Role of prostaglandin E2 in the modulation of renal water transport / 生理学报

Prostaglandin E2 (PGE2), a bioactive lipid mediator, is one of the most important locally acting factors involved in a variety of physiological and pathophysiological processes. PGE2 binds with four EP receptors (EP1-4) to activate G protein-coupled receptor signaling responses. Recent functional and molecular studies have revealed that PGE2 plays an essential role in regulation of renal fluid transport via a variety of mechanisms. The water balance mainly depends on the regulation of aquaporin-2 (AQP2) by arginine vasopressin (AVP) in renal collecting duct principal cells. In recent years, increasing evidence suggests that PGE2 plays an important role in renal water reabsorption in the collecting ducts. In this paper, we reviewed the role of PGE2 and its receptors in the regulation of water reabsorption in the kidney, which may provide a new therapeutic strategy for many diseases especially nephrogenic diabetes insipidus.

Farnesoid X receptor (FXR) inhibits coagulation process via inducing hepatic antithrombin III expression in mice / 生理学报

Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.

Diagnostic Performance of Intestinal in Colorectal Cancer: A Meta-Analysis / 中华医学杂志(英文版)

<p><b>Background</b>Increasing evidence has supported the link of intestinal Fusobacterium nucleatum infection to colorectal cancer (CRC). However, the value of F. nucleatum as a biomarker in CRC detection has not been fully defined. In order to reduce the random error and bias of individual research, this meta-analysis aimed to evaluate the diagnostic performance of intestinal F. nucleatum in CRC patients and provide evidence-based data to clinical practice.</p><p><b>Methods</b>An article search was performed from PubMed, Embase, Cochrane Library, and Web of Science databases up to December 2017, using the following key words: "Fusobacterium nucleatum", "Fusobacterium spp.", "Fn", "colorectal cancer(s)", "colorectal carcinoma(s)", "colorectal neoplasm(s)", and "colorectal tumor(s)". Articles on relationships between F. nucleatum and CRC were selected according to the preestablished inclusion and exclusion criteria. This meta-analysis was performed using STATA 12.0 software, which included mapping of forest plots, heterogeneity tests, meta-regression, subgroup analysis, sensitivity analysis, and publication bias. The sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and their corresponding 95% confidence interval (CI) of each eligible study were summarized.</p><p><b>Results</b>Finally, data for 1198 participants (629 CRC and 569 healthy controls) in 10 controlled studies from seven articles were included. The summary receiver operator characteristic curve was mapped. The diagnostic performance of intestinal F. nucleatum infection on CRC was as follows: the area under the curve: 0.86 (95% CI: 0.83-0.89), the pooled sensitivity: 0.81 (95% CI: 0.64-0.91), specificity: 0.77 (95% CI: 0.59-0.89), and DOR: 14.00 (95% CI: 9.00-22.00).</p><p><b>Conclusion</b>Intestinal F. nucleatum is a valuable marker for CRC diagnosis.</p>

General characteristics and clinical practices of Chinese patients with non-alcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To assess the characteristics and daily treatment compliance of non-alcoholic fatty liver disease (NAFLD) patients in China.</p><p><b>METHODS</b>NAFLD adult patients from 21 clinics of 12 cities in China were enrolled in this registry. Physical examination such as demographic characteristics (height, weight, waist circumference measurement), blood pressure and clinical laboratory and ultrasonographic examination of liver were undertaken. Daily practice including life style and medication were recorded and assessed in accordance with 2006 Chinese NAFLD treatment guidelines.</p><p><b>RESULTS</b>A total of 1656 patients were enrolled (1146 male and 510 female), mean of 45.8 ± 12.6 years old, mean duration of NAFLD history was (47.2 ± 47.7) months. 44.9% of NAFLD were suffering from metabolic syndromes. Patients with central obesity have higher incidence of hypertension and lower level of high-density lipoprotein cholesterol (HDL-C) than those without central obesity, P < 0.05. Body mass index (BMI), waist circumference, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in ALT abnormal group were higher than those in ALT normal group (P < 0.05), HDL-C was lower in ALT abnormal group (P < 0.05). Significant differences existed between the BMI, female waist circumference, TG, fast insulin, HOMA index, ALT, AST and HDL-C among subgroups with mild, moderate and severe steatosis. Majority of the patients did not follow recommendations of NAFLD treatment guidelines. Among targeted population only 15.3% of patients used insulin sensitizers and 23.8% took lipid lowering medicine according to the guideline.</p><p><b>CONCLUSION</b>Data indicated that nearly half of NAFLD patients co-morbid with metabolic disorders. Therapy compliance was unsatisfactory and the gap between current practice and Chinese NAFLD treatment guidelines was not optimal.</p>

Interference of osteopontin expression inhibits the invasion and metastasis of human hepatocellular carcinoma cell lines / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of osteopontin (OPN) on the invasion and metastasis of human hapatocellular carcinoma (HCC).</p><p><b>METHODS</b>HCC cell lines (HCC-LM3) were transfected with the chemically synthesized small interfering RNA (siRNA). Real-time PCR and Western blot were used to quantify the mRNA and OPN protein levels. The malignant phenotypes including cellular growth, colony formation and invasion capability of the HCC cells were analyzed.</p><p><b>RESULTS</b>The OPN mRNA and proteins levels were decreased by 75% and 80% in OPN siRNA treated cells. Colony formation and migratory capability were reduced in OPN siRNA treated cells (P < 0.05).</p><p><b>CONCLUSION</b>The specific siRNA is able to reduce the OPN expression at both the mRNA and protein levels and significantly inhibits the invasiveness of HCC cells.</p>

Decreased macrophage migration inhibitor factor expression up-regulats p27 in hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To observe the expression of macrophage migration inhibition factor (MIF) and p27 in hepatocellular carcinoma tissue, and to investigate the effect of MIF on the expression of p27 in hepatocellular carcinoma (HCC) cells.</p><p><b>METHODS</b>Immunohistochemistry and quantitative RT-PCR were performed to detect the expression of MIF and p27 in HCC tissues and peri-tumor tissues. Specific small interfering RNA (siRNA) targeting MIF gene was chemically synthesized and then transfected at the concentration of 50 nmol/L and 100 nmol/L into PLC cells and Hep3B cells. The mRNA levels of MIF and p27 after MIF siRNA treatment were quantified by real-time RT-PCR.</p><p><b>RESULTS</b>MIF protein and mRNA were over-expressed in the HCC tumor tissues compared to these in the peri-tumor tissues (P less than 0.01). The expression of p27 protein and mRNA was significantly lower in the HCC tumor tissues compared to these in the peri-tumor tissues (P less than 0.01). Compared to normal liver cell line L-02, HCC cell lines expressed higher level of MIF (F=61.036, P less than 0.01) and lower level of p27 (F=529.853, P less than 0.01). In MIF siRNA treated PLC and Hep3B cells, the MIF mRNA was decreased in a dose-dependent manner (F=320.1, P less than 0.01; F=201.2, P less than 0.01). The p27 mRNA was significantly up-regulated in MIF siRNA treated PLC and Hep3B cells compared to control siRNA transfected cells (F=419.4, P less than 0.01; F=459.9, P less than 0.01).</p><p><b>CONCLUSIONS</b>MIF is over-expressed in HCC tumor tissues, and the expression of p27 is repressed by MIF.</p>

Association of hepatic lipase gene promoter polymorphism -514C/T with nonalcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the prevalence of the hepatic lipase gene (LIPC) promoter polymorphism (at position -514) in patients with nonalcoholic fatty liver disease (NAFLD), and its relationship with the susceptibility to NAFLD.</p><p><b>METHODS</b>Genotype of LIPC promoter was detected with PCR-RFLP in 106 patients with NAFLD. Body mass index, waist-to-hip ratio (WHR), blood pressure, CHOL, HDL, LDL, TG, FPG and FINS of the patients were measured. Index of insulin resistance was determined using the homeostasis model assessment (HOMA) method. One hundred six healthy subjects matched for age and sex served as controls.</p><p><b>RESULTS</b>The frequency of CC genotype and C allele in the NAFLD group were significantly higher than those in the control group (31.1% vs 26.4%, 62.7% vs 54.2%, P<0.05). Compared with TT genotype, both CC genotype and CT genotypes had higher relative risk of NAFLD (OR: 3.73, 95% CI: 1.31, 10.63; OR: 3.60, 95% CI: 1.35, 9.60). At the same time, the non-carriers of T allele in -514 had higher WHR than the T carriers (0.877+/-0.06 vs 0.848+/-0.06, t=2.072, P<0.05)). Logistic regression analysis showed that T substitution in LIPC-514 position (OR: 1.28, 95% CI 0.10-0.74) had a lower susceptibility to NAFLD.</p><p><b>CONCLUSION</b>The LIPC-514C/T polymorphism is associated with WHR, and the T substitution of LIPC-514 may lower the susceptibility to NAFLD.</p>

The relationship between insulin resistance and adiponectin gene expression in nonalcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between insulin resistance (IR) and adiponectin gene expression in patients with nonalcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>Subcutaneous (SC) and omental (OM) adipose tissues were obtained from 21 NAFLD patients with obesity (n=10) and nonobesity (n=11) and also from 24 subjects (without NAFLD) with obesity (n=11) and nonobesity (n=13) who served as controls. Adiponectin mRNA expression levels in subcutaneous and omental adipose tissues were measured using SYBR Green I quantitative real-time PCR. The levels of plasma adiponectin and insulin were measured with ELISA. IR was estimated using the homeostasis assessment (HOMA).</p><p><b>RESULTS</b>The scores of HOMA-IR levels of the NAFLD patients and the controls with obesity and nonobesity were: 3.0+/-0.8, 2.8+/-0.9, 2.0+/-0.6, 1.2+/-0.5 respectively. The relative mRNA expression of adiponectin and blood adiponectin levels in NAFLD patients differed significantly from those of the controls. The HOMA-IR negatively correlated with the adiponectin mRNA expression levels of adipose tissues (r = -0.5) and blood adiponectin; it positively correlated with body mass index (r = 0.4), waist-hip-ratio (r = 0.4) and serum triglyceride (r = 0.3), but did not correlate with serum total cholesterol (r = 0.2).</p><p><b>CONCLUSION</b>IR of NAFLD patients was linked to low adiponectin gene expression in their adipose tissues. This finding suggests that low adiponectin gene expression may play a role in the pathogenesis of insulin resistance and NAFLD.</p>

Relationship between leptin gene of adipose tissues and nonalcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate leptin mRNA expressions in subcutaneous (SC) and omental (OM) adipose tissues of patients with nonalcoholic fatty liver disease (NAFLD), and their relationships with insulin resistance (IR), blood leptin, blood triglyceride, total blood cholesterol, blood glucose, body weight index and waist-hip ratio.</p><p><b>METHODS</b>SC and OM adipose tissues were obtained from 10 obese and 11 nonobese NAFLD patients and from 11 obese and 13 nonobese patients without NAFLD, who served as controls. Leptin mRNA expression levels in the subcutaneous and omental adipose tissues were measured using SYBR Green I quantitative real-time PCR. IR was estimated using homeostasis assessment (HOMA). The levels of plasma leptin and insulin were measured using ELISA.</p><p><b>RESULTS</b>The relative mRNA expression of leptin, HOMA-IR and blood leptin levels in NAFLD differed significantly from those of the controls (P < 0.05). The leptin/GAPDH ratio of the obese and nonobese NAFLD and control cases were 1.32 +/- 0.12, 0.99 +/- 0.05, 1.10 +/- 0.09, 0.87 +/- 0.13 respectively. The expression levels of SC and OM adipose leptin mRNA in NAFLD patients were positively correlated with HOMA-IR (r=0.72, P < 0.05), blood leptin (r=0.69, P < 0.05), blood triglyceride (r=0.32, P < 0.05), body weight index (r=0.57, P < 0.05) and waist-hip ratio (r=0.50, P <0.05).</p><p><b>CONCLUSION</b>The primary reason for high levels of blood leptin is high leptin mRNA expression in adipose tissues; in both obese and nonobese patients with NAFLD; high levels of blood leptin and the leptin mRNA expression in adipose tissues and IR exist. These findings suggest that leptin resistance exists in patients with NAFLD and leptin resistance is positively correlated with NAFLD, the same as in insulin resistance.</p>

An epidemiological survey of subclinical hepatic encephalopathy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the prevalence and correlative factors of subclinical hepatic encephalopathy (SHE) in patients with cirrhosis in China by using psychometric tests with big sample size.</p><p><b>METHODS</b>409 patients with cirrhosis and 416 patients with chronic hepatitis were investigated for the prevalence of SHE. In prevalence study questionnaire, psychometric tests (NCT and DST), laboratory data were used to estimate their liver function.</p><p><b>RESULTS</b>According to age, the patients were divided into 5 groups (including<35, 35 to 44, 45 to 54, 55 to 64 and >65 groups). There was highly statistical significance on the results of NCT and DST, between the cirrhosis patients and the controls (t> or =4.108, P<0.01). The prevalence of SHE in cirrhosis patients was 51.3%. Highly statistical significance was found (chi 2=23.910, P<0.01) among the Child-Pugh A, B, C groups (39.9%, 55.2% and 71.8%). According to age, gender, smoking, etiology and education, no statistical significance was found. Logistic regression showed that there was a close relationship between the SHE prevalence and the Child-Pugh score only, and no relationship had been found between the SHE prevalence and other factors including age, gender, smoking, etiology and education.</p><p><b>CONCLUSION</b>The SHE prevalence in hepatic cirrhosis patients is 51.3%, and the Child-Pugh score may be an important risk factor</p>

The effect of anal electrical stimulation on anal sphincter pressure in conscious dogs / 中华消化杂志

Objective To investigate the effects and mechanisms of anal electrical stimulation (AES) with long pulses on anal sphincter pressure (ASP) in conscious dogs.Methods Nine healthy female hound dogs were used for the study,composed of 4 randomized sessions including AES with vari- ous stimulation parameters,20-min sustained AES to assess anal sphincter fatigue,atropine or phentolamine were used to block corresponding receptor.ASP was measured with manometry and the contractile area under the contraction curve.AES was performed via a pair of ring electrodes attached to the manometric catheter.The stimulation parameters in all sessions but the first session included a frequency of 20 ppm,width of 200 ms and amplitude of 3 mA.Results ASP was 55.7?6.0 at baseline and increased by 37% to 76.4?6.5 during AES (P