1.Treatment of Hyperlipidemia from the Perspective of Cold
Yuhan YANG ; Tong TONG ; Wenxi ZUO ; Qingqing WANG ; Xiaoxiao ZHANG ; Kuiwu YAO
Journal of Traditional Chinese Medicine 2026;67(13):1451-1454
It is proposed that cold pathogen plays an important promoting role in the onset and progression of hyperlipidemia. External exposure to cold, the gradual generation of internal cold, and the covert consumption of yang qi caused by modern lifestyle factors may all provide a pathological basis for the development of hyperlipidemia. Based on the pathogenic characteristics of cold, namely its tendency to damage yang, induce stagnation, and cause contraction, this paper suggests that the treatment of hyperlipidemia should focus on warming and tonifying, warming and resolving, and warming and unblocking, respectively. This provides a theoretical reference for the diagnosis and treatment of hyperlipidemia with traditional Chinese medicine.
2.Incidence and influencing factors of atrial fibrillation in elderly patients with chronic obstructive pulmonary disease
Jiajia LI ; Hui HU ; Jian ZHANG ; Ju ZHAO ; Qiumei YANG ; Qingqing TANG ; Ling YUAN
Journal of Public Health and Preventive Medicine 2026;37(4):86-90
Objective To analyze the incidence rate and risk factors of atrial fibrillation (AF) in elderly patients with chronic obstructive pulmonary disease (COPD). Methods A total of 392 patients with COPD in the hospital were selected from December 2020 to December 2024. Patients' data (medical history, echocardiographic data, etc.) were recorded. The incidence rate of AF in patients was recorded and the patients were grouped according to whether or not they developed AF. The differences were compared between the two groups, and the risk factors of AF occurrence in elderly patients with COPD were analyzed. Results Among the 392 patients with COPD, 127 cases (32.40%) met the diagnostic criteria of AF. There were statistically significant differences in age, pulmonary infection, heart failure, diabetes, smoking history, disease duration, LAD, severe renal insufficiency and coronary heart disease between the AF group and the non-AF group (P<0.05). Multivariate logistic regression analysis suggested that age, pulmonary infection, heart failure, diabetes mellitus, smoking history, disease course, LAD, severe renal insufficiency and coronary heart disease were all risk factors for elderly patients with COPD (OR=1.129, 4.246, 3.955, 4.125, 2.038, 1.112, 1.102, 4.397, and 3.865, P<0.05). Conclusion The incidence rate of AF is high in elderly patients with COPD. Age, pulmonary infection, heart failure, diabetes mellitus, smoking history, course of disease, LAD, severe renal insufficiency, and coronary heart disease are all risk factors for AF.
3.A Novel Risk Prediction Model for Chronic Atrophic Gastritis Based on Traditional Chinese Medicine Spleen Deficiency and Blood Stasis Syndromes and Gastric Stem Cell Dynamics
Qingqing ZHANG ; Di WU ; Fengyun GUO ; Shengnan YANG ; Ruiying ZHANG ; Lijing BAO ; Ping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):191-200
ObjectiveTo construct a risk prediction model for chronic atrophic gastritis (CAG) that combines disease and syndrome by integrating spleen deficiency and blood stasis syndrome scores, gastric stem cell marker analysis, and network pharmacology and to elucidate the mechanism link between spleen deficiency, blood stasis, and gastric stem cell dysregulation. MethodsA total of 60 patients were stratified into high-risk CAG, low-risk CAG, and non-atrophic groups based on the operative link for gastritis assessment (OLGA)/operative link for gastric intestinal metaplasia assessment (OLGIM) stages. General data and syndrome scores of the patients were collected. Immunohistochemistry was employed to measure the protein levels of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), trefoil factor 2 (TFF2), and β-catenin in gastric mucosa across groups. Transcriptomic data (GSE130823) from the Gene Expression Omnibus (GEO) database were analyzed to validate the expression of these molecular markers at the gene level. A Firth penalized maximum likelihood logistic regression model was employed to integrate clinical, molecular, and TCM syndrome data to develop a CAG risk prediction model. Finally, network pharmacology analysis was conducted on spleen-invigorating herbs (Astragali Radix, Atractylodis Macrocephalae Rhizoma, and Dioscorea Rhizoma) and blood-activating herbs (Hedyotis diffusa, Salviae Miltiorrhizae Radix et Rhizoma, and Curcumae Rhizoma) to identify overlapping targets between these herbs and differentially expressed genes between low-grade intraepithelial neoplasia (LGIN) and gastritis, thereby clarifying the role of spleen deficiency and blood stasis in CAG progression from a pharmacological perspective. ResultsHigh-risk CAG patients exhibited higher blood stasis scores (4.60±1.50,2.62±1.32, P<0.01), progressive nuclear accumulation of β-catenin (A 0.28-0.53, P<0.01), and an increased LGR5+/TFF2+ ratio (A 1.02-1.92, P<0.01). Blood stasis scores were correlated with LGR5/TFF2 imbalance (P=0.03) and activation of the Wnt/β-catenin signaling pathway (CTNNB1 increase, log2=0.78). The integrated prediction model (blood stasis score≥5 + β-catenin>0.38 + LGR5/TFF2>1.5) outperformed a pure biomarker approach [Area Under the Curve (AUC) 0.92,0.89, ΔAUC=0.03, P=0.02]. Moreover, network pharmacology revealed 66 overlapping targets between spleen-invigorating/blood-activating herbs and LGIN, which were functionally enriched in mucosal repair and anti-oxidative stress, and negatively correlated with the Wnt/β-catenin signaling pathway (P<0.01). ConclusionThis study developed an integrated risk prediction model for CAG by combining TCM spleen deficiency and blood stasis syndromes with gastric stem cell molecular markers. Furthermore, it proposed for the first time the "blood stasis-Wnt/β-catenin-stem cell axis" hypothesis, preliminarily elucidating that spleen deficiency and blood stasis may exacerbate gastric stem cell dysregulation and promote malignant transformation of CAG through hypoxia-induced Wnt activation. This provides a theoretical foundation and a translational tool for risk stratification and multi-target TCM intervention in CAG.
4.A Novel Risk Prediction Model for Chronic Atrophic Gastritis Based on Traditional Chinese Medicine Spleen Deficiency and Blood Stasis Syndromes and Gastric Stem Cell Dynamics
Qingqing ZHANG ; Di WU ; Fengyun GUO ; Shengnan YANG ; Ruiying ZHANG ; Lijing BAO ; Ping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):191-200
ObjectiveTo construct a risk prediction model for chronic atrophic gastritis (CAG) that combines disease and syndrome by integrating spleen deficiency and blood stasis syndrome scores, gastric stem cell marker analysis, and network pharmacology and to elucidate the mechanism link between spleen deficiency, blood stasis, and gastric stem cell dysregulation. MethodsA total of 60 patients were stratified into high-risk CAG, low-risk CAG, and non-atrophic groups based on the operative link for gastritis assessment (OLGA)/operative link for gastric intestinal metaplasia assessment (OLGIM) stages. General data and syndrome scores of the patients were collected. Immunohistochemistry was employed to measure the protein levels of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), trefoil factor 2 (TFF2), and β-catenin in gastric mucosa across groups. Transcriptomic data (GSE130823) from the Gene Expression Omnibus (GEO) database were analyzed to validate the expression of these molecular markers at the gene level. A Firth penalized maximum likelihood logistic regression model was employed to integrate clinical, molecular, and TCM syndrome data to develop a CAG risk prediction model. Finally, network pharmacology analysis was conducted on spleen-invigorating herbs (Astragali Radix, Atractylodis Macrocephalae Rhizoma, and Dioscorea Rhizoma) and blood-activating herbs (Hedyotis diffusa, Salviae Miltiorrhizae Radix et Rhizoma, and Curcumae Rhizoma) to identify overlapping targets between these herbs and differentially expressed genes between low-grade intraepithelial neoplasia (LGIN) and gastritis, thereby clarifying the role of spleen deficiency and blood stasis in CAG progression from a pharmacological perspective. ResultsHigh-risk CAG patients exhibited higher blood stasis scores (4.60±1.50,2.62±1.32, P<0.01), progressive nuclear accumulation of β-catenin (A 0.28-0.53, P<0.01), and an increased LGR5+/TFF2+ ratio (A 1.02-1.92, P<0.01). Blood stasis scores were correlated with LGR5/TFF2 imbalance (P=0.03) and activation of the Wnt/β-catenin signaling pathway (CTNNB1 increase, log2=0.78). The integrated prediction model (blood stasis score≥5 + β-catenin>0.38 + LGR5/TFF2>1.5) outperformed a pure biomarker approach [Area Under the Curve (AUC) 0.92,0.89, ΔAUC=0.03, P=0.02]. Moreover, network pharmacology revealed 66 overlapping targets between spleen-invigorating/blood-activating herbs and LGIN, which were functionally enriched in mucosal repair and anti-oxidative stress, and negatively correlated with the Wnt/β-catenin signaling pathway (P<0.01). ConclusionThis study developed an integrated risk prediction model for CAG by combining TCM spleen deficiency and blood stasis syndromes with gastric stem cell molecular markers. Furthermore, it proposed for the first time the "blood stasis-Wnt/β-catenin-stem cell axis" hypothesis, preliminarily elucidating that spleen deficiency and blood stasis may exacerbate gastric stem cell dysregulation and promote malignant transformation of CAG through hypoxia-induced Wnt activation. This provides a theoretical foundation and a translational tool for risk stratification and multi-target TCM intervention in CAG.
5.Risk factors for low blood pressure in patients with refractory heart failure: a discussion based on comorbidities and clinical indicators
Jiamin ZAN ; Bailing ZHANG ; Fenglai ZHOU ; Shuling ZHANG ; Rong ZHANG ; Tiantian YUAN ; Jingli DAI ; Yuanxin KANG ; Qingqing YANG
Journal of Public Health and Preventive Medicine 2026;37(5):101-105
Objective To analyze the occurrence status of low blood pressure (BP) in patients with refractory heart failure (RHF) and its relationship with comorbidities. Methods A retrospective analysis was conducted on the clinical data of 360 patients with RHF who were hospitalized in department of cardiology of Affiliated Nantong Hospital of Shanghai University from May 2021 to May 2025. These patients were divided into the RHF with BP group and the RHF group based on their blood pressure at admission. The general data and comorbidities were compared between both groups. Multivariate logistic regression analysis was used to identify the risk factors for coexisting BP. Results The heart rate (HR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), blood urea nitrogen, high-sensitivity cardiac troponin T, right atrial diameter, proportion of cardiac function grade IV, use rate of diuretics and prevalence rate of dilated cardiomyopathy (DCM) in the RHF with BP group were higher while the high-density lipoprotein cholesterol (HDL-C), albumin, left ventricular ejection fraction, use rate of lipid-lowering drugs and prevalence rate of coronary heart disease were lower compared to the RHF group, and the differences were statistically significant (P<0.05). Multivariate logistic regression analysis suggested that increased HR (OR=1.685, 95%CI: 1.106-2.569), increased NT-proBNP (OR=1.772, 95%CI: 1.138-2.759), decreased HDL-C (OR=0.605, 95%CI: 0.400-0.917) and DCM (OR=1.956, 95%CI: 1.176-3.255) were independent risk factors affecting BP in RHF patients (P<0.05). Conclusion The incidence rate of low blood pressure in elderly RHF patients is about 19.17%. Increased heart rate, increased NT-proBNP, decreased HDL-C and dilated cardiomyopathy are closely linked to the occurrence of low blood pressure, and they can be used as clinically related factors to identify patients at high risk of low blood pressure.
6.Huoxue Wentong Prescription Ameliorates Post-myocardial Infarction Ventricular Remodeling in Rats via HIF-1α/TGF-β1/POSTN-mediated Regulation of EndMT
Xiaoning SUN ; Xiaoxiao ZHANG ; Cheng LI ; Qingqing WANG ; Jianguo LIN ; Mingyue WANG ; Ying YANG ; Kuiwu YAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(22):148-158
ObjectiveTo explore the potential mechanism by which Huoxue Wentong prescription (HXWT) ameliorates post-myocardial infarction (MI) ventricular remodeling by regulating endothelial-to-mesenchymal transition (EndMT) via the hypoxia-inducible factor-1α (HIF-1α)/transforming growth factor-β1 (TGF-β1)/periostin (POSTN) signaling pathway. MethodsEighty SPF-grade male Sprague-Dawley rats were randomly assigned to a sham-operated group (n=10) and a modeling group (n=70). The MI model was established by left anterior descending coronary artery ligation. Successfully modeled rats were further randomized into a model group, a sacubitril/valsartan (Entresto, 0.021 g·kg-1) group, and low, medium, and high-dose (4.15, 8.30, and 16.60 g·kg-1, respectively) HXWTF groups (n=10 per group). From postoperative day 2, rats received HXWTF or sacubitril/valsartan by gavage once daily for 4 weeks, and those in sham and model groups received an equal volume of normal saline. After intervention, general conditions were assessed. Echocardiography was performed to measure the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end diastolic diameter (LVEDD), and left ventricular end systolic diameter (LVESD). Hematoxylin and eosin (HE) staining was employed to evaluate myocardial histopathology, and Masson's trichrome staining to assess myocardial fibrosis. Serum levels of B-type natriuretic peptide (BNP), interleukin (IL)-6, IL-10, and matrix metalloproteinase-9 (MMP-9) were determined by enzyme-linked immunosorbent assay (ELISA). Collagen type Ⅰ (ColⅠ) expression was assessed by immunohistochemistry. Immunofluorescence double staining was adopted to detect the expression of platelet endothelial cell adhesion molecule-1 (CD31) and α-smooth muscle actin (α-SMA). Western blot was performed to quantify the expression of collagen type Ⅰ α2 (Col1A2), VE-cadherin, CD31, α-SMA, HIF-1α, TGF-β1, and POSTN. ResultsCompared with the sham group, the model group exhibited thinning and collapse of the left ventricular wall, decreased LVEF and LVFS and increased LVEDD and LVESD (P<0.01), disrupted myocardial fibers with marked inflammatory cell infiltration, increased collagen deposition, enhanced ColⅠ immunoreactivity, elevate serum BNP, IL-6, and MMP-9 levels, a reduced IL-10 level (P<0.01), downregulated expression of CD31 and VE-cadherin, and upregulated expression of α-SMA, Col1A2, HIF-1α, TGF-β1, and POSTN (P<0.05,P<0.01), accompanied by increased CD31/α-SMA co-localization. Compared with the model group, the sacubitril/valsartan group and all HXWTF groups showed improved ventricular wall structure, increased LVEF and LVFS, decreased LVEDD and LVESD, attenuated myocardial injury with reduced inflammatory infiltration and collagen deposition, declined serum BNP, IL-6, and MMP-9 levels, an elevated serum IL-10 level, upregulated expression of CD31 and VE-cadherin, downregulated expression of α-SMA, Col1A2, HIF-1α, TGF-β1, and POSTN, and reduced CD31/α-SMA co-localization (P<0.05,P<0.01). No significant differences were observed between the sacubitril/valsartan group and the medium- and high-dose HXWTF groups. ConclusionHXWTF may regulate the HIF-1α/TGF-β1/POSTN pathway to inhibit EndMT, thereby ameliorating post-MI ventricular remodeling.
7.Evaluation of the Efficacy of an Eye-Protective Compound Formula on the Retina in a Mouse Model of Blue Light-Induced Damage
Haochen XU ; Qingqing LE ; Xiwen HE ; Bing CAI ; Longhe YANG
Laboratory Animal and Comparative Medicine 2026;46(5):650-659
ObjectiveTo investigate the time-dependent pattern of blue light-induced retinal damage in mice, establish a suitable animal model, and evaluate the protective effects of a compound formula containing lutein esters, DHA algal oil, Lycium ruthenicum, and other ingredients used as both food and medicine. MethodsThirty-two of the 56 SPF-grade male C57BL/6J mice were randomly divided into a control group and model groups (1 h, 3 h, and 6 h irradiation) (n=8 per group) to determine the optimal blue light irradiation time. First, mice were exposed to blue light from a 467 nm light-emitting diode at (5 000±200) lx for 1 h, 3 h, and 6 h, respectively. Retinal histopathology and thickness were examined using hematoxylin‑eosin (HE) staining. Serum malondialdehyde (MDA) and glutathione (GSH) levels were measured using assay kits. Retinal inflammatory cytokine mRNA expression was assessed by real-time fluorescent quantitative reverse transcription PCR. After 3 h of blue light exposure was confirmed as the appropriate modeling condition, the remaining 24 mice were used in an intervention experiment to evaluate the protective effect of the eye-protective compound formula on blue light-induced retinal damage. The mice were administered the compound formula (1 000 mg·kg-1·d-1) by gavage for 14 days, followed by 3 h of blue light irradiation, and the same indicators were evaluated as described above. ResultsWith prolonged irradiation time, the thickness of each retinal layer gradually decreased (P<0.05 to P<0.01) and cell arrangement became disordered. Serum MDA levels progressively increased (P<0.01), while GSH levels gradually decreased (P<0.01). The mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in retinal tissue was significantly upregulated with increasing irradiation time. The 1 h irradiation group showed only minor changes (P>0.05), whereas the 6 h irradiation group exhibited the most pronounced changes (P<0.000 1). Therefore, 3 h of blue light irradiation (P<0.001), which showed significant yet moderate differences in all indicators, was selected as the subsequent modeling condition. After intervention with the eye-protective compound formula, compared with the model group, serum MDA level was significantly reduced (P<0.01), and serum GSH level was significantly increased (P<0.05). The expression levels of retinal inflammatory cytokines IL-1β (P<0.000 1), IL-6 (P<0.001), and TNF-α (P<0.01) were significantly downregulated. Total retinal thickness (P<0.01), as well as the thicknesses of the inner plexiform layer (P<0.05), inner nuclear layer (P<0.05), outer plexiform layer (P<0.05), and outer nuclear layer (P<0.01), were significantly increased compared with the model group. Histopathological examination also showed that the regularity and density of retinal cell arrangement were markedly better than those in the model group. ConclusionBlue light irradiation at a specific illuminance for 3 h can establish a stable mouse model of retinal damage. The compound formula alleviates retinal damage through antioxidant and anti-inflammatory pathways, providing an experimental basis for the development of related functional foods.
8.A preliminary study on the implementation effects of a proactive health management model for geriatric multimorbidity in comprehensive hospital on the basis of the concept of person-centered integrated care
Xin CHEN ; Yang LI ; Jianli GE ; Shasha GENG ; Qingqing LI ; Yingqian ZHU ; Hua JIANG
Chinese Journal of General Practitioners 2025;24(8):938-944
Objective:To explore the implementation effects of an proactive health management model for elderly patients with multimorbidity in comprehensive hospitals based on the concept of people-centered integrated care (PCIC).Methods:This study was a randomized controlled trial. Elderly patients who were hospitalized in the Department of General Practice at Shanghai East Hospital Tongji University and also suffered from hypertension, type 2 diabetes and dyslipidemia from November 2022 to January 2024 were included, and were divided into the control group (traditional health management, n=25) and the intervention group (proactive health management, n=25) using the random number table method. A research team comprising experts in general medicine, pharmacy, nutrition, rehabilitation medicine, psychology, and other relevant specialties was formed. Based on literature analysis, clinical experience, and hospital resources, the team collaborated to develop a comprehensive, hospital-based proactive health management model for elderly patients with comorbidities based on the PCIC concept. Patients in the control group were managed using the traditional health management model. Patients in the intervention group were managed using the proactive health management model. Baseline clinical data was collected and the patients were followed up for 6 months. At the 6-month follow-up, data on blood pressure, fasting blood glucose, and blood lipids were collected, as well as information on polypharmacy, activities of daily living (ADL) ability, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, and unplanned rehospitalization were recorded. Results:A total of 50 patients were enrolled, with 25 patients in each group. The control group had an average age of (70.40±6.54) years, with 15 males(60.0%). The intervention group had an average age of (71.20±5.14) years, with 16 males(64.0%). At the 6-month follow-up, the standardization rates of blood pressure, fasting blood glucose, glycated hemoglobin, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG) in both groups were higher than those in the baseline (all P<0.05).In addition, patients in the intervention group had the compliance rates for higher blood pressure, fasting blood glucose, 2-hour postprandial blood glucose, HbA1c, LDL-C, non-HDL-C, and TG than the control group (all P<0.05).At the 6-month follow-up, the 10-year ASCVD high-risk patient percentage decreased in the intervention group compared with baseline ( P=0.023) and was lower than that of the control group ( P=0.045), and the unanticipated readmission rate of patients in the intervention group was also lower than that of the control group ( P=0.042). Conclusions:A proactive health management model for elderly patients with geriatric multimorbidity in a comprehensive hospital, based on the concept of PCIC, was applied to an elderly population with concurrent hypertension, type 2 diabetes and dyslipidemia. The results of the management were favorable.
9.Clinicopathologic features and renin-angiotensin-aldosterone system inhibitor usage of malignant hypertension patients with acute kidney injury
Lingyi XU ; Linger TANG ; Shuo XUE ; Qingqing ZHOU ; Lei JIANG ; Li YANG ; Xizi ZHENG
Chinese Journal of Nephrology 2025;41(4):250-257
Objective:To summarize the clinicopathologic characteristics of malignant hypertension (MHT) patients with acute kidney injury (AKI) and application of renin-angiotensin-aldosterone system inhibitor (RAASi).Methods:It was a retrospective cohort study. The adult patients with MHT and AKI admitted to Peking University First Hospital from January 1, 2012 to July 14, 2022. The patients were categorized into RAASi group and non-RAASi group based on RAASi administration from AKI onset to discharge. The clinicopathological data between the two groups were compared, and application of RAASi was analyzed.Results:A total of 179 patients were enrolled with age of 31 (26, 37) years and 148 males (82.7%). Ninety-five patients (53.1%) received dialysis treatment. The common causes of MHT were essential hypertension (125 patients, 69.8%), renal hypertension (39 patients, 21.8%) and endocrine hypertension (7 patients, 3.9%). AKI severity distribution showed 41 patients (22.9%) in stage 1, 1 patient (0.5%) in stage 2 and 137 patients (76.5%) in stage 3. Among MHT patients, 94 patients (52.5%) had been treated with RAASi before AKI, and 13 patients (7.3%) discontinued RAASi after AKI. Among 85 patients (47.5%) without receiving RAASi treatment before AKI, 68 new patients (38.0%) received RAASi treatment after AKI, and 40 patients (22.3%) were treated with the support of dialysis. Compared with non-RAASI group ( n=30), proportions of chronic kidney disease ( χ2=6.324, P=0.012) and post-AKI hyperkalemia ( χ2=4.048, P=0.044) in RAASi group ( n=149) were lower, and the proportion of dialysis treatment ( χ2=5.638, P=0.018), admission diastolic blood pressure ( Z=-3.609, P<0.001) and maximum diastolic blood pressure during hospitalization ( Z=-1.978, P=0.048) were higher. There were no statistically significant differences in the rates of target blood pressure control and renal function recovery between the two groups during hospitalization (all P>0.05). During hospitalization, 64 patients received renal biopsies, of which 50 patients (78.1%) had typical MHT vascular lesions such as "onion skin" in renal arterioles. Twenty-seven patients (42.2%) were complicated with glomerular diseases, and IgA nephropathy was the most common type (85.2%, 23/27). The proportions of glomerular ischemia and sclerosis, endothelial cell proliferation and acute renal tubular injury in RAASi group ( n=54) were lower than those in non-RAASi group ( n=10), and proportions of thrombosis and "onion skin" change were higher than those in RAASi group ( n=10), but the differences were not statistically significant (all P>0.05). Renal function recovery occurred in 47 patients (26.3%) by discharge. Among 95 dialysis patients, 26 patients (27.4%) achieved dialysis independence at discharge. Conclusions:MHT patients with AKI exhibit severe renal pathology and short-term poor prognosis. RAASi is primarily prescribed to those with relatively better kidney function or those receiving dialysis support.
10.Association Between Low Birth Weight and Dementia Risk:A Large-scale Prospective Study
Xinyue YU ; Qingping XUE ; Jingyi LI ; Peiqi ZHANG ; Qingqing OUYANG ; Xiaoxue LUO ; Qian HE ; Yongliu WANG ; Ying ZHAO ; Xiangwang HE ; Fan LI ; Yunhaonan YANG ; Xiongfei PAN
Journal of Sichuan University (Medical Sciences) 2025;56(3):697-710
Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.


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