Graph Theory Further Revealed Visual Spatial Working Memory Impairment in Patients with Inflammatory Bowel Disease.

Background: Inflammatory Bowel Disease (IBD) patients may experience cognitive impairments in Visuospatial Working Memory (VSWM), significantly impacting their quality of life. However, the mechanisms underlying these impairments remain poorly understood. Methods: We studied functional MRI and graph theory analysis to investigate changes in functional connectivity networks during the Mental Rotation Task (MRT) in IBD patients. Twenty IBD patients (13 males, 7 females; mean age = 34.95 ± 13.80 years; mean disease duration = 2.43 ± 2.37 years) participated in the study. Exclusion criteria encompassed recent use of analgesics, 5-Aminosalicylate, corticosteroids, or immunosuppressants within the past three months. Additionally, we recruited 20 age-, gender-, and education-matched healthy controls for comparison. Results: Compared to a control group, IBD patients exhibited significantly longer reaction times and reduced accuracy during the MRT. Our analysis revealed abnormalities in multiple nodal attributes within the functional connectivity network, particularly in regions such as the bilateral orbitofrontal cortex, right supplementary motor area, bilateral parahippocampal gyrus, and bilateral anterior temporal lobe. We observed that the nodal efficiency in the left temporal pole is negatively correlated with Red Blood Cell Distribution Width (RDW) and positively correlated with response time of MRT. Conclusion: Our findings revealed notable abnormalities in multiple node attributes among IBD patients during MRT, providing evidence of cognitive impairments in VSWM in IBD patients. This study found RDW maybe can serve as a clinical indicator for predicting early VSWM impairment in patients with IBD.

Scale-Up Preparation of Manganese-Iron Prussian Blue Nanozymes as Potent Oral Nanomedicines for Acute Ulcerative Colitis.

Prussian blue (PB) nanozymes are demonstrated as effective therapeutics for ulcerative colitis (UC), yet an unmet practical challenge remains in the scalable production of these nanozymes and uncertainty over their efficacy. With a novel approach, a series of porous manganese-iron PB (MnPB) colloids, which are shown to be efficient scavengers for reactive oxygen species (ROS) including hydroxyl radical, superoxide anion, and hydrogen peroxide, are prepared. In vitro cellular experiments confirm the capability of the nanozyme to protect cells from ROS attack. In vivo, the administration of MnPB nanozyme through gavage at a dosage of 10 mg kg-1 per day for three doses in total potently ameliorates the pathological symptoms of acute UC in a murine model, resulting in mitigated inflammatory responses and improved viability rate. Significantly, the nanozyme produced at a large scale can be achieved at an unprecedented yield weighting ≈11 g per batch of reaction, demonstrating comparable anti-ROS activities and treatment efficacy to its small-scale counterpart. This work represents the first demonstration of the scale-up preparation of PB analog nanozymes for UC without compromising treatment efficacy, laying the foundation for further testing of these nanozymes on larger animals and promising clinical translation.

Altered dynamic functional network connectivity in rheumatoid arthritis associated with peripheral inflammation and neuropsychiatric disorders.

OBJECTIVE: This study explored the dynamic functional connective (DFC) alterations in patients with rheumatoid arthritis (RA) and investigated the correlation between the neuropsychiatric symptoms, peripheral inflammation and DFC alterations. METHOD: Using resting-state functional MRI, we investigated the DFC based on spatial independent component analysis and sliding window method for 30 patients with RA and 30 healthy controls (HCs). The Spearman correlation was calculated between aberrant DFC alterations, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HAD), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Diagnostic efficacy of indicators was assessed using receiver operating characteristic analysis (ROC). RESULTS: Three dynamic functional states were identified. Compared with HC, patients with RA showed reduced FC variabilities between sensorimotor network (SMN) and insula, SMN and orbitofrontal cortex, which were the crucial regions of sensory processing network. The above FC variabilities were correlated with the MoCA, HAD, CRP and ESR in patients with RA. Additionally, the CRP and ESR were negatively correlated to MoCA and positively related to HAD in patients with RA. The ROC analysis results showed that MoCA, HAD and FC variabilities of the sensory processing network could distinguish patients with RA from HC and also identify patients with RA with high ESR. CONCLUSION: Our findings demonstrated that abnormal DFC patterns in sensory processing networks in patients with RA were closely associated with peripheral inflammation and neuropsychiatric symptoms. This indicates that the dynamic temporal characteristics of the brain functional network may be potential neuroimaging biomarkers for revealing the pathological mechanism of RA.

Functional dysconnectivity and microstructural impairment of the cortico-thalamo-cortical network in women with rheumatoid arthritis: A multimodal MRI study.

Background: Cognitive deficits are common in rheumatoid arthritis (RA) patients, but the mechanisms remain unclear. We investigated the effective connectivity and structural alterations of the core brain regions in RA patients with cognitive impairment. Methods: Twenty-four female patients with RA and twenty-four healthy controls were enrolled. We analyzed abnormal brain activity patterns using functional MRI during the Iowa gambling task (IGT) and core regions effective connectivity using dynamic causal model (DCM). Structural alterations of white matter volume (WMV) and gray matter volume (GMV) were detected using voxel-based morphometry (VBM). Results: RA patients showed altered activation patterns of the cortico-thalamo-cortical network, increased coupling strength from the left ventromedial prefrontal gyrus to the anterior cingulate cortex (ACC), the ACC to the right thalamus, and decreased connectivity from the thalamus to left hippocampus. VBM structural analysis showed increased GMV in the bilateral orbital frontal gyrus, bilateral hippocampus and right putamen, and reduced GMV and WMV in the bilateral thalamus in RA patients. Right thalamic GMV and WMV were positively correlated with the right thalamus-to-hippocampus connective strength. Additionally, the bold signal, GMV and WMV of the right thalamus were positively correlated with cognitive performance (IGT score) in RA patients. Conclusion: Results suggest a structural and functional deficiency in the cortico-thalamo-cortical network, which is characterized by increased ACC-to-thalamus strength and reduced thalamus-to-hippocampus coupling in RA patients. The cognitive dysfunction may be the result of compensatory measures against imbalanced cortico-thalamic-cortical coupling.

Enhanced activity of the left precuneus as a predictor of visuospatial dysfunction correlates with disease activity in rheumatoid arthritis.

OBJECTIVE: To identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and assess the relation between visuospatial dysfunction and disease activity in RA patients using mental rotation task (MRT)-based functional magnetic resonance imaging (fMRI). METHODS: A total of 27 RA patients (11 in remission, 16 in active) and 27 well-matched controls were enrolled. The visuospatial function of the subjects was measured by MRT. Brain activity data were collected using blood oxygen level dependent fMRI technique under MRT. Disease activity score 28 (DAS28) was used to evaluate the disease severity of RA patients. An analysis of the correlations between abnormal visuospatial-related brain regions, MRT performance, and DAS28 was conducted. RESULTS: RA patients performed worse on MRT than controls. Compared to the control group, RA patients showed enhanced activation in the left precuneus, left superior frontal gyrus and right cingulate gyrus during the rotation task, with left hemisphere dominance. RA patients in active showed enhanced activation in the left precuneus, left middle frontal gyrus and right cingulate gyrus compared to the patients in remission. The left precuneus activation was negatively correlated with MRT accuracy (r = -0.621, p = 0.01) and positively correlated with DAS28 (r = 0.710, p = 0.002), and MRT accuracy was negatively correlated with DAS28 in RA patients (r = -0.702, p = 0.002). CONCLUSION: Enhanced activation of the left precuneus in RA patients affects visuospatial function and is closely related to disease activity. These changes may provide a valuable diagnostic neuroimaging biomarker of RA.

[Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism].

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

Dietary Patterns in Association With Hypertension: A Community-Based Study in Eastern China.

Objective: This study aimed to explore the association between dietary patterns and hypertension based on a community-based survey in Suzhou, Eastern China. Methods: This cross-sectional analysis was undertaken from the subset of the Suzhou Food Consumption and Health State Survey in 2018-2019. Adults aged ≥ 18 years were invited to participate in this survey. Dietary intake was collected by a 24-h dietary recall and a weighing method over three consecutive days (including two weekdays and one weekend day). Dietary patterns were defined using factor analysis. Association between the dietary patterns and hypertension was examined by multivariable logistic regression models with adjustment for covariates. Moreover, sensitivity analysis was used to reinforce our findings. Results: A total of 2,718 participants were included in the final analysis. Rice-vegetable pattern, fast food pattern, fruit-dairy pattern, and wheat-meat pattern were identified. We observed that the fruit-dairy pattern was inversely associated with hypertension after adjustment for all the covariates (OR = 0.55; 95% CI: 0.40, 0.75; P = 0.002). The association between the wheat-meat pattern and hypertension was attenuated and became statistically nonsignificant in sensitivity analyses. The other two patterns were not significantly associated with hypertension (P > 0.05). Conclusion: The fruit-dairy pattern was inversely associated with the risk of hypertension among Chinese adults. Our findings further emphasize the important role of optimal diet combination in the prevention of hypertension.

Self-reported sleep-disordered breathing and insomnia in association with hypertension: a community-based study in Eastern China.

OBJECTIVE: We aimed to explore the associations of self-reported sleep-disordered breathing (SDB) and insomnia with hypertension based on a community-based survey among adults in Suzhou, Eastern China. METHODS: The Suzhou Food Consumption and Health Survey was conducted from 2018 to 2019. A multistage random sampling method was used to recruit potential participants. Associations of SDB and insomnia with hypertension were examined by multivariable logistic regression models with adjustment for covariates. In addition, sensitivity analysis was used to reinforce our findings. RESULTS: A total of 2728 participants were included in the final analysis. SDB (OR, 1.83; 95% CI, 1.44-2.34; P < 0.001) and insomnia (OR, 1.31; 95% CI, 1.04-1.65; P < 0.001) were significantly associated with prevalent hypertension after multivariable adjustments. In the subgroup analysis by age groups and sex, the association between SDB and hypertension persisted in all groups, whereas the association between insomnia and hypertension remained significant in males and different age groups. In addition, SDB was positively correlated with DBP. Notably, participants with comorbid SDB and insomnia had the highest risk for hypertension (OR, 1.95; 95% CI, 1.40-2.72; P < 0.001). CONCLUSION: Both SDB and insomnia were associated with the prevalence of hypertension among the Chinese adults, whereas the comorbid conditions conveyed the highest risk for hypertension. Our findings provide a new insight for the potential pathogenesis of hypertension and a prevention strategy of hypertension among community adults.

Changes of Structural and Functional Attention Control Networks in Subclinical Hypothyroidism.

Objective: This study aimed to explore the structural changes in patients with subclinical hypothyroidism (SCH) using voxel-based morphometry (VBM) and to investigate the altered attentional control networks using functional MRI (fMRI) during the performance of a modified Stroop task with Chinese characters. Methods: High-resolution three-dimensional (3D) T1-weighted images and an fMRI scan were taken from 18 patients with SCH and 18 matched control subjects. The Montreal Cognitive Assessment Chinese-revised (MoCA-CR) and the Stroop task were used to evaluate the cognitive and attention control of the participants. Results: Compared to controls, the VBM results showed decreased gray matter volumes (GMVs) in bilateral prefrontal cortices (PFCs, including middle, medial, and inferior frontal gyri), cingulate gyrus, precuneus, left middle temporal gyrus, and insula in patients with SCH. The fMRI results showed a distributed network of brain regions in both groups, consisting of PFCs (including superior and middle and inferior frontal cortices), anterior cingulate cortex (ACC), posterior cingulate cortex, and precuneus, as well as the insula and caudate nucleus. Compared to controls, the SCH group had lower activation of the above brain areas, especially during the color-naming task. In addition, the normalized GMV (nGMV) was negatively correlated with thyroid-stimulating hormone (TSH) level (r = -0.722, p < 0.001). Conclusion: Results indicate that patients with SCH exhibit reduced GMVs, altered BOLD signals, and activation in regions associated with attention control, which further suggest that patients with SCH may have attentional control deficiency, and the weakened PFC-ACC-precuneus brain network might be one of the neural mechanisms. Negative correlations between nGMV and TSH suggest that TSH elevation may induce abnormalities in the cortex.

Sex differences in risk factors of uncomplicated colonic diverticulosis in a metropolitan area from Northern China.

As the world's most populated and rapidly aging country, there is limited information on sex-related differences in factors regarding uncomplicated colonic diverticulosis in China. We aimed to investigate sex differences in individual risk factor in a northern metropolis. Patients with colonic diverticulosis who underwent indicated colonoscopy were queried with respect to medical history and demographic features. Demographic information, life style factors and co-morbidities were retrieved from a prospective dataset. Multiple regression analyses were performed to determine precipitating factors of diverticula. Of 4,386 enrolled patients, colonic diverticulosis were detected in 218 cases (4.97%). Multiple logistic regression analysis implicated increasing age (OR = 1.05, 95%CI 1.03-1.06, P < 0.001), red meat ≥100 g/d (OR = 2.53, 95%CI 1.72-3.70, P < 0.001), smoking (OR = 2.14, 95%CI 1.05-4.33, P = 0.035), rheumatologic diseases (OR = 3.38, 95%CI 1.09-10.5, P = 0.035) and NSAIDs (OR = 2.11, 95%CI 1.12-3.97, P = 0.020) were significantly associated with diverticulosis in men, whilst advancing age (OR = 1.03, 95%CI 1.01-1.05, P = 0.013), BMI (OR = 1.12, 95%CI 1.04-1.19, P = 0.001), smoking (OR = 10.2, 95%CI 2.81-37.4, P < 0.001), rheumatologic diseases (OR = 8.04, 95%CI 3.05-21.2, P < 0.001), hypertension (OR = 1.76, 95%CI 1.01-3.06, P = 0.047), colonic polyps (OR = 3.12, 95%CI 1.82-5.36, P < 0.001) and antihypertensive medications (OR = 2.99, 95%CI 1.66-5.39, P < 0.001) in women. In conclusion, it is pivotal to take account of differentially sex-related factors in regard to the development of uncomplicated colonic diverticulosis.

Prognostic nomogram incorporating neutrophil-to-lymphocyte ratio for early mortality in decompensated liver cirrhosis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation. However, its predictive utility of 30-day mortality remains elusive in decompensated cirrhotics. AIMS: We aimed to combine NLR and other variables associated with early mortality of cirrhotics with acute insults in to a predictive nomogram. METHODS: We retrospectively analyzed 352 decompensated cirrhotics. The 30-day mortality was regarded as primary outcome. Multivariate Cox analysis was performed, and a NLR-based nomogram was developed. The performance of nomogram was determined in terms of its calibration, discrimination and clinical usefulness. Serum cytokines were evaluated by Milliplex cytokine assay. RESULTS: On multiple analysis, independent factors for early mortality were albumin, MELD and NLR, which were all selected into the nomogram. The nomogram showed good discrimination, with a concordance index of 0.88. Calibration of the nomogram predicted survival corresponding optimally with the actual outcomes. Decision curve analysis indicated our nomogram was useful in clinical practice. Among circulating cytokines we investigated, IL-6 and IL-8 were substantially elevated in cirrhotics compared to healthy subjects. High NLR was positively correlated with the expression of IL-6 and IL-8. CONCLUSION: The proposed nomogram incorporating NLR offered an individualized predictive tool for 30-day mortality in decompensated cirrhotics. The escalating value of NLR likely implicated excessive inflammatory response.

Effects of silenced PAR-2 on cell proliferation, invasion and metastasis of esophageal cancer.

The present study aimed to investigate the effect of protease-activated receptor 2 (PAR-2) on cell proliferation, invasion and metastasis in the esophageal EC109 cell line. Two short hairpin RNA (shRNA) expression plasmids were constructed based on the PAR-2 mRNA sequence in humans, and they were transfected into the EC109 esophageal cancer cell line, and the stable interference cell line (shRNA-PAR-2 EC109) was obtained by puromycin selection. Following transfection of PAR-2 shRNA-1, PAR-2 expression was significantly downregulated in mRNA level and protein level in EC109 cells (P<0.05). The proliferation of EC109 cells transfected with PAR-2 shRNA was significantly lower than the negative control group (P<0.05). At 24, 48 and 72 h, the ratio of proliferation inhibition was 15.92, 24.89 and 32.28%, respectively. Compared with the control group, S-phase arrest was observed in cells transfected with shRNA-PAR-2. The ratio of cells in the S phase was 32.79±4.06, 26.54±1.37 and 33.45±2.46% at 24, 48 and 72 h, respectively. For invasion, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.05). For metastasis assay, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.01). In the present study, the PAR-2 shRNA plasmid was constructed successfully, which can significantly downregulate PAR-2 expression in EC109 cells. Subsequent to silencing of PAR-2, the proliferation of EC109 cells was inhibited and the capabilities of invasion and migration were reduced. It is indicated that PAR-2 may be a potential target in esophageal cancer.

Association of elevated resting pulse rate with increased risk of hypertension development in children: A prospective study in Suzhou, China.

BACKGROUND: Elevated resting heart rate (RHR) or resting pulse rate (RPR) is associated with increased risk of hypertension development. However, information is limited to adults. The purpose of this study is to analyze this association among Chinese children in a prospective design. METHODS: A total of 4861 children who participated in the Blood Pressure Surveillance Program (2011-2017) were selected in this research. To investigate the association between RPR and hypertension development, children were divided into 4 groups according to the quartiles of RPR at baseline. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression model. RESULTS: Over a mean follow-up of 3.0 ±â€Š0.1 years, there were 384 cases of incident hypertension. Compared to boys and girls in the 1st quartile, those in the 4th quartile were 1.73 (95% CI 1.13, 2.65), 2.22 (95% CI 1.43, 3.45) times more likely to have hypertension, respectively. Every 10 bpm increase in RPR was associated with a 26% greater risk of hypertension development in boys (OR: 1.26; 95% CI 1.10, 1.44), while this risk was 1.28 (95% CI 1.13, 1.44) in girls. Baseline blood pressure (BP) and body mass index (BMI) did not have significant interactions with RPR on risk of hypertension development. CONCLUSION: This study confirms the relationship between elevated RPR and increased risk of hypertension development in children, independent of confounders including baseline BP and BMI. An elevated RPR could be considered as a risk factor for the assessment of hypertension, no matter from a clinical setting or a public health perspective.

Higher urinary bisphenol A concentration is associated with unexplained recurrent miscarriage risk: evidence from a case-control study in eastern China.

BACKGROUND: Evidence about the association between Bisphenol A (BPA) and the risk of recurrent miscarriage (RM) in human being is still limited. OBJECTIVE: We evaluated the association of urinary BPA concentrations with RM in human being. METHODS: A hospital-based 1:2 matched case-control study on RM was carried out in Suzhou and Kunshan in Jiangsu Province in China between August 2008 and November 2011. Total urinary BPA concentrations in 264 eligible urine samples (102 RM patients and 162 controls) were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The Wilcoxon test and conditional logistic regression were used to estimate the differences between the groups and odds ratios (OR) with 95% confidence intervals (CI), respectively. RESULTS: The median ± IQR (interquartile range) (P75-P25) values of non-creatinine-adjusted total urinary BPA levels in the RM patients and the controls were 1.66 ± 3.69 ng/ml and 0.58 ± 1.07 ng/ml, respectively (0.98 ± 2.67 µg/g Cr (creatinine) and 0.40 ± 0.77 µg/g Cr. The adjusted BPA level was significantly higher in the RM patients than in the controls (Wilcoxon test, Z = 4.476, P < 0.001). Higher level of urinary BPA was significantly associated with an increased risk of RM (P-trend < 0.001). Compared to the groups with urinary BPA levels less than 0.16 µg/g Cr, the women with levels of 0.40-0.93 µg/g Cr and 0.93 µg/g Cr or above had a significantly higher risk of RM (OR = 3.91, 95%CI: 1.23-12.45 and OR = 9.34, 95%CI: 3.06-28.44) that persisted after adjusting for confounding factors. The time from recently RM date to recruitment does not significantly influence the urinary BPA level (P = 0.090). CONCLUSION: Exposure to BPA may be associated with RM risk.

Protease-activated receptor 2 agonist increases cell proliferation and invasion of human pancreatic cancer cells.

The aim of this study was to determine the expression of protease-activated receptor 2 (PAR-2) in the human pancreatic cancer cell line SW1990, and to evaluate its effect on cell proliferation and invasion. The expression of PAR-2 protein and mRNA in SW1990 cells was determined by immunocytochemistry and reverse transcription polymerase chain reaction (PCR), respectively. MTT and cell invasion and migration assays, as well as semi-quantitative PCR and zymography analysis, were additionally performed. PAR-2 mRNA was significantly upregulated in the cells treated with trypsin or the PAR-2 activating peptide Ser-Leu-Ile-Gly-Lys-Val (SLIGKV) (P<0.01), but not in the Val-Lys-Gly-Ile-Leu-Ser group (P>0.05). Trypsin and SLIGKV significantly promoted SW1990 cell proliferation in a dose- and time-dependent manner (P<0.05). Compared with the control group, trypsin and SLIGKV significantly increased the mRNA expression (P<0.01) and gelatinolytic activity (P<0.01) of matrix metalloproteinase (MMP)-2. In conclusion, PAR-2 is expressed in SW1990 cells. PAR-2 activation may promote the invasion and migration of human pancreatic cancer cells by increasing MMP-2 expression.

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes.

The aim of this study was to investigate the association between polymorphisms in folic acid metabolism-related genes and idiopathic recurrent early pregnancy loss (REPL). A prospective case-control study was performed on a cohort of 82 REPL patients and 166 healthy controls. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C was assessed by applying polymerase chain reaction for amplification followed by DNA sequencing, for methionine synthase reductase A66G, solute carrier family 19, member 1 (SLC19A1) G80A and C696T, and genotyping was done by utilizing the Sequenom MassARRAY system. The results revealed a significant association between MTHFR A1298C polymorphism and idiopathic REPL. Haplotype analysis indicated that the MTHFR 677C-MTHFR 1298C allele combination was associated with REPL (P < 0.001). The MTHFR 677C-MTHFR 1298A and SLC19A1 80G-SLC19A1 696C allele combinations had lower frequencies in patients with REPL, but with P > 0.05 (P = 0.093 and P = 0.084, respectively).

Enhanced proliferation of human hepatoma cells by PAR-2 agonists via the ERK/AP-1 pathway.

To investigate the expression and role of PAR-2 in the proliferation of the human hepatoma cell line HepG2, PAR-2 protein and mRNA expression were evaluated by immuno-histochemistry, immunofluorescence and RT-PCR analysis. The signaling pathways downstream of PAR-2 activation that lead to hepatoma cell proliferation were analyzed. The results showed that PAR-2 is expressed in human hepatoma cells and PAR-2 mRNA expression was found to be upregulated in cells treated with trypsin or SLIGKV-NH2 (P<0.001). The proliferation rate of HepG2 cells treated with trypsin or SLIGKV-NH2 was significantly increased (P<0.001). The percentage of S phase, G2/M phase and the proliferation index (PI) of HepG2 cells treated with trypsin or SLIGKV-NH2 were significantly elevated (P<0.001). The proliferative responses of HepG2 to trypsin and SLIGKV-NH2 were associated with the upregulation of c-fos and PCNA, which were significantly blocked by PD98059 pretreatment. In conclusion, our results indicate that PAR-2 enhances proliferation of human hepatoma cells possibly via the ERK/AP-1 pathway.

[Association between serum bisphenol-A and recurrent spontaneous abortion: a 1:2 case-control study, China].

OBJECTIVE: This study was to investigate the association between serum Bisphenol-A (BPA) and unexplained recurrent spontaneous abortion (RSA). METHODS: A hospital-based 1:2 matched case-control study was conducted.Sixty-two patients with unexplained recurrent abortion were included and matched with 2 normal controls by factors as age (± 2 years), living in the same district and the same gestational age.The levels of BPA in serum for 62 cases and 108 controls were detected under high performance liquid chromatography after fluorescent derivatization. Levels of serum BPA in each case was compared with that in control of age, BMI, education levels, occupation, exposure for passive smoking. RESULTS: The values of serum BPA in cases and controls were (0.009 ± 0.002) and (0.004 ± 0.012) µg/ml, respectively. The levels of serum BPA in cases was significantly higher than in controls (Z = 3.506, P = 0.0005). After adjusted by age, BMI, education levels, occupation, passive smoking history and other factors, when compared to BPA below 0.004 µg/ml. The adjusted ORs were 4.39 (1.15 - 16.71) for BPA levels between 0.004 µg/ml and 0.012 µg/ml, and 4.95 (1.77 - 13.82) for BPA over 0.012 µg/ml. The risk of unexplained recurrent spontaneous abortion increased progressively with the growth of serum BPA levels (χ(2) = 9.179, trend test P = 0.0024). There were significant differences on BPA among controls that with histories of two, three or more abortions (the levels were 0.004, 0.008, 0.018 µg/ml, respectively, F = 8.92, P = 0.0002). CONCLUSION: High BPA level might be associated with unexplained recurrent spontaneous abortion.

[Association between gestational weight gain and birth weight (2001-2009): a cohort study carried outin Kunshan city, Jiangsu province, China].

OBJECTIVE: To identify the association between gestational weight gain and birth weight over the past 9 years in Kunshan city, Jiangsu province, China. METHODS: This population-based study was conducted between 2001 to 2009. Data were retrieved from Perinatal Monitoring System of Maternal and Child Health Care Hospital of Kunshan. The study population consisted of 33 631 women and singleton live fetus. Gestational weight gain was defined as the total weight gain during the last and first prenatal care program and divided by the interval weeks. RESULTS: From 2001 to 2009, the average incidence of low birth weight was 1.86%, while the average incidence of macrosomia was a bit higher, fluctuating around 8.47%. On those underweight mothers, after adjustment for potential confounders, and stratified by the BMI levels, which were evaluated at the first prenatal care program, we found that weight gain in the 3rd and 4th intervals, could reduce the risk of low birth weight (less than 2500 g). With those mothers with normal-weight, weight gain in the 2 nd, 3 rd and 4th intervals, would reduce the risk of low birth weight. Risks in the 4th quantile among underweight and normal-weight group were prevalence odds radio (POR) 95%CI: 0.51 (0.32-0.80) and 0.58 (0.42-0.79), respectively. The risks showed a significant downward trend in underweight and normal-weight groups with increased gestational weight gain. As for macrosomia (≥4000 g), the risks increased (POR 95%CI) 4.69 (2.82-7.81) in underweight, 4.15 (3.43-5.03) in normal-weight, in overweight, 3.64 (2.62-5.06) and 1.96 (1.48-2.60) in obese mothers with increased levels of gestational weight gain. Trend tests indicated that the risks of marcosomia increased in all levels of BMI, with the increase of gestational weight gain. CONCLUSION: Findings from this population-based study suggested that gestational weight gain could reduce the risks of low birth weight among underweight and normal-weight groups, while increase the risks of macrosomia in all parturients, as compared with lowest levels of gestational weight gain.