Dalian Municipal Central Hospital

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

BACKGROUND: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited. METHODS: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications. RESULTS: Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P<0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation. CONCLUSIONS: In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

ABSTRACT A number of studies investigated the distribution of BMD values and the prevalence of osteoporosis in China, but their findings varied. Until now, a BMD reference database based on uniform measurements in a large-scale Chinese population has been lacking. A total of 75,321 Chinese adults aged 20 years and older were recruited from seven centers between 2008 and 2018. BMD values at the lumbar spine (L1–L4), femoral neck, and total femur were measured by GE Lunar dual-energy X-ray absorptiometry systems. BMD values measured in each center were cross-calibrated by regression equations that were generated by scanning the same European spine phantom 10 times at every center. Cubic and multivariate linear regression were performed to assess associations between BMD values and demographic variables. Sex-specific prevalence of osteoporosis was age-standardized based on the year 2010 national census data for the Chinese population. The sex-specific BMD values at each site were negatively associated with age, positively associated with body mass index levels, and lower in the participants from southwest China than in those from other geographic regions after multivariate adjustment. Furthermore, BMD values at the femoral neck and total femur decreased with the year of BMD measurement. The peak BMD values at the lumbar spine, femoral neck, and total femur were 1.088 g/cm2, 0.966 g/cm2, and 0.973 g/cm2, respectively, for men, and 1.114 g/cm2, 0.843 g/cm2, and 0.884 g/cm2, respectively, for women. The age-standardized prevalence of osteoporosis at the spine or hip was 6.46% and 29.13% for men and women aged 50 years and older, respectively. Currently a total of 10.9 million men and 49.3 million women in China are estimated to have osteoporosis. In our national examination of BMD, we found that BMD values differed by demographic characteristics. We estimated the age-standardize prevalence of osteoporosis in China to be 6.46% and 29.13% respectively, for men and women aged 50 years and older.

Metabolic diseases are the most common and rapidly growing health issues worldwide. The massive population-based human genetics is crucial for the precise prevention and intervention of metabolic disorders. The China Metabolic Analytics Project (ChinaMAP) is based on cohort studies across diverse regions and ethnic groups with metabolic phenotypic data in China. Here, we describe the centralized analysis of the deep whole genome sequencing data and the genetic bases of metabolic traits in 10,588 individuals from the ChinaMAP. The frequency spectrum of variants, population structure, pathogenic variants and novel genomic characteristics were analyzed. The individual genetic evaluations of Mendelian diseases, nutrition and drug metabolism, and traits of blood glucose and BMI were integrated. Our study establishes a large-scale and deep resource for the genetics of East Asians and provides opportunities for novel genetic discoveries of metabolic characteristics and disorders.

CONTEXT: Guidelines of the American Thyroid Association (ATA) proposed that the upper limit of the TSH reference range should be 2.5 mIU/L in first trimester, but the reported ranges in China are significantly higher. OBJECTIVE: Our objective was to establish a rational reference range of serum TSH for diagnosis of subclinical hypothyroidism in the first trimester of pregnant women in China. DESIGN: We screened 4800 pregnant women in the first trimester and 2000 women who planned to become pregnant and evaluated 535 pregnant women in follow-up visits during the second and third trimester. RESULTS: Median concentrations of serum TSH decreased significantly from the seventh week of gestation. The median of TSH from 4 to 6 weeks was significantly higher than from 7 to 12 weeks (2.15 [0.56-5.31] mIU/L vs 1.47 [0.10-4.34] mIU/L, P<.001); however, there was no significant difference compared with nonpregnant women (2.07 [0.69-5.64] mIU/L; P=.784). The median of free T4 was not significantly altered in the first trimester. The prevalence of subclinical hypothyroidism in the 4800 pregnant women was 27.8% on the diagnostic criteria of TSH>2.5 mIU/L and 4.0% using the reference interval derived by our laboratory (0.14-4.87 mIU/L).Additionally, of 118 pregnant women who had serum TSH>2.5 mIU/L in the first trimester, only 30.0% and 20.3% of them at the 20th and 30th week of gestation had TSH>3.0 mIU/L. CONCLUSIONS: The reference range for nonpregnant women can be used for the assessment of pregnant women at 4 to 6 weeks of gestation. The upper limit of serum TSH in the first trimester was much higher than 2.5 mIU/L in Chinese pregnant women.

CONTEXT: The WHO Technical Consultation recommends urinary iodine concentrations (UIC) from 250 to 499 μg/L as more-than-adequate iodine intake and UIC ≥ 500 μg/L as excessive iodine for pregnant and lactating women, but scientific evidence for this is weak. OBJECTIVE: We investigated optimal and safe ranges of iodine intake during early pregnancy in an iodine-sufficient region of China. METHOD: Seven thousand one hundred ninety pregnant women at 4-8 weeks gestation were investigated and their UIC, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroglobulin (Tg) were measured. RESULTS: The prevalence of overt hypothyroidism was lowest in the group with UIC 150-249 μg/L, which corresponded to the lowest serum Tg concentration (10.18 μg/L). Prevalences of subclinical hypothyroidism (2.4%) and isolated hypothyroxinemia (1.7%) were lower in the group with UIC 150-249 μg/L. Multivariate logistic regression indicated that more-than-adequate iodine intake (UIC 250-499 μg/L) and excessive iodine intake (UIC ≥ 500 μg/L) were associated with a 1.72-fold and a 2.17-fold increased risk of subclinical hypothyroidism, respectively. Meanwhile, excessive iodine intake was associated with a 2.85-fold increased risk of isolated hypothyroxinemia. Moreover, the prevalence of TPOAb positivity and TgAb positivity presented a U-shaped curve, ranging from mild iodine deficiency to iodine excess. CONCLUSION: The upper limit of iodine intake during early pregnancy in an iodine-sufficient region should not exceed UIC 250 μg/L, because this is associated with a significantly high risk of subclinical hypothyroidism, and a UIC of 500 μg/L should not be exceeded, as it is associated with a significantly high risk of isolated hypothyroxinemia.

OBJECTIVE: To report the performance of massively parallel sequencing (MPS) based prenatal noninvasive fetal trisomy test based on cell-free DNA sequencing from maternal plasma in a routine clinical setting in China. METHOD: The MPS-based test was offered as a prenatal screening test for trisomies 21 and 18 to pregnant women in 49 medical centers over 2 years. A total of 11,263 participants were recruited and the MPS-based test was performed in 11,105 pregnancies. Fetal outcome data were obtained after the expected date of confinement. RESULTS: One hundred ninety cases were classified as positive, including 143 cases of trisomy 21 and 47 cases of trisomy 18. With the karyotyping results and the feedback of fetal outcome data, we observed one false positive case of trisomy 21, one false positive case of trisomy 18 and no false negative cases, indicating 100% sensitivity and 99.96% specificity for the detection of trisomies 21 and 18. CONCLUSION: Our large-scale multicenter study proved that the MPS-based test is of high sensitivity and specificity in detecting fetal trisomies 21 and 18. The introduction of this screening test into a routine clinical setting could avoid about 98% of invasive prenatal diagnostic procedures.

A substantial knowledge on the pathogenesis of diabetes mellitus (DM) by oxidative stress and inflammation is available. Berberine is a biologically active botanical that can combat oxidative stress and inflammation and thus ameliorate DM, especially type 2 DM. This article describes the potential of berberine against oxidative stress and inflammation with special emphasis on its mechanistic aspects. In diabetic animal studies, the modified levels of proinflammatory cytokines and oxidative stress markers were observed after administering berberine. In renal, fat, hepatic, pancreatic and several others tissues, berberine-mediated suppression of oxidative stress and inflammation was noted. Berberine acted against oxidative stress and inflammation through a very complex mechanism consisting of several kinases and signaling pathways involving various factors, including NF-κB (nuclear factor-κB) and AMPK (AMP-activated protein kinases). Moreover, MAPKs (mitogen-activated protein kinases) and Nrf2 (nuclear factor erythroid-2 related factor 2) also have mechanistic involvement in oxidative stress and inflammation. In spite of above advancements, the mechanistic aspects of the inhibitory role of berberine against oxidative stress and inflammation in diabetes mellitus still necessitate additional molecular studies. These studies will be useful to examine the new prospects of natural moieties against DM.

OBJECTIVE Uncertainty remains regarding the predictive value of various glycemic measures as they relate to the risk of diabetes and its complications. Using the cutoffs recommended by the American Diabetes Association’s 2010 criteria, we determined the associations of fasting plasma glucose (FPG), 2-h postload glucose (2h-PG), and HbA1c with the outcomes. RESEARCH DESIGN AND METHODS Baseline medical history, FPG, 2h-PG, and HbA1c were obtained from a population-based cohort of 193,846 adults aged ≥40 years in China during 2011–2012. A follow-up visit was conducted during 2014–2016 in order to assess incident diabetes, cardiovascular disease (CVD), cancer, and mortality. RESULTS We documented 8,063 cases of diabetes, 3,014 CVD-related events, 1,624 cases of cancer, and 2,409 deaths during up to 5 years of follow-up. Multivariable-adjusted risk ratios (95% CIs) of diabetes associated with prediabetes based on FPG of 100–125 mg/dL, 2h-PG of 140–199 mg/dL, or HbA1c of 5.7–6.4% (39–47 mmol/mol) were 1.60 (1.43–1.79), 2.72 (2.43–3.04), and 1.49 (1.36–1.62), respectively. Restricted cubic spline analyses suggested J-shaped associations of FPG, 2h-PG, and HbA1c levels with CVD, cancer, and mortality. Multivariable-adjusted hazard ratios (95% CIs) associated with untreated diabetes based on FPG ≥126 mg/dL, 2h-PG ≥200 mg/dL, or HbA1c ≥6.5% (48 mmol/mol) were 1.18 (1.05–1.33), 1.31 (1.18–1.45), and 1.20 (1.07–1.34) for CVD; 1.10 (0.92–1.32), 1.44 (1.25–1.67), and 1.08 (0.92–1.28) for cancer; and 1.37 (1.20–1.57), 1.57 (1.41–1.76), and 1.33 (1.17–1.52) for mortality, respectively. 2h-PG remained significantly associated with outcomes in models including FPG and HbA1c as spline terms. Furthermore, 2h-PG significantly improved the ability of the C statistic to predict diabetes, CVD, and mortality. CONCLUSIONS 2h-PG remains independently predictive of outcomes in models including FPG and HbA1c. Therefore, in addition to FPG and HbA1c, routine testing of 2h-PG should be considered in order to better assess the risks of outcomes.

BACKGROUND: Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. METHODS: A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. RESULTS: Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. CONCLUSIONS: The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy.

Importance: Whether optimal cardiovascular health metrics may counteract the risk of cardiovascular events among patients with prediabetes or diabetes is unclear. Objective: To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with subsequent development of cardiovascular disease (CVD) among participants with prediabetes or diabetes as compared with participants with normal glucose regulation. Design, Setting, and Participants: The China Cardiometabolic Disease and Cancer Cohort Study was a nationwide, population-based, prospective cohort study of 20 communities from various geographic regions in China. The study included 111 765 participants who were free from CVD or cancer at baseline. Data were analyzed between 2011 and 2016. Exposures: Prediabetes and diabetes were defined according to the American Diabetes Association 2010 criteria. Seven ICVHMs were adapted from the American Heart Association recommendations. Main Outcomes and Measures: The composite of incident fatal or nonfatal CVD, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure. Results: Of the 111 765 participants, 24 881 (22.3%) had normal glucose regulation, 61 024 (54.6%) had prediabetes, and 25 860 (23.1%) had diabetes. Mean (SD) age ranged from 52.9 (8.6) years to 59.4 (8.7) years. Compared with participants with normal glucose regulation, among participants with prediabetes, the multivariable-adjusted hazard ratio for CVD was 1.34 (95% CI, 1.16-1.55) for participants who had 1 ICVHM or less and 0.57 (95% CI, 0.43-0.75) for participants who had at least 5 ICVHMs; among participants with diabetes, the hazard ratios for CVD were 2.05 (95% CI, 1.76-2.38) and 0.80 (95% CI, 0.56-1.15) for participants who had 1 ICVHM or less and at least 5 ICVHMs, respectively. Such pattern of association between ICVHMs and CVD was more prominent for participants younger than 55 years (prediabetes and at least 5 ICVHMs: hazard ratio [HR], 0.32; 95% CI, 0.16-0.63; 1 ICVHM or less: HR, 1.58; 95% CI, 1.13-2.21; diabetes and at least 5 ICVHMs: HR, 0.99; 95% CI, 0.44-2.26; 1 ICVHM or less: HR, 2.46; 95% CI, 1.71-3.54; compared with normal glucose regulation) than for participants 65 years or older (prediabetes and at least 5 ICVHMs: HR, 0.80; 95% CI, 0.50-1.26; 1 ICVHM or less: HR, 1.01; 95% CI, 0.79-1.31; diabetes and at least 5 ICVHMs: HR, 0.79; 95% CI, 0.46-1.35; 1 ICVHM or less: HR, 1.73; 95% CI, 1.36-2.22, compared with normal glucose regulation; P values for interaction ≤.02). Additionally, the hazard ratio for CVD per additional ICVHM was 0.82 (95% CI, 0.79-0.86) among participants with prediabetes and was 0.85 (95% CI, 0.80-0.89) among participants with diabetes. Conclusions and Relevance: Participants with prediabetes or diabetes who had 5 or more ICVHMs exhibited lower or no significant excess CVD risks compared with the participants with normal glucose regulation.

Abstract Background Both lipid and glucose abnormalities are associated with hypertension (HTN). However, it is unclear whether the triglyceride-glucose (TyG) index is associated with HTN. Therefore the aim of this study is to investigate the association of the TyG index and HTN and to compare the discriminative power of the TyG index, lipid, glycemic parameters for the risk of HTN in elderly individuals. Methods The present study was nested in a longitudinal (REACTION) study from May 2011 to December 2011, which was designed to demonstrate the association of abnormal glucose metabolism with the risk of cancer in the Chinese population. In total, 47,808 participants were recruited in this cross-sectional study. The TyG index was divided into five groups: the &lt; 20% group, the 20–39% group, the 40–59% group, the 60–79% group and the ≥ 80% group, according to quintile division of the subjects. Three multivariate logistic regression models were used to evaluate the association between the TyG vs. lipid parameters, glycemic parameters and HTN. Results Multivariate logistic regression analysis shows that compared with lipid and glycemic parameters, the TyG index remains significantly associated with HTN in either total subjects or subjects separated into men and women (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.18–1.51, p &lt; 0.0001 in total subjects; OR 1.39, 95% CI 1.11–1.74, p = 0.0042 in men; OR 1.28, 95% CI 1.11–1.49, p = 0.0010 in women). In a stratified analysis, an elevated TyG index is significantly associated with HTN in the subgroup of the oldest age (≥ 65) (OR 1.67, 95% CI 1.30–2.14, p &lt; 0.0001), as well as with obesity (Body mass index (BMI) ≥ 28 kg/m 2 ) (OR 1.85, 95% CI 1.29–2.66, p = 0.0009) or lower estimated glomerular filtration rate (eGFR) (&lt; 90 mL/(min·1.73 m 2 )) (OR 1.72, 95% CI 1.33–2.21, p &lt; 0.0001). Conclusion The TyG index is significantly associated with HTN and shows the superior discriminative ability for HTN compared with lipid and glycemic parameters in the Chinese elderly population.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown. METHODS: RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C, let-7c-5p, and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry. RESULTS: circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3, which promoted the epithelial-mesenchymal transition and finally facilitated the malignant progression of LSCC. CONCLUSIONS: circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.

BACKGROUND: China is one of the countries with the highest burden of stroke. Implementing multidimensional management guidelines will help clinicians practise evidence-based care, improve patient outcomes and alleviate societal burdens. This update of the 2019 edition will provide the latest comprehensive recommendations for the diagnosis and treatment of ischaemic cerebrovascular diseases. METHODS: We conducted a comprehensive search on MEDLINE (via PubMed) up to 31 August 2023. The writing team established the recommendations through multiple rounds of online and offline discussions. Each recommendation was graded using the evidence grading algorithm developed by the Chinese Stroke Association (CSA). The draft was reviewed and finalised by the CSA Stroke Guidelines Writing Committee. RESULTS: This update included revisions of 15 existing recommendations and 136 new recommendations in the following areas of stroke care: emergency assessment and diagnosis of ischaemic cerebrovascular disease, acute-phase reperfusion therapy, evaluation of underlying mechanisms, antithrombotic therapy, prevention and treatment of complications, and risk factor management. CONCLUSIONS: This guideline updated the recommendations for the clinical management of ischaemic cerebrovascular disease from 2019.

Dysregulated cellular proliferation represents a hallmark feature across all cancers. Aberrant activation of the cyclin-dependent kinase 4 and 6 (CDK4/6) pathway, independent of mitogenic signaling, engenders uncontrolled breast cancer cell proliferation. Consequently, the advent of CDK4/6 inhibition has constituted a pivotal milestone in the realm of targeted breast cancer therapy. The combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) has emerged as the foremost therapeutic modality for patients afflicted with hormone receptor-positive (HR + )/HER2-negative (HER2-) advanced breast cancer. At present, the Food and Drug Administration (FDA) has sanctioned various CDK4/6i for employment as the primary treatment regimen in HR + /HER2- breast cancer. This therapeutic approach has demonstrated a substantial extension of progression-free survival (PFS), often amounting to several months, when administered alongside endocrine therapy. Within this comprehensive review, we systematically evaluate the utilization strategies of CDK4/6i across various subpopulations of breast cancer and explore potential therapeutic avenues following disease progression during application of CDK4/6i therapy.

OBJECTIVE: To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status. RESEARCH DESIGN AND METHODS: We analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 SD of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality. RESULTS: In participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82-1.30), 1.23 (1.07-1.42), and 1.61 (1.30-2.00), respectively; the corresponding values for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92-1.18), 1.12 (1.06-1.18), and 1.15 (1.09-1.21), respectively (P for interaction = 0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI 2-34%) higher risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15-17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44-77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters. CONCLUSIONS: Glucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risk related to insulin resistance remained, regardless of obesity.

Osteoarthritis (OA) is a chronic joint disease and hard to cure at present. Accumulating evidence suggests long noncoding RNA-HOTAIR (lncRNA-HOTAIR) plays important role in OA progression. However, the underlying molecular mechanism of HOTAIR in OA progression has not been well elucidated. In the present study, we identified that HOTAIR level was upregulated in OA cartilage tissues. High expression of HOTAIR was correlated with modified Mankin scale, extracellular matrix (ECM) degradation and chondrocytes apoptosis. The expression of miR-17-5p was down-regulated, while alpha-1, 2 fucosyltransferase 2 (FUT2) was increased in OA progression. Luciferase reporter and RNA immunoprecipitation (RIP) assays indicated that HOTAIR could directly bind to miR-17-5p and indirectly upregulate FUT2 level. Functional investigation revealed HOTAIR and FUT2 aggravated ECM degradation and chondrocytes apoptosis, and this effect could be reversed by miR-17-5p. Altered FUT2 modulated the activity of wnt/β-catenin pathway and HOTAIR/miR-17-5p also mediated wnt/β-catenin pathway through FUT2. Collectively, our findings indicated that HOTAIR/miR-17-5p/FUT2 axis contributed to OA progression via wnt/β-catenin pathway, which might provide novel insights into the function of lncRNA-driven in OA.

BackgroundAbelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease.Study DesignProspective, open-label, multicenter, randomized, controlled, clinical trial.Setting & ParticipantsFrom May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study.InterventionsA manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50 mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50 mg/d. The duration of intervention was 24 weeks.Outcomes & MeasurementsThe primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks.ResultsMean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of −508, −376, and −545 mg/d, respectively (P = 0.003 for A manihot vs losartan and P < 0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P > 0.05), and there were no severe adverse events in any group.LimitationsResults cannot be generalized to those with nephrotic syndrome or reduced eGFR.ConclusionsA manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria. Abelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease. Prospective, open-label, multicenter, randomized, controlled, clinical trial. From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50 mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50 mg/d. The duration of intervention was 24 weeks. The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of −508, −376, and −545 mg/d, respectively (P = 0.003 for A manihot vs losartan and P < 0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P > 0.05), and there were no severe adverse events in any group. Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.

Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by loss of recognition and memory. Neuroinflammation plays pivotal roles in the pathology of AD and affects the progression of the disease. Astrocyte and microglia, as main immune executors in the central nervous system (CNS), participate into the inflammatory response in AD. Glia polarize into different phenotypes during neurodegeneration. Pro-inflammatory glia produce cytokines (IL-1β, TNF-α, and IL-6) resulting into debris aggregates and neurotoxicity. Anti-inflammatory phenotypes produce cytokines (IL-4 and IL-10) to release the inflammation. Electroacupuncture is a useful treatment that has been found to slow the neurodegeneration in animals through experimentation and in humans through clinical trials. The aim of this study was to uncover the mechanisms of glia activation, microglia polarization, and cytokine secretion regulated by electroacupuncture as a treatment for AD. Methods: Twenty male Sprague–Dawley (SD) rats were randomly divided into four groups: Control group (Control), Normal saline group (NS), AD group (AD), and Electroacupuncture group (Acupuncture). The AD and Acupuncture groups were bilaterally injected with Aβ 1 – 42 into the CA1 field of the hippocampus. The Acupuncture group received electroacupuncture stimulation on the acupoint “Baihui” (GV20) for 6 days per week for a total of 3 weeks. The Morris Water Maze (MWM) was used to evaluate learning and memory capacity. Immunofluorescence was used to stain GFAP and Iba1 of the DG and CA1 in the hippocampus, which, respectively, expressed the activation of astrocyte and microglia. The M1 microglia marker, inducible nitric oxide synthase (iNOS), and M2 marker Arginase 1 (Arg1) were used to analyze the polarization of microglia. The pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), anti-inflammatory cytokines (IL-4 and IL-10), and pathway-molecules (p65 and Stat6) were tested to analyze the glia inflammatory response by immunofluorescence and polymerase chain reaction (PCR). Results: The MWM results showed that electroacupuncture improves the escape latency time and the swimming distance of AD rats. The number of GFAP and Iba1 cells significantly increased in AD rats, but electroacupuncture decreased the cells. The iNOS-positive cells were significantly increased in AD, and electroacupuncture decreased the positive cells. Electroacupuncture elevated Arg1-positive cells in AD rats. Electroacupuncture decreased the glia pro-inflammatory cytokine expression and increased the anti-inflammatory cytokine expression in AD rats. Furthermore, electroacupuncture inhibited the NF-κB pathway molecule (p65) while raising the Stat6 pathway molecule (Stat6). Conclusion: These results provide evidence that electroacupuncture improves the recognition abilities and memory of AD rats. Electroacupuncture inhibits the activation of glia and polarizes microglia toward the M2 phenotype. Electroacupuncture decreased the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) and increased the anti-inflammatory cytokines (IL-4 and IL-10). Furthermore, electroacupuncture affects the immune responses through inhibition of NF-κB pathway but activation of Stat6 pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death among the whole world. The most urgent needs are to find sensitive markers for early diagnosis or monitor postoperative recurrence and to give adequate treatment for HCC. MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of the targeted genes. This study was conducted to detect the application of miR-143 and miR-215 in the diagnosis of HCC. METHODS: A total of 340 serum samples (127 samples from controls, 118 samples from hepatitis and 95 samples from HCC patients) were collected. The levels of the two mature miRNAs (miR-143 and miR-215) were detected by probe-based stem-loop quantitative reverse-transcriptase PCR (RT-qPCR) in controls, hepatitis and HCC patients. Besides, the relationship between miR-143 and miR-215 levels and clinical and pathological factors was explored. RESULTS: We found that the expression of serum miR-215 was distinctly increased in chronic hepatitis compared with controls (mean ± SD: 6.79 ± 0.72 vs. 3.46 ± 0.37, P < 0.001 and mean ± SD: 8.38 ± 0.87 vs. 3.46 ± 0.37, P < 0.001). In addition, we conduct ROC analyses to detect the potential application of miR-143 and miR-215 in the diagnosis of chronic hepatitis and HCC. Our results showed that miR-143 and miR-215 might be a potential biomarker for the hepatitis and HCC. CONCLUSIONS: In conclusion, the expression of miR-143 and miR-215 in serum were significantly up-regulated in patients with chronic hepatitis and HCC. Due to its reasonable sensitivity and specificity for both diseases, miR-143 and miR-215 could be as potential circulating biomarkers. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1048932281272754.