Early-life exposure to the Great Chinese Famine and gut microbiome disruption across adulthood for type 2 diabetes: three population-based cohort studies.

BACKGROUND: The early life stage is critical for the gut microbiota establishment and development. We aimed to investigate the lifelong impact of famine exposure during early life on the adult gut microbial ecosystem and examine the association of famine-induced disturbance in gut microbiota with type 2 diabetes. METHODS: We profiled the gut microbial composition among 11,513 adults (18-97 years) from three independent cohorts and examined the association of famine exposure during early life with alterations of adult gut microbial diversity and composition. We performed co-abundance network analyses to identify keystone taxa in the three cohorts and constructed an index with the shared keystone taxa across the three cohorts. Among each cohort, we used linear regression to examine the association of famine exposure during early life with the keystone taxa index and assessed the correlation between the keystone taxa index and type 2 diabetes using logistic regression adjusted for potential confounders. We combined the effect estimates from the three cohorts using random-effects meta-analysis. RESULTS: Compared with the no-exposed control group (born during 1962-1964), participants who were exposed to the famine during the first 1000 days of life (born in 1959) had consistently lower gut microbial alpha diversity and alterations in the gut microbial community during adulthood across the three cohorts. Compared with the no-exposed control group, participants who were exposed to famine during the first 1000 days of life were associated with consistently lower levels of keystone taxa index in the three cohorts (pooled beta - 0.29, 95% CI - 0.43, - 0.15). Per 1-standard deviation increment in the keystone taxa index was associated with a 13% lower risk of type 2 diabetes (pooled odds ratio 0.87, 95% CI 0.80, 0.93), with consistent results across three individual cohorts. CONCLUSIONS: These findings reveal a potential role of the gut microbiota in the developmental origins of health and disease (DOHaD) hypothesis, deepening our understanding about the etiology of type 2 diabetes.

Alpiniamides E-G from the Saline Lake-Derived Streptomyces sp. QHA48 and Their Lipid Accumulation Inhibitory Activity.

Alpiniamides E-G, three previously unreported linear polyketide derivatives, along with two known compounds, were isolated from Streptomyces sp. QHA48, which was isolated from the saline lakes of Qinghai-Tibet Plateau. The structures of these compounds were determined through analysis of their spectroscopic data, as well as density functional theory prediction of NMR chemical shifts, application of the DP4+ algorithm and electronic circular dichroism (ECD) calculations. In a cell-based lipid-lowering assay, all five alpiniamides exhibited significant inhibition of lipid accumulation in HepG2 cells without inducing cytotoxic effects at a concentration of 27 µM.

Erythrocyte Membrane Polyunsaturated Fatty Acids Are Associated with Incidence of Metabolic Syndrome in Middle-Aged and Elderly People-An 8.8-Year Prospective Study.

BACKGROUND: The total and specific types of polyunsaturated fatty acids (PUFAs) related to metabolic syndrome (MetS) remain inconsistent. OBJECTIVE: We assessed the association of erythrocyte n-3 and n-6 PUFAs with MetS and the components of MetS in a cohort population. METHODS: This prospective analysis included 2754 participants (aged 40-75 y) from the Guangzhou Nutrition and Health Study (2008-2019) in China. Erythrocyte PUFAs at baseline were measured using gas chromatography. MetS was assessed every 3 y according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariable Cox proportional hazard models were used to evaluate HRs and 95% CIs. RESULTS: We identified 716 incident cases of MetS. The primary analyses showed that the HRs (95% CIs) of MetS (tertile 3 versus 1) were 0.67 (0.56, 0.80) for n-3 PUFAs and 0.70 (0.58, 0.85) for n-6 PUFAs (all Ps trend <0.001). The secondary outcomes showed that, higher erythrocyte very-long-chain (VLC) PUFAs [20:3n-3, docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), arachidonic acid (ARA), and 22:4n-6], but lower α-linolenic acid (ALA) and γ-linolenic acid (GLA), tended to be associated with lower incidences of MetS and its components; among individual MetS components, the associations of PUFAs were more pronounced for hypertriglyceridemia (HTG) and hypertension, followed by low high-density lipoproten (HDL) cholesterol. Significantly higher concentrations of n-3 PUFAs (total, DPA, and DHA) and n-6 PUFAs (total, ARA, and 22:4) were observed in participants with improved (versus progressed) status of MetS (all Ps trend ≤0.003). CONCLUSION: This study reveals that higher erythrocyte VLC n-3 and n-6 PUFAs, but lower 18-carbon PUFAs (ALA and GLA), are associated with lower risks of MetS components (HTG, hypertension, and low HDL cholesterol) and thereby lower MetS incidence in Chinese adults.

Urinary equol, but not daidzein and genistein, was inversely associated with the risk of type 2 diabetes in Chinese adults.

PURPOSE: Many studies have examined the association of isoflavone intake with type 2 diabetes (T2D), and produced inconsistent results. Few studies, however, explored the association using objective biomarkers (particular for daidzein metabolite-equol) of isoflavones. We aimed to explore the association of urinary equol, daidzein and genistein concentrations with T2D and examine the mediating roles of high-sensitivity C-reactive protein (hsCRP) and retinol binding protein 4 (RBP4). METHODS: This prospective study included 2818 subjects. Urinary concentrations of equol, daidzein and genistein were measured by high-performance liquid chromatography-tandem mass spectrometry. The associations between urinary isoflavones and T2D incidence were evaluated by cox proportional hazards model. RESULTS: After adjustment for covariates, urinary equol except daidzein and genistein was inversely associated with T2D incidence. In comparison with the first tertile, multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for T2D incidence in the second and third tertile of equol concentration were 0.52 (0.37, 0.73) and 0.72 (0.53, 0.97), respectively. In stratified analyses by sex, the HR (95% CI) of men in the second vs. first tertile of equol was 0.29 (0.14, 0.58). Equivalent estimation in women was 0.67 (0.45, 1.01). Neither women nor men in the third tertile showed significant difference of T2D incidence compared with the first tertile. In path analyses, there was no evidence of mediating effects of hsCRP and RBP4 on the "equol-T2D" relationship. CONCLUSIONS: Urinary equol was favorably associated with a decreased T2D incidence in Chinese adults. The equol-T2D relationship might not be mediated by hsCRP and RBP4. TRIAL REGISTRATION: This study has been registered at http://www.clinicaltrials.gov as NCT03179657.

Sinomenine Hydrochloride Protects IgA Nephropathy Through Regulating Cell Growth and Apoptosis of T and B Lymphocytes.

Purpose: Sinomenine hydrochloride (SH) is used to treat chronic inflammatory diseases such as rheumatoid arthritis and may also be efficacious against Immunoglobulin A nephropathy (IgAN). However, no trial has investigated the molecular mechanism of SH on IgAN. Therefore, this study aims to investigate the effect and mechanism of SH on IgAN. Methods: The pathological changes and IgA and C3 depositions in the kidney of an IgAN rat model were detected by periodic acid-Schiff (PAS) and direct immunofluorescence staining. After extracting T and B cells using immunomagnetic beads, we assessed their purity, cell cycle phase, and apoptosis stage through flow cytometry. Furthermore, we quantified cell cycle-related and apoptosis-associated proteins by Western blotting. Results: SH reduced IgA and C3 depositions in stage 4 IgAN, thereby decreasing inflammatory cellular infiltration and mesangial injury in an IgAN model induced using heteroproteins. Furthermore, SH arrested the cell cycle of lymphocytes T and B from the spleen of IgAN rats. Regarding the mechanism, our results demonstrated that SH regulated the Cyclin D1 and Cyclin E1 protein levels for arresting the cell cycle and it also regulated Bax and Bcl-2 protein levels, thus increasing Cleaved caspase-3 protein levels in Jurkat T and Ramos B cells. Conclusion: SH exerts a dual regulation on the cell cycle and apoptosis of T and B cells by controlling cell cycle-related and apoptosis-associated proteins; it also reduces inflammatory cellular infiltration and mesangial proliferation. These are the major mechanisms of SH in IgAN.

Epigallocatechin-3-gallate confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis, apoptosis, and autophagy via modulation of 14-3-3η.

Previous studies have demonstrated that the underlying mechanisms of myocardial ischemia/reperfusion injury (MIRI) are complex and involve multiple types of regulatory cell death, including ferroptosis, apoptosis, and autophagy. Thus, we aimed to identify the mechanisms underlying MIRI and validate the protective role of epigallocatechin-3-gallate (EGCG) and its related mechanisms in MIRI. An in vivo and in vitro models of MIRI were constructed. The results showed that pretreatment with EGCG could attenuate MIRI, as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) activity and apoptosis, inhibited iron overload, abnormal lipid metabolism, preserved mitochondrial function, decreased infarct size, maintained cardiac function, decreased reactive oxygen species (ROS) level, and reduced TUNEL-positive cells. Additionally, EGCG pretreatment could attenuate ferroptosis, apoptosis, and autophagy induced by MIRI via upregulating 14-3-3η protein levels. Furthermore, the protective effects of EGCG could be abolished with pAd/14-3-3η-shRNA or Compound C11 (a 14-3-3η inhibitor) but not pAd/NC-shRNA. In conclusion, EGCG pretreatment attenuated ferroptosis, apoptosis, and autophagy by mediating 14-3-3η and protected cardiomyocytes against MIRI.

Impact of dairy supplementation on bone acquisition in children's limbs: a 12-month cluster-randomized controlled trial and meta-analysis.

The impact of milk on bone health in rural preschoolers is under-researched. This study, through a clinical trial and a meta-analysis, finds that milk supplementation enhances forearm and calcaneus bone acquisition in children, supporting the benefits of daily milk consumption. PURPOSE: This study evaluated the impact of dairy supplementation on bone acquisition in children's limbs through a cluster-randomized controlled trial and a meta-analysis. METHODS: The trial involved 315 children (4-6 year) from Northwest China, randomized to receive either 390 ml of milk daily (n = 215) or 20-30 g of bread (n = 100) over 12 months. We primarily assessed bone mineral density (BMD) and content (BMC) changes at the limbs, alongside bone-related biomarkers, measured at baseline, the 6th and 12th months. The meta-analysis aggregated BMD or BMC changes in the forearm/legs/calcaneus from published randomized trials involving children aged 3-18 years supplemented with dairy foods (vs. control group). RESULTS: Of 278 completed the trial, intention-to-treat analysis revealed significant increases in BMD (4.05% and 7.31%) and BMC (4.69% and 7.34%) in the left forearm at the 6th and 12th months in the milk group compared to controls (P < 0.001). The calcaneus showed notable improvements in BMD (2.01%) and BMC (1.87%) at 6 months but not at 12 months. Additionally, milk supplementation was associated with beneficial changes in bone resorption markers, parathyroid hormone (- 12.70%), insulin-like growth factor 1 (6.69%), and the calcium-to-phosphorus ratio (2.22%) (all P < 0.05). The meta-analysis, encompassing 894 children, indicated that dairy supplementation significantly increased BMD (SMD, 0.629; 95%CI: 0.275, 0.983) and BMC (SMD, 0.616; 95%CI: 0.380, 0.851) (P < 0.05) in the arms, but not in the legs (P > 0.05). CONCLUSION: Milk supplementation significantly improves bone health in children's forearms, underscoring its potential as a strategic dietary intervention for bone development. Trial registration NCT05074836.

Mapping the gut microecological multi-omics signatures to serum metabolome and their impact on cardiometabolic health in elderly adults.

BACKGROUND: Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health. METHODS: This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics. FINDINGS: Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%-10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%-49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%-95%) and 19% (95% CI: 11%-27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks. INTERPRETATION: This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites. FUNDING: This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the 'Pioneer' and 'Leading goose' R&D Program of Zhejiang.

Two new di-tert-butyl-type compounds from a saline-lake derived Streptomyces sp. XZB42.

Two novel di-tert-butyl-type structures (1-2), and five known compounds (3-7) were isolated from the chemical investigations of a saline lake actinomycete, Streptomyces sp. XZB42. The structures of the new compounds were elucidated by extensive NMR spectroscopic analysis, HRESIMS data, GIAO (gauge-including atomic orbitals) NMR and specific optical rotation (SOR).

Increased Dietary Intakes of Total Protein, Animal Protein and White Meat Protein Were Associated with Reduced Bone Loss-A Prospective Analysis Based on Guangzhou Health and Nutrition Cohort, South China.

In this study, we aimed to prospectively investigate the relationships between different types of dietary protein and changes in bone mass in Chinese middle-aged and elderly people. Dietary intakes were evaluated by means of a validated food frequency questionnaire. Bone mineral density (BMD) was measured using a dual-energy bone densitometer at multiple bone sites. Multivariable regression models were applied to investigate the associations of the participants' dietary intakes of total protein, intakes of protein from various sources, and amino acid intakes with the annualized changes in BMD during a 3-year follow-up. A total of 1987 participants aged 60.3 ± 4.9 years were included in the analyses. Multivariable linear regression results showed that dietary intakes of total protein, animal protein, and protein from white meat were positively correlated with BMD changes, with standardized coefficients (ß) of 0.104, 0.073, and 0.074 at the femur neck (p < 0.01) and 0.118, 0.067, and 0.067 at the trochanter (p < 0.01), respectively. With each increase of 0.1g·kg-1·d-1 in animal protein and white meat protein intakes, the BMD losses were reduced by 5.40 and 9.24 mg/cm2 at the femur neck (p < 0.05) and 1.11 and 1.84 mg/cm2 at the trochanter (p < 0.01), respectively. Our prospective data, obtained from Chinese adults, showed that dietary total and animal protein, especially protein from white meat, could significantly reduce bone loss at the femur neck and trochanter.

The gut microbiota-bile acid axis mediates the beneficial associations between plasma vitamin D and metabolic syndrome in Chinese adults: A prospective study.

BACKGROUND & AIMS: Previous studies have suggested that circulating 25-hydroxyvitamin D (25 [OH]D, VD) and the gut microbiota-bile acid axis play crucial roles in metabolic health. Exploring the mediating role of the gut microbiota-bile acid axis would improve our understanding of the mechanisms underlying the effects of VD on human metabolic health. This study examined the association between plasma 25(OH)D and the prevalence/incidence of metabolic syndrome (MetS) and the mediating role of the gut microbiota-bile acid axis. METHODS: This prospective study included 3180 participants with plasma 25(OH)D data at baseline and 2966 participants with a 9-year follow-up. MetS was determined every three years. The gut microbiota was analyzed by 16S rRNA sequencing in 1752 participants, and targeted bile acid metabolites in feces were further determined in 974 participants using UPLC‒MS/MS at the middle of the study. Mediating roles of microbiota and bile acids in the VD-MetS associations were analyzed using mediation/path analyses adjusted for potential confounders. RESULTS: Among the 2966 participants who were followed-up, 1520, 193, 647, and 606 were MetS-free (normal), recovered, had incident MetS, and had persistent MetS, respectively. The multivariable-adjusted ORs (95% CIs) of MetS prevalence were 0.65 (0.50, 0.84) for baseline MetS and 0.46 (0.33, 0.65) for 9-year persistent MetS in quartile 4 (compared to quartile 1) of plasma 25(OH)D (median: 37.7 vs. 19.6, ng/ml). The corresponding HR (95% CI) of 9-year MetS incidence was 0.71 (0.56, 0.90) (all P-trend < 0.05). Higher VD concentrations were associated with greater α-diversity of the gut microbiota, which was inversely correlated with MetS risk. The groups classified by VD and MetS status had significantly different ß-diversity. Ruminiclostridium-6 and Christensenellaceae R-7 group were enriched in the high-VD group and were inversely associated with MetS. However, opposite associations were observed for Lachnoclostridium and Acidaminococcus. The overlapping differential microbial score (ODMS) developed from the four differential genera explained 12.2% of the VD-MetS associations (Pmediation = 0.015). Furthermore, the fecal bile acid score created from 11 differential bile acids related to ODMS and MetS mediated 34.2% of the association between ODMS and MetS (Pmediation = 0.029). Path analyses showed that the inverse association between plasma 25(OH)D and MetS could be mediated by the gut microbiota-bile acid axis. CONCLUSIONS: The findings suggest that the gut microbiota-bile acid axis partially mediates the beneficial association between plasma 25(OH)D and the risk of persistent MetS and incident MetS in the Chinese population.

Maternal and embryonic signals cause functional differentiation of luminal epithelial cells and receptivity establishment.

Embryo implantation requires temporospatial maternal-embryonic dialog. Using single-cell RNA sequencing for the uterus from 2.5 to 4.5 days post-coitum (DPC) and bulk sequencing for the corresponding embryos of 3.5 and 4.0 DPC pregnant mice, we found that estrogen-responsive luminal epithelial cells (EECs) functionally differentiated into adhesive epithelial cells (AECs) and supporting epithelial cells (SECs), promoted by progesterone. Along with maternal signals, embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, respectively, enhancing the attachment of embryos to the endometrium and furthering embryo development. This differentiation process was largely conserved between humans and mice. Notably, the developmental defects of SOX9-positive human endometrial epithelial cells (similar to mouse EEC) were related to thin endometrium, whereas functional defects of SEC-similar unciliated epithelial cells were related to recurrent implantation failure (RIF). Our findings provide insights into endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is crucial for endometrial receptivity.

Percutaneous contrast-enhanced ultrasound for localization and qualitative diagnosis of sentinel lymph nodes in cutaneous malignant melanoma of lower extremities: a preliminary study.

BACKGROUND: To explore the feasibility of sentinel lymph node (SLN) tracing by percutaneous contrast-enhanced ultrasound (pCEUS) in patients with cutaneous malignant melanoma (CMM) and the ability to enhance patterns of SLNs in diagnosing lymph nodes (LNs) metastases. METHODS: Fifty-three patients with CMM of the lower extremities treated at our hospital were included in the study. All the participants received pCEUS preoperatively. The enhanced lymphatic channels (LCs) and associated SLNs were observed and tracked in real-time. The number of enhanced LCs and enhancing patterns of SLNs were recorded. Subsequently, SLNs localized by pCEUS were pathologically examined. RESULTS: Of the 53 cases, SLNs were successfully localized by pCEUS in 48 cases. In total, there were 59 detected SLNs averaging 1.23±0.42 SLNs per case. The main lymphatic drainage patterns (LDPs) were the following: one enhanced LC pointed to one or more than one SLN, and multiple enhanced LCs pointed to one or multiple SLNs. There were four enhancing patterns of SLNs (uniform, annular, uneven, and no enhancement), among which the first two were considered benign nodes, while the latter two were considered metastatic nodes. With pathological results as the gold standard, the diagnostic sensitivity and specificity by pCEUS were 90.9% and 75.0%, respectively. CONCLUSIONS: Contrast-enhanced ultrasound (US) is a feasible approach for SLN identification in patients with CMM of the lower extremities. Enhancing patterns of SLNs may help predict metastasizing SLNs. This novel method may be a promising technique for clinical application.

Circulating Proteome and Progression of Type 2 Diabetes.

CONTEXT: Circulating proteomes may provide intervention targets for type 2 diabetes (T2D). OBJECTIVE: We aimed to identify proteomic biomarkers associated with incident T2D and assess its joint effect with dietary or lifestyle factors on the T2D risk. METHODS: We established 2 nested case-control studies for incident T2D: discovery cohort (median 6.5 years of follow-up, 285 case-control pairs) and validation cohort (median 2.8 years of follow-up, 38 case-control pairs). We integrated untargeted mass spectrometry-based proteomics and interpretable machine learning to identify T2D-related proteomic biomarkers. We constructed a protein risk score (PRS) with the identified proteomic biomarkers and used a generalized estimating equation to evaluate PRS-T2D relationship with repeated profiled proteome. We evaluated association of PRS with trajectory of glycemic traits in another non-T2D cohort (n = 376). Multiplicative interactions of dietary or lifestyle factors with PRS were evaluated using logistic regression. RESULTS: Seven proteins (SHBG, CAND1, APOF, SELL, MIA3, CFH, IGHV1-2) were retained as the proteomic biomarkers for incident T2D. PRS (per SD change) was positively associated with incident T2D across 2 cohorts, with an odds ratio 1.29 (95% CI, 1.08-1.54) and 1.84 (1.19-2.84), respectively. Participants with a higher PRS had a higher probability showing unfavored glycemic trait trajectory in the non-T2D cohort. Red meat intake and PRS showed a multiplicative interaction on T2D risk in the discovery (P = 0.003) and validation cohort (P = 0.017). CONCLUSION: This study identified proteomic biomarkers for incident T2D among the Chinese populations. The higher intake of red meat may synergistically interact with the proteomic biomarkers to exaggerate the T2D risk.

Continuous renal replacement therapy rescued life-threatening capillary leak syndrome in an extremely-low-birth-weight premature: a case report.

BACKGROUND: Capillary leak syndrome (CLS) is a rare disease characterized by profound vascular leakage and presents as a classic triad of hypotension, hypoalbuminemia and hemoconcentration. Severe CLS is mostly induced by sepsis and generally life-threatening in newborns, especially in premature infants. Continuous renal replacement therapy (CRRT) plays an important role of supportive treatment for severe CLS. Unfortunately, CRRT in preterm infants has rarely been well defined. CASE PRESENTATION: We report the case of a 11-day-old girl with CLS caused by sepsis, who was delivered by spontaneous vaginal delivery (SVD) at gestational age of 25 weeks and 4 days, and a birth weight of 0.89 Kilograms(kg). The infant received powerful management consisting of united antibiotics, mechanical ventilation, intravenous albumin and hydroxyethyl starch infusion, vasoactive agents, small doses of glucocorticoids and other supportive treatments. However, the condition rapidly worsened with systemic edema, hypotension, pulmonary exudation, hypoxemia and anuria in about 40 h. Finally, we made great efforts to perform CRRT for her. Fortunately, the condition improved after 82 h' CRRT, and the newborn was rescued and gradually recovered. CONCLUSION: CRRT is an effective rescue therapeutic option for severe CLS and can be successfully applied even in extremely-low-birth-weight premature.

Isoflavone biomarkers are inversely associated with atherosclerosis progression in adults: a prospective study.

BACKGROUND: Many studies have examined associations between dietary isoflavones and atherosclerosis, but few used objective biomarkers. OBJECTIVES: We examined the associations of isoflavone biomarkers (primary analyses) and equol production (secondary analyses) with the progression of carotid intima-media thickness (cIMT), and whether inflammation, systolic blood pressure (SBP), blood lipids, and sex hormone-binding globulin (SHBG) mediated these associations, in Chinese adults. METHODS: This 8.8-y prospective study included 2572 subjects (40-75 y old) from the GNHS (Guangzhou Nutrition and Health Study; 2008-2019). The concentrations of daidzein, genistein, and equol were assayed by an HPLC-tandem MS in serum (n = 2572) at baseline and in urine (n = 2220) at 3-y intervals. The cIMT of the common carotid artery (CCA) and bifurcation segment were measured by B-mode ultrasound every 3 y, and the progressions of cIMT ( ∆cIMT) were estimated using the regression method. RESULTS: Multivariable linear mixed-effects models (LMEMs) and ANCOVA revealed that subjects with higher serum isoflavones tended to have lower increases of CCA-cIMT. The mean ± SEM differences in 8.8-y ∆CCA-cIMT between extreme tertiles of serum isoflavones were -17.1 ± 8.4, -20.6 ± 8.3, and -23.3 ± 10.4 µm for daidzein, total isoflavone, and equol (P-trends < 0.05), respectively. LMEMs showed that the estimated yearly changes (95% CIs) (µm/y) in CCA-IMT were -2.0 (-3.8, -0.3), -1.9 (-3.6, -0.1), and -2.1 (-3.8, -0.3) in the highest (compared with the lowest) tertile of daidzein, genistein, and total isoflavones, respectively (P-interaction < 0.05). Path analyses indicated that the serum equol-atherosclerosis association was mediated by increased SHBG and decreased SBP. Similar beneficial associations were observed in the secondary analyses. CONCLUSIONS: Serum isoflavones and equol exposure were associated with reduced cIMT progression, mediated by SHBG and SBP.

Associations of Serum Carotenoids with DXA-Derived Body Fat and Fat Distribution in Chinese Adults: A Prospective Study.

BACKGROUND: Most previous studies have examined the associations between carotenoids and anthropometrics with cross-sectional designs. Few studies have investigated the associations between serum carotenoids and fat mass and fat distribution (general vs central type). OBJECTIVE: This study aimed to explore the associations of serum carotenoids with body fat and fat distribution in Chinese adults. DESIGN: Cross-sectional and longitudinal analyses of a prospective, community-based cohort were performed. PARTICIPANTS/SETTING: There were 4,048 participants aged 40 to 75 years recruited in the Guangzhou Nutrition and Health Study from 2008 to 2013. MAIN OUTCOME MEASURES: Serum carotenoids were assessed at baseline. Anthropometrics, fat mass (FM), and percentage FM (%FM) over the total body, trunk, limbs, and android and gynoid regions were obtained by dual-energy x-ray absorptiometry for 3,002 participants between 2011 and 2013 and for 2,537 participants after 3.1 years. STATISTICAL ANALYSIS: Cross-sectional and longitudinal analyses were performed to compare the mean differences in adiposity indices among the quartiles of carotenoids. RESULTS: Covariance analyses showed significant inverse associations between serum total carotenoid levels and adiposity indices cross-sectionally (all P trends<0.05). The percentage mean differences in quartile 4 (vs 1) in FM and %FM were much more pronounced in the trunk (-15.4% and -7.74%) and android area (-16.6% and -8.59%) than those in the limbs (-8.31% and -4.51%) and gynoid area (-7.76% and -2.71%) (all P<0.001). Longitudinal results revealed that higher total carotenoids were associated with significantly lower 3-year increases in body mass index (calculated as kg/m2); waist circumference; waist-to-hip ratio; body FM in the limbs and android and gynoid area; and %FM in total body, trunk, and limbs (all P trends<0.05). Regarding individual carotenoids, ß-carotene tended to have the most notable beneficial associations with the majority of fat indices, especially for cross-sectional analyses. CONCLUSIONS: Serum carotenoid concentrations are inversely associated with body fat, especially in the abdominal region, in Chinese adults.

Clinicopathological characteristics and prognosis of colorectal mucinous adenocarcinoma and nonmucinous adenocarcinoma: a surveillance, epidemiology, and end results (SEER) population-based study.

BACKGROUND: Mucinous adenocarcinoma (MC) is a rare histological subtype of colorectal adenocarcinoma. Previous studies investigating the prognosis of MC have conflicting results and the proper treatment of MC remains unclear. METHODS: This retrospective study presents the clinicopathological characteristics and prognosis of MC. This cohort study collected data from April 1 through August 01, 2018. This study used data on 107,735 patients with nonmucinous adenocarcinoma (NMC) and 9,494 with MC between 2009 and 2013 from the Surveillance, Epidemiology, and End Results program (SEER). Clinicopathological features were analyzed by chi-square test and survival curves by the Kaplan-Meier method. We used propensity score matching (PSM) to account for potential bias. Logistic regression and Cox proportional hazards models were used to compare and calculate adjusted risks of MC death. RESULTS: MC was more frequent in patients with older age, large tumor size and moderate tumor grade compared with NMC (P<0.001). Five-year survival was lower for MC patients than NMC patients (P<0.001). Older age, later tumor node metastasis (TNM) stage and multiple tumors indicated a poorer prognosis while surgery gave better survival outcomes [hazard ratio (HR) =0.38; 95% confidence interval (CI), 0.33 to 0.44; P<0.001]. Younger age, left-side colon location and early disease stage were associated with better survival after surgery (P<0.001). CONCLUSIONS: Age, TNM stage, tumor number and treatment were indicators of prognosis and surgery gave better survival for MC patients compared with those without surgery. Our study contributes to their clinical treatment.

The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.

Objective: This study aimed to investigate the potential value of circumferential resection margin (CRM) in colon cancer prognostics. Summary Background Data: CRM has been extensively studied as an important prognostic factor in rectal and esophageal cancer, but not in colon cancer. Methods: Data from 6,681 CRM-positive patients and 25,908 CRM-negative patients diagnosed with colon cancer in 2010-2015 were obtained from the Surveillance, Epidemiology, and End Results database. Statistical analysis methods utilized included the chi-square test, Kaplan-Meier estimates, Cox proportional, and X-tile software analyses. Results: After propensity score matching, CRM positivity was found to be negatively related with survival (P < 0.001). X-tile software identified 0 and 30 mm as optimal cutoff values (P < 0.001) for prognosis, which was applicable only in stage II-IV patients. A 20 and 33% risk decrease were observed in patients with CRM between 0 and 30 mm [95% confidence interval (CI) = 0.76-0.84], and larger than 30 mm (95% CI = 0.62-0.71), respectively. Chemotherapy strongly benefited prognosis with a hazard ratio of 0.36 (95% CI = 0.34-0.38) for overall survival (OS). Patients with a CRM value of 0-30 mm seemed to benefit most from chemotherapy compared with other groups. CRM and number of regional lymph nodes are independent risk factors, and the latter is a good substitute for CRM in AJCC stage I patients. Conclusion: CRM positivity is a strong unfavorable survival indicator for colon cancer patients. A better outcome is expected with CRM values larger than 30 mm. This cutoff value only applied to stage II-IV patients. For stage I patients, number of regional lymph nodes is a good substitute to predict survival. Chemotherapy was another favorable prognostic factor, especially for patients with a CRM value between 0 and 30 mm.

Association Between Diet Inflammatory Index and Osteoporotic Hip Fracture in Elderly Chinese Population.

BACKGROUND: Chronic inflammation provides the substrate for various mechanisms involved in osteoporotic fracture. The Dietary Inflammatory Index (DII) could shed light on the effect of the inflammatory potential of the diet on osteoporotic hip fracture. OBJECTIVE: This study tested the hypothesis that higher DII scores are associated with greater hip fracture risk in an elderly Chinese population. METHODS: A 1:1 age- (±3 years), sex- and region-matched case-control study of 1050 pairs (female/male: 781/269) of elderly (age range = 52-83 years) Chinese was conducted in Guangdong, China (2009-2015). Cases were newly diagnosed (within 2 weeks) hip fracture patients and controls were recruited from either communities (n = 835 controls) or the hospital (n = 215). DII scores were calculated from self-reports using a validated 79-item food frequency questionnaire. Odds ratios (ORs) and their 95% confidence intervals (CIs) of the risk of hip fracture for DII scores were estimated from conditional logistic regression. RESULTS: The multivariable-adjusted ORs (95% CIs) for hip fracture across quartiles of DII scores were 1 (reference), 1.42 (1.01, 1.99), 1.63 (1.16, 2.28), and 2.44 (1.73, 3.45) (P trend <.001). Comparing extreme quartiles, the adjusted ORs (95% CIs) for hip fractures were 2.08 (1.38, 3.12) for female and 4.30 (1.89, 9.80) for male participants, respectively (P interaction = .26). When stratified by the source of controls, a dose-response positive relationship was observed between DII scores and hip fracture risk among community-based controls but not those from the hospital (P interaction = .16). CONCLUSIONS: A proinflammatory diet appears to be positively associated with hip fracture risk.