Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Objective:To characterize the epidemiology of respiratory syndrome across healthcare facilities of different types and tiers in Beijing City, to compare pathogen-testing modalities and their associations with adverse outcomes, and to identify key factors associated with progression to severe illness, thereby informing regional prevention, control, and clinical optimization.Methods:The multicenter observational cohort study was performed using outpatient and emergency department data from five sentinel hospitals in Beijing (Beijing Xiaotangshan Hospital, Beijing Chaoyang District Shuangqiao Hospital, Beijing Haidian Hospital, Beijing You′an Hospital, Capital Medical University (Beijing You′an Hospital), and Beijing Ditan Hospital, Capital Medical University (Beijing Ditan Hospital)) from October 1st, 2023 to April 9th, 2025. Dual-target (two-plex) and triple-target (three-plex) respiratory specimens were collected. Demographic characteristics, visit information, pathogen-testing modalities and results were collected, and the epidemiologic features of patients who progressed to severe illness between the influenza high-incidence season (December to May) and the non-influenza season (June to November) were compared. Categorical variables were analyzed using the chi-square test. Multivariable logistic regression was used to estimate associations between covariates and risk of progression to severe illness.Results:Among the 192 131 cases, patients visited at Beijing You′an Hospital were concentrated in the 16 to 44 year age group, accounting for 66.79%(32 532/48 708). Beijing Xiaotangshan Hospital had a broad age distribution, with older adults comprising up to 22.35% (885/3 960). Of the 47 349 respiratory specimens across the five hospitals, Beijing You′an Hospital had the highest positivity rate for dual-target testing (46.76%(1 585/3 390)), while Beijing Haidian Hospital conducted the largest number of this tests ( n=12 514). For triple-target testing, Beijing You′an Hospital again had the highest positivity rate (45.03%(2 835/6 296)), whereas Beijing Ditan Hospital tested the most specimens ( n=12 011; positivity rate was 29.73%(3 571/12 011)). The influenza season within the same period (November 2023 to January 2024) exhibited a bimodal pattern, with alternating circulation of influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among 32 744 outpatients/emergency patients who progressed to severe illness, significant seasonal differences were observed by sex, age, comorbidity status, and infection type ( χ2=6.60, 189.24, 32.71 and 189.99, respectively; all P<0.05). After adjustment for sex, age group, comorbidities, and infection type, testing modality remained significantly associated with risk of progression (dual-target testing, odds ratio ( OR)=0.116, 95% confidence interval ( CI) 0.111 to 0.122, P<0.001); no testing, OR=0.063, 95% CI 0.060 to 0.065, P<0.001). Conclusions:The epidemiological pattern of respiratory pathogens undergo significant changes after October 2023, which is characterized by alternating waves of influenza viruses and SARS-CoV-2 with pronounced seasonality and diversity. Substantial inter-hospital differences are observed in testing modalities and positivity rates. Risk of progression to severe illness varies significantly by sex, age, comorbidity burden, and infection type, and is closely associated with the testing modality. These findings support strengthening multiplex pathogen testing and targeted surveillance of high-risk groups to improve early identification and precise control of febrile-respiratory syndromes.

Objective:To characterize the epidemiology of respiratory syndrome across healthcare facilities of different types and tiers in Beijing City, to compare pathogen-testing modalities and their associations with adverse outcomes, and to identify key factors associated with progression to severe illness, thereby informing regional prevention, control, and clinical optimization.Methods:The multicenter observational cohort study was performed using outpatient and emergency department data from five sentinel hospitals in Beijing (Beijing Xiaotangshan Hospital, Beijing Chaoyang District Shuangqiao Hospital, Beijing Haidian Hospital, Beijing You′an Hospital, Capital Medical University (Beijing You′an Hospital), and Beijing Ditan Hospital, Capital Medical University (Beijing Ditan Hospital)) from October 1st, 2023 to April 9th, 2025. Dual-target (two-plex) and triple-target (three-plex) respiratory specimens were collected. Demographic characteristics, visit information, pathogen-testing modalities and results were collected, and the epidemiologic features of patients who progressed to severe illness between the influenza high-incidence season (December to May) and the non-influenza season (June to November) were compared. Categorical variables were analyzed using the chi-square test. Multivariable logistic regression was used to estimate associations between covariates and risk of progression to severe illness.Results:Among the 192 131 cases, patients visited at Beijing You′an Hospital were concentrated in the 16 to 44 year age group, accounting for 66.79%(32 532/48 708). Beijing Xiaotangshan Hospital had a broad age distribution, with older adults comprising up to 22.35% (885/3 960). Of the 47 349 respiratory specimens across the five hospitals, Beijing You′an Hospital had the highest positivity rate for dual-target testing (46.76%(1 585/3 390)), while Beijing Haidian Hospital conducted the largest number of this tests ( n=12 514). For triple-target testing, Beijing You′an Hospital again had the highest positivity rate (45.03%(2 835/6 296)), whereas Beijing Ditan Hospital tested the most specimens ( n=12 011; positivity rate was 29.73%(3 571/12 011)). The influenza season within the same period (November 2023 to January 2024) exhibited a bimodal pattern, with alternating circulation of influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among 32 744 outpatients/emergency patients who progressed to severe illness, significant seasonal differences were observed by sex, age, comorbidity status, and infection type ( χ2=6.60, 189.24, 32.71 and 189.99, respectively; all P<0.05). After adjustment for sex, age group, comorbidities, and infection type, testing modality remained significantly associated with risk of progression (dual-target testing, odds ratio ( OR)=0.116, 95% confidence interval ( CI) 0.111 to 0.122, P<0.001); no testing, OR=0.063, 95% CI 0.060 to 0.065, P<0.001). Conclusions:The epidemiological pattern of respiratory pathogens undergo significant changes after October 2023, which is characterized by alternating waves of influenza viruses and SARS-CoV-2 with pronounced seasonality and diversity. Substantial inter-hospital differences are observed in testing modalities and positivity rates. Risk of progression to severe illness varies significantly by sex, age, comorbidity burden, and infection type, and is closely associated with the testing modality. These findings support strengthening multiplex pathogen testing and targeted surveillance of high-risk groups to improve early identification and precise control of febrile-respiratory syndromes.

Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by＞99％in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P＜0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.

ObjectiveTo systematically analyze international disability data policies and standards, as well as the application of disability data in policymaking, service optimization and inclusive social development, and to clarify the importance of international disability data policies, standard systems and disability data application for the development of disability-related services. MethodsThrough the analysis of policy content and research on the data standard system, this study explored the disability data policy framework, standard system and technical path of data interoperability and integration of international organizations including the United Nations (United Nations Statistics Division and United Nations Children's Fund), World Health Orgnization, United Nations Educational Scientific and Cultural Organization, and International Labour Organization. ResultsInternational organizations established disability data policy frameworks based on their respective mandates, involving data and service development, data standards, data governance, and data application. The international community established a disability data standard system for disability data collection, coding, exchange, interoperability, statistical analysis, data fusion and application. Building a standardized disability data standard system based on the framework of international health classification standards such as International Classification of Functioning, Disability and Health, and International Classification of Diseases, Eleventh Revision would ensure the consistency of cross-national disability data policies, and the interoperability and comparability of disability data, promoting the development of data-driven disability-related services, accurately identifying the service needs of people with disabilities, and optimizing service provision, thereby improving the quality of life and social participation of people with disabilities. ConclusionThe construction and implementation of international disability data policies and data standards have promoted the standardization and interoperability of disability data. With the application of big data, artificial intelligence and blockchain technologies in disability data, international cooperation and cross-industry data fusion in the field of disability data have been promoted, further promoting the development of data-driven disability services, ensuring equal opportunities for people with disabilities to enjoy service resources, and improving the coverage and quality of disability services.

Objective:To observe the incidence of retinopathy of prematurity (ROP) at different altitudes in Yunnan Province.Methods:A retrospective case-control study. From July 1, 2010 to June 30, 2019, 1 352 premature infants (Kunming group) and 579 premature (Dehong group) infants who received ROP screening in the Neonatology Department of Kunming Maternal and Child Health Hospital and the Neonatology Department of Dehong Dai and Jingpo Autonomous Prefecture People's Hospital were included in the study. A wide field digital retinal imaging system combined with binocular indirect ophthalmoscope and scleral oppressor was used for fundus examination. Inspection results were recorded according to the international ROP classification. The incidence of ROP in recent 10 years was retrospectively analyzed. Independent sample t test was used for comparison between groups. Results:Among the 1 352 preterm infants in Kunming group, 716 were males and 636 were females. The birth weight was (1 765.75±357.64) g; gestational age of birth were (32.51±2.07) weeks. The altitude of the residence was (1 920±30) m. Among 579 premature infants in Dehong group, 302 were males and 277 were females. The birth weight was (1 762.54±401.73) g; gestational age of birth were (32.10±2.36) weeks. The altitude of the residence was (920±80) m. There was no significant difference in sex composition ratio ( χ2=0.10, P=0.75) and birth weight ( t=0.17, P=0.87) between the two groups ( P≥0.05). Gestational age and elevation of residence were compared, and the difference was statistically significant ( t=3.82, 35.15; P<0.01). ROP was detected in 72 cases 144 eyes (5.32%, 72/1 352) in Kunming group and 55 cases 110 eyes (9.5%, 55/579) in Dehong group. Both cases were binocular. There was significant difference in the detection rate of ROP between the two groups ( χ2=11.49, P<0.01). ROP stages 1 to 3 in Kunming and Dehong groups were 128 (88.89%, 128/144), 6 (4.17%, 6/144), 6 (4.17%, 6/144) eyes and 18 (16.36%, 18/110), 66 (60.00%, 66/110), 22 (20.00%, 22/110) eyes. The acute ROP (A-ROP) was 4 (2.78, 4/144) and 4 (3.63%, 4/110) eyes in Kunming and Dehong groups, respectively. There were significant differences in the detection rates of ROP in stages 1 to 3 between the two groups ( χ2=11.26, 66.48, 15.86, 0.76; P<0.05). There was no significant difference in the detection rate of A-ROP ( χ2=0.76, P>0.05). Conclusion:The detection rate of ROP in high altitude area of Yunnan Province is significantly lower than that in low altitude area.

Objective:To observe the incidence of retinopathy of prematurity (ROP) at different altitudes in Yunnan Province.Methods:A retrospective case-control study. From July 1, 2010 to June 30, 2019, 1 352 premature infants (Kunming group) and 579 premature (Dehong group) infants who received ROP screening in the Neonatology Department of Kunming Maternal and Child Health Hospital and the Neonatology Department of Dehong Dai and Jingpo Autonomous Prefecture People's Hospital were included in the study. A wide field digital retinal imaging system combined with binocular indirect ophthalmoscope and scleral oppressor was used for fundus examination. Inspection results were recorded according to the international ROP classification. The incidence of ROP in recent 10 years was retrospectively analyzed. Independent sample t test was used for comparison between groups. Results:Among the 1 352 preterm infants in Kunming group, 716 were males and 636 were females. The birth weight was (1 765.75±357.64) g; gestational age of birth were (32.51±2.07) weeks. The altitude of the residence was (1 920±30) m. Among 579 premature infants in Dehong group, 302 were males and 277 were females. The birth weight was (1 762.54±401.73) g; gestational age of birth were (32.10±2.36) weeks. The altitude of the residence was (920±80) m. There was no significant difference in sex composition ratio ( χ2=0.10, P=0.75) and birth weight ( t=0.17, P=0.87) between the two groups ( P≥0.05). Gestational age and elevation of residence were compared, and the difference was statistically significant ( t=3.82, 35.15; P<0.01). ROP was detected in 72 cases 144 eyes (5.32%, 72/1 352) in Kunming group and 55 cases 110 eyes (9.5%, 55/579) in Dehong group. Both cases were binocular. There was significant difference in the detection rate of ROP between the two groups ( χ2=11.49, P<0.01). ROP stages 1 to 3 in Kunming and Dehong groups were 128 (88.89%, 128/144), 6 (4.17%, 6/144), 6 (4.17%, 6/144) eyes and 18 (16.36%, 18/110), 66 (60.00%, 66/110), 22 (20.00%, 22/110) eyes. The acute ROP (A-ROP) was 4 (2.78, 4/144) and 4 (3.63%, 4/110) eyes in Kunming and Dehong groups, respectively. There were significant differences in the detection rates of ROP in stages 1 to 3 between the two groups ( χ2=11.26, 66.48, 15.86, 0.76; P<0.05). There was no significant difference in the detection rate of A-ROP ( χ2=0.76, P>0.05). Conclusion:The detection rate of ROP in high altitude area of Yunnan Province is significantly lower than that in low altitude area.

The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Objective To analyze the epidemiological characteristics of newly reported advanced schistosomiasis cases in Sichuan Province, so as to provide the evidence for analyzing the causes and formulating targeted control measures of newly reported advanced schistosomiasis cases. Methods Individual case investigation forms for advanced schistosomiasis cases were collected from the Sichuan Provincial Epidemic Annual Report System from 2011 to 2022, and patients’ demographics, previous medical history and liver parenchymal grading were retrieved. All advanced schistosomiasis cases’ medical records were reviewed, and the subtypes of schistosomiasis-endemic villages where the cases’ household registration were, floating population, survival and death and time of death were collected. Results A total of 321 newly reported advanced schistosomiasis cases were found in Sichuan Province from 2011 to 2022, with a male to female ratio of 0.99 to 1. There were 274 cases at ages of over 50 years (85.4%), with the highest proportion seen at ages of 60 to 69 years (87 cases, 27.1%), and splenomegaly was the most common type (180 cases, 56.1%), with no dwarfism type detected. The highest number of cases was reported in 2011 (78 cases), followed by in 2022 (74 cases), and the highest number of cases were reported in Meishan City (199 cases, 62.0%), Dongpo District (131 cases, 40.8%), and hilly subtype areas (136 cases, 42.4%). As of the end of 2022, there were 111 deaths due to advanced schistosomiasis, with the highest number of deaths seen in 2018 (25 deaths), and the highest mortality was seen among patients with the ascites type (41.2%). There were 47 (37.3%), 40 (59.5%) and 4 (23.5%) cases with grade III liver parenchyma among patients with splenomegaly, ascites, and colonic proliferation types, respectively, and there was a significant difference in the grading of III liver parenchyma among three types of patients (H = 12.092, P < 0.05), with more severe liver parenchyma injuries seen among patients with the ascites type than among those with splenomegaly and colonic proliferation type (Z = 24.262 and 44.738, both P_adjusted values < 0.05). Conclusions There have been newly reported advanced schistosomiasis cases in Sichuan Province during recent years, and patients with the ascites type should be given a high priority among advanced schistosomiasis cases in Sichuan Province. Intensified clue surveys are needed for early identification and treatment of advanced schistosomiasis cases, so as to increase the survival rate and improve the quality of life.

Objective:To evaluate the humoral and cellular immunoreactivity of recombinant Mycobacterium tuberculosis ( M. tuberculosis) PstS1 and HspX protein antigens in order to provide reference for immunodiagnosis of tuberculosis and screening of candidates for vaccine antigens. Methods:Purified recombinant M. tuberculosis PstS1 and HspX proteins were obtained using molecular cloning expression and Ni 2+ affinity chromatography. Blood samples and epidemiological data of healthy individuals and patients with M. tuberculosis infection were collected. Specific IgG antibodies and IFN-γ-producing antigen-specific T cells were respectively detected by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT) with the recombinant proteins used as antigens. The humoral and cellular immunoreactivity of the recombinant PstS1 and HspX proteins were assessed with statistical analysis of data. Results:Both the recombinant PstS1 and HspX proteins could induce the secretion of IFN-γ by more specific effector T cells in patient with M. tuberculosis infection, and the differences between the infection and healthy control groups were statistically significant ( P<0.05). The specificity and sensitivity of the recombinant PstS1 and HspX as the diagnostic antigens of ELISPOT were 92.11% (35/38) and 65.96% (31/47), and 68.42% (26/38) and 91.49% (43/47), respectively. The two proteins also possessed some humoral immunoreactivity, but statistically significant difference was only observed in the HspX-specific antibody level between the two groups ( P<0.05). Conclusions:Both the recombinant PstS1 and HspX proteins had good cellular immunoreactivity and were the immunodominant antigens of cellular immunity. They performed well in cellular immunodiagnosis and were good potential candidate antigens for anti-tuberculosis vaccines.