CRKL but not CRKII contributes to hemin-induced erythroid differentiation of CML.

Destruction of erythropoiesis process leads to various diseases, including thrombocytopenia, anaemia, and leukaemia. miR-429-CT10 regulation of kinase-like (CRKL) axis involved in development, progression and metastasis of cancers. However, the exact role of miR-429-CRKL axis in leukaemic cell differentiation are still unknown. The current work aimed to uncover the effect of miR-429-CRKL axis on erythropoiesis. In the present study, CRKL upregulation was negatively correlated with miR-429 downregulation in both chronic myeloid leukaemia (CML) patient and CR patient samples. Moreover, CRKL expression level was significantly decreased while miR-429 expression level was increased during the erythroid differentiation of K562 cells following hemin treatment. Functional investigations revealed that overexpression and knockdown of CRKL was remarkably effective in suppressing and promoting hemin-induced erythroid differentiation of K562 cells, whereas, miR-429 exhibited opposite effects to CRKL. Mechanistically, miR-429 regulates erythroid differentiation of K562 cells by downregulating CRKL via selectively targeting CRKL-3'-untranslated region (UTR) through Raf/MEK/ERK pathway. Conversely, CRKII had no effect on erythroid differentiation of K562 cells. Taken together, our data demonstrated that CRKL (but not CRKII) and miR-429 contribute to development, progression and erythropoiesis of CML, miR-429-CRKL axis regulates erythropoiesis of K562 cells via Raf/MEK/ERK pathway, providing novel insights into effective diagnosis and therapy for CML patients.

Influence of Cirrhosis on 68Ga-FAPI PET/CT in Intrahepatic Tumors.

Background Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) is of great diagnostic value for intrahepatic tumors. However, cirrhosis may lead to increased 68Ga-FAPI uptake in background liver, affecting the diagnostic ability of 68Ga-FAPI. Purpose To assess the effect of cirrhosis on liver parenchyma and intrahepatic tumor uptake of 68Ga-FAPI and to compare the ability of 68Ga-FAPI and fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) PET/CT to depict intrahepatic tumors in patients with cirrhosis. Materials and Methods In this secondary analysis of a prospective trial, patients who underwent both 68Ga-FAPI and 18F-FDG PET/CT and those who underwent only 68Ga-FAPI PET/CT between August 2020 and May 2022 were considered for inclusion in the cirrhotic or noncirrhotic group, respectively. Patients with cirrhosis were chosen via a comprehensive assessment of imaging and clinical data, and patients without cirrhosis were randomly selected. 68Ga-FAPI and 18F-FDG PET/CT data were measured by two radiologists. Between-groups and within-group data were tested with the Mann-Whitney U test and the Wilcoxon signed-rank test, respectively. Results A total of 39 patients with cirrhosis (median age, 58 years [IQR, 50-68]; 29 male; 24 intrahepatic tumors) and 48 patients without cirrhosis (median age, 59 years [IQR, 51-67]; 30 male; 23 intrahepatic tumors) were evaluated. In patients without intrahepatic tumors, the liver 68Ga-FAPI average standardized uptake value (SUVavg) was higher in the cirrhotic group than in the noncirrhotic group (median SUVavg, 1.42 [IQR, 0.55-2.85] vs 0.45 [IQR, 0.41-0.72]; P = .002). However, no difference was observed in the diagnosis of intrahepatic tumor sensitivity (98% vs 93%, respectively). When compared with 18F-FDG, the sensitivity of 68Ga-FAPI PET/CT in the detection of intrahepatic tumors in patients with cirrhosis (41% vs 98%, respectively) and maximum standardized uptake value of tumors (median SUVmax, 2.60 [IQR, 2.14-4.49] vs 6.68 [IQR, 4.65-10.08]; P < .001) were higher. Conclusion The sensitivity of 68Ga-FAPI in the diagnosis of intrahepatic tumors was not affected by cirrhosis, and diagnostic accuracy of 68Ga-FAPI was higher than that of 18F-FDG in patients with cirrhosis. © RSNA, 2023 Supplemental material is available for this article.

[68Ga]Ga-FAPI-04 PET/CT on assessing Crohn's disease intestinal lesions.

BACKGROUND: Fibrosis and inflammation are major pathological changes of Crohn's disease (CD). Early detection and accurate severity evaluation of CD are critical for patient's prognosis. Endoscopy is widely used to evaluate CD progression. Herein, we evaluated the efficacy of [68Ga]Ga-FAPI-04 PET/CT to identify lesions and assess the progression of CD. METHODS: All CD patients received computed tomography enterography (CTE), [68Ga]Ga-FAPI-04 PET/CT examination, and ileocolonoscopy within 1 week. Two independent gastroenterologists computed the Crohn's disease activity index (CDAI) of all patients. Two radiology physicians assessed the CTE images separately, and the CTE scores were calculated. Lastly, two nuclear medicine physicians independently examined the [68Ga]Ga-FAPI-04 PET/CT images. Once the FAPI uptake of the intestinal segment was equal or higher relative to the liver (considered FAPI-positive), the target-to-background ratio (TBR) and global FAPI PET/CT score were computed, representing the independent intestinal activity and activity of all intestinal segments, respectively. Levels of fecal calprotectin (FCP) and C-reactive protein (CRP) were determined before the endoscopy. The Crohn's disease endoscopy index of severity (CDEIS) and the simple endoscopic score for Crohn's disease (SES-CD) were calculated during the endoscopy. Finally, all data were obtained and analyzed. RESULTS: There were 74 intestinal segments in 16 patients were assessed. [68Ga]Ga-FAPI-04 PET/CT identified 42 of 45 endoscopically lesioned segments (endoscopic lesions detection sensitivity: 93.3%), while CTE identified 39 of them (endoscopic lesions detection sensitivity: 86.7%). According to the receiver operating characteristic (ROC) analysis, [68Ga]Ga-FAPI-04 PET/CT showed better performance in the detection of endoscopic lesions compared with CTE (P < 0.05). The TBR was significantly associated with the CTE score (r = 0.81; (95% CI): 0.736-0.869; P < 0.0001) and SES-CD values (r = 0.86; (95% CI): 0.776-0.908; P < 0.0001). In addition, the global FAPI PET/CT score was significantly correlated with FCP (r = 0.52; 95% CI, 0.02-0.81; P = 0.039), CRP (r = 0.60; 95% CI, 0.13-0.85; P = 0.014), CDEIS (r = 0.55; 95% CI, 0.06-0.83; P = 0.028), and CDAI (r = 0.81; 95% CI, 0.50-0.93; P < 0.0001). CONCLUSION: In summary, [68Ga]Ga-FAPI-04 PET/CT correlated well with endoscopic, CTE, clinical, and biomarkers of CD. It was also highly sensitive in the detection of different classes of lesions in all intestinal segments, and unlike other examinations, this technique required no patient fasting or bowel preparation. Therefore, [68Ga]Ga-FAPI-04 PET/CT may be a promising method for assessing the activity of CD.

Integrated analysis of probability of type 2 diabetes mellitus with polymorphisms and methylation of SLC30A8 gene: a nested case-control study.

To estimate the associations between single-nucleotide polymorphisms (SNPs) and methylation of SLC30A8 gene and T2DM risk, and the interactions among SNPs, methylation, and environmental factors on T2DM risk. We genotyped 9 SNPs and tested methylation at 46 CpG loci of SLC30A8 in the baseline DNA of 290 T2DM cases and 290 matched controls nested in the Rural Chinese Cohort Study. A conditional logistic regression model was used to estimate the associations between SNPs and SLC30A8 methylation and T2DM risk. Multifactor Dimensionality Reduction analysis was used to estimate the effect of interactions among SNPs, methylation, and environment on T2DM risk. Probability of T2DM was decreased with rs11558471 (GG vs. AA, OR = 0.55, 95% CI 0.32, 0.96), with rs13266634 (TT vs. CC, OR = 0.55, 95% CI 0.32, 0.94), with rs3802177 (AA vs. GG, OR = 0.54, 95%CI 0.31, 0.94), and its probability was increased with rs2466293 of SLC30A8 (GA vs. AA, OR = 1.63, 95% CI 1.08-2.47). Its probability was also significantly associated with methylation of CG9 and CG45 (OR = 0.56 [95% CI 0.33-0.97] and 1.61 [95%CI 1.03--2.51]). T2DM probability was significantly associated with the interaction effect between rs2466293 and hypertension (p = 0.045). T2DM probability was also significantly associated with the combination effects of rs2466293 with BMI, hypertension, and hypertriglyceridemia, with the combination effects of hypertriglyceridemia with rs11558471, rs13266634, and methylation of CG45.

Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer.

BACKGROUND: The surveillance and therapy of early-stage cancer would be better for patients' prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer. METHODS: In this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC). RESULTS: We identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic. CONCLUSION: We disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic.

ETV6 Regulates Hemin-Induced Erythroid Differentiation of K562 Cells through Mediating the Raf/MEK/ERK Pathway.

As a member of transcription factor E-Twenty Six (ETS) family, ETS variant 6 (ETV6) plays significant role in hematopoiesis and embryonic development. ETV6 dysexpression also involved in the occurrence, development and progression of cancers and leukemia. In current work, we hypothesized that ETV6 plays a role in erythroid differentiation of chronic myeloid leukemia (CML). We found the protein expression level of ETV6 was significantly upregulated during hemin-induced erythroid differentiation of K562 cells. Moreover, overexpression of ETV6 inhibited erythroid differentiation in hemin-induced K562 cells with decreased numbers of benzidine-positive cells and decreased expression levels of erythroid differentiation specific markers glycophorin (GPA), CD71, hemoglobin A (HBA), α-globin, γ-globin and ε-globin. Conversely, ETV6 knockdown promoted erythroid differentiation in hemin-induced K562 cells. Furthermore, ETV6 expression level slightly positively with the proliferation capacity of K562 cells treated with hemin. Mechanistically, ETV6 overexpression inhibited fibrosarcoma/mitogen activated extracellular signal-regulated kinase/extracellular regulated protein kinase (Raf/MEK/ERK) pathway, ETV6 knockdown activated the Raf/MEK/ERK pathway. Collectively, the current work demonstrates that ETV6 plays an inhibitory role in the regulation of K562 cell erythroid differentiation via Raf/MEK/ERK pathway, it would be a potentially therapeutic target for dyserythropoiesis.

CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt.

Abnormal glucose metabolism may contribute to cancer progression. As a member of the CRK (v-crk sarcoma virus CT10 oncogene homologue) adapter protein family, CRKL (CRK-like) associated with the development and progression of various tumours. However, the exact role and underlying mechanism of CRKL on energy metabolism remain unknown. In this study, we investigated the effect of CRKL on glucose metabolism of hepatocarcinoma cells. CRKL and PI3K were found to be overexpressed in both hepatocarcinoma cells and tissues; meanwhile, CRKL up-regulation was positively correlated with PI3K up-regulation. Functional investigations revealed that CRKL overexpression promoted glucose uptake, lactate production and glycogen synthesis of hepatocarcinoma cells by up-regulating glucose transporters 1 (GLUT1), hexokinase II (HKII) expression and down-regulating glycogen synthase kinase 3ß (GSK3ß) expression. Mechanistically, CRKL promoted glucose metabolism of hepatocarcinoma cells via enhancing the CRKL-PI3K/Akt-GLUT1/HKII-glucose uptake, CRKL-PI3K/Akt-HKII-glucose-lactate production and CRKL-PI3K/Akt-Gsk3ß-glycogen synthesis. We demonstrate CRKL facilitates HCC malignancy via enhancing glucose uptake, lactate production and glycogen synthesis through PI3K/Akt pathway. It provides interesting fundamental clues to CRKL-related carcinogenesis through glucose metabolism and offers novel therapeutic strategies for hepatocarcinoma.

Association of ABCG1 gene methylation and its dynamic change status with incident type 2 diabetes mellitus: the Rural Chinese Cohort Study.

To explore whether DNA methylation of the ATP-binding cassette G1 (ABCG1) gene and its dynamic change are associated with incident type 2 diabetes mellitus (T2DM). We conducted a nested case-control study with 286 pairs of T2DM cases and matched controls nested in the Rural Chinese Cohort Study. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for incident T2DM risk according to ABCG1 methylation level at baseline and its dynamic change at follow-up examination. Spearman's rank correlation coefficients were used to analyze the association between ABCG1 methylation and its possible risk factors in the control group. We found that T2DM risk increased by 16% (OR = 1.16, 95% CI = 1.02-1.31) with each 1% increase in DNA methylation levels of the ABCG1 loci CpG13 and CpG14. DNA methylation change of the ABCG1 locus CpG15 during the 6-year follow-up was associated with increased T2DM risk: T2DM risk increased by 78% in the upper tertile group (methylation gain ≥5%) versus lower tertile group (methylation gain <1%) (OR = 1.78, 95% CI = 1.01-3.15). Furthermore, body mass index was positively correlated with the DNA methylation level of the ABCG1 loci CpG13, CpG14 and CpG15. In conclusion, DNA methylation levels of the ABCG1 loci CpG13 and CpG14 and the methylation gain of locus CpG15 were positively associated with incident T2DM risk, which may suggest a possible etiologic pattern for T2DM and potentially improve T2DM prediction in rural Chinese people.

Chinese visceral adiposity index: A reliable indicator of visceral fat function associated with risk of type 2 diabetes.

BACKGROUND: The evidence of the association between Chinese visceral adiposity index (CVAI) and risk of type 2 diabetes mellitus (T2DM) is limited. We explored the association of CVAI with T2DM and directly compared with the predictive power of CVAI with other visceral obesity indices (visceral adiposity index, waist to height ratio, waist circumference and body mass index) based on a large prospective study. METHODS: We conducted a population-based study of 12 237 Chinese participants. Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between CVAI and T2DM. RESULTS: During follow-up (median: 6.01 years), the incidence of T2DM was 3.29, 7.34, 12.37 and 23.72 per 1000 person-years for quartiles 1, 2, 3 and 4 of CVAI, respectively. The risk of T2DM was increased with quartiles 2, 3 and 4 vs quartile 1 of CVAI (HR 2.12 [95% CI 1.50-3.00], 2.94 [2.10-4.13] and 5.01 [3.57-7.04], Ptrend < 0.001). Per-SD increase in CVAI was associated with a 72% increased risk of T2DM (HR 1.72 [95% CI 1.56-1.88]). Sensitivity analyses did not alter the association. The area under receiver operating characteristic curve was significantly higher for CVAI than other visceral obesity indices (all P <.001). Similar results were observed in stratified analyses by sex. CONCLUSIONS: Our findings show a positive association between CVAI and risk of T2DM. CVAI has the best performance in predicting incident T2DM, so the index might be a reliable and applicable indicator identifying people at high risk of T2DM.

Chinese visceral adiposity index, a novel indicator of visceral obesity for assessing the risk of incident hypertension in a prospective cohort study.

The present study aimed to investigate the association of the Chinese visceral adiposity index (CVAI) and its 6-year change with hypertension risk and compare the ability of CVAI and other obesity indices to predict hypertension based on the Rural Chinese Cohort Study. Study participants were randomly recruited by a cluster sampling procedure, and 10 304 participants ≥18 years were included. Modified Poisson regression was used to derive adjusted relative risks (RR) and 95 % CI. We identified 2072 hypertension cases during a median of 6·03 years of follow-up. The RR for the highest v. lowest CVAI quartile were 1·29 (95 % CI 1·05, 1·59) for men and 1·53 (95 % CI 1·22, 1·91) for women. Per-sd increase in CVAI was associated with hypertension for both men (RR 1·09, 95 % CI 1·02, 1·16) and women (RR 1·14, 95 % CI 1·06, 1·22). Also, the area under the receiver operating characteristic curve value for hypertension was higher for CVAI than the four other obesity indices for both sexes (all P < 0·05). Finally, per-sd increase in CVAI change was associated with hypertension for both men (RR 1·26, 95 % CI 1·16, 1·36) and women (RR 1·23, 95 % CI 1·15, 1·30). Similar results were observed in sensitivity analyses. CVAI and its 6-year change are positively associated with hypertension risk. CVAI has better performance in predicting hypertension than other visceral obesity indices for both sexes. The current findings suggest CVAI as a reliable and applicable predictor of hypertension in rural Chinese adults.

Solid fuel use and cardiovascular events: A systematic review and meta-analysis of observational studies.

Although solid fuel use has been increasingly linked to cardiovascular events (CVEs), conclusions have been inconsistent. We systematically searched 3 databases (PubMed, Embase, and Web of Science) up to July 3, 2020, to identify English language reports that assessed the association of solid fuel use with CVEs. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated with a random-effects model. Subgroup analyses and sensitivity analyses were conducted to explore the potential sources of heterogeneity and to test the stability of the results. We finally included 13 observational studies (8 cohort, 3 cross-sectional, and 2 case-control studies comprising 791,220 participants) in the meta-analysis. The risk of CVEs was increased 21% with the highest versus the lowest solid fuel use (highest/lowest, RRpooled  = 1.21, 95% CI: 1.10-1.34). As for the subgroup analyses on study design, the pooled RR for cohort studies, case-control studies, and cross-sectional studies were 1.11 (95%CI: 1.03-1.19), 4.80 (95%CI: 2.22-10.39), and 1.46 (95%CI: 0.82-2.62), respectively. The results of this study suggested that high solid fuel use was associated with increased CVE risk, and that reducing the use of solid fuel will be important for improving the health of the populations in developing countries.

BMI and risk of all-cause mortality in normotensive and hypertensive adults: the rural Chinese cohort study.

OBJECTIVE: The impact of baseline hypertension status on the BMI-mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI-mortality association using a rural Chinese cohort. DESIGN: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. SETTING: Longitudinal population-based cohort. PARTICIPANTS: 17 262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. RESULTS: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤ 18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the hazard ratios for mortality in normotensive participants were 1·92 (95% CI 1·23, 3·00), 1·44 (95% CI 1·01, 2·05), 1·14 (95% CI 0·82, 1·58), 0·96 (95% CI 0·70, 1·31), 0·96 (95% CI 0·65, 1·43), 1·32 (95% CI 0·81, 2·14) and 1·32 (95% CI 0·74, 2·35), respectively, and in hypertensive participants were 1·85 (95% CI 1·08, 3·17), 1·67 (95% CI 1·17, 2·39), 1·29 (95% CI 0·95, 1·75), 1·20 (95% CI 0·91, 1·58), 1·10 (95% CI 0·83, 1·46), 1·10 (95% CI 0·80, 1·52) and 0·61 (95% CI 0·40, 0·94), respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity v. normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. CONCLUSIONS: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

Dose-response association between adult height and all-cause mortality: a systematic review and meta-analysis of cohort studies.

BACKGROUND: We conducted a systematic review and meta-analysis from published cohort studies to examine the association of adult height and all-cause mortality and to further explore the dose-response association. METHODS: PubMed, The Cochrane Library, The Ovid, CNKI, CQVIP and Wanfang databases were searched for articles published from database inception to 6 February 2018. We used the DerSimonian-Laird random-effects model to estimate the quantitative association between adult height and all-cause mortality and the restricted cubic splines to model the dose-response association. RESULTS: We included 15 articles, with 1 533 438 death events and 2 854 543 study participants. For each 5-cm height increase below the average, the risk of all-cause mortality was reduced by 7% [relative risk (RR) = 0.93, 95% confidence interval (CI), 0.89-0.97] for men and 5% (RR = 0.95, 95% CI, 0.90-0.99) for women. All-cause mortality had a U-shaped association with adult height, the lowest risk occurring at 174 cm for men and 158 cm for women (both Pnonlinearity < 0.001). Relative to the shortest adult height (147 cm for men and 137 cm for women), men at 174 cm had a 47% lower likelihood of all-cause mortality and women at 158 cm a 33% lower risk of all-cause mortality. CONCLUSIONS: Our study suggests that the relation between adult height and all-cause mortality is approximately U-shaped in both men and women.

Dose-Response Association Between High-Density Lipoprotein Cholesterol and Stroke: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

INTRODUCTION: Studies investigating the effect of high-density lipoprotein cholesterol (HDL-C) on stroke and stroke subtypes have reached inconsistent conclusions. The purpose of our study was to clarify the dose-response association between HDL-C level and risk of total stroke and stroke subtypes by a systematic review and meta-analysis. METHODS: We performed a systematic search of PubMed, Embase, and Web of Science databases through July 30, 2020, for prospective cohort studies that reported the HDL-C-stroke association and extracted the estimate that was adjusted for the greatest number of confounding factors. Restricted cubic splines were used to evaluate the linear and nonlinear dose-response associations. RESULTS: We included 29 articles, which reported on 62 prospective cohort studies including 900,501 study participants and 25,678 with stroke. The summary relative risk per 1-mmol/L increase in HDL-C level for total stroke was 0.82 (95% CI, 0.76-0.89; I2 = 42.9%; n = 18); ischemic stroke (IS), 0.75 (95% CI, 0.69-0.82; I2 = 50.1%; n = 22); intracerebral hemorrhage (ICH), 1.21 (95% CI, 1.04-1.42; I2 = 33.4%; n = 10); and subarachnoid hemorrhage (SAH), 0.98 (95% CI, 0.96-1.00; I2 = 0%; n = 7). We found a linear inverse association between HDL-C level and risk of total stroke and SAH, a nonlinear inverse association for IS risk, but a linear positive association for ICH risk. The strength and the direction of the effect size estimate for total stroke, IS, ICH, and SAH remained stable for most subgroups. We found no publication bias with Begg's test and Egger's test for the association of HDL-C level with risk of total stroke, IS, and ICH. CONCLUSION: A high HDL-C level is associated with reduced risk of total stroke and IS and an increased risk of ICH.

Baseline serum albumin and its dynamic change is associated with type 2 diabetes risk: A large cohort study in China.

BACKGROUND: The study aimed to investigate the associations of baseline serum albumin level and its dynamic change with type 2 diabetes mellitus (T2DM) risk in a large Chinese cohort study. METHODS: This cohort study included 30 442 adults without T2DM at first entry, who completed at least one follow-up of annual examinations between 2009 and 2016. Serum albumin level was measured at baseline and at every annual check-up. The dynamic change in serum albumin level (∆ALB) was calculated by subtracting serum albumin level at baseline from that at the last follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox regression models. RESULTS: During 7 years of follow-up, we identified 1634 T2DM events. From the lowest to the highest quartile of serum albumin level, adjusted HRs (95% CI) were 1.00 (reference), 0.96 (0.94, 1.01), 0.98 (0.95, 1.02) and 0.88 (0.85, 0.98), respectively. As compared with stable change in serum albumin (-0.2 ≤ ∆ALB <1.0 g/L), the risk of T2DM increased for ∆ALB < -2.0 g/L (HR 1.44, 95% CI 1.24-1.68) and decreased for ∆ALB ≥3.0 g/L (0.81, 0.68-0.97) after adjusting for potential confounding factors. Restricted cubic splines showed a linear dose-response association between baseline serum albumin level and T2DM risk (Pnonlinearity 0.715) and a nonlinear dose-response association between ∆ALB and T2DM risk (Pnonlinearity 0.011). CONCLUSIONS: Baseline serum albumin level appears to be inversely associated with T2DM risk. Adults with reduced serum albumin level could be early identified for diabetes risk in clinical practice.

Association of total sedentary behaviour and television viewing with risk of overweight/obesity, type 2 diabetes and hypertension: A dose-response meta-analysis.

AIMS: To explore the quantitative dose-response association of total sedentary behaviour and television viewing with overweight/obesity, type 2 diabetes and hypertension in a meta-analysis. MATERIALS AND METHODS: We searched three databases to identify English-language reports that assessed the association of total sedentary behaviour or television viewing with the aforementioned health outcomes. Restricted cubic splines were used to evaluate possible linear or non-linear associations of total sedentary behaviour and television viewing with these health outcomes. RESULTS: We included 48 articles (58 studies) with a total of 1 071 967 participants in the meta-analysis; 21 (six cohort and 15 cross-sectional) studies examined the association of total sedentary behaviour with overweight/obesity, 23 (13 cohort and 10 cross-sectional) studies examined the association with type 2 diabetes and 14 (one cohort and 13 cross-sectional) studies examined the association with hypertension. We found linear associations between total sedentary behaviour and type 2 diabetes (Pnon-linearity = 0.190) and hypertension (Pnon-linearity = 0.225) and a non-linear association between total sedentary behaviour and overweight/obesity (Pnon-linearity = 0.003). For each 1-h/d increase in total sedentary behaviour, the risk increased by 5% for type 2 diabetes and 4% for hypertension. We also found linear associations between television viewing and type 2 diabetes (Pnon-linearity = 0.948) and hypertension (Pnon-linearity = 0.679) and a non-linear association for overweight/obesity (Pnon-linearity = 0.007). For each 1-h/d increase in television viewing, the risk increased by 8% for type 2 diabetes and 6% for hypertension. CONCLUSIONS: High levels of total sedentary behaviour and television viewing were associated with overweight/obesity, type 2 diabetes and hypertension.

Metabolically healthy general and abdominal obesity are associated with increased risk of hypertension.

Metabolically healthy obesity refers to a subset of obese people with a normal metabolic profile. We aimed to explore the association between metabolically healthy and obesity status and risk of hypertension among Chinese adults from The Rural Chinese Cohort Study. This prospective cohort study enrolled 9137 Chinese adults without hypertension, type 2 diabetes or treatment for lipid abnormality at baseline (2007-2008) and followed up during 2013-2014. Modified Poisson regression models were used to examine the risk of hypertension by different metabolically healthy and obesity status, estimating relative risks (RR) and 95 % CI. During 6 years of follow-up, we identified 1734 new hypertension cases (721 men). After adjusting for age, sex, smoking and other confounding factors, risk of hypertension was increased with metabolically healthy general obesity (MHGO) defined by BMI (RR 1·75, 95 % CI 1·02, 3·00) and metabolically healthy abdominal obesity (MHAO) defined by waist circumference (RR 1·51, 95 % CI 1·12, 2·04) as compared with metabolically healthy non-obesity. The associations between metabolically healthy and obesity status and hypertension outcome were consistent after stratifying by sex, age, smoking, alcohol drinking and physical activity. Both MHGO and MHAO were associated with increased risk of hypertension. Obesity control programmes should be implemented to prevent or delay the development of hypertension in rural China.

Sugar and artificially sweetened beverages and risk of obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies.

Although consumption of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) has increasingly been linked with obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality, evidence remains conflicted and dose-response meta-analyses of the associations are lacking. We conducted an updated meta-analysis to synthesize the knowledge about their associations and to explore their dose-response relations. We comprehensively searched PubMed, EMBASE, Web of Science, and Open Grey up to September 2019 for prospective cohort studies investigating the associations in adults. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated for the dose-response association. Restricted cubic splines were used to evaluate linear/non-linear relations. We included 39 articles in the meta-analysis. For each 250-mL/d increase in SSB and ASB intake, the risk increased by 12% (RR = 1.12, 95% CI 1.05-1.19, I2 = 67.7%) and 21% (RR = 1.21, 95% CI 1.09-1.35, I2 = 47.2%) for obesity, 19% (RR = 1.19, 95% CI 1.13-1.25, I2 = 82.4%) and 15% (RR = 1.15, 95% CI 1.05-1.26, I2 = 92.6%) for T2DM, 10% (RR = 1.10, 95% CI 1.06-1.14, I2 = 58.4%) and 8% (RR = 1.08, 95% CI 1.06-1.10, I2 = 24.3%) for hypertension, and 4% (RR = 1.04, 95% CI 1.01-1.07, I2 = 58.0%) and 6% (RR = 1.06, 95% CI 1.02-1.10, I2 = 80.8%) for all-cause mortality. For SSBs, restricted cubic splines showed linear associations with risk of obesity (Pnon-linearity = 0.359), T2DM (Pnon-linearity = 0.706), hypertension (Pnon-linearity = 0.510) and all-cause mortality (Pnon-linearity = 0.259). For ASBs, we found linear associations with risk of obesity (Pnon-linearity = 0.299) and T2DM (Pnon-linearity = 0.847) and non-linear associations with hypertension (Pnon-linearity = 0.019) and all-cause mortality (Pnon-linearity = 0.048). Increased consumption of SSBs and ASBs is associated with risk of obesity, T2DM, hypertension, and all-cause mortality. However, the results should be interpreted cautiously because the present analyses were based on only cohort but not intervention studies.

Association of weight-adjusted-waist index with incident hypertension: The Rural Chinese Cohort Study.

AIMS: To explore the association between WWI and the incidence of HTN in the Rural Chinese Cohort Study. METHODS AND RESULTS: We examined data for 10,338 non-hypertensive participants (39.49% men) aged ≥ 18 years from the Rural Chinese Cohort Study who completed a baseline examination during 2007-2008 and follow-up during 2013-2014. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). Multiple logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the probability of HTN across four WWI categories. Restricted cubic splines analysis was used to model the dose-response association of WWI and HTN. A total of 2078 participants had HTN during a median follow-up of 6 years. After adjusting for potential confounders, as compared with the lowest WWI category (<9.94 cm/√kg), with WWI 9.94 to 10.42, 10.42 to 10.91 and ≥ 10.91 cm/√kg, the ORs (95% CIs) for HTN were 1.12 (0.93-1.35), 1.40 (1.17-1.69) and 1.50 (1.24-1.82), respectively. Results of the sensitivity analyses were robust. The ORs were generally consistent on subgroup analysis by sex, smoking status, systolic blood pressure and diastolic blood pressure. Multiple logistic regression models with restricted cubic splines showed a non-linear positive association between WWI and HTN (Pnonlinearity < 0.001). CONCLUSION: The highest WWI category was significantly associated with increased risk of HTN. Our findings may facilitate the development and promotion of obesity prevention strategies aimed at reducing the risk of HTN and provide evidence for healthcare policy in rural China.

Association of homocysteine level with risk of stroke: A dose-response meta-analysis of prospective cohort studies.

BACKGROUND AND AIMS: Homocysteine (Hcy) level has been increasingly linked with stroke and ischemic stroke (IS). However, a dose-response meta-analysis of prospective cohort studies of the association is lacking. We aimed to explore the quantitative dose-response association of Hcy level with stroke and IS in a meta-analysis of prospective cohort studies. METHODS AND RESULTS: We performed a systematic search of PubMed, Embase and Web of Science databases up to April 25, 2019 for prospective cohort studies assessing the association of Hcy level with stroke and IS. We used random-effect models to estimate the pooled relative risk (RRs) (with 95% confidence intervals [CIs]) for the association of Hcy with risk of stroke and IS. Restricted cubic splines were used to evaluate possible linear or nonlinear association of Hcy level with stroke and IS. We included 10 prospective cohort studies (7 articles) with 11,061 participants in the meta-analysis. Hcy level was associated with increased risk of stroke (RR = 1.58, 95% CI 1.25-2.00, I2 = 39.5%) and IS (RR = 1.54, 95% CI 1.21-1.97, I2 = 36.4%) for the highest versus the lowest categories. We found a linear association between Hcy level and stroke (Pnonlinearity = 0.660) and IS (Pnonlinearity = 0.981). For each 1-µmol/L increase in Hcy, the pooled RR was 1.06 (95% CI 1.01-1.12, I2 = 59.0%) for stroke and 1.05 (95% CI 1.00-1.11, I2 = 58.6%) for IS. CONCLUSION: This meta-analysis indicated that elevated Hcy level was associated with increased risk of stroke and IS.