1.Mechanism of Huangqin decoction in improving ulcerative colitis based on the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor axis
Ying CHEN ; Rong XU ; Yao HE ; Ying LI ; Zhiyu ZHANG ; Zhijiu WU
China Pharmacy 2026;37(9):1173-1179
OBJECTIVE To investigate the mechanism of Huangqin decoction in improving ulcerative colitis (UC) through the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor (AhR) axis. METHODS Mice were randomly divided into normal group (normal saline), model group (normal saline), microbiota depletion-model group (normal saline), microbiota depletion-Huangqin decoction group (9.1 g/kg, by crude drug, similarly hereinafter), Huangqin decoction group and mesalazine group (positive control group, 0.4 g/kg), with 6 mice in each group. Microbiota depletion was achieved by providing free access to a mixed antibiotics for 10 days. The UC model was induced by administering 2.5% dextran sulfate sodium solution for 7 days. After successful modeling, each treatment group received corresponding drugs or normal saline intragastrically once daily for 10 days. After the final administration, body weight change ratio, disease activity index (DAI) score, and colon length were evaluated; colon pathological changes were observed; serum levels of interleukin-6 (IL-6), IL-10, IL-22, and tumor necrosis factor-α (TNF-α) were measured; the expressions of Occludin, zonula occluden-1 (ZO-1), and AhR in colon tissue were detected; fecal samples were subjected to high-throughput sequencing to analyze targeted tryptophan metabolomics. RESULTS Compared with the model group, Huangqin decoction group showed reduced infiltration of inflammatory cells in the colon tissue and restoration of the intestinal mucosal structure. Body weight change ratio, colon length, serum content of IL-10, the expressions of Occludin, ZO-1 and AhR in colon tissue and the contents of tryptophan metabolites indole-3-propionic acid (IPA), N -acetylserotonin (NAS) and indole-3-acetic acid (IAA) were all significantly increased ( P <0.05); DAI score, serum levels of IL-6, TNF-α, and IL-22 and the content of tryptophan metabolite indole-3-ethanol were significantly decreased ( P <0.05); gut microbiota structure was improved, with increased relative abundances of beneficial bacteria such as Lactobacillus , and decreased relative abundances of pathogenic bacteria such as Escherichia-Shigella . However, after antibiotic-induced microbiota depletion, although Huangqin decoction significantly increased the content of NAS in the feces of mice, the expression of AhR protein in colon tissue did not increase concurrently. CONCLUSIONS Huangqin decoction can repair the intestinal mucosal barrier in UC mice by regulating the gut microbiota and promoting the production of IPA and IAA, thereby activating AhR. This suggests that an intact gut microbiota is an important prerequisite for Huangqin decoction to exert its AhR-regulating effects.
2.Mechanism of Yangjing Zhongyutang in Regulating SIRT1/PGC-1α Signaling Pathway to Promote Mitochondrial Function and Alleviate Oxidative Stress Damage in Rats with Diminished Ovarian Reserve
Ping ZHANG ; Lijuan YANG ; Shenghui CHEN ; Wenliang YAO ; Yuliang ZHOU ; Ling MA ; Huiying WU ; Yanwen XU ; Ziyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):46-55
ObjectiveTo observe the effects of Yangjing Zhongyutang (YJZYT) on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) signaling pathway in cyclophosphamide (CTX)-induced rats with diminished ovarian reserve (DOR), and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group (n=7) and a model group (n=35). Rats in the model group received a single intraperitoneal injection of CTX (90 mg·kg-1) to establish the DOR model. After modeling, estrous cycles were monitored for 7 consecutive days, and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling, rats were divided into groups for intervention: estradiol valerate group (0.09 mg·kg-1), and YJZYT high-, medium-, and low-dose groups (19.98, 9.99, 5.00 g·kg-1). The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state, body weight, and ovarian wet weight of rats were observed and recorded, and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Hematoxylin-eosin (HE) staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species (ROS) expression levels. Colorimetric assays were employed to measure adenosine triphosphate (ATP) and malondialdehyde (MDA) content in ovarian tissues. Quantitative Real-time polymerase chain reaction (Real-time PCR) was used to detect mitochondrial DNA (mtDNA) copy number and the mRNA expression levels of key genes including SIRT1, PGC-1α, nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). Western blot was performed to detect the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM. ResultsCompared with the blank group, rats in the model group exhibited disrupted estrous cycles, obviously reduced body weight, and decreased ovarian index (P<0.05). Ovarian histopathology revealed cortical thinning, loose structure, and a significant reduction in both primordial and growing follicles (P<0.01). Serum FSH and LH levels were significantly elevated (P<0.01), while E2 and AMH levels were obviously reduced (P<0.05, P<0.01). ATP content and mtDNA copy number decreased in ovarian tissue (P<0.01), ROS expression increased, MDA levels rose, while SOD and GSH-Px activities obviously decreased (P<0.05, P<0.01), mRNA and protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM were obviously downregulated (P<0.05, P<0.01). After treatment, compared with the model group, body weight and ovarian index obviously recovered in rats administered various doses of YJZYT (P<0.05), serum E2 and AMH levels increased, while FSH and LH levels obviously decreased (P<0.05, P<0.01), ovarian tissue ATP content and mtDNA copy number were up-regulated, ROS and MDA levels decreased, and antioxidant enzymes SOD and GSH-Px activity obviously increased (P<0.05, P<0.01), Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group (P<0.05, P<0.01), HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups, with a obviously increase in the number of primordial and growing follicles (P<0.05, P<0.01). Granulosa cells were neatly arranged, indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway, promoting mitochondrial biogenesis, enhancing mitochondrial function, and alleviating oxidative stress damage.
3.Analysis of undernutrition and associated factors among left behind and nonleftbehind primary and secondary school students in the Nutrition Improvement Program areas in central and western China
Chinese Journal of School Health 2026;47(3):327-331
Objective:
To investigate the prevalence of undernutrition and its associated factors among left behind and non left behind primary and secondary school students in the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) areas of central and western China, so as to provide evidence for improving the nutritional status of children and adolescents.
Methods:
A survey was conducted among 123 782 students selected by random cluster sampling method in grades 3-9 from NIPRCES in central (Hebei, Shanxi, Heilongjiang, Jilin, Anhui, Jiangxi, Henan, Hunan, Hubei, and Hainan) and western (Gansu, Guangxi, Inner Mongolia, Ningxia, Tibet, Shaanxi, Guizhou, Sichuan, Xinjiang, the Xinjiang Production and Construction Corps, Yunnan, Qinghai, and Chongqing) China in 2023. Anthropometric measurements and questionnaires were used to assess nutritional and dietary status. The prevalence of undernutrition was compared between left behind and non left behind students by Chi square test, and associated factors were analyzed by three level Logistic mixed effects model.
Results:
The prevalence of undernutrition was 8.5% (4 326) in left behind students and 8.1% (5 905) in non left behind students. Three level Logistic mixed effect model analysis showed that whether left behind or non left behind, the undernutrition rates of primary and secondary students in western regions were higher than those of students in central regions [ OR (95% CI )=1.72(1.57-1.87),2.25(2.07- 2.43 )]; the undernutrition risk was lower for those whose fathers had a cultural level of high school or above [ OR (95% CI )=0.69(0.62-0.77),0.90(0.82-0.98)] or junior high school [ OR (95% CI )=0.72(0.66-0.79),0.92(0.85-0.99)] compared to those with primary school or below; picky eating or selective eating increased the risk of undernutrition [ OR (95% CI )=2.36(2.07-2.68),2.28(2.04-2.55)], and primary and secondary school students without nutritional content in health education classes had higher rates of undernutrition [ OR (95% CI )=1.12(1.03-1.23),1.09(1.01-1.17)](all P <0.05).
Conclusion
The prevalence of undernutrition is slightly higher in left behind primary and secondary students than in non left behind primary and secondary students in central and western NIPRCES areas, with variations across different characteristics.
4.Impact of height-desk-chair matching intervention on viewing distance of primary school students
ZHANG Yaxin*, YAO Yuan, FENG Mian, WU Yuxuan, CHEN Guoping, TAO Fangbiao, XU Shaojun
Chinese Journal of School Health 2026;47(1):51-54
Objective:
To compare the effects of height-desk-chair matching on the viewing distance of primary school students before and after intervention, so as to provide scientific basis for the hygiene management of desks and chairs.
Methods:
From April to June 2025, a random cluster sampling method was used to select 141 third grade students from three classes equipped with adjustable desks and chairs in a primary school in Hefei City for a height-desk-chair matching intervention study. The height of students desks and chairs was adjusted according to the standard height and height range specified in the Functional Sizes and Technical Requirements of Chairs and Tables for Educational Institutions (GB/T 3976-2014), with an intervention period of one week. Before and after the intervention, eye use data were measured by using the electronic smart device "Cloud Clip", while collecting data on vision data viewing distance, time spent using eyes at close range and outdoor time, desk and chair height, and physical examination. Linear regression analysis was used to investigate the factors related to viewing distance before the intervention of height-desk-chair matching, and a paired t-test was used to analyze the difference in viewing distance before and after the intervention. A mixed effects model was used to explore the effect of height desk and chair adaptation intervention on viewing distance.
Results:
The compliance rates for desk and chair adjustments before and after the intervention were 1.4% and 18.4%, respectively, with a statistically significant difference ( χ 2=22.84, P <0.01). The viewing distance increased from (30.48±5.01) cm before intervention to (32.06±5.75) cm post intervention, with a statistically significant difference ( t=4.57, P <0.01). The proportion of students meeting the viewing distance standard increased from 33.3% to 51.1%. The linear mixedeffects model results indicated that the association between height appropriate desk and chair interventions and viewing distance was statistically significant, regardless of whether covariates such as time spent using eyes at close range and outdoor time were adjusted ( β=-1.58, 95%CI = -2.25 to -0.91; β=-1.14, 95%CI =-1.85 to -0.43, both P <0.05).
Conclusion
Height adjusted desks and chairs, which can effectively increase the viewing distance for primary school students, has positive implications for improving healthy eye care behaviors among children and adolescents.
5.Value of OCT imaging features in predicting the prognosis of Conbercept therapy for diabetic macular edema
International Eye Science 2026;26(9):1603-1608
AIM: To explore the value of optical coherence tomography(OCT)imaging features in predicting the prognosis of intravitreal injection of conbercept in the treatment of diabetic macular edema(DME). METHODS: A retrospective selection was made of patients with DME who underwent intravitreal injection of conbercept at the hospital from July 2021 to August 2024. All patients received intravitreal injection of conbercept once a month for a total of 3 mo. OCT and best corrected visual acuity(BCVA)examinations were conducted at 4 mo after the treatment. The change in BCVA at 4 mo post-treatment served as the primary efficacy evaluation metric, with patients achieving a 2-line or greater improvement classified into the favorable prognosis group, while those with less than a 2-line improvement were categorized into the unfavorable prognosis group. Clinical data and OCT-related imaging features of the two groups were collected, and the factors influencing the unfavorable prognosis of patients treated with conbercept for DME and the predictive value of OCT-related imaging features for treatment efficacy were analyzed.RESULTS:A total of 115 DME patients(115 eyes)were included in this study [for patients with bilateral DME, only the eye with greater central macular thickness(CMT)was included]. After 4 mo of treatment, 78 cases(78 eyes)were in the good prognosis group, including 45 males and 33 females, with an average age of 60.57±7.46 y. There were 37 cases(37 eyes)in the poor prognosis group, including 24 males and 13 females, with an average age of 59.36±8.72 y. The poor prognosis rate was 32.2%. The BCVA and CMT before treatment in the poor prognosis group were higher than those in the good prognosis group(all P<0.05). The proportions of ELM integrity destruction, EZ integrity destruction, and retinal inner layer structure disorder in the poor prognosis group were all higher than those in the good prognosis group(all P<0.05). The factors influencing the prognosis of DME patients treated with conbercept were pre-treatment CMT(OR=1.030, P<0.001), ELM integrity destruction(OR=22.475, P=0.002), EZ integrity destruction(OR=23.584, P=0.001), and retinal inner layer structure disorder(OR=7.901, P=0.016). The AUC values for predicting poor prognosis of DME patients treated with conbercept by each of the indicators of ELM integrity destruction, EZ integrity destruction, and retinal inner layer structure disorder alone and in combination were 0.699, 0.653, 0.637, and 0.843, respectively.CONCLUSION: Clinically, OCT examination should be emphasized in patients with DME. In the early stage, by identifying high-risk imaging features, the prognosis of DME patients can be evaluated, providing objective evidence for the formulation of individualized treatment plans.
6.Analysis of sarcopenia prevalence and related factors in community-dwelling older adults based on C-MSRA-7 combined with Ishii score
Lijun WANG ; Ping WU ; Haimin XU ; Kewen CHENG ; Fen RAO ; Miaomiao YAO ; Yu ZHANG
Chinese Journal of Clinical Medicine 2026;33(4):643-650
Objective To investigate the prevalence and related factors of sarcopenia among non–bedridden older adults in the community of Baoshan District using the China mini sarcopenia risk assessment 7 (C-MSRA-7) combined with Ishii scoring system. Methods The older individuals consulting at 20 community health stations in Baoshan District between April 2025 and June 2025 were enrolled. Data were collected using a general information questionnaire, a dietary and lifestyle habits survey, the C-MSRA-7, and the mini nutritional assessment-short form (MNA-SF). Handgrip strength and anthropometric measurements were also obtained. Individuals with both Ishii score and C-MSRA-7 results positive were classified into the sarcopenia risk group, while the remaining participants were assigned to the non–sarcopenia risk group. Differences in lifestyle habits, dietary patterns, and nutritional status between the two groups were compared. Results A total of 2 611 valid questionnaires were retrieved. Univariate analysis showed statistically significant differences in alcohol consumption, physical activity frequency, body mass index (BMI), nutritional status, activities of daily living, and regularity of three meals in sarcopenia risk group (n=486) and non–sarcopenia risk group (n=2 125, P<0.05). Logistic regression analysis showed that advanced age (75–84 years: OR=2.55, 95%CI 2.03–3.21; ≥85 years: OR=3.98, 95%CI 2.24–7.07), underweight status (OR=2.19, 95%CI 1.50–3.19), weight loss>2 kg (OR=4.52, 95%CI 2.68–7.64) past 3 months, lack of regular physical activity (OR=1.77, 95%CI 1.24–2.52) , and alcohol consumption (OR=1.48, 95%CI 1.07–2.05) were independent risk factors for sarcopenia (P<0.05). Behaviors related to healthy diet, including daily milk consumption (OR=0.40, 95%CI 0.30–0.52), regular three meals (OR=0.56, 95%CI 0.41–0.78), and high-quality protein intake (OR=0.70, 95%CI 0.52–0.94), were protective factors (P<0.05). Conclusions Sarcopenia among community–dwelling, non–bedridden older adults is closely associated with physical activity levels, dietary habits, and nutritional status. Early identification of individuals at risk, enhanced nutritional education, and timely implementation of nutritional interventions and exercise programs are recommended for this population.
7.Expert consensus on basic public services for vision health management of primary and secondary school students
YANG Lihua , WU Xi, TAO Shuman, YAO Jun, WU Fengbo, LIU Fangli, MA Yinghua, FENG Zhanchun, SUN Renbiao, LIU Dongru, CHEN Qiusheng, CHEN Jie, YU Yizhen, ZHANG Mingchang, WU Xiaoyan, DU Yukai, LI Xiaoqing, LI Li, WU Xixi, JIN Xiaoqin, XU Ting, WU Mengjia, TANG Jia, Society of Student Vision Health Management of Chinese Health Association, Vision Health Branch of Chinese Association for Student Nutrition & ; Health Promotion
Chinese Journal of School Health 2026;47(8):1069-1074
Abstract
To clarify the service targets, service contents, and safeguard mechanisms of the basic public service program for student vision health management, the study grounded in the current status of child and adolescent myopia prevention and control in China and integrated with the practical experience and innovative practices of Wuhan National Demonstration Area for Student Vision Health Management, takes education as the main thread and schools as the base, consolidating resources from multiple stakeholders including education administrative departments, schools, families, and professional technical service institutions. Centering on four core components—vision health education, monitoring and record keeping, risk prevention and control, and dynamic management, the study constructs a multi tiered basic public service system for vision health management of primary and secondary school students. It further proposes the use of an intelligent management platform and a "three tier color coded early warning" mechanism (red, yellow, blue) to prevent and control student myopia at the source, providing schools with replicable and operable implementation pathways to enhance the level of student vision health management.
8.Protective effect and mechanism of glycosides of cistanches on Parkinson's disease mouse via the Nrf2/HO-1 pathway
Zhipeng XU ; Xingyu WANG ; Shuqing YAO ; Jiayi ZHANG ; Chaoran XU ; Fengyan LIU ; Dongsheng HUO
Acta Universitatis Medicinalis Anhui 2026;61(9):1603-1610
ObjectiveTo investigate the neuroprotective effect of glycosides of cistanches (GCs) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) model mice and its potential mechanism. MethodsForty mice were randomly divided into control group, PD group, GCs group and levodopa (L-DOPA) group, with 10 mice in each group. The control group received intraperitoneal injection of normal saline, while the other groups were intraperitoneally injected with MPTP (30 mg/kg) once daily for 5 consecutive days. After model establishment, the control group and PD group were intragastrically administered normal saline, and the GCs group and L-DOPA group received intragastric administration once daily for 28 consecutive days, at doses of 100 mg/kg and 50 mg/kg, respectively. The open field test and rotarod test were used to evaluate motor function. Immunohistochemistry was performed to detect the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra of the midbrain. Transmission electron microscopy was adopted to observe the ultrastructure of mitochondria in the substantia nigra. Biochemical assays were used to determine the levels of glutathione (GSH), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and reactive oxygen species (ROS) in substantia nigra tissues. Western blot was applied to detect the protein expression of TH, nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap-1) and heme oxygenase-1 (HO-1) in substantia nigra tissues. ResultsCompared with the control group, mice in the PD group exhibited markedly impaired motor function, significantly decreased T-SOD activity, obvious reductions in the number of TH-positive neurons and GSH content, as well as elevated MDA and ROS levels in the substantia nigra (P<0.01). Compared with the PD group, mice in the GCs group showed improved motor function, increased T-SOD activity, higher number of TH-positive neurons and elevated GSH content, accompanied by decreased MDA and ROS levels (P<0.05). In the control group, mitochondria in the substantia nigra displayed normal morphology without obvious blurred membrane structures or vacuolar degeneration. The PD group presented mitochondrial swelling, disordered cristae and vacuolar changes, whereas these mitochondrial pathological alterations were alleviated in the GCs group. Compared with the control group, the protein levels of TH, Nrf2 and HO-1 were significantly downregulated, while Keap-1 protein expression was markedly upregulated in the PD group (P<0.01). Compared with the PD group, the GCs group showed significant upregulation of TH, Nrf2 and HO-1 protein levels and a notable reduction in Keap-1 protein level (P<0.05). ConclusionGCs ameliorate motor dysfunction and attenuate dopaminergic neuronal and mitochondrial damage in MPTP-induced PD model mice. These effects may be associated with modulation of Nrf2/HO-1 pathway-related protein expression, enhancement of antioxidant capacity, and alleviation of oxidative stress.
9.Relationship between plasma proteins and pulmonary arterial hypertension and potential therapeutic targets
Cuicui ZHANG ; Huanyu CHEN ; Qiao YU ; Yuxuan HUANG ; Gengzhen YAO ; Xu ZOU
Chinese Journal of Tissue Engineering Research 2026;30(5):1331-1340
BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P<0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95%confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95%CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95%CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95%CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4>0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.
10.Relationship between plasma proteins and pulmonary arterial hypertension and potential therapeutic targets
Cuicui ZHANG ; Huanyu CHEN ; Qiao YU ; Yuxuan HUANG ; Gengzhen YAO ; Xu ZOU
Chinese Journal of Tissue Engineering Research 2026;30(5):1331-1340
BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P<0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95%confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95%CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95%CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95%CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4>0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.


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