Nesterenkonia marinintestina sp. nov., isolated from the fish intestine.

A Gram-positive, aerobic, non-motile, irregular short rod, nonspore-forming actinobacterial strain, designated GX14115T, was isolated from fish intestine in Beihai City, Guangxi, China and subjected to a taxonomic polyphasic investigation. Colonies were yellow‒green, circular, smooth, central bulge, convex, opaque and 2.0-3.0 mm in diameter after growth on 2216E medium at 30 °C for 72 h. Growth occurred at 4-45 °C (optimum 30 °C), at pH 4.5-10.0 (optimum pH 7.5) and in the presence of 0-12% NaCl (w/v) (optimum 3.5%). Chemotaxonomic analysis showed that the main menaquinone of strain GX14115T was MK-7. The major cellular fatty acids were anteiso-C15:0 (44.8%), anteiso-C17:0 (20.5%), and iso-C15:0 (16%). The whole-cell sugars were galactose and xylose. The peptidoglycan type was L-Lys-Gly-D-Asp, and the polar lipids were phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), one unknown phospholipid (UP), and one unknown glycolipid (UG). The DNA G + C content of the type of strain was 69.5 mol%. The 16S rRNA gene sequence analysis revealed that strain GX14115T is affiliated with the genus Nesterenkonia and is closely related to Nesterenkonia sandarakina YIM 70009T (96.5%) and Nesterenkonia lutea YIM 70081T (96.8%). The calculated results indicated that the average nucleotide identity (ANI) values of GX14115T were 74.49-74.78%, to the two aforementioned type strains, and the digital DNA-DNA hybridization (dDDH) values were 20.1-20.7%. Strain GX14115T was proposed as a novel species of the genus Nesterenkonia by the physiological, chemotaxonomic, and phylogenetic data, for whose the name is Nesterenkonia marinintestina sp. nov. The type of strain is GX14115T (= MCCC 1K06658T = KCTC 49495T).

Tumor- and metastasis-promoting roles of miR-488 inhibition via HULC enhancement and EZH2-mediated p53 repression in gastric cancer.

Dysregulation of microRNAs (miRNAs or miRs) is implicated in the development of gastric cancer (GC), which is possibly related to their roles in targeting tumor-suppressive or tumor-promoting genes. Herein, the current study was intended to ascertain the function of miR-488 and its modulatory mechanism in GC. Initially, human GC cells were assayed for their in vitro malignancy after miRNA gain- or loss-of-function and RNA interference or overexpression. Also, tumorigenesis and liver metastasis were evaluated in nude mouse models. Results demonstrated that miR-488 elevation suppressed GC (MKN-45 and OCUM-1) cell proliferation, migration, and invasiveness in vitro and reduced their tumorigenesis and liver metastasis in vivo. The luciferase assay identified that miR-488 bound to HULC and inhibited its expression. Furthermore, HULC could enhance EZH2-H3K27me3 enrichment at the p53 promoter region and epigenetically repress the p53 expression based on the data from RIP- and ChIP-qPCR assay. Additionally, HULC was validated to enhance GC growth and metastasis in vitro and in vivo. Overall, HULC re-expression elicited by miR-488 inhibition can enhance EZH2-H3K27me3 enrichment in the p53 promoter and repress the p53 expression, thus promoting the growth and metastasis of GC.

AMPK activation suppresses mTOR/S6K1 phosphorylation and induces leucine resistance in rats with sepsis.

Although it has been known that protein synthesis is suppressed in sepsis, which cannot be corrected by leucine supplement (also known as leucine resistance), the molecular signaling mechanism remains unclear. This study aimed to investigate the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway in sepsis-induced leucine resistance and its upstream signals, and to seek a way to correct leucine resistance in sepsis. Sepsis was produced by cecal ligation and puncture (CLP) model in rat. Both septic rats and sham operation rat received total parenteral nutrition (TPN) with or without leucine for 24 h, and then protein synthesis and AMPK/mTOR and protein kinase B (PKB) were tested. In vitro C2C12 cells were treated with or without leucine, and we tested the AMPK/mTOR pathway and protein synthesis. We blocked AMPK by compound C and stimulated it by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) individually. The results showed that AMPK was highly phosphorylated and suppressed mTOR/S6K1 activation in CLP rats. In vitro when AMPK was activated by AICAR, protein synthesis was suppressed and leucine resistance was observed. High phosphorylation of AMPK was accompanied by PKB inactivation in CLP rats. When PKB was blocked, both AMPK activation and leucine resistance were observed. In CLP rats, nutrition support with intensive insulin therapy reversed leucine resistance by activating PKB and suppressing AMPK phosphorylation. These findings suggest that high phosphorylation of AMPK induced by PKB inactivation in sepsis suppresses mTOR, S6K1 phosphorylation, and protein synthesis and leads to leucine resistance. Intensive insulin treatment can reverse leucine resistance by suppressing AMPK activation through activation of PKB.

Preoperative Oral Carbohydrate Reduces Postoperative Insulin Resistance by Activating AMP-Activated Protein Kinase after Colorectal Surgery.

BACKGROUND: Postoperative insulin resistance (PIR) is a common response after colorectal surgery and an independent risk factor for recovery. Preoperative oral carbohydrate (POC) has been known to reduce PIR. Herein, we investigated whether its mechanism of action involves AMP-activated protein kinase (AMPK) and mTOR/S6K1/insulin receptor substrate-1 (IRS-1) pathways. METHODS: Patients undergoing colorectal cancer resection were randomly assigned to a POC, fasting, or placebo group. The exclusion criteria were association with diseases or intake of medication affecting insulin sensitivity. Pre- and postoperative insulin resistance, and protein phosphorylation of AMPK, mTOR, and IRS-1 in the rectus abdominis muscle were evaluated. RESULTS: From January 2017 to December 2017, 70 patients were randomized and 63 were evaluated. No difference was found in the clinical and operative characteristics among the 3 groups. In the POC group, the levels of blood glucose, blood insulin, and homeostasis model assessment of insulin resistance were significantly lower in the POC group than the fasting and placebo groups, and the insulin sensitivity index was significantly higher. The phosphorylation of AMPK in the POC group was significantly higher than that in the other 2 groups, whereas the phosphorylation of mTOR and IRS-1 was significantly lower. CONCLUSION: PIR involves AMPK and mTOR/S6K1/IRS-1 pathways. POC reduces PIR by the stimulation of AMPK, which suppresses the phosphorylation of mTOR/IRS-1 and attenuates PIR after colorectal resection.

SIRT6-mediated transcriptional suppression of Txnip is critical for pancreatic beta cell function and survival in mice.

AIMS/HYPOTHESIS: Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. METHODS: Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system. Mice were assayed for islet morphology, glucose tolerance, glucose-stimulated insulin secretion and susceptibility to streptozotocin. Transcriptional regulatory functions of SIRT6 in primary islets were evaluated by RNA-Seq analysis. Reverse transcription-quantitative (RT-q)PCR and immunoblot were used to verify and investigate the gene expression changes. Chromatin occupancies of SIRT6, H3K9Ac, H3K56Ac and active RNA polymerase II were evaluated by chromatin immunoprecipitation. RESULTS: Deletion of Sirt6 in pancreatic endocrine progenitor cells did not affect endocrine morphology, beta cell mass or insulin production but did result in glucose intolerance and defective glucose-stimulated insulin secretion in mice. Conditional deletion of Sirt6 in adult beta cells reproduced the insulin secretion defect. Loss of Sirt6 resulted in aberrant upregulation of thioredoxin-interacting protein (TXNIP) in beta cells. SIRT6 deficiency led to increased acetylation of histone H3 lysine residue at 9 (H3K9Ac), acetylation of histone H3 lysine residue at 56 (H3K56Ac) and active RNA polymerase II at the promoter region of Txnip. SIRT6-deficient beta cells exhibited a time-dependent increase in H3K9Ac, H3K56Ac and TXNIP levels. Finally, beta cell-specific SIRT6-deficient mice showed increased sensitivity to streptozotocin. CONCLUSIONS/INTERPRETATION: Our results reveal that SIRT6 suppresses Txnip expression in beta cells via deacetylation of histone H3 and plays a critical role in maintaining beta cell function and viability. DATA AVAILABILITY: Sequence data have been deposited in the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) with the accession code GSE104161.

TRIM32 promotes cell proliferation and invasion by activating ß-catenin signalling in gastric cancer.

The tripartite motif (TRIM) family comprises more than 70 members involved in the regulation of many cellular pathways. TRIM32 acts as an E3 ubiquitin ligase and has been reported to participate in many human cancers. Here, we aimed to investigate the role of TRIM32 in gastric cancer (GC) and the clinical implications. High expression of TRIM32 was observed in GC tissues and cell lines, and was significantly associated with poor prognosis. Knockdown TRIM32 expression remarkably suppressed the proliferation, migration, and invasion of GC cells in vitro and tumour growth in vivo, whereas overexpression of TRIM32 yielded the opposite results. Western blotting and quantitative reverse-transcription PCR (qRT-PCR) analyses revealed that up-regulation of TRIM32 significantly enhanced expression of ß-catenin protein and of its downstream targets TCF1, cyclin D1, Axin2 and MMP7 mRNAs. Moreover, we found that the mechanism behind the TRIM32-promoted GC progression was related to the ß-catenin signalling pathway. Collectively, these data suggest that TRIM32 promotes GC cell proliferation, migration, and invasion by activating the ß-catenin signalling pathway.

A cross-sectional survey of nutrition labelling use and its associated factors on parents of school students in Shanghai, China.

OBJECTIVE: To understand parents' knowledge and use of nutrition labelling and to explore its associated factors. DESIGN: Cross-sectional survey. SETTING: Two schools providing a nine-year educational programme in Putuo District, Shanghai, China, were selected for the study. Information was included on demographic data and knowledge of the Chinese Food Pagoda. SUBJECTS: Students and their parents (n 1770) participated in a questionnaire survey. RESULTS: Of questionnaires, 1766 were completed (response rate 99·8 %). Utilization rate of nutrition labelling was 19·3 %. Among 624 parents knowing nutrition labelling, 22·1 % understood all the information included, 70·7 % understood it partially and 7·2 % could not understand it at all. Use of nutrition labelling by parents was related to the following factors (OR; 95 % CI): high educational level of parent (1·465; 1·165, 1·841), parent's knowledge of the Chinese Food Pagoda (1·333; 1·053, 1·688), parent's consumption of top three snacks which are unhealthy (1·065; 1·023, 1·109), parent's assumption that nutrition labelling would affect their choice of food (1·522; 1·131, 2·048), student's willingness to learn about labels (1·449; 1·093, 1·920) and student's knowledge and use of labels (2·214; 1·951, 2·513). CONCLUSIONS: Parents' knowledge and use of nutrition labelling are still at a lower level, and some information included in the nutrition labels is not understood by parents. The forms of the existing nutrition labelling need to be continuously improved to facilitate their understanding and usefulness. It is necessary to establish nutrition projects focusing on education and use of nutrition labels which help parents and their children make the right choices in selecting foods.

The MSHA strain of Pseudomonas aeruginosa (PA-MSHA) inhibits gastric carcinoma progression by inducing M1 macrophage polarization.

Macrophages play crucial roles in promoting tumor development and progression. In the present study, we found that the mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa (PA-MSHA) was efficient in inducing M1 macrophage polarization. PA-MSHA treatment increases expression of M1-related cytokines and promotes activation of murine peritoneal macrophages (MPM). Interestingly, PA-MSHA inhibits cell proliferation and migration and induces the apoptosis of gastric carcinoma cells. These effects of PA-MSHA on M1 polarization were associated with activation of NF-κB expression. Thus, inducing polarization of M1 by PA-MSHA may be one potential strategy for inhibiting gastric carcinoma progression in mice.

A Chinese risk score model for identifying postprandial hyperglycemia without oral glucose tolerance test.

BACKGROUND: The aim of the study is to develop a risk score model for identifying postprandial hyperglycemia without oral glucose tolerance tests (OGTT) in Chinese population, and minimize the number of subjects needing further OGTT. METHODS: Multivariable stepwise logistic regression was used to develop risk score models in a derivation cohort (7953 participants without known diabetes). The developed models were verified in a validation cohort (another 1455 subjects without known diabetes). All subjects had completed questionnaires, physical examination and OGTT. Performances of the risk score models were estimated using receiver operating characteristic curves. RESULTS: Two risk score models for screening postprandial hyperglycemia were developed. The simple model used non-invasive risk factors (age, height, weight, waist, systolic blood pressure, pulse, hypertension, dyslipidemia and family history of diabetes mellitus), and the full model contained additional variables [fasting blood glucose (FBG), triglyceride/high density lipoprotein cholesterol] obtainable by invasive laboratory tests. The area under receiver operating characteristic curve (AUC) of simple model was similar to FBG and glycated haemoglobin. The full model has the largest AUC [0.799 (0.789-0.809) and 0.730 (0.702-0.758)] in both derivation and validation cohorts (p < 0.001 compared with simple model, FBG, and glycated haemoglobin). At a cutoff point of 80, the sensitivity, specificity and percentage that needed subsequent OGTT were 75.97, 67.56 and 48.38%, respectively. CONCLUSIONS: We developed a risk score model for screening postprandial hyperglycemia based on routine clinical information. It could effectively identify patients at high-risk for postprandial hyperglycemia and remarkably reduce the number of subjects requiring OGTT.

Association of calcaneal quantitative ultrasound parameters with metabolic syndrome in middle-aged and elderly Chinese: a large population-based cross-sectional study.

BACKGROUND: The possible association between metabolic syndrome (MS) and bone mineral density (BMD) has been highlighted recently. However, the exact effects of MS on calcaneal quantitative ultrasound (QUS) parameters remains uncertain. The aim of this study was to assess the impact of MS states, different componets of MS, as well as the number of MS componets on QUS. METHODS: A total of 7489 Chinese adults aged 40 years or older in Nanjing were enrolled in this cross-sectional study. MS was defined according to recommendations generated by the International Diabetes Federation (IDF) in 2005. QUS was measured for each participant. RESULTS: The prevalence of MS was 34.6% in men and 42.8% in women (over 40 years old). In postmenopausal women with MS, 25-hydroxyvitamin D[25(OH)D], age adjusted quantitative ultrasound index (QUI) and broadband ultrasound attenuation (BUA) were all lower than those without (p < 0.001, p = 0.023, p = 0.021, respectively), the difference of QUI and BUA disappeared after adjustment for body mass index (BMI) and waist circumference (WC). In stepwise analysis, BMI, WC, high density lipoprotein cholesterol (HDL-C) and fasting plasma glucose (FPG) were related to QUS (p < 0.05). The number of MS components had no influence on QUS. Fragile fracture incidence was higher in women with MS (6.8% VS. 5.3%, P = 0.034). CONCLUSION: Chinese postmenopausal women with MS have worse BMD measured by QUS and more chances to develop osteoporotic fractures than the controls, which partially due to central obesity as well as vitamin D deficiency. People having less central obesity, higher FPG or HDL-C are less likely to have bone mineral loss.

Influence of patient-controlled epidural analgesia versus patient-controlled intravenous analgesia on postoperative pain control and recovery after gastrectomy for gastric cancer: a prospective randomized trial.

BACKGROUND: Patient-controlled epidural analgesia (PCEA) has not been widely used after gastrectomy, although, in other abdominal surgery, it benefits patients more than patient-controlled intravenous analgesia (PCIA). We attempted to determine the effect of PCEA compared with PCIA on postoperative pain control and recovery after gastrectomy for gastric cancer. METHODS: A randomized controlled clinical trial that included patients undergoing D2 radical gastrectomy for gastric cancer was conducted for this study. Patients were randomized to a morphine-bupivacaine PCEA group and a morphine PCIA group. Postoperative outcomes such as pain, fasting blood glucose (FBG), time to first passage of flatus, complications, and time staying in hospital after surgery were compared with an intention-to-treat analysis. RESULTS: Between March 2010 and October 2010, 67 patients were randomized and 60 were evaluated. The PCEA group showed lower pain scores both at rest and on coughing after the operation (P < 0.05). FBG after the operation was significantly lower in the PCEA group than that in the PCIA group (P < 0.05). Time to first passage of flatus after surgery was shorter in the PCEA group (P < 0.05), while there were no significant differences regarding the incidence of complications between the two groups in terms of the clinical records. The length of hospital stay in the PCEA group was 10.7 ± 1.7 days, which was significantly shorter than that in the PCIA group (11.9 ± 1.8 days, P < 0.05). CONCLUSIONS: After gastrectomy for gastric cancer, PCEA, compared with PCIA, offered safer pain relief with superior pain control and resulted in a lower stress response and a quicker return of bowel activity.

Association between erythrocyte parameters and metabolic syndrome in urban Han Chinese: a longitudinal cohort study.

BACKGROUND: Although various cross-sectional studies have shown that erythrocyte parameters, including red blood cell (RBC), hemoglobin (Hb) and hematocrit (HCT), were linked with metabolic syndrome (MetS), few longitudinal studies have been used to confirm their relationship. The study, therefore, constructed a large-scale longitudinal cohort in urban Chinese population to highlight and confirm the association between erythrocyte parameters and MetS/its components. METHODS: A longitudinal cohort with 6,453 participants was established based on the routine health check-up systems to follow up MetS, and Generalized Estimating Equation (GEE) model was used to detect the association between erythrocyte parameters and MetS/its components (obesity, hyperglycemia, dyslipidemia, and hypertension). RESULTS: 287 MetS occurred over the four-year follow-up, leading to a total incidence density of 14.19 per 1,000 person-years (287/20218 person-years). Both RBC and Hb were strongly associated with MetS (RR/95% CI, P value; 3.016/1.525-5.967, 0.002 for RBC; 3.008/1.481-6.109, 0.002 for Hb), with their dose-response trends detected. All three erythrocyte parameters (RBC, Hb and HCT) were found to be associated with obesity, hypertension and dyslipidemia with similar dose-response trends respectively, while only Hb showed a significant association with hyperglycemia. CONCLUSIONS: Elevated erythrocyte parameters were confirmed to be associated with MetS/its components in urban Chinese population, suggesting that erythrocyte parameters might be served as a potential predictor for risk of MetS.

[Path analysis of lifestyle habits to the metabolic syndrome].

OBJECTIVE: To evaluate the relationship between lifestyle habits and the components of metabolic syndrome (MS). METHODS: Based on the routine health check-up system in a certain Center for Health Management of Shandong Province, a longitudinal surveillance health check-up cohort from 2005 to 2010 was set up. There were 13 225 urban workers in Jinan included in the analysis. The content of the survey included demographic information, medical history, lifestyle habits, body mass index (BMI) and the level of blood pressure, fasting blood-glucose, and blood lipid, etc. The distribution of BMI, blood pressure, fasting blood-glucose, blood lipid and lifestyle habits between MS patients and non-MS population was compared, latent variables were extracted by exploratory factor analysis to determine the structure model, and then a partial least squares path model was constructed between lifestyle habits and the components of MS. RESULTS: Participants'age was (46.62 ± 12.16) years old. The overall prevalence of the MS was 22.43% (2967/13 225), 26.49% (2535/9570) in males and 11.82% (432/3655) in females. The prevalence of the MS was statistically different between males and females (χ(2) = 327.08, P < 0.01). Between MS patients and non-MS population, the difference of dietary habits was statistically significant (χ(2) = 166.31, P < 0.01) in MS patients, the rate of vegetarian, mixed and animal food was 23.39% (694/2967), 42.50% (1261/2967) and 34.11% (1012/2967) respectively, while in non-MS population was 30.80% (3159/10 258), 46.37% (4757/10 258), 22.83% (2342/10 258) respectively. Their alcohol consumption has statistical difference (χ(2) = 374.22, P < 0.01) in MS patients, the rate of never or past, occasional and regular drinking was 27.37% (812/2967), 24.71% (733/2967), 47.93% (1422/2967) respectively, and in non-MS population was 39.60% (4062/10 258), 31.36% (3217/10 258), 29.04% (2979/10 258) respectively. The difference of their smoking status was statistically significant (χ(2) = 115.86, P < 0.01) in MS patients, the rate of never or past, occasional and regular smoking was 59.72% (1772/2967), 6.24% (185/2967), 34.04% (1010/2967) respectively, while in non-MS population was 70.03% (7184/10 258), 5.35% (549/10 258), 24.61% (2525/10 258) respectively. Both lifestyle habits and the components of MS were attributable to only one latent variable. After adjustment for age and gender, the path coefficient between the latent component of lifestyle habits and the latent component of MS was 0.22 with statistical significance (t = 6.46, P < 0.01) through bootstrap test. Reliability and validity of the model:the lifestyle latent variable: average variance extracted was 0.53, composite reliability was 0.77 and Cronbach's a was 0.57. The MS latent variable: average variance extracted was 0.45, composite reliability was 0.76 and Cronbach's a was 0.59. CONCLUSION: Unhealthy lifestyle habits are closely related to MS. Meat diet, excessive drinking and smoking are risk factors for MS.

Gallic Acid Restores the Sulfonamide Sensitivity of Multidrug-Resistant Streptococcus suis via Polypharmaceology Mechanism.

Due to the large amount of antibiotics used for human therapy, agriculture, and even aquaculture, the emergence of multidrug-resistant Streptococcus suis (S. suis) led to serious public health threats. Antibiotic-assisted strategies have emerged as a promising approach to alleviate this crisis. Here, the polyphenolic compound gallic acid was found to enhance sulfonamides against multidrug-resistant S. suis. Mechanistic analysis revealed that gallic acid effectively disrupts the integrity and function of the cytoplasmic membrane by dissipating the proton motive force of bacteria. Moreover, we found that gallic acid regulates the expression of dihydrofolate reductase, which in turn inhibits tetrahydrofolate synthesis. As a result of polypharmacology, gallic acid can fully restore sulfadiazine sodium activity in the animal infection model without any drug resistances. Our findings provide an insightful view into the threats of antibiotic resistance. It could become a promising strategy to resolve this crisis.

Celastrol Combats Methicillin-Resistant Staphylococcus aureus by Targeting Δ1 -Pyrroline-5-Carboxylate Dehydrogenase.

The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) raise a critical need for alternative therapeutic options. New antibacterial drugs and targets are required to combat MRSA-associated infections. Based on this study, celastrol, a natural product from the roots of Tripterygium wilfordii Hook. f., effectively combats MRSA in vitro and in vivo. Multi-omics analysis suggests that the molecular mechanism of action of celastrol may be related to Δ1 -pyrroline-5-carboxylate dehydrogenase (P5CDH). By comparing the properties of wild-type and rocA-deficient MRSA strains, it is demonstrated that P5CDH, the second enzyme of the proline catabolism pathway, is a tentative new target for antibacterial agents. Using molecular docking, bio-layer interferometry, and enzyme activity assays, it is confirmed that celastrol can affect the function of P5CDH. Furthermore, it is found through site-directed protein mutagenesis that the Lys205 and Glu208 residues are key for celastrol binding to P5CDH. Finally, mechanistic studies show that celastrol induces oxidative stress and inhibits DNA synthesis by binding to P5CDH. The findings of this study indicate that celastrol is a promising lead compound and validate P5CDH as a potential target for the development of novel drugs against MRSA.

A new isoflavone from the stems of Derris eriocarpa How.

A preliminary screening test was performed to discover new antihyperlipidaemic active compounds from the leguminous plant Derris eriocarpa How. A new compound, derris-isoflavone F (1), and derrubone dimethyl ether (6), a known synthetic compound of natural origin, were isolated from the stems of D. eriocarpa alongside eight recognised compounds. To our knowledge, this is the first instance of documenting the identification of compounds 1-10 from this plant. The new compound were evaluated for their antihyperlipidemic and antiproliferative properties. Compound 1 evidently reduced the triglyceride (TG) content in oleic acid-treated HepG2 cells, which validated its efficacy as a potential TG-lowering agent.

A longitudinal cohort based association study between uric acid level and metabolic syndrome in Chinese Han urban male population.

BACKGROUND: It has been recently demonstrated that serum uric acid (UA) is associated with metabolic syndrome (MetS) or its related clinical indications based on cross-sectional or prospective cohort studies. Nonetheless, due to the fact that UA level constantly fluctuates from time to time even for the person, using a single measure of UA level at baseline of those studies may not be sufficient for estimating the UA-Mets association. METHODS: To further estimate this time-dependent association, we fitted a generalized estimating equation (GEE) regression model with data from a large-scale 6-year longitudinal study, which included 2222 participants aged > =25 years with an average of 3.5 repeated measures of UA per person in the Health Management Center of Shandong Provincial Hospital, Shandong, China. RESULTS: After adjusting for other potential confounding factors (i.e., total cholesterol, low-density lipoprotein), it was verified that time-dependent UA level was an independent risk factor for MetS (OR = 1.6920, p < 0.0001). It was found that UA level was positively associated with obesity, hypertension, and dyslipidemia, but was inversely associated with hyperglycemia. CONCLUSIONS: Serum UA level may serve as an important risk factor of MetS. Additionally, our study suggested that UA level be an independent risk factor to obesity, hypertension and dyslipidemia, but a protective factor to hyperglycemia. These findings are concordant with results from other studies on Asian populations, and jointly provide a basis to further develop a risk assessment model for predicting MetS using UA levels and other factors in China.

Comparative Study of Pyloromyotomy and H-M Pyloroplasty in Proximal Gastrectomy for Adenocarcinoma of Esophageal-Gastric Junction.

INTRODUCTION: The incidence of adenocarcinoma of esophageal-gastric junction (AEJ) has been increasing in recent years. Esophagogastrostomy after proximal gastrectomy (PG-EG) is the most commonly used surgical method for this disease which causes a constant spasm of the pyloric sphincter by cutting the vagus nerve around the esophagus, so H-M pyloroplasty (Heineke-Mikulicz pyloroplasty) is often operated after PG-EG to prevent delayed gastric emptying. However, H-M pyloroplasty destroys anti-reflux structure of pylorus and leads to serious bile reflux. The present study was designed to compare pyloromyotomy and H-M pyloroplasty in proximal subtotal gastrectomy through clinical studies and animal experiments. METHODS: We retrospectively evaluated the outcomes of 73 AEJ patients (39 underwent PG-EG with an H-M pyloroplasty and 34 underwent PG-EG with a pyloromyotomy) between January 2016 and August 2020, and perioperative variables were compared. In the animal experiment, 48 rats were randomly divided into four groups (n = 12): vagotomy group (V group), H-M pyloroplasty group (HM group), pyloromyotomy group (PM group), and control group (O group). Gastric emptying and bile reflux were evaluated in each group. RESULTS: In the retrospective clinic study, pyloromyotomy and H-M pyloroplasty could all prevent delayed gastric emptying effectively, and the incidence of bile reflux found by electronic gastroscopy in the PM group was significantly lower than that in the HM group (HM, 14/39; PM, 4/34; P = 0.028). In the animal experiment, there was no significant between-group difference of gastric emptying rate (%) in the HM group and PM group (HM, 70.6 ± 16; PM, 72.3 ± 12; P = 0.68) while the gastric emptying rate (%) was significantly lower in the V group than in the HM, PM, and control group (P values were 0.037, 0.021, and 0.001 respectively). The gastric mucosa bile acid concentration was significantly higher in the HM group than other group (P values were all less than 0.001). CONCLUSIONS: The pyloromyotomy could prevent delayed gastric emptying effectively after PG-EG for types II and III AEJ and reduce bile reflux compared to Heineke-Mikulicz pyloroplasty.

Neoadjuvant Intraperitoneal and Systemic Chemotherapy Versus Neoadjuvant Systemic Chemotherapy With Docetaxel, Oxaliplatin, and S-1 for Gastric Cancer With Peritoneal Metastasis: A Propensity Score Matched Analysis.

BACKGROUND: The optimal treatment for gastric cancer with peritoneal metastasis (GCPM) remains debatable. This study aimed to compare the efficacy and safety of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) versus neoadjuvant systemic chemotherapy (NSC) for GCPM. METHODS: Patients of GCPM received neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 between January 2011 and June 2019 were retrospectively evaluated. Propensity score matched (PSM) analysis was carried out to reduce the selection bias. Multivariate Cox regression model was applied to screen the prognostic factors. RESULTS: After PSM processing, 71 patients in each group were matched among the 186 GCPM patients included. NIPS yielded a better ascites and cytology response to chemotherapy, higher conversion resection rate and R0 resection rate than NSC. The overall survival (OS) rate in NIPS group was better than that in NSC group. Multivariate analysis revealed that the P stage, ascites response, conversion surgery rate and R0 resection rate were independent prognostic factors. Subgroup analysis indicated that NIPS showed a survival benefit over NSC only in patients with cT3-4a, P1-2, whose cytology turned negative, and who received conversion surgery; while not in patients with cT4b, P0 or P3, whose cytology did not turn negative, or who did not receive conversion surgery. CONCLUSIONS: NIPS is a safe and feasible treatment for GCPM, which showed more benefit than NSC.

CircHIPK3 Promotes the Tumorigenesis and Development of Gastric Cancer Through miR-637/AKT1 Pathway.

Circular RNA is a kind of RNA with a covalently closed loop, which has a complex ability to modulate genes in the process of tumorigenesis and metastasis. Nevertheless, how circular RNA functions in gastric cancer (GC) remains unclear. The effect of circHIPK3 in vitro was studied here. Quantitative real-time PCR (qRT-PCR) was employed to found that circHIPK3 markedly increased in GC tissues and cell lines. And low expression of circHIPK3 suppressed the GC cells growing and metabolizing. Then the bioinformatics tool predicted the downstream target of circHIPK3, and it was proved by the dual-luciferase report experiment. According to the results of bioinformatics analysis and experimental data, it was clarified that circHIPK3 acted as a sponge of miR-637, releasing its direct target AKT1. The dual-luciferase assay revealed that mir-637 could bind circHIPK3 and AKT1. qRT-PCR data indicated that overexpression circHIPK3 led to the low level of miR-637 and overexpressed miR-637 would reduce AKT1 level. Finally, we demonstrated that the low expression of miR-637 or overexpression of AKT1 could attenuate the anti-proliferative effects of si-circHIPK3. These results suggest that the circHIPK3/miR-637/AKT1 regulatory pathway may be associated with the oncogene and growth of gastric cancer. In short, a new circular RNA circHIPK3 and its function are identified, and the regulatory pathway of circHIPK3/miR-637/AKT1 in the tumorigenesis and development of gastric cancer is discovered.