Mendelian randomization evidence for the causal effect of mental well-being on healthy aging.

Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (ß [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (ß [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.

Association of cardiovascular disease prevalence with BMD and fracture in men with T2DM.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to cardiovascular disease (CVD). Bone mineral density (BMD) is linked to CVD, but most studies focused on women. Our analysis aims to explore the association of BMD and fracture with the prevalence of CVD in men with T2DM. METHODS: In this retrospective cross-sectional study, 856 men with T2DM were enrolled. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The CVD outcome was determined as the sum of the following conditions: congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction, the requirement for coronary artery revascularization, and stroke. The relationship between BMDs and CVD was investigated by restricted cubic spline curves and logistic regression models. RESULTS: A total of 163 (19.0%) patients developed CVD. The restricted cubic spline curve revealed a linear and negative association between FN-BMD, TH-BMD, and CVD. After full adjustments for confounding covariates, the odds ratios were 1.34 (95% confidence interval [CI] [1.11-1.61], p < .05), 1.3 (95% CI [1.05-1.60], p < .05), and 1.26 (95% CI [1.02-1.55], p < .05) for each 1-SD decrease in BMDs of L2-4, FN and TH, respectively. T-scores of < -1 for BMD of L2-4 and FN were independently associated with CVD (p < .05). Subgroup analyses further supported our findings. CONCLUSIONS: The prevalence of CVD was inversely correlated with BMD levels in men with T2DM, particularly at the FN. We hypothesized that monitoring FN-BMD and early intervention would help reduce CVD risk in men with T2DM, especially those with hypertension.

Mendelian randomization evidence for the causal effects of socio-economic inequality on human longevity among Europeans.

Human longevity correlates with socio-economic status, and there is evidence that educational attainment increases human lifespan. However, to inform meaningful health policies, we need fine-grained causal evidence on which dimensions of socio-economic status affect longevity and the mediating roles of modifiable factors such as lifestyle and disease. Here we performed two-sample Mendelian randomization analyses applying genetic instruments of education, income and occupation (n = 248,847 to 1,131,881) to estimate their causal effects and consequences on parental lifespan and self-longevity (n = 28,967 to 1,012,240) from the largest available genome-wide association studies in populations of European ancestry. Each 4.20 years of additional educational attainment were causally associated with a 3.23-year-longer parental lifespan independently of income and occupation and were causally associated with 30-59% higher odds of self-longevity, suggesting that education was the primary determinant. By contrast, each one-standard-deviation-higher income and one-point-higher occupation was causally associated with 3.06-year-longer and 1.29-year-longer parental lifespans, respectively, but not independently of the other socio-economic indicators. We found no evidence for causal effects of income or occupation on self-longevity. Mediation analyses conducted in predominantly European-descent individuals through two-step Mendelian randomization suggested that among 59 candidates, cigarettes per day, body mass index, waist-to-hip ratio, hypertension, coronary heart disease, myocardial infarction, stroke, Alzheimer's disease, type 2 diabetes, heart failure and lung cancer individually played substantial mediating roles (proportion mediated, >10%) in the effect of education on specific longevity outcomes. These findings inform interventions for remediating longevity disparities attributable to socio-economic inequality.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population.

OBJECTIVE: The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population. METHODS: From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria. RESULTS: During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01). CONCLUSION: NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai.

OBJECTIVE: This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease (CKD) in Shanghai community residents. METHODS: We used data from a cohort study of community residents who participated in three examinations in 2008, 2009, and 2013, respectively. Fasting plasma glucose (FPG) level, blood pressure (BP), and lipid levels were determined in 2,109 participants at all three visits, and CKD was evaluated between the second and the third visits. Visit-to-visit variabilities in metabolic factors were described by coefficients of variation (CV) at three visits. A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV. CKD was defined as the estimated glomerular filtration rate < 60 mL/min per 1.73 m 2 or urinary albumin-to-creatinine ratio ≥ 30 mg/g. RESULTS: A total of 200 (9.5%) participants had CKD at the third visit. Compared with the lowest quartile of CV, the highest quartile was associated with a 70% increased risk of CKD for FPG [odds ratio, OR = 1.70; 95% confidence interval ( CI) 1.06-2.72], 62% for systolic BP ( OR = 1.62, 95% CI 1.04-2.50), and 85% for low-density lipoprotein cholesterol ( OR = 1.85, 95% CI 1.23-2.80). Furthermore, the risk of CKD increased significantly with an increasing variability score. Compared with participants with score 0, participants with scores of 1, 2, and 3 were associated with 58% ( OR = 1.58, 95% CI 1.08-2.32), 121% ( OR = 2.21, 95% CI 1.40-3.49), and 548% ( OR = 6.48, 95% CI 3.18-13.21) higher risks of CKD, respectively. CONCLUSION: The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Phytochemical Profile and Anti-Inflammatory Activity of the Fraction from Artemisia lavandulaefolia.

Artemisia lavandulaefolia, a traditional herbal medicine, has been utilized as anti-inflammatory and analgesia agent in clinic. Bioassay-guided fractionation resulted in a fraction (ALDF) with anti-inflammatory effect obtained from A. lavandulaefolia. Its main constituents were analyzed and identified by UPLC-ESI-Q-TOF-MS technology. ALDF showed the strong inhibitory activity on the nitrogen oxide (NO) production in LPS-induced RAW 264.7 macrophages with an IC50 value of 1.64±0.41 µg/mL. Further results displayed that ALDF also significantly suppressed the secretion of key pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2 ) and interleukin-1ß (IL-1ß), and the increase of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression induced by LPS stimulation. Mechanism study indicated that ALDF was able to block NF-κB signaling pathway through inhibiting IκB and p65 phosphorylation, as well as NF-κB p65 nuclear translocation. Furthermore, in vivo results in mice revealed that treatments with ALDF evoked significant inhibition on ear edema induced by xylene and on the writhing responses induced by acetic acid. These results suggest that ALDF holds great potential in the prevention and treatment of inflammatory disorders.

Peripheral Artery Disease and Risk of Fibrosis Deterioration in Nonalcoholic Fatty Liver Disease: A Prospective Investigation.

OBJECTIVE: Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Peripheral artery disease (PAD) and liver fibrosis share many common metabolic dysfunctions. We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients. METHODS: The study recruited 1,610 NAFLD patients aged ≥ 40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015. Fibrosis deterioration was defined as the NAFLD fibrosis score (NFS) status increased to a higher category at the follow-up visit. PAD was defined as an ankle-brachial index of < 0.90 or > 1.40. RESULTS: During an average of 4.3 years' follow-up, 618 patients progressed to a higher NFS category. PAD was associated with 92% increased risk of fibrosis deterioration [multivariable-adjusted odds ratio ( OR): 1.92, 95% confidence interval ( CI): 1.24, 2.98]. When stratified by baseline NFS status, the OR for progression from low to intermediate or high NFS was 1.74 (95% CI: 1.02, 3.00), and progression from intermediate to high NFS was 2.24 (95% CI: 1.05, 4.80). There was a significant interaction between PAD and insulin resistance (IR) on fibrosis deterioration ( P for interaction = 0.03). As compared with non-PAD and non-IR, the coexistence of PAD and IR was associated with a 3.85-fold (95% CI: 2.06, 7.18) increased risk of fibrosis deterioration. CONCLUSION: PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients, especially in those with IR. The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.

Nitric Oxide Production Inhibitory Eudesmane-Type Sesquiterpenoids from Artemisia argyi.

Six new eudesmane-type sesquiterpene derivatives, artemargyinins A-F were isolated from the leaves of Artemisia argyi. Their structures were elucidated based on the extensive analysis of spectroscopic data. Artemargyinins A-F feature a lactone ring-opening eudesmane-type sesquiterpene with an isoprenoid group at C(8). All compounds were tested for their inhibitory effects on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 macrophages. Artemargyinins A-F showed more potent NO production inhibitory activity with IC50 values ranging from 7.66±0.53 to 61.19±2.54 µM than the positive control quercetin (IC50 =74.34±1.39 µM). Among them, artemargyinins C and D exhibited strong inhibitory activity with IC50 values of 8.08±0.21 and 7.66±0.53 µM, respectively.

Textual Research and Suggestions on Dosage of Pinelliae Rhizoma in Famous Classical Formulas / 中国实验方剂学杂志

Pinelliae Rhizoma is a toxic traditional Chinese medicine, and its dose differs greatly between at ancient and modern times, so that it is difficult for researchers to determine its dosage during research and development of famous classical formulas. According to the literature research, it is found that the dose of Pinelliae Rhizoma in famous classical formulas has undergone a process from large to small. Based on the principle of " following the classic and conforming to pharmacopoeia" , and in combination with the modern actual situation, the reasonable dose of Pinelliae Rhizoma in the 17 formulas from the Catalogue of Ancient Famous Classical Formulas (The First Batch) is determined. According to the records of the original book, the evolution of past dynasties and the consideration of the current clinical application, dosage regimen and administration methods of the 17 famous classical formulas and so on, the authors suggested that the dosages of Pinelliae Rhizoma in Banxia Houpotang and Maimendong Tang are 15.0 g, its dosages in Wendantang and Sangbaipi Tang are 6.0 g, dosages of Pinelliae Rhizoma in Xuanfu Daizhe Tang, Zhuye Shigaotang, Banxia Xiexintang, Gancao Xiexintang, Huangliantang, Gualou Xiebai Banxiatang, Houpo Mahuangtang and Jinshui Liujunjian are 7.5 g, the dosages of Pinelliae Rhizoma in Zhurutang, Shengyang Yiweitang and Yangweitang are 6.7, 4.5, 5.0 g, respectively, dosages of Pinelliae Rhizoma in Banxia Baizhu Tianma Tang and Huopo Xialing Tang are 5.6 g.

Analysis of Banxia Houpo Tang Based on Ancient Literatures / 中国实验方剂学杂志

Banxia Houpo Tang is widely used in modern clinics with definite curative effect. It is one of the classic famous prescriptions in the Catalogue of Ancient Classic Famous Recipes（First Batch） published by the State Administration of Traditional Chinese Medicine（TCM） in 2018. Using bibliometrics methods，collect relevant literatures of Banxia Houpo Tang in ancient medical books，analyze and verify the origin，historical evolution，composition，prescription，function，dosage，artillery，preparation method and decoction method of prescription. A total of 259 related ancient literature data were obtained，involving 107 TCM books. The inductive analysis found that Banxia Houpo Tang originated from ZHANG Zhong-jing's Synopsis of the Golden Chamberin the Han dynasty and consisted of the five flavors of Pinelliae Rhizoma，Magnoliae Officinalis Cortex，Poria，Perillae Folium and Zingiberis Rhizoma Recens. Houpo Tang，Qiqi Tang，Siqi Tang，Daqiqi Tang and other synonyms have appeared in the records of medical records of all dynasties. The prescription composition，preparation method and decoction method are used by later generations of medical practitioners. The analysis of related prescriptions is also rarely disputed. The dosage of drugs used in Banxia Houpo Tang can be calculated as 1g or 3 g. The drug processing method is different from the original one. Pinelliae Rhizoma should choose Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine and Magnoliae Officinalis Cortex as "Jianghoupu". The rest of the drug processing methods respect the 2015 edition of Chinese Pharmacopoeia. The cardiology of its treatment has also been extended and expanded. In addition to the symptoms of "burning in the pharynx" recorded by the original party，this side can also be used for heart diseases such as heartache，chest tightness，sorrow，vomiting，choking noisy and other spleen and stomach disease syndrome and spermatorrhea，turbidity，scorching and other lower coke disease syndrome.

Discussion on Use of Pinelliae Rhizoma Processed Products in Famous Classical Formulas / 中国实验方剂学杂志

There are 17 formulas containing Pinelliae Rhizoma in the Catalogue of Ancient Famous Classical Formulas (the First Batch), most of which are only labeled with " washing with decoction" or without any processing method, which is inconsistent with the current use requirements and brings confusion to research and development of related famous classical formulas. Through combing the records of famous classical formulas in the original book, contemporary works and later works, the usage of processed products of Pinelliae Rhizoma in the evolution of past dynasties was contrasted, and the efficacy, indications and compatibility significance of different formulas were analyzed, according to the principle of " respecting the ancient but not confining the ancient" , the authors suggested that the 17 famous classical formulas should use the processed products of Pinelliae Rhizoma in the 2015 edition of Chinese Pharmacopoeia, including Pinelliae Rhizoma Praeparatum, Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Pinelliae Rhizoma Praeparatum cum Alumine. Among them, Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine should be used in Banxia Xiexintang, Gancao Xiexintang, Huangliantang, Xuanfu Daizhe Tang, Zhuye Shigaotang, Banxia Houpotang, Maimendong Tang, Gualou Xiebai Banxiatang, Wendantang, Zhurutang, Jinshui Liujun Jian and Yangweitang, Pinelliae Rhizoma Praeparatum should be used in Shengyang Yiweitang, Houpo Mahuangtang, Banxia Baizhu Tianma Tang and Huopo Xialing Tang, and Pinelliae Rhizoma Praeparatum cum Alumine should be used in Sangbaipi Tang.

Association between Lipoprotein (a) Levels and Metabolic Syndrome in a Middle-aged and Elderly Chinese Cohort.

OBJECTIVE: The association between lipoprotein (a) [Lp(a)] levels and metabolic syndrome (MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between Lp(a) levels and MetS in a middle-aged and elderly Chinese cohort. METHODS: A cross-sectional study of 10,336 Chinese adults aged 40 years or older was conducted in Jiading District, Shanghai, China. Logistic regression analysis was used to evaluate the association between serum Lp(a) levels and MetS. RESULTS: In the overall population, 37.5% of participants had MetS. Compared with individuals in the lowest quartile of serum Lp(a) levels, those in the highest quartile had a lower prevalence of MetS (30.9% vs. 46.9%, P for trend < 0.0001). Multivariate logistic regression analyses showed that compared with participants in the bottom quartile of serum Lp(a) levels, those in the top quartile had decreased odds ratio (OR) for prevalent MetS [multivariate-adjusted OR 0.45 (95% confidence interval 0.39-0.51); P < 0.0001]. Additionally, Lp(a) level was conversely associated with the risk of central obesity, high fasting glucose, high triglycerides, and low HDL cholesterol, but not with hypertension. Stratified analyses suggested that increasing levels of Lp(a) was associated with decreased risk of MetS in all the subgroups. CONCLUSION: Serum Lp(a) level was inversely associated with the risk of prevalent MetS in a middle-aged and elderly Chinese cohort.

Ideal Cardiovascular Health is Inversely Associated with Subclinical Atherosclerosis: A Prospective Analysis.

OBJECTIVE: Ideal cardiovascular health (CVH) could predict a lower risk of developing cardiovascular diseases. This study was conducted to investigate the association between ideal CVH and subclinical atherosclerosis in a population cohort of Chinese adults aged ⪖ 40 years. METHODS: This study was designed as a cross-sectional analysis of 8,395 participants who had complete data at baseline and a prospective analysis of 4,879 participants who had complete data at 4.3 years of follow-up. Ideal CVH metrics were defined according to the American Heart Association. Subclinical atherosclerosis was evaluated by plaques in carotid arteries, carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), and urinary albumin-to-creatinine ratio (UACR). RESULTS: Both the prevalence and incidence of atherosclerosis measures were found to be decreased with increasing numbers of ideal CVH metrics at baseline (all P values for trend < 0.01). The levels of CIMT and UACR at follow-up showed an inverse and significant association with the numbers of ideal CVH metrics at baseline (both P values for trend < 0.05) but a borderline significant association with baPWV (P for trend = 0.0505). Taking participants with 0-1 ideal metric as reference, we found that participants with 5-6 ideal metrics had significantly lower risks of developing carotid plaques (odds ratio, OR = 0.46; 95% confidence interval, CI 0.27-0.79), increased CIMT (OR = 0.60; 95% CI 0.42-0.84), and increased baPWV (OR = 0.57; 95% CI 0.34-0.97) after full adjustments. A significant interactive effect of age and CVH was detected on CIMT and baPWV progression (both P values for interaction < 0.05). CONCLUSION: The numbers of ideal CVH metrics showed a significant and inverse association with the risk of developing subclinical atherosclerosis in middle-aged and elderly Chinese adults, whereas its dose-response effect was attenuated in individuals aged ≥ 60 years and partially weakened in male participants.

Association between Coronary Atherosclerotic Plaque Composition and Cardiovascular Disease Risk.

OBJECTIVE: The objective of this study is to determine whether coronary atherosclerotic plaque composition is associated with cardiovascular disease (CVD) risk in Chinese adults. METHODS: We performed a cross-sectional analysis in 549 subjects without previous diagnosis or clinical symptoms of CVD in a community cohort of middle-aged Chinese adults. The participants underwent coronary computed tomography (CT) angiography for the evaluation of the presence and composition of coronary plaques. CVD risk was evaluated by the Framingham risk score (FRS) and the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score. RESULTS: Among the 549 participants, 267 (48.6%) had no coronary plaques, 201 (36.6%) had noncalcified coronary plaques, and 81 (14.8%) had calcified or mixed coronary plaques. The measures of CVD risk including FRS and ASCVD risk score and the likelihood of having elevated FRS significantly increased across the groups of participants without coronary plaques, with noncalcified coronary plaques, and with calcified or mixed coronary plaques. However, only calcified or mixed coronary plaques were significantly associated with an elevated ASCVD risk score [odds ratio (OR) 2.41; 95% confidence interval (CI) 1.09-5.32] compared with no coronary plaques, whereas no significant association was found for noncalcified coronary plaques and elevated ASCVD risk score (OR 1.25; 95% CI 0.71-2.21) after multivariable adjustment. CONCLUSION: Calcified or mixed coronary plaques might be more associated with an elevated likelihood of having CVD than noncalcified coronary plaques.

Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population.

BACKGROUND: Matrix metalloproteinases (MMPs) are capable of degrading and modifying most components of the extracellular matrix (ECM) and the basal membrane (BM), and play crucial roles in cancer invasion and metastasis. MMP gene expressions were regulated primarily at the transcriptional level, which was associated with tumor spread and patient prognosis. Polymorphisms in MMPs have been reported to be associated with non-small cell lung cancer (NSCLC). The objective of this study aim to evaluate the serum levels and polymorphisms of MMP-9 and MMP-13 in non-small cell lung cancer patients compared to normal subjects and their correlation to non-small cell lung cancer histopathology findings in Southern Chinese people. METHODS: This case⁻control study included 245 patients with NSCLC and 258 healthy controls. Genomic DNA was extracted by using DNA extraction kit, genotyping was confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing, and serum levels of MMP-9 and MMP-13 were measured by using a specific ELISA, Human Matrix Metalloproteinase Enzyme Immunoassay Kits. Statistical analysis was carried out using the SPSS 23.0 software package. RESULTS: The subjects carrying the TT genotype had a decreased risk of lung cancer in MMP9-1562C/T comparing with the CC genotype (p = 0.00, OR = 0.45, 95% CI = 0.29⁻0.68), and the MMP13-77 AA genotype was associated with a decreased risk of NSCLC by comparing with the GG genotype (p = 0.03, OR = 0.56, 95% CI = 0.33⁻0.94). Moreover, the C allele of MMP9-1562C/T could increase serum level of NSCLC in compared with the A allele (OR = 1.19, 95% CI = 0.75⁻1.89). Similarly, the AA genotype of MMP13 might be a marker of decreased serum level of lung cancer (OR = 0.76, 95% CI = 0.51⁻1.14). CONCLUSIONS: The results of these analyses underline the support of the notion that the CC genotype of MMP9-1562C/T and GG genotypes of MMP13-77G/A were associated with the increased risk NSCLC, and the serum levels of MMP9 and MMP13 were consistent with the results of the SNP analysis. MMP13 and MMP9 might be function as a key oncogene in NSCLC with a Southern Chinese population. Combined detection of SNP and enzyme activity between MMP9 and MMP13 are expected to be a potential diagnostic method of non-small cell lung cancer.