Background: Absolute handgrip strength has been correlated with metabolic profile and metabolic disease. Whether relative handgrip strength is also associated with metabolic disease has not been assessed. This study aimed at assessing the association of relative handgrip strength with metabolic profile and metabolic disease in the general population in China.Methods: Data were derived from an ongoing cross-sectional survey of the 2013 National Physical and Health in Shanxi Province, which involved 5520 participants. Multiple linear regression or multiple logistic regression analysis were used to assess the association of absolute/relative handgrip strength with the metabolic profile, preclinical, and established stages of metabolic diseases.Results: This study revealed that relative handgrip strength, that is when normalized to BMI, was associated with: (1) in both genders for more favorable blood lipid levels of high-density lipoprotein cholesterol [males: b = 0.19 (0.15, 0.23); females: b = 0.22 (0.17, 0.28)], low-density lipoprotein cholesterol [males: b = −0.14 (−0.23, −0.05); females: b = −0.19 (−0.31, −0.18)], triglycerides [males: b = −0.58 (−0.74, −0.43); females: b = −0.55 (−0.74, −0.36)] and total cholesterol [males: b = −0.20 (−0.31, −0.10); females: b = −0.19 (−0.32, −0.06)]; and better serum glucose levels in males [b = −0.30 (−0.46, −0.15)]. (2) lower risk of impaired fasting glucose in males {third quartile [OR = 0.66 (0.45–0.95)] and fourth quartile [OR = 0.46 (0.30–0.71)] vs. first quartile} and dyslipidemia in both genders {third quartile [males: OR = 0.65 (0.48–0.87); females: OR = 0.68 (0.53–0.86)] and fourth quartile [males: OR = 0.47 (0.35–0.64); females: OR = 0.47(0.36–0.61)] vs. first quartile}. (3) lower risk of hyperlipidemia in both genders third quartile [males: OR = 0.66 (0.50–0.87); females: OR = 0.57 (0.43–0.75)] and fourth quartile [males: OR = 0.35 (0.26–0.47); females: OR = 0.51 (0.38–0.70)] vs. first quartile. However, contrary to relative handgrip strength, higher absolute handgrip strength was associated with unfavorable metabolic profiles and higher risk of metabolic diseases. These paradoxical associations were retained even after adjusted for BMI by employed a multivariate analysis.Conclusion: We conclude that measurement of relative handgrip strength can be used as a reasonable clinical predictor of metabolic health and disease.

Abstract. Cytokines are a group of peptides which form a sophisticated network to modulate multiple cellular events. Within such a network, and through complex feedback mechanisms, cytokine functions are largely interdependent and closely associated with a number of pathological processes. In the present study, the EVIDENCE 180 system was used to study the effects of storage temperature and repeated freeze/thaw cycles on the concentration of 12 cytokines in various sample types. Samples were collected from 9 healthy volunteers and stored by 3 methods: gel, glass and lithium heparin (LH) tubes. Immediately following collection, the concentration of each cytokine in the samples was measured. Cytokine concentrations of the 3 sample types that did not undergo repeated freeze/thaw cycles were compared with those subjected to 1-10 freeze/thaw cycles. In addition, the dynamic changes of 6 sample types which were stored at 4˚C for 6 h to 6 days was analyzed. In addition, the withinand between-run precision of 12 cytokines on the biochip array was evaluated. Interleukin (IL)-8, vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) concentrations were lower in plasma compared with serum. Cytokine levels in serum and plasma were affected by several freeze/thaw cycles with IL-1β, -4 and -10 increasing significantly following 1 freeze/thaw cycle and remaining at stable increased levels for the duration of the additional 9 cycles. In separated serum samples in gel and glass tubes stored at 4˚C for 6 days, no difference in concentration of the 12 cytokines was identified. In the other 4 sample types, IL-8, VEGF, tumor necrosis factor α and EGF levels were altered when stored at 4˚C. Results indicate that the EVIDENCE 180 system is stable and plasma was observed as the best sample type to determine concentration of the 12 cytokines using this biochip array. Repeated freeze/thaw cycles and storage at 4˚C was identified to affect the concentration of the 12 cytokines.The current study demonstrates that repeated freeze/thaw cycles of samples must be avoid. In addition, results indicate that plasma or serum must be separated immediately following centrifugation and sample concentration should be measured as soon as possible.

Purpose: Diverse circular RNAs (circRNAs) participate in the regulation of drug resistance in human cancers. However, the role of circRNAs in drug resistance in colorectal cancer (CRC) is dismal. In this study, we aimed to explore the effect of circ-PRKDC on 5-fluorouracil (5-FU) resistance in CRC. Materials and Methods: The levels of circ-PRKDC, microRNA-375 (miR-375) and forkhead box protein M1 (FOXM1) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). IC 50 of 5-FU, cell colony formation ability and invasion were assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and transwell assay, respectively. The protein levels of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), FOXM1, β-catenin and c-Myc were measured via Western blot assay. The targeting relationship between miR-375 and circ-PRKDC or FOXM1 was investigated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The effect of circ-PRKDC in vivo was explored by murine xenograft model assay. Results: Circ-PRKDC was upregulated in 5-FU-resistant CRC tissues and cells. Circ-PRKDC silencing repressed 5-FU resistance, cell colony formation and invasion in 5-FUresistant CRC cells in vitro and inhibited 5-FU resistance in vivo. MiR-375 was a target of circ-PRKDC and miR-375 inhibition reversed the effects of circ-PRKDC silencing on 5-FU resistance, cell colony formation and invasion. FOXM1 was a direct target gene of miR-375. MiR-375 suppressed 5-FU resistance by targeting FOXM1. Moreover, circ-PRKDC knockdown decreased FOXM1 expression by targeting miR-375. Additionally, circ-PRKDC knockdown impeded wnt/β-catenin pathway by regulating miR-375 and FOXM1. Conclusion: Circ-PRKDC enhanced 5-FU resistance in CRC by regulating FOXM1/miR-375 axis and wnt/β-catenin pathway.

Background: Inflammatory bowel disease is a chronic immunoinflammatory disease of the gastrointestinal tract. Piperine, an alkaloid, has been reported to possess antioxidant, anti-inflammatory, antiapoptotic, and antiulcer potential. Aim: To elucidate the plausible mechanisms of action of piperine on experimental trinitrobenzenesufonic acid (TNBS)-induced colitis by assessing various biochemical, molecular, histological, and ultrastructural modifications. Methods: Colitis was induced in male Sprague–Dawley rats via intrarectal instillation of TNBS. Then, the rats were treated with piperine (10, 20, and 40 mg/kg, p.o.) for 14 days. Results: TNBS induced significant ( p < 0.05) colonic damage, which was assessed by disease activity index, macroscopic score, and stool consistency. The administration of piperine (20 and 40 mg/kg) significantly inhibited ( p < 0.05) these damages. Treatments with piperine (20 and 40 mg/kg) notably inhibited ( p < 0.05) the TNBS-induced elevation of oxido-nitrosative stress (superoxide dismutase, glutathione, malondialdehyde, and nitric oxide), 5-hydroxytryptamine, and hydroxyproline content in the colon. Furthermore, colonic inducible nitric oxide synthase (iNOs), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma, and cyclooxygenase-2 (COX-2) messenger RNA (mRNA) expressions were upregulated after TNBS instillation and piperine (20 and 40 mg/kg) significantly attenuated ( p < 0.05) these elevated mRNA expressions. TNBS decreased the expressions of tight junction (TJ) protein (claudin-1, occludin, and zonula occludens-1 (ZO-1)) and increased the expressions of proapoptotic (caspase-1) protein. These expressions were markedly inhibited ( p < 0.05) by piperine treatment. Histological and ultrastructural studies of transmission electron microscopy suggested that piperine significantly ameliorated ( p < 0.05) TNBS-induced colonic aberrations. Conclusion: Piperine ameliorated the progression of TNBS-induced colitis by modulating the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha/nuclear factor-kappa B signaling pathway, thus inhibiting the overexpression of proinflammatory cytokines (TNF-α and IL’s), COX-2, iNOs, oxido-nitrosative stress, and proapoptotic proteins (caspase-1) that may improve the expression of TJ protein (claudin-1, occludin, and ZO-1).

BackgroundThe TESTIN gene was demonstrated to be a tumor suppressor in prostate and breast cancer through inhibiting tumor growth and invasion. Herein, we aimed to investigate the detailed functions of TESTIN in the highly sexual hormone (estrogen)-dependent malignancy, endometrial carcinoma.Material/MethodsTESTIN mRNA and protein expression were measured by qRT-PCR, Western blot and immunohistochemistry. Upregulation of TESTIN was achieved by transfecting the pcDNA3.1-TESTIN plasmids into AN3CA cells. Knockdown of TESTIN was achieved by transfecting the shRNA-TESTIN into Ishikawa cells. MTT assay, colony formation assay, and Transwell assay were used to investigate the effects of TESTIN on cellular proliferation and invasion. The apoptotic status and cell cycle were analyzed using flow cytometry. MMP2 secretion was determined by ELISA assay. The xenograft assay was used to investigate the functions of TESTIN in nude mice.ResultsCompared to the non-malignant adjacent endometrium, 54% of tumor samples presented downregulation of TESTIN (P<0.001). Loss of TESTIN protein was correlated with advanced tumor stage (P=0.047), high grade (P=0.034), and lymphatic vascular space invasion (P=0.036). In vitro, overexpression of TESTIN suppressed cell proliferation, induced dramatic G1 arrest, and inhibited tumor invasion through blocking the secretion of MMP2. Loss of TESTIN accelerated cellular proliferation, promoted cell cycle progression, and enhanced tumor invasion by increasing the secretion of MMP2. Consistently, TESTIN could significantly delay the growth of xenografts in nude mice.ConclusionsTESTIN was commonly downregulated in human endometrial carcinoma and was associated with poor prognostic markers. Moreover, TESTIN significantly inhibited tumor growth and invasion via arresting cell cycle in in vitro and in vivo experiments. Therefore, we propose that TESTIN might be a prognostic marker and therapeutic target for endometrial carcinoma.

ObjectivesTo assess the clustering of cardiovascular disease (CVD) risk factors in Han and Mongolian adults with prehypertension or hypertension in Northern China.MethodsWe selected 3227 Han and Mongolian participants (20–80 years old) using a multistage cluster sampling method in 2014. The participants were interviewed by standard questionnaires and underwent anthropometric measurement and biochemical testing. Han and Mongolian participants were divided into optimal, prehypertension, and hypertension groups based on blood pressure. A multinomial logit analysis was performed to explore relationships between CVD risk factor clustering and prehypertension or hypertension, and the heterogeneity between Han and Mongolian was evaluated by the Cochran Q test. The differences between the ethnic groups in the proportions of risk factors was tested with the χ2 test.ResultsThe clustering of two or three CVD risk factors in the prehypertension or hypertension groups was consistently higher than in the optimal group (Bonferroni, p<0.0167). The odds ratios (ORs) of prehypertension and hypertension increased with the number of CVD risk factors (ptrend <0.0001). In multivariate modelling, the adjusted ORs of one, two, and ≥3 CVD risk factors versus no risk factors was, respectively, 1.95, 2.25, and 2.28 in Han prehypertensive participants, and 1.73, 2.83, and 3.69 in Mongolian prehypertensive participants. In addition, the adjusted ORs were 3.15, 4.75, and 6.49 in Han hypertensive participants, and 1.90, 5.29, and 8.13 in Mongolian hypertensive participants (all p<0.05). There was no significant heterogeneity between Han and Mongolian participants in the prehypertension or hypertension groups. The age-standardised prevalence of ≥3 risk factors was 38.30% in Han men and 39.79% in Mongolian men. The rate was significantly lower in Han women than Mongolian women (9.18% vs 14.55%, p=0.002).ConclusionsThese findings showed clustering of CVD risk factors in prehypertensive Han and Mongolian adults, and showed prehypertension may be a useful target for intervention.

The aim of this study is to investigate the associations between EZH2 gene polymorphisms and colorectal cancer (CRC) risk. We undertook a case-control study to analyze three EZH2 polymorphisms (148505302C>T, 2110+6A>C and 626-394T>C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 512 patients with CRC and 546 control participants, and performed EZH2 genotyping using DNA sequencing. The obtained results indicated that overall, no statistically significant association was observed in 2,110+6A>C. Nevertheless, 148505302C>T genotype demonstrated a protective effect in CRCs (P=0.014; odds ratio (OR) 0.777, CI 95%:0.647-0.933). Furthermore, 148505302 T allele CRC was more significantly common in patients with tumor size of <4 cm than C allele CRC and in cases of good differentiation and lower advanced pathological stage. However, 626-394T>C genotype was at increased risk of CRCs (P<0.001; odds ratio (OR) 1.457, CI 95%:1.160-1.829). Moreover, 626-394C/C genotype CRCs were more significantly common in patients with tumor size of >4 cm than T allele CRC and in cases of poor differentiation and lower advanced pathological stage. In conclusion, polymorphism in 626-394T>C was observed to be associated with susceptibility of CRC. However, 148505302C>T polymorphism indicated to play a protective role in susceptibility to CRC. Nevertheless, further investigation with a larger sample size is needed to support our results.

For the treatment of chronic hemorrhagic radiation proctopathy, 4 % should be the preferred formalin concentration.