence data for nursery children in Shenzhen from 2015 to 2024 were obtained from the China Disease Prevention and Control Information System. The study period was divided into three phases:one dose self pay VarV (January 2015 to October 2017), two dose self pay VarV (November 2017 to October 2019), and two dose free VarV (November 2019 to December 2024). Interrupted time series (ITS) analysis was conducted to assess changes in the level and trend of varicella incidence associated with each phase of policy implementation. Results: A total of 27 517 varicella cases was reported among nursery children from 2015 to 2024, with an average annual incidence of 514.01/100 000. During the same period, 136 clustered outbreaks were reported in nursery institutions, involving a cumulative total of 1 091 cases. ITS analysis showed that during the self pay 1 dose stage, the varicella incidence among nursery children showed an upward trend, with an average monthly increase of 2.58/100 000 (95% CI =2.21/ 100 000 -2.95/100 000, P <0.01). After the implementation of the self pay 2 dose strategy, the incidence decreased, with a change in incidence of -26.12/100 000 (95% CI =-37.30/100 000 to -14.94/100 000) and a change in slope of -2.65/100 000 (95% CI = -3.38/100 000 to -1.93/100 000)(all P <0.01). After the implementation of the free 2 dose strategy, the incidence decreased further, with a change in incidence of -40.03/100 000 (95% CI =-50.39/100 000 to -29.66/100 000, P <0.01) and a change in slope of -0.56/100 000 (95% CI =-1.20/100 000-0.08/100 000, P =0.09). Conclusion The gradual optimization of the VarV vaccination strategy in Shenzhen from self pay 1 dose to free 2 dose has significantly reduced the varicella incidence among nursery children, demonstrating good short term control and long term intervention effectiveness.

Oculopharyngodistal myopathy （OPDM） is a hereditary neuromuscular disorder occurring in adolescence or early adulthood and is characterized by slowly progressive external ophthalmoplegia， facial muscle weakness， dysphagia， and distal limb weakness. This article reports a patient with OPDM type 4 who had the initial presentation of bilateral pyroptosis and external ophthalmoplegia and was misdiagnosed with thyrotoxic myopathy， and later the patient developed the clinical manifestations of bilateral masticatory and facial muscle weakness， bulbar paralysis， and limb weakness. Genetic testing revealed abnormal CGG repeat expansion in the RILPL1 gene. The clinical data of the patient was analyzed， and a literature review was performed， so as to improve the awareness of this condition among clinicians.