Objective To investigate the effect and mechanism of hypoxia inducible factor-1 α/aquaporin-4(HIF-1α/AQP4)pathway in high altitude cerebral edema(HACE)after blood-brain barrier injury in rats.Methods Adult male SD rats(n=40)were randomly divided into two groups:control group(Ctrl,n=20)and high altitude cerebral edema group(HACE,n=20).The rats in the control group were reared in Xining(altitude 2261 m)for 4 days,and the rats in HACE group were reared in low-pressure simulation chamber(altitude 5000 m)for 4 days.Brain water content was measured by the method of dry and wet weight.The intracranial structure,morphology and signal changes of small animals were observed through T2 weighted image of 7.0 T MRI.The morphological changes of neurons and the apoptosis of nerve cells in the CA1 region of hippocampal tissue were observed by the staining of Nissl and TUNEL.Immunohistochemical staining was performed to observe the extravasation of immunoglobulin G(IgG).The expressions of HIF-1α,AQP4,matrix metalloproteinase-9(MMP-9),claudin-5,occludin and zonula occludens-1(ZO-1)in the tissue of hippocampal were detected by the method of Western blotting and immunofluorescent staining.Results The brain water content increased significantly in the HACE group(P＜0.05).The neurons in CA1 region of hippocampal tissue were atrophic and deformed,the arrangement of neurons was disordered in the HACE group.The number of neurons decreased significantly,the apoptosis of nerve cells increased significantly,and the IgG exudates obviously in the CA1 region of hippocampal tissue in the HACE group.The expressions of HIF-1α,AQP4 and MMP-9 proteins increased significantly,while claudin-5,occludin and ZO-1 proteins decreased significantly in the CA1 region of hippocampal tissue,which detected by the method of Western blotting and immunofluorescent staining(P＜0.05).Conclusion Acute high-altitude hypoxia can induce to blood-brain barrier disruption through the HIF-1α/AQP4 pathway,resulting in high-altitude cerebral edema.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Hydroxyectoine, a vital compatible solute, is widely utilized in cosmetics, food, pharmaceutical industries, and biologics. However, the current microbial fermentation methods for hydroxyectoine production face challenges including insufficient precursor supply and low yields. Therefore, developing engineering microbial strains capable of efficiently synthesizing hydroxyectoine is of great significance. In this study, we first constructed a high-yield ectoine-producing strain ECT04 by multi-copy integration of the ectoine synthesis genes ectABC into the pseudogene loci of Escherichia coli MG1655(DE3), achieving an ectoine titer of 6.03 g/L. Subsequently, we employed plasmids with varying copy numbers to express ectD from Chromohalobacter salexigens to enable the conversion for hydroxyectoine production. We further investigated the effects of promoter, co-substrate ɑ-ketoglutarate, Fe²⁺ concentration, and dissolved oxygen on hydroxyectoine synthesis. Through fed-batch fermentation in a 7-L bioreactor, we significantly enhanced the hydroxyectoine production efficiency, attaining a final titer of 8.58 g/L and a productivity of 0.24 g/(L·h). This work successfully achieved the de novo synthesis of hydroxyectoine in E. coli, laying a foundation for the efficient bioproduction of this compound.
Escherichia coli/genetics* ; Fermentation ; Amino Acids, Diamino/biosynthesis* ; Bioreactors/microbiology* ; Metabolic Engineering/methods* ; Chromohalobacter/genetics* ; Plasmids/genetics*

Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.

Objective To systematically explore the characteristics of speech,language functioning and adaptation in children with intellectual and developmental disabilities(IDD)based on framework of International Classification of Function-ing,Disability and Health(ICF),to construct an integrated system that merges curricula and rehabilitation based on an analysis of the content and functional goals within language-related curriculum standards for Peizhi(spe-cial education for children with IDD)schools.Methods Using the bio-psycho-social model of the ICF,the characteristics of speech and communication disorders in children with IDD were systematically analyzed across the three dimensions of body functions and structures,ac-tivities and participation,and environmental factors.A content analysis was conducted on the three core curricu-lum standards for Peizhi schools issued by the Ministry of Education of China,extracting and summarizing the goals and core content related to linguistic ability development,which were then mapped and coded using the ICF classification system.Guided by the ICF's functioning-oriented principles,these curriculum goals were inte-grated with evidence-based rehabilitation strategies to construct a comprehensive curriculum and rehabilitation interventions that included assessment,goal setting,curriculum module design and intervention strategies.Results For the speech and language functioning in children with IDD,at the body functions level,impairments were identified in areas such as mental functions of language(b167)and articulation(b320);at the activities and partic-ipation level,limitations manifested as significant difficulties in communication(d3)and interpersonal interac-tions(d7);and environmental factors(e.g.,family support,e310;educational services,e585)impacted on func-tional performance and adaptation.Main curriculum standards of China related to language functioning for Pei-zhi schools addressed three domains respectively:body functions(Rehabilitation Training Curriculum Standard),communication skills[Living Language(Chinese)Curriculum Standard],and social participation and environ-ment(the Life Adaptation Curriculum Standard).Together,they constructed a standardized system for education-al curricula and rehabilitation interventions for children's speech and language functioning.Conclusion The speech therapy,the courses of Chinese language and adaptation are the complex and multidimensional processes.Based on the theoretical framework of the ICF's bio-psycho-social model,this study systematically in-tegrates China's Living Language(Chinese),Rehabilitation Training,and Life Adaptation curriculum standards to construct a speech rehabilitation program and a language ability curriculum oriented by the children's speech,lan-guage functioning and adaptation,which emphasizes a process beginning with functional assessment,grounded in real-life contexts,and actualized through interdisciplinary collaboration,to provide individualized,multimodal and evidence-based education,rehabilitation interventions and support for every child with special needs.By im-plementing the integrated rehabilitation interventions and language-related curriculum system,it enhances chil-dren's speech,language functioning and adaptation,promotes their functional communication,empowers their communication activities and social participation,and improves their social adaptation and overall development.

Designation of ideological and political teaching of Medical Immunology courses focuses on"cultivate talent for Party and the State",and adheres to goal of"build morality and cultivate people".From perspective of big ideology and politics,with basic foundation of"major guiding,disciplines supporting and curriculum shaping",principle of"six combinations"is applied to con-struct ideological and political cases of Medical Immunology courses,to create an infiltrating teaching pattern,which simultaneously cultivate talent for the Party and the State,and forms a synergistic effect of professional course learning and ideological and political learning.

Objective To systematically explore the characteristics of speech,language functioning and adaptation in children with intellectual and developmental disabilities(IDD)based on framework of International Classification of Function-ing,Disability and Health(ICF),to construct an integrated system that merges curricula and rehabilitation based on an analysis of the content and functional goals within language-related curriculum standards for Peizhi(spe-cial education for children with IDD)schools.Methods Using the bio-psycho-social model of the ICF,the characteristics of speech and communication disorders in children with IDD were systematically analyzed across the three dimensions of body functions and structures,ac-tivities and participation,and environmental factors.A content analysis was conducted on the three core curricu-lum standards for Peizhi schools issued by the Ministry of Education of China,extracting and summarizing the goals and core content related to linguistic ability development,which were then mapped and coded using the ICF classification system.Guided by the ICF's functioning-oriented principles,these curriculum goals were inte-grated with evidence-based rehabilitation strategies to construct a comprehensive curriculum and rehabilitation interventions that included assessment,goal setting,curriculum module design and intervention strategies.Results For the speech and language functioning in children with IDD,at the body functions level,impairments were identified in areas such as mental functions of language(b167)and articulation(b320);at the activities and partic-ipation level,limitations manifested as significant difficulties in communication(d3)and interpersonal interac-tions(d7);and environmental factors(e.g.,family support,e310;educational services,e585)impacted on func-tional performance and adaptation.Main curriculum standards of China related to language functioning for Pei-zhi schools addressed three domains respectively:body functions(Rehabilitation Training Curriculum Standard),communication skills[Living Language(Chinese)Curriculum Standard],and social participation and environ-ment(the Life Adaptation Curriculum Standard).Together,they constructed a standardized system for education-al curricula and rehabilitation interventions for children's speech and language functioning.Conclusion The speech therapy,the courses of Chinese language and adaptation are the complex and multidimensional processes.Based on the theoretical framework of the ICF's bio-psycho-social model,this study systematically in-tegrates China's Living Language(Chinese),Rehabilitation Training,and Life Adaptation curriculum standards to construct a speech rehabilitation program and a language ability curriculum oriented by the children's speech,lan-guage functioning and adaptation,which emphasizes a process beginning with functional assessment,grounded in real-life contexts,and actualized through interdisciplinary collaboration,to provide individualized,multimodal and evidence-based education,rehabilitation interventions and support for every child with special needs.By im-plementing the integrated rehabilitation interventions and language-related curriculum system,it enhances chil-dren's speech,language functioning and adaptation,promotes their functional communication,empowers their communication activities and social participation,and improves their social adaptation and overall development.

Designation of ideological and political teaching of Medical Immunology courses focuses on"cultivate talent for Party and the State",and adheres to goal of"build morality and cultivate people".From perspective of big ideology and politics,with basic foundation of"major guiding,disciplines supporting and curriculum shaping",principle of"six combinations"is applied to con-struct ideological and political cases of Medical Immunology courses,to create an infiltrating teaching pattern,which simultaneously cultivate talent for the Party and the State,and forms a synergistic effect of professional course learning and ideological and political learning.

Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.

OBJECTIVE To develop a questionnaire of the Knowledge-Attitude-Practice （KAP） for patients receiving oral anticoagulant therapy. METHODS Under the guidance of the theory of KAP， literature analysis and interview method were used to design the initial KAP questionnaire for patients treated with oral anticoagulants. Delphi method was adopted to consult the initial questionnaire and modify the questionnaire based on expert suggestions to form the final questionnaire. RESULTS Two rounds of consultation were conducted with 18 experts， and 18 questionnaires were sent out and recovered in each round， so the positive coefficient of experts was 100%. The expert authority coefficient was 0.94. The average importance scores for all dimensions， factors， and items of the questionnaire in both rounds were ≥4 points. The coefficient of variation was ≤0.25. The Kendall’s concordance coefficient for the overall questionnaire and the three dimensions of knowledge， attitude， and practice ranged from 0.09 to 0.34 （all P＜0.05）. Following the first round of expert consultation， four items were modified， two items were deleted， and five items were added； after the second round of expert consultation， ten items were modified. The final version of the questionnaire included three dimensions （knowledge， attitudes， and practice）， 17 questionnaire factors， and 40 items. CONCLUSIONS The questionnaire has high reliability and scientific validity with relatively concentrated expert opinions. It is suitable for assessing the knowledge， attitudes， and practice status of patients receiving oral anticoagulant therapy.