1.Association of Genetically Predicted Obesity and Stool Frequency: Evidence From an Observational and Mendelian Randomization Study
Ke HAN ; Xiangyao WANG ; Shimin CHEN ; Xiaotong NIU ; Yan WANG ; Jingyuan XIANG ; Nan RU ; Miao LIU ; Ningli CHAI ; Enqiang LINGHU
Journal of Neurogastroenterology and Motility 2025;31(2):267-275
Background/Aims:
Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency.
Methods:
Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations.
Results:
For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association.
Conclusions
Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.
2.Association of Genetically Predicted Obesity and Stool Frequency: Evidence From an Observational and Mendelian Randomization Study
Ke HAN ; Xiangyao WANG ; Shimin CHEN ; Xiaotong NIU ; Yan WANG ; Jingyuan XIANG ; Nan RU ; Miao LIU ; Ningli CHAI ; Enqiang LINGHU
Journal of Neurogastroenterology and Motility 2025;31(2):267-275
Background/Aims:
Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency.
Methods:
Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations.
Results:
For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association.
Conclusions
Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.
3.Association of Genetically Predicted Obesity and Stool Frequency: Evidence From an Observational and Mendelian Randomization Study
Ke HAN ; Xiangyao WANG ; Shimin CHEN ; Xiaotong NIU ; Yan WANG ; Jingyuan XIANG ; Nan RU ; Miao LIU ; Ningli CHAI ; Enqiang LINGHU
Journal of Neurogastroenterology and Motility 2025;31(2):267-275
Background/Aims:
Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency.
Methods:
Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations.
Results:
For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association.
Conclusions
Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.
4.Effect of Qishao Huoxue Prescription on Hemorheological Parameters and Serum Levels of Inflammatory Mediators in Lumbar Disc Herniation Due to Qi Stagnation and Blood Stasis
Guojun WANG ; Shimin ZHANG ; Jiao JIN ; Ning LIU ; Hai LIN ; Fudong SHI ; Chun CHEN ; Yadi FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):159-166
ObjectiveTo observe the therapeutic effects of Qishao Huoxue prescription on patients with lumbar disc herniation due to Qi stagnation and blood stasis and the effects of this prescription on hemorheological parameters and serum levels of inflammatory mediators. MethodA total of 86 patients with lumbar disc herniation due to Qi stagnation and blood stasis treated in the Wangjing Hospital of China Academy of Chinese Medical Sciences from January 2023 to February 2024 were selected and assigned according to the random number table into observation and control groups (n=43). Patients in both groups received lumbar traction treatment. In addition, the observation group was orally treated with Qishao Huoxue prescription and the control group with celebrex for 3 weeks. The visual analogue scale (VAS) score, Oswestry disabilitiy index (ODI) score, 12-item Short-Form Survey (SF-12) score, traditional Chinese medicine (TCM) symptom score, hemorheological parameters [whole blood high shear viscosity, middle shear viscosity, low shear viscosity, plasma viscosity (PV), and fibrinogen (FIB)], and the serum levels of inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and transforming growth factor-β1 (TGF-β1)] were determined before and after treatment. In addition, the clinical efficacy and adverse reactions were observed and compared between the two groups. ResultAfter treatment, both groups showed declined VAS, ODI, and TCM symptom scores (P<0.05), increased SF-12 physical component summary (PCS) and mental component summary (MCS) scores (P<0.05). After treatment, the whole blood high shear viscosity, middle shear viscosity, low shear viscosity, PV, and FIB decreased in the observation group (P<0.05), while they did not show significant variations in the control group. After treatment, both groups of patients showed reductions in TNF-α, IL-6, and IL-1β levels and an elevation in the TGF-β1 level (P<0.05). Compared with the control group after treatment, the observation group showed decreases in VAS, ODI, TCM symptom scores and main symptom scores (P<0.05), no significant differences in the secondary symptom scores, increased PCS and MCS scores (P<0.05). The observation group outperformed the control group in terms of recovering whole blood high shear viscosity, middle shear viscosity, low shear viscosity, PV, FIB, TNF-α, IL-6, IL-1β, and TGF-β1 (P<0.05). The total response rate in the observation group was 97.5% (40/41), which was higher than that (88.1%, 37/42) in the control group (P<0.05). No serious adverse reaction was observed in the two groups during the observation period. One case in the observation group showed subcutaneous bruising on the lower limbs, which gradually disappeared after withdrawal. ConclusionQishao Huoxue prescription demonstrated definite effect in treating lumbar disc herniation due to qi stagnation and blood stasis by recovering hemorheological parameters and inhibiting the expression of inflammatory mediators in the serum without inducing adverse reactions. It is worth applying in clinical practice.
5.Study on the cognition, learning habit and learning effect of Clinical Epidemiology among different types of postgraduates
Shimin CHEN ; Miao LIU ; Yang SONG ; Shengshu WANG ; Jianhua WANG ; Wangping JIA ; Ke HAN ; Shaohua LIU ; Xuehang LI ; Yao HE
Chinese Journal of Medical Education Research 2024;23(3):364-370
Objective:To investigate the cognition and learning habits of different types of postgraduates and evaluate learning effect and its potential risk factors on clinical epidemiology in a medical college, so as to provide relevant data for improving the teaching method and learning effect of clinical research methods for postgraduates.Methods:A cross-sectional study design was conducted to enroll all the postgraduates of Grade 2020 in a military medical school. A self-filled questionnaire was adopted to collect data. The discrepancy of cognition and learning habits between different types of postgraduates was evaluated by univariate analysis. Discussion was conducted to clarify the potential risk factors of learning effect. t tests or Mann-Whitney U tests were conducted to test the differences between groups for continuous variables. Chi-squared tests or McNemar tests were applied to evaluate the difference between groups for categorical variables. Results:A total of 652 postgraduate students were enrolled for analysis, including 409 master students (62.7) and 243 doctoral students (37.3). The proportion of doctoral students who have heard of clinical epidemiology ( χ2=19.99, P<0.001), who have learned clinical epidemiology ( χ2=9.20, P=0.002), who are interested in ( χ2=11.41, P=0.001) and think the course is important ( χ2=10.71, P=0.001), who previewed before class( χ2=11.21, P=0.001), reviewed after class ( χ2=3.29, P=0.001) and actively discuss in class ( χ2=11.64, P=0.001) is significantly higher than that of master students, the difference was statistically significance. The average score of all the postgraduates was (5.50±1.62) points before teaching and (7.47±1.90) points after teaching, the difference was statistically significant ( t=-23.49, P<0.001). After teaching, the grades of full-time students improved more than that of part-time graduate students, there was statistical significance in the master group ( t=4.41, P<0.001), while not in the doctor group ( t=0.94, P=0.351). Conclusions:The mastery of key points on clinical epidemiology have significantly improved after teaching among the postgraduates of different types. Different teaching methods and processes should be adopted to the variety of postgraduates according to their knowledge foundations and shortcomings. Besides, standardizing their learning habits are of certain significance to improve the learning effect.
6.Prevalence of comorbidity of hypertension, diabetes and dyslipidemia and the association between comorbidity and cardiovascular mortality in population aged 40 years and over in Liaoning Province
Li JING ; Yuanmeng TIAN ; Han YAN ; Qun SUN ; Shubao LI ; Shimin CUI ; Jixu SUN ; Lei SHI ; Yuyao MA ; Guangxiao LI ; Shuang LIU ; Liying XING
Chinese Journal of Cardiology 2024;52(11):1311-1316
Objective:To investigate the comorbidity status of hypertension, diabetes, and dyslipidemia (the"three diseases") among residents aged≥40 in Liaoning Province, and to explore the correlation between the comorbidity and cardiovascular disease mortality.Methods:This investigation was a prospective cohort study. From February 2017 to March 2019, a multi-stage stratified cluster random sampling method was used to carry out a baseline survey of 18 758 permanent residents aged≥40 years in Liaoning Province. Demographic information and history of hypertension, diabetes, and dyslipidemia were collected and followed up every year. Death was mainly identified by linkage to the Population Death Information Registration Management System. Cox proportional hazard regression model was used to analyze the association between the comorbidity of the "three diseases" and cardiovascular disease mortality risk.Results:A total of 18 758 residents aged≥40 in Liaoning Province were included, with an age of (60.3±9.9) years and 7 325 males (39.1%). The comorbidity rate of hypertension, diabetes, and dyslipidemia was 6.7% (1 256/18 758), and the standardized prevalence rate was 5.4%. The comorbidity rate increased with age (P<0.001), which was higher in women than in men, and more significant in urban areas than in rural areas (all P<0.001). The comorbidity of "three diseases" accounted for 39.3% (1 256/3 198), 18.7% (1 256/6 710), and 11.8% (1 256/10 653) in patients with diabetes, dyslipidemia, and hypertension, respectively. With a follow-up of (4.3±0.6) years, 463 people died of cardiovascular disease. The mortality rate of cardiovascular disease in the comorbidity of hypertension, diabetes, and dyslipidemia was 8.74/1 000 person-years. After adjusting potential confounders, Cox proportional hazard regression model analysis showed that compared with normal individuals, the hazard ratio of cardiovascular disease mortality in patients with the "three diseases" was 2.55 (95% CI: 1.63-3.99). Conclusion:The prevalence of comorbidity of hypertension, diabetes, and dyslipidemia among residents aged≥40 in Liaoning Province was relatively high, and the risk of cardiovascular disease mortality in patients with the "three diseases" was increased.
7.Preparation of an amino hybrid mesoporous silica-based nanotopography protective coating on a titanium im-plant surface and evaluation of its osteogenic effect
Shimin DU ; Yunxian LIU ; Xiaofeng CHANG ; Zhe LI
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(5):341-349
Objective To deposit degradable amino-hybrid mesoporous silica(AHMS)in situ on the surface of tita-nium nanotube(TNT)and explore its protective effect on nanomorphology and osteogenesis.Methods TNT and TNT@AHMS were sequentially prepared via an anodizing method:the oil-water two-phase method(experimental group)and the acid-etched titanium method[control group(Ti)].The parameters for synthesis were explored by changing the silicon source dosage ratio(3∶1,1∶1,1∶3);the surface morphology was observed by scanning electron microscope(SEM),hydrophilicity was detected by Water Contact Angle Tester,elemental composition was detected by X-ray photo-electron spectroscopy(XPS);nanoindentation test and ultrasonic oscillator were used to observe the morphological hold-ing effect as mechanical strength of TNT@AHMS in vitro;simulated immersion experiments in vitro was used to observe the degradation behavior of the material.the MC3T3-E1 cell line was used to observe the effect of cell adhesion,prolif-eration and differentiation on the material;and an SD rat femoral implant model and micro-CT were used to verify the protective effect and osseointegration effect of AHMS on TNT morphology.Results The morphologies of TNT and TNT@AHMS were successfully prepared,and the silicon source ratio was 1∶3.SEM showed that the titanium nanotubes were uniformly covered with AHMS coating,and the mesoporous pore size was about 4 nm.After AHMS was incorporat-ed,the surface of the material was hydrophilic(12.78°),the presence of amino groups(NH2-)was detected,the material was completely degraded within 12 h in vitro,and the active morphology of the TNT was re-exposed with a cumulative silicon release of 10 ppm.Nanoindentation test showed that TNT@AHMS exhibited more ideal surface mechanical strength.SEM revealed that TNT maintains its own morphology under the protection of AHMS,and the TNT group suf-fered severe exfoliation.In addition,the early adhesion and proliferation rates,ALP activity,and bone volume fraction of cells on the TNT@AHMS surface 4 weeks after implantation were significantly higher than those in the TNT group.Con-clusion By depositing AHMS on the surface of TNT,the nanotopography can be protected.It not only prevents the ac-tive base topography from exerting subsequent biological effects but also further endows the material with the ability to promote bone regeneration,laying a foundation for the future development of nanotopography-modified titanium im-plants.
8.Analysis of blood testing indicators in HIV patients co-infected with different genotypes of HCV in Kunming area of Yunnan Province
LIU Junyi ; KANG Lijuan ; WANG Shimin ; ZHU Yantao ; ZHANG Mi ; ZHANG Nian ; XIE Qi ; LIU Shifang ; YANG Jiantao ; LI Xiao ; HE Quanying ; WANG Jiali
China Tropical Medicine 2024;24(3):252-
Objective To understand the genotyping of human immunodeficiency virus (HIV) co-infected hepatitis C virus (HCV) patients in Yunnan Province, and to analyze the differences in viral load, biochemical indicators, and blood routine indicators among different genotypes, in order to provide a laboratory basis for the diagnosis and clinical treatment of HIV/HCV co-infected patients. Methods From November 2022 to June 2023, the serum samples and basic information of patients diagnosed with HIV/HCV co-infection were collected in the antiviral outpatient clinic of Yunnan Provincial Hospital of Infectious Diseases. The HCV viral load was detected by one-step qRT-PCR amplification, the positive samples were sequenced, and genotyping was determined based on NS5 gene sequence. The differences in biochemical and blood routine indexes between HIV patients co-infected with different HCV genotypes and low/high viral loads were analyzed. Results A total of 126 HIV/HCV co-infected patients were collected, including 20 HCV genotype 1 (15.9%), 91 HCV genotype 3 (72.2%), and 15 HCV genotype 6 (11.9%). The maximum and minimum viral load of the three HCV genotypes were as follows: HCV type 1 (1.0×108, 4.8×104 IU/mL), HCV type 3 (2.2×108, 2.9×102 IU/mL), and HCV type 6 (8.1×107, 6.8×104 IU/mL). The results showed that there was no significant difference between HIV co-infection with different genotypes of HCV and three HIV treatment schemes, including nucleoside reverse transcriptase inhibitors+integrase strand transfer inhibitors (NRTIs+INSTIs), nucleoside reverse transcriptase inhibitors+non-nucleoside reverse transcriptase inhibitors (NRTIs+NNRTIs) and nucleoside reverse transcriptase inhibitors+protease inhibitor (NRTIs+PLs), and the viral load of patients (P>0.05). The analysis of biochemical indexes such as total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), and blood routine indexes such as white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), platelet (PLT), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) among different HCV genotypes and low/high viral loads showed that there was no significant difference in biochemical indexes and blood routine indexes between low/high viral loads of HIV co-infected HCV patients (P>0.05); however, the biochemical indicators TBIL, IBIL and MCHC were significantly different statistically between patients with genotype 3 HCV infection and those with genotype 1 HCV infection (P<0.05), while other biochemical and blood routine indexes were not statistically different among different HCV genotypes (P>0.05). Conclusions There are six subtypes of HCV co-infection in HIV patients in Kunming, Yunnan Province, including three genes of genotype 1, 3, and 6. Among them, genotype 3 HCV is the main prevalent genetic virus among HIV co-infected populations. The TBIL, IBIL and MCHC values of HIV patients co-infected with HCV type 3 are different from those infected with HCV type 1.
9.Clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder
Shuping ZHOU ; Shimin LI ; Yingguang SHI ; Liwu ZHENG ; Chaonan CHANG ; Junjie CHEN ; Huanpeng WANG ; Ke SUN ; Xiuhuan WANG ; Linbo LIU
Chinese Journal of Burns 2024;40(7):665-672
Objective:To explore the clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder.Methods:The study was a retrospective observational study. From April 2016 to December 2022, 4 cases with circular hot crush injuries in limbs with blood supply disorder were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 3 males and 1 female, aged from 24 to 48 years. Among them, 2 cases were injured in the calf and 2 cases were injured in the forearm. After emergency debridement, the area of skin and soft tissue defects was from 20 cm×20 cm to 44 cm×20 cm. The patients had defects in tibialis anterior and posterior tibial arteries with a length of 13 to 18 cm, and in ulnar and radial arteries with a length of 9 to 12 cm. Flaps were designed and cut, including a flow-through anterolateral thigh perforator flap with area of 20 cm×9 cm to 24 cm×21 cm carrying the descending branch of the lateral circumflex femoral artery and the accompanying veins of 8 to 18 cm in length; and a flow-through posterior tibial artery perforator flap with area of 21 cm×13 cm and 20 cm×14 cm carrying the posterior tibial artery, the accompanying veins with a length of 14 and 17 cm respectively, and the great saphenous vein with a length of 22 and 21 cm. The circular hot crush injury wounds in the calf with blood supply disorder were repaired by a parallel combination of flow-through posterior tibial artery perforator flap and flow-through anterolateral thigh perforator flap, and the circular hot crush injury wounds in the forearm with blood supply disorder were repaired by a parallel combination of bilateral flow-through anterolateral thigh perforator flap, and the injured main vessels were reconstructed. The donor site wounds of flap were closed directly or treated with split-thickness skin grafts from abdomen. After surgery, the blood supply and survival of the flap and distal affected limb, the healing of wounds in the donor and recipient sites, the survival of the skin graft in the flap donor site were observed. During follow-up, the condition of flaps, the appearance, blood supply, and function of affected limbs were observed. At the last follow-up, the foot and ankle functions were evaluated according to the scoring standards of American Orthopedic Foot and Ankle Association, and the wrist and hand function was evaluated according to the trial standard of replantation of amputated upper limb function assessment of the Hand Surgery of Chinese Medical Association. Results:The flaps and distal affected limbs of 4 patients had good blood circulation and successfully survived after surgery. The wounds of 3 cases successfully healed, while one patient with circular hot crush injury in the forearm experienced exudation in the recipient site in the later stage, and the wound healed after re-expansion and suturing. The donor site wounds healed smoothly, and the skin grafts successfully survived. During follow-up of 12 to 24 months after surgery, the flaps were slightly swollen, the limbs had good appearance, normal blood circulation, and fine functional recovery. At the last follow-up, the foot and ankle function of 2 patients with circular hot crush injuries in the calf was evaluated as good in 1 case and commonly in 1 case; the wrist and hand function of 2 patients with circular hot crush injuries in the forearm was evaluated as excellent in 1 case and good in 1 case.Conclusions:The parallel combined flow-through perforator flap can reconstruct the damaged main blood vessels and repair the wound at the same time. It can not only effectively save the limb, but also restore part of the function of the affected limb. It is one of the effective methods to treat the circular hot crush injuries in limbs with blood supply disorder.
10.Effects of cognition-related lifestyles on early cognitive decline in community older adults in China
Haowei LI ; Shige QI ; Shengshu WANG ; Shanshan YANG ; Shimin CHEN ; Rongrong LI ; Xuehang LI ; Shaohua LIU ; Junhan YANG ; Huaihao LI ; Yinghui BAO ; Yueting SHI ; Zhihui WANG ; Yao HE ; Miao LIU
Chinese Journal of Epidemiology 2024;45(1):63-70
Objective:To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline.Methods:The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline.Results:In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 ( OR=0.683, 95% CI: 0.457-1.019; OR=0.623, 95% CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 ( OR=0.491, 95% CI: 0.297-0.812; OR=0.556, 95% CI: 0.332-0.929; trend P=0.024). Conclusion:Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.

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