[Efficacy of alternate mucosa-submucosa clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection].

Objective: To analyze the efficacy of alternate titanium clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection (ESD). Methods: Clinical data of patients with gastric mucosal lesions who underwent ESD in the Department of Gastroenterology, Zhongda Hospital, Southeast University, were retrospectively collected from January 1, 2013 to August 31, 2023. According to the postoperative wound closure status, the patients were divided into completely closed group (complete closure of ESD wounds using alternate titanium clip closure), partially closed group (partial closure of ESD wounds), and unclosed group (without use of clips for treatment of ESD wounds). The incidence of postoperative complications as well as wound healing at 1 month and 3 months after surgery were compared among three groups, and the factors related to delayed bleeding after ESD for gastric mucosal lesions were analyzed through multiple logistic regression analysis. Results: A total of 846 patients were included, 430 cases in the completely closed group, including 300 males and 130 females, age [M (Q1, Q3)] was 65(56, 72) years old; one hundred and nine cases in unclosed group, including 78 males and 31 females, aged 66 (60, 71) years; and 307 cases in the partially closed group, including 214 males and 93 females, aged 66 (59, 71) years. The difference in the rate of delayed postoperative bleeding between the completely closed group [2.1% (9/430)] and the unclosed group [5.5% (6/109)] was not statistically significant (P=0.072), but both were lower than that of the partially closed group [9.4% (29/307), P<0.05)]. Further stratified analysis showed that, for the lesions located in the lower 1/3 of the stomach, the rate of postoperative bleeding was lower in the completely closed group than in the partially closed and unclosed groups [0.9% (2/222) vs 11.4% (4/35) vs 9.5% (7/74), respectively, P<0.001]. For lesions≥50 mm in length, the rate of postoperative bleeding was lower in the completely closed group than that in the partially closed and unclosed group[0 vs 11.8% (2/17) vs 20.5% (15/73), respectively, P=0.004]. The incidence of postoperative abdominal pain in the completely closed group [84.2% (363/430)] was lower than that in the unclosed group [97.2% (106/109)] and the partially closed group [95.4% (293/307), both P<0.001)]. The score of postoperative abdominal pain in the completely closed group [0 (0, 1)], was lower than that in the unclosed group [3 (2, 3)], and that in the partially closed group [2 (1, 3)] (both P<0.001). The wound healing rate of the completely closed group [80% (176/220)] was higher than that of the unclosed group [52.3% (33/63)] and the partially closed group [52.2% (83/159)] at 1 month postoperatively (both P<0.001); the healing rate of all three groups reached 100% at 3 months postoperatively. Multiple logistic regression analysis showed that the presence of ulcers or scars on the surface of the lesion (OR=2.930, 95%CI:1.503-5.712, P=0.002), and the diameter (OR=1.031, 95%CI:1.015-1.047,P<0.001) were related factors for postoperative bleeding. Conclusions: The alternate titanium clip closure surgery can reduce postoperative abdominal pain and shorten wound healing time in patients with gastric mucosal lesions after ESD surgery. The risk of postoperative bleeding can be reduced for lesions with a diameter≥50 mm and located in the lower 1/3 of the stomach.

[Current status and influencing factors for physicians in different departments prescribing novel hypoglycemic agent with cardiovascular benefits].

Objective: To investigate the knowledge, use and barriers when prescribing GLP-1RA and SGLT2i among cardiologists, endocrinologists and general practitioners, and explore the influencing factors that hinder the use of these medications. Methods: A questionnaire was conducted among physicians in the above departments in Peking University Third Hospital and health service institutions at all levels in its medical consortium. A total of 342 physicians were involved. Among them, 40.6% (139) were cardiologists, 28.9% (99) were endocrinologists and 30.4% (104) were general practitioners; 66.7% (270) came from Beijing while 33.3% (72) from other provinces. The survey included clinicians' knowledge and current use of GLP-1RA and SGLT2i, and the possible reasons that influenced the prescription of these medications. Medical therapies of physicians were investigated by simulating different clinical scenarios. The difference of measures among physicians in different departments was compared. Results: A total of 342 physicians were involved, with the average age of 40 (35, 46) years old and the average working time of 13 (7, 20) years. Among them, 40.6% (139) were male. 77.5% (265) physicians had comprehensive knowledge of SGLT2i and prescribed it, which was higher than that for GLP-1RA (70.5%, 241) (P<0.001). 21.1% (72) physicians prescribed SGLT2i more than 20 times per month, which was higher than that for GLP-1RA (8.2%, 28) (P<0.001). Endocrinologists had more knowledge and prescribed more GLP-1RA and SGLT2i compared with other physicians (both P values<0.001). 38.1% (53) cardiologists, 22.2% (22) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust GLP-1RA, which was the primary barrier for the use of medications (P=0.042). 27.4% (38) cardiologists, 14.1% (14) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust SGLT2i, which was the primary barrier for the use of medications (P=0.018). 21.6% (30) cardiologists, 45.5% (45) endocrinologists, and 31.7% (33) general practitioners believed side effects of SGLT2i was the primary barrier for the use of medications (P<0.001). For patients with unqualified glycemic control and cardiovascular complications, 65.4% (75) cardiologists, 69.7% (69) endocrinologists, and 43.3% (45) general practitioners chose the above medications (P<0.001). For patients with qualified glycemic control, combined with cardiovascular complications and diabetic organ damage, 35.3% (49) cardiologists, 52.5% (52) endocrinologists, and 25.0% (26) general practitioners chose the above medications (P<0.001). Conclusions: Physicians had more knowledge and prescription of SGLT2i than that of GLP-1RA. Endocrinologists had more knowledge and prescription of the above medications than other physicians. The side effect of medications was potential primary barrier for the use of the novel hypoglycemic agent with cardiovascular benefits. In clinical practice, most of physicians considered that high-risk patients with cardiovascular comorbidities need to be referred to cardiologist or endocrinologist to adjust clinical therapies.

[Effects of caloric restriction and rope-skipping exercise on cardiometabolic risk factors in overweight or obese college students].

Objective: To explore the effect of three interventions including caloric restriction, rope-skipping exercise and caloric restriction combined with rope-skipping exercise on cardiometabolic risk factors in overweight or obese college students. Methods: This study was a pilot randomized controlled trial. Overweight or obese students who met the inclusion criteria were recruited at Sun Yat-sen University in September 2019 and were randomly divided into four groups: caloric restriction group (CR), rope-skipping group (RS), combined group (CR-RS) and control group (CT). The intervention in each group lasted 8 weeks, specifically: the daily energy intake of CR was 100% to 110% of the basal metabolic energy; RS was instructed to rope three times a week, and CR-RS combined caloric restriction with rope-skipping. At the baseline and end of 8-week intervention, basic information, anthropometric indicators and fasting vein blood of students were collected. Paired t test and Wilcoxon paired-samples signed rank test were used for comparison before and after intervention, and analysis of covariance was used for comparison between groups after intervention. Results: A total of 29 students completed the trial and were included in the final analysis (7, 9, 7 and 6 students in CR, RS, CR-RS and CT, respectively). The mean age of students were (19.00±1.00) years, including 11 males and 18 females. The baseline characteristics of four groups were comparable. After 8 weeks of intervention, compared with CT, there was an increase in the body fat percentage and fat mass index in CR and CR-RS (P<0.05). Insulin level decreased in CR-RS (P<0.05). Systolic blood pressure in CR and diastolic blood pressure in CR-RS were higher (P<0.05). Compared with baseline, fat mass index decreased in CR (P<0.05), while body weight, BMI, and fat mass index decreased in CR-RS (P<0.05). Conclusion: It is suggested that the caloric restriction alone and calorie restriction combined with rope-skipping exercise can benefit overweight or obese college students with cardiometabolic risk factors.

Effect of Interleukin-17 gene on glomerular ultrastructure and podocyte injury in adriamycin nephropathy rat models.

The aim of this study was to investigate the mechanism of interleukin-17 (IL-17) gene in renal tissues of rats suffering from adriamycin (ADM) nephropathy and its effect on the expression level of characteristic proteins, such as Podocalyxin and Nephrin, in podocytes. Sprague-Dawley (SD) rats were randomly divided into a control group (treated with normal saline) and an ADM group (treated with adriamycin). ADM model rats were transfected with lentivirus and divided into a transfection group (transfected with recombinant plasmid IL-17-shRNA) and a negative control group (transfected with plasmid shNC). Coomassie brilliant blue G-250 (CBB) method was adopted to detect the levels of albumin in urine to validate the model. The ultrastructure of rat glomeruli was observed, and the ratio of T helper 17 cells/regulatory T cells (Th17/Treg) was measured by flow cytometry (FCM). The expression levels of IL-17, forkhead box P3 (Foxp3), Nephrin, and Podocalyxin were detected by real-time quantitative PCR (RT-qPCR) and western blot analysis. Results of the study showed that the proteinuria content of the ADM group was significantly higher than that of the control group (P<0.05). In the ADM group, the glomerular basement membrane had uneven thickness and incomplete structure, which showed foot process fusion and electron dense accumulation. However, the glomerular basal membrane in the transfected rats was thin and intact, and a small amount of epithelial foot process fusion and electron density accumulation were observed. The percentages of Th17 cells and IL-17 levels in the ADM group were significantly higher than those in the control group, while the percentages of Treg cells, Foxp3, Nephrin, and Podocalyxin levels were significantly lower than those in the control group (P<0.05). The percentages of Th17 cells, IL-17, Nephrin, and Podocalyxin in the transfection group were significantly higher than those in the ADM group and the negative control group, while the percentages of Treg cells and Foxp3 were significantly lower than those in the ADM group and the negative control group (P<0.05). The results of this study showed that abnormal activation of Th17/IL-17 cells caused podocyte injury and promoted the occurrence and progression of ADM nephropathy. In addition, inhibition of IL-17 gene expression could improve the imbalance of number of Th17 and Treg cells, which may be potentially applied in treatment of patients with primary nephrotic syndrome (PNS).

[Respiratory pathogen spectrum in pulmonary exacerbation of bronchiectasis in adults and its association with disease severity].

Objective: To determine the pattern of respiratory pathogens at bronchiectasis exacerbation and its associations with disease severity. Methods: A total of 119 steady-state bronchiectasis patients [42 males, 77 females, age range 19 to 74 years, mean age (45±14)years], diagnosed by a compatible history combined with evidence of bronchial dilatation on high-resolution computed tomography (HRCT), were recruited prospectively from out-patient clinics in the First Affiliated Hospital of Guangzhou Medical University between September 2012 and March 2013. A comprehensive history taking, radiologic appearance, spirometry, sputum bacterial culture and 16 respiratory viruses in nasopharyngeal swabs and sputum samples by PCR assays were collected at steady-state bronchiectasis. All bronchiectasis patients were followed up one year and assessed for bacteriology, virology and systemic inflammatory indices [including white blood cell, C-reactive protein (CRP), interleukin-6, 8 and tumor necrosis factor-α] during bronchiectasis exacerbation. Results: Fifty-eight bronchiectasis patients [20 males, 38 females, age range 19 to 74 years, mean age (44±14) years] reported 100 exacerbations (1 to 5 exacerbation events per patient) during one year follow-up. Respiratory viruses were found more frequently in sputum and nasal swab during exacerbation [35.0% (35/100) and 39% (39/100)] than those during steady-state in bronchiectasis [sputum: 13.8% (8/58), nasal swab: 8.6% (5/58)] (χ(2)=8.33,χ(2)=13.51; respectively, all P<0.05). The rate of bacterial detection during exacerbation in sputum was 56% (56/100), which was not significantly different compared with those at steady-state (35/58, 60.3%;χ(2)=0.284, P=0.59). Of these respiratory infections, viral-bacterial co-infection accounted for 30% exacerbation events. The most common bacteria and viruses during exacerbation in mild bronchiectasis (n=18, with 25 exacerbation events) were Haemophilus parainfluenzae (4 cases) in sputum and influenza A in nasal swab or sputum (4 cases), respectively. In patients with moderate (n=17, with 29 exacerbation events)-severe bronchiectasis (n=23, with 46 exacerbation events), pseudomonas aeruginosa was the most common bacteria in sputum (35 cases), and the most common respiratory viruses were rhinovirus in nasal swab or sputum (11 cases). In these 100 exacerbation events, patients with bacterial and viral co-infection, pure bacteria infection, pure virus infection, no bacteria and virus infection accounted for 30, 29, 16 and 25 exacerbation events, respectively. And patients with co-infection had higher serum CRP (45±23) mg/L and IL-8 [9.0 (4.4-15.5) ng/L] (F=23.32, F=9.81,respectively; all P<0.05), and increased risk of hospitalization (30% vs. 0] compared with those in non-infectious group(χ(2)=9.0, P=0.003). Conclusions: Pseudomonas aeruginosa, rhinovirus and influenza A were common causative agents of exacerbation in bronchiectasis.In patients with moderate-severe bronchiectasis, pseudomonas aeruginosa was the most common bacterium in sputum, and the most common respiratory virus was rhinovirus in nasal swab or sputum, compared to Haemophilus parainfluenzae in sputum and influenza A in nasal swab or sputum in mild bronchiectasis. Patients with co-infection had more severe systemic inflammatory response and higher risk of hospitalization during exacerbation.

[Clinical application of Acutegastrointestinal injury grading system assocaited with clinical severity outcome in critically ill patients: a multi-center prospective, observational study].

Objective: To investigate the feasibility of utilizing the current acute gastrointestinal injury(AGI) grading system, and explore the association of severity of AGI grade with clinical outcome in critically ill patients. Methods: The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24 h were recruited, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed based on GIsymptoms, feeding details and organ dysfunctionon the first week of admission to ICU.The intra-abdominal pressures(IAP) was measured using AbViser device. Results: Of 550 patients enrolled, mean values for age and APACHE Ⅱ score were (64.9±17.2) years and (19.5±7.4), respectively. 456 patients(82.9%) took mechanical ventilation, and 470 patients were identified for AGI. The distribution of AGI grade on the frist day of ICU admission were 50.6%(Ⅰ grade, n=238), 34.2%(Ⅱ grade, n=161), 12.4%(Ⅲ grade, n=58) and 2.8%(Ⅳ, n=13), respectively, while the distribution of the global AGI grade based on the 7-day AGI assessment of ICU admission were 24.5%(Ⅰ grade, n=115), 49.4%(Ⅱ grade, n=232), 20.6%(Ⅲ grade, n=97) and 5.5%(Ⅳ, n=26), respectively. 28- and 60-day mortality rate was 29.3%(n=161) and 32.5%(n=179), respectively. The patients with AGI had a higher 28-(31.1% vs 18.8%, P=0.025) and 60-day survival rate(34.7% vs 20.0%, P=0.01) than those with non-AGI, and also there were positive correlations between AGI grade and 28- and 60-day mortality(P<0.001). Univariate Cox regression analysis showed that age, the source of medicial admission, diabetes mellitus, coronary heart disease, the use of vasoactive drugs, serum creatinine and lactate, mechanical ventilation, APACHE Ⅱ score, the AGI grade in the first day of ICU admission and feeding intolerance within the first week of ICU stay were significantly(P≤0.02) associated with mortality. In multivariate analysis including all these variables, the source of medical admission(χ(2)=4.34, P=0.04), diabete mellitus(χ(2)=3.96, P=0.05), the use of vasoactive drugs(χ(2)=6.55, P=0.01), serum lactate(χ(2)=4.73, P=0.03), the global AGI grade in the 7-day of ICU admission(χ(2)=7.10, P=0.008), and APACHE Ⅱ score(χ(2)=12.1, P<0.001) remained independent predictors for 60-day mortality.In the further subgroup analysis including 402 patients with 7-day survival, the feeding intolerance within the first week of ICU stay could provide independent and incremental prognostic value of 60-day mortality wtih increased χ(2)value of Cox regression model(χ(2)=52.2 vs 41.9, P=0.007) . Conclusion: The AGI grading system is useful for identifying the severity of gastrointestinal dysfunction, and could be used as a strong predictor of impaired outcome. The results provide evidence to support that feeding intolerance within 7 days of admission to ICU was an independent determinant of mortality.

Body roundness index and body adiposity index: two new anthropometric indices to identify metabolic syndrome among Chinese postmenopausal women.

OBJECTIVES: Body roundness index (BRI) and body adiposity index (BAI) have been recently proposed to assess obesity. The objectives of this cross-sectional study were to compare their potential for identifying metabolic syndrome (MetS) with traditional obesity indices in Chinese postmenopausal women. METHODS: A total of 817 participants were involved in this study. Odds ratio and corresponding 95% confidence intervals (CI) between MetS and all indices were evaluated by binary logistic regression analysis. Receiver operating characteristic curve and area under curve (AUC) were employed to evaluate the abilities to identify MetS among all the indices. The differences in the AUC values between traditional indices and BAI as well as BRI were also evaluated. RESULTS: The upper values of all indices were significantly associated with the presence of MetS after adjusting for potential confounders, except for BAI. There were no significant differences in the AUC values between BRI and the traditional indices; however, the AUC values of all the traditional indices were significantly larger than that of BAI. CONCLUSIONS: Neither BAI nor BRI was superior to traditional obesity indices for predicting MetS. BAI showed the weakest predictive ability, while BRI showed potential for use as an alternative obesity measure in assessment of MetS.

Hepcidin and iron metabolism associated with cardiometabolic risk factors in children: A case-control study.

BACKGROUND AND AIMS: Iron metabolism plays a crucial role in the development of cardiometabolic disease; however, the association between cardiometabolic risk factors (CMRFs) and hepcidin as well as other iron parameters remains unclear in children. The aims of this study were to compare the circulating hepcidin levels and iron metabolism between children with and without CMRFs and to investigate the association between those iron parameters and CMRFs. METHODS AND RESULTS: A case-control study was conducted among 1126 children aged 7-14 years in the case group (n = 563) with CMRFs and the healthy control group (n = 563). Iron parameters, lipids, and anthropometric characteristics were evaluated. The information on demographics, diet, and physical activities was either children reported or parent reported. Compared with the healthy controls, children with CMRFs had higher levels of hepcidin and lower levels of serum iron, transferrin, and soluble transferrin receptor (sTfR; P < 0.001). Besides, the odds ratios (ORs) for low levels of high-density lipoprotein (HDL) were 2.03, 0.21, and 0.33 in children with higher hepcidin, transferrin, and sTfR levels (P < 0.05). Furthermore, ORs for cardiometabolic risk were 0.50 (95% confidence interval (CI): 0.30-0.85, P < 0.05), 0.22 (95% CI: 0.12, 0.42, P < 0.01) and 0.19 (95% CI: 0.10, 0.36, P < 0.01) in children with higher serum iron, transferrin, and sTfR levels, respectively. CONCLUSION: The levels of hepcidin were higher, while those of iron, transferrin, and sTfR were lower in children with CMRF. Hepcidin was positively associated with the risk of low HDL levels, whereas transferrin and sTfR levels negatively correlated with the risk of low HDL levels. In addition, serum iron, transferrin, and sTfR levels were negatively associated with cardiometabolic risk.

AMFR gene silencing inhibits the differentiation of porcine preadipocytes.

Our study clarifies the role of the autocrine motility factor receptor (AMFR) gene in porcine preadipocyte differentiation. AMFR-siRNA was transfected into porcine preadipocytes and the preadipocytes were induced to differentiation. Subsequently, qRT-PCR was conducted to examine changes in mRNA expression of a series of genes in porcine preadipocytes, including AMFR, sterol-regulatory element-binding protein-1a (SREBP1a), SREBP2, insulin-induced gene 1 (Insig1), and Insig2. Expression changes in the mRNA of genes regulating adipocyte differentiation were also analyzed using qRT-PCR, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and Kruppel-like factor 2 (KLF2). Western blot analysis was conducted to examine the changes in AMFR protein expression in porcine preadipocytes. Additionally, morphological changes in differentiated porcine preadipocytes were examined by oil red O staining, and changes in optical density (OD) values were measured using an ultraviolet spectrophotometer. At 24 h after transfection with AMFR-siRNA, AMFR mRNA expression significantly reduced (P < 0.01), and AMFR protein expression markedly decreased (P < 0.05). The mRNA expression of SREBP1a, SREBP2, Insig1, and C/EBPα was significantly reduced (P < 0.01), whereas the expression of KLF2 mRNA was significantly elevated (P < 0.01). After induction of preadipocyte differentiation, the number of lipid droplets decreased in the AMFR-silenced group, and the OD value markedly reduced (P < 0.05). In addition, the expression of C/EBPα mRNA significantly decreased (P < 0.05), whereas the expression of KLF2 mRNA considerably increased (P < 0.05). Taken together, silencing of the AMFR gene inhibits the differentiation of porcine preadipocytes.

Genetic analysis of STR markers on chromosome 21 in a Han population from southeast China.

Short tandem repeats (STRs) are highly polymorphic sequences and have been extensively used as genetic markers in mapping studies, disease diagnosis, and human identity testing. In this study, 11 STR markers on chromosome 21, including D21S1432, D21S11, D21S1246, D21S1412, D21S1437, D21S1442, D21S2039, D21S1270, D21S1435, D21S1409, and D21S1446, were analyzed in 740 unrelated Han individuals from southeast China. A total of 132 alleles, ranging from 7-21 for each locus, were named according to the guidelines of the International Society for Forensic Haemogenetics. The distributions of allelic frequencies for the 11 STRs and population genetic parameters were determined. All 11 STR markers showed high polymorphism and heterogeneity in the southeast Han population, with polymorphism information content of 0.61-0.87, heterogeneity of 64.5-86.1%, and power of discrimination of 0.835-0.973. Among the 11 STR markers, D21S1412, D21S1270, D21S11, and D21S1442 showed relatively higher heterogeneity. Their combination was relatively informative and was used in a quantitative fluorescence-polymerase chain reaction assay to diagnose Down syndrome (trisomy 21) in a southeast Chinese Han population. The genetic information and population data for these 11 STRs may be used not only in quantitative fluorescence-polymerase chain reaction assays but also in forensic studies and other genetic tests.

Relationship between serum uric acid levels and hepatic steatosis in non-obese postmenopausal women.

OBJECTIVE: Serum uric acid levels have been reported to be associated with non-alcoholic fatty liver disease (NAFLD). However, very few studies specifically examining the relationship between serum uric acid (SUA) levels and NAFLD in postmenopausal women have been reported in China, especially in postmenopausal women with normal body mass index (BMI) in whom NAFLD is not uncommon. METHODS: A cross-sectional study was employed of 528 Chinese normal-BMI postmenopausal women (aged 41-79 years) who participated in annual health check-ups. NAFLD is defined as a hepatic steatosis observed on liver ultrasonography in the absence of a second cause. Of all the participants, 121 women were diagnosed with hepatic steatosis (NAFLD group) and the others were without (non-NAFLD group). SUA quartiles were defined as follows: Q1, < 3.8 mg/dl; Q2, 3.8-4.4 mg/dl; Q3, 4.5-5.0 mg/dl; Q4, 5.1-6.0 mg/dl. Stepwise multivariable regression analysis was used to assess the relationships between SUA level and other variables. The association between SUA quartiles and hepatic steatosis was assessed using binary logistic regression. RESULTS: Compared to the non-NAFLD group, the mean level of SUA was significantly higher in the NAFLD group (p < 0.01). The adjusted odds ratio (95% confidence interval) for the presence of hepatic steatosis in the highest SUA quartile vs. the lowest quartile was 2.774 (1.396-5.513) for all women (p < 0.01) after adjusting for the factors which were independently associated with uric acid level including waist circumference, high blood pressure, blood urea nitrogen, creatinine, γ-glutamyltransferase, and triglycerides. Most estimates changed little after further adjustment for age, metabolic syndrome, drinking status, and smoking status. The presence of hepatic steatosis significantly increased in the third and fourth quartiles of SUA. The prevalence of hepatic steatosis increased gradually with an increasing SUA quartile (p for trend < 0.01). CONCLUSION: Higher SUA levels even within the normal range are positively and independently associated with the presence of hepatic steatosis in Chinese postmenopausal women with normal BMI.

Relationship between serum uric acid levels and metabolic syndrome in Chinese postmenopausal women.

OBJECTIVE: Serum uric acid levels have been reported to be associated with metabolic syndrome (MetS). However, few studies specifically examining the relationship between serum uric acid (SUA) levels and MetS in postmenopausal women have been reported in China. Thus, we conducted this study in order to assess the relationship between SUA levels and MetS in Chinese postmenopausal women. METHODS: A cross-sectional study of 1022 Chinese postmenopausal women (aged 42-80 years) who participated in annual health check-ups was employed. MetS was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria (NCEP-ATP III). Of all the participants, 385 women were diagnosed with MetS (MetS group) and the others were without MetS (non-MetS group). SUA quartiles were defined as follows: Q1, < 3.9 mg/dl; Q2, 3.9-4.5 mg/dl; Q3, 4.6-5.1 mg/dl; Q4, 5.2-6.0 mg/dl. The association between SUA quartiles and MetS was assessed using binary logistic regression. RESULTS: The adjusted odds ratio (95% confidence interval) for the presence of metabolic syndrome in the highest SUA quartile vs. the lowest quartile was 3.768 (2.386-5.950) for all women (p < 0.01) after adjusting for age, body mass index, blood urea nitrogen, serum creatinine, total cholesterol, low density lipoprotein cholesterol and C-reactive protein. The presence of MetS significantly increased in the second, third and fourth quartiles of SUA. The prevalence of MetS increased gradually with an increasing serum uric acid quartile (p for trend < 0.001). CONCLUSION: Higher SUA levels are positively and independently associated with the presence of MetS in Chinese postmenopausal women.

Inflammatory mediators induce sequestration of VE-cadherin in cultured human endothelial cells.

The mechanisms through which inflammatory mediators modify endothelial junctional structure are not well understood. Endothelial cells exposed to 1 mM H2O2, 0.1 mM histamine or 4 mM EDTA displayed decreased amounts of VE-cadherin on the cell surface in a time-dependent manner. H2O2 and EDTA-treated cells showed a sustained reduction in surface VE-cadherin, but histamine (0.1 mM) decreased cell surface VE-cadherin only at 5 and 15 min, not at 30 and 60 min. Sequestering of VE-cadherin could also be visualized as a decrease in immunofluorescent labeling of endothelial junctions in fixed, non-extracted monolayers. However, junctional staining was observed in these cells after membrane extraction. This decreased surface expression of VE-cadherin was actin-filament, but not PKC/MAP kinase dependent. VE-cadherin binding to the cytoskeleton was decreased by EDTA, but was not diminished by histamine or H2O2. Therefore, by promoting sequestration of junctional cadherins, inflammatory mediators may decrease adhesive bonds between apposed endothelial cells and increase solute permeability.

Palmitoyl ascorbate: selective augmentation of procollagen mRNA expression compared with L-ascorbate in human intestinal smooth muscle cells.

The effect of 6-O-palmitoyl ascorbate on procollagen mRNA levels, collagen synthesis, and collagen secretion was investigated and compared with the effect of L-ascorbate in human intestinal smooth muscle (HISM) cells in vitro. Collagen synthesis, determined by the incorporation of 3H-proline into pepsin-resistant, salt-precipitated collagen, increased in a concentration-dependent manner in response to palmitoyl ascorbate. There was a twofold increase in collagen synthesis at 2.5 and 5 microM. By contrast, L-ascorbate was required at 4-5 times the concentration for the same response. However, at 20 microM, both palmitoyl and L-ascorbate induced similar 2.7-fold increases in collagen synthesis. Palmitoyl ascorbate induced a 1.6- and 3.5-fold increase in steady-state levels of procollagen I and III mRNA levels respectively, whereas L-ascorbate had no effect. Palmitoyl ascorbate and L-ascorbate induced similar increases in the amounts of newly synthesized procollagen secreted into the medium and in the amounts of collagen types I, III and V accumulating in the cell layer. There was no effect of either palmitoyl ascorbate or L-ascorbate on the activity of a procollagen alpha2 (I) promoter construct transiently transfected into HISM cells. Palmitoyl ascorbate augments HISM cell procollagen synthesis and mRNA levels more efficiently than L-ascorbate. This property may be due to the greater resistance of the ascorbate ester to oxidation and suggests that palmitoyl ascorbate could be an important agent for studies of collagen synthesis in vitro.

Development of pseudointima and stenosis after transjugular intrahepatic portasystemic shunts: characterization of cell phenotype and function.

The clinical utility of transjugular intrahepatic portasystemic shunts (TIPS) is frequently complicated by the ingrowth of tissue into the stent lumen, causing stent stenosis. These studies were undertaken to define the cellular and matrix components of the pseudointima, define the phenotype and function of the mesenchymal cells in the pseudointima and maintain them in culture, and to study the differences between stenotic and nonstenosed stents. A total of 35 stents were evaluated. TIPS pseudointima were examined histologically, by immunohistochemistry and in situ hybridization to determine the cellular and connective tissue constituents. Mesenchymal cells were grown from tissue within the TIPS and around it, and their phenotype was studied and compared with control smooth muscle cells and fibroblasts. Masson's trichrome staining of histological sections demonstrated that TIPS tissue was composed of collagen and palisades of mesenchymal cells and was lined by an endothelium. Immunostaining demonstrated strong and uniform alpha-smooth muscle staining in TIPS mesenchymal cells and peri-TIPS cells. Type I procollagen mRNA expression was demonstrated in mesenchymal cells in and around the stent by in situ hybridization. TIPS mesenchymal cells secreted less radiolabeled fibronectin, and far more type III, relative to type I, collagen compared with peri-TIPS cells. TIPS cells also expressed high levels of type III procollagen mRNA compared with peri-TIPS cells. There was no difference between stenotic stents and nonstenosed stents with respect to clinical features, time from stenting, gross morphology, histology, presence of bile fistulae, and cell phenotype. However, smooth muscle cells (SMC) from stenotic stents demonstrated both greater cell proliferation and collagen I and III secretion compared with those from nonstenosed stents. These data demonstrate that TIPS stenosis results from an accumulation of collagen and proliferation of SMC within the stent lumen.

Corticosteroids repress the interleukin 1 beta-induced secretion of collagenase in human intestinal smooth muscle cells.

BACKGROUND & AIMS: The cytokine interleukin (IL)-1 beta induces collagenase expression and inhibits collagen expression in human intestinal smooth muscle (HISM) cells. Corticosteroids cause transrepression of certain genes, including the collagenase gene. The aim of this study was to determine if corticosteroids repress the induction of collagenase expression and the inhibition of collagen secretion by IL-1 beta in HISM cells. METHODS: HISM cells were exposed to IL-1 beta (1-100 pmol/L) for 24 hours in the presence or absence of dexamethasone (10(-6) mol/L). Collagenase messenger RNA (mRNA) levels were determined by ribonuclease protection assay. Collagenase and tissue inhibitor of metalloproteinase protein secretion were determined by enzyme-linked immunosorbent assay of culture medium. Procollagen and collagen secretion were determined by polyacrylamide slab gel analysis of radiolabeled proteins in culture medium. RESULTS: A 30-fold induction of collagenase mRNA and collagenase protein secretion by IL-1 beta was completely abrogated by dexamethasone. Dexamethasone at 10(-6) mol/L also reduced basal levels of collagenase mRNA by 50% and blocked the IL-1 beta-induced inhibition of collagen secretion. CONCLUSIONS: Corticosteroids repress the collagenolytic action of IL-1 beta on HISM cells in vitro and therefore should promote healing in the inflamed intestine.

Effect of brucine on mouse nonspecific immune responses.

AIM: To evaluate the effect of brucine (Bru) i.p. at analgesic doses on the nonspecific immune responses in normal and cyclophosphamide (Cyc)-treated mice. METHODS: The clearance of charcoal particles, the immune organ weights, the white blood cell counts in peripheral blood, the phagocytosis to neutral red (NR) of PMO and its IL-1 production in vitro were tested. RESULTS: In normal mice, Bru slightly enhanced the clearance of charcoal particles, the phagocytosis of PMO, IL-1 production, the immune organ weights and the WBC counts (P > 0.05), whereas in Cyc-induced subnormal immunity model mice, Bru greatly enhanced these nonspecific immune responses (P < 0.05 or P < 0.01). The effects of Bru were most marked i.p. at 10 mg.kg-1 in vivo or 0.1-10 mg.L-1 in vitro. CONCLUSION: Bru i.p. at an analgesic dosage has dose- and function-dependent immunoregulatory effects.