Objective:To explore whether transjugular intrahepatic portosystemic shunt (TIPS) can improve the prognosis of esophagogastric variceal bleeding (EGVB) combined with sarcopenia in cirrhotic patients.Methods:A retrospective cohort study was performed. A total of 464 cases with cirrhotic EGVB who received standard or TIPS treatment between January 2017 and December 2019 were selected. Regular follow-up was performed for the long-term after treatment. The primary outcome was transplantation-free survival. The secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). The obtained data were statistically analyzed. The t-test and Wilcoxon rank-sum test were used to compare continuous variables between groups. The χ2 test, or Fisher's exact probability test, was used to compare categorical variables between groups. Results:The age of the included patients was 55.27±13.86 years, and 286 cases were male. There were 203 cases of combined sarcopenia and 261 cases of non-combined sarcopenia. The median follow-up period was 43 months. The two groups had no statistically significant difference in follow-up time. There was no statistically significant difference in transplant-free survival between the TIPS group and the standard treatment group in the overall cohort ( HR=1.31, 95% CI: 0.97-1.78, P=0.08). The TIPS patient group with cirrhosis combined with sarcopenia had longer transplant-free survival (median survival: 47.76 vs. 52.45, χ2=4.09; HR=1.55, 95 CI: 1.01~2.38, P=0.04). There was no statistically significant difference in transplant-free survival between the two kinds of treatments for patients without sarcopenia ( HR=1.22, 95% CI: 0.78~1.88, P=0.39). Rebleeding time was prolonged in TIPS patients with or without sarcopenia combination (patients without combined sarcopenia: median rebleeding time: 39.48 vs. 53.61, χ2=18.68; R=2.47, 95 CI: 1.67~3.65, P<0.01; patients with sarcopenia: median rebleeding time: 39.91 vs. 50.68, χ2=12.36; HR=2.20, 95 CI: 1.42~3.40, P<0.01). TIPS patients had an increased 1-year OHE incidence rate compared to the standard treatment group (sarcopenia patients: 6.93% vs. 16.67%, χ2=3.87, P=0.049; patients without sarcopenia combination: 2.19% vs. 9.68%, χ2=8.85, P=0.01). There was no statistically significant difference in the long-term OHE incidence rate between the two kinds of treatment groups ( P>0.05). Conclusion:TIPS can significantly prolong transplant-free survival compared to standard treatment as a secondary prevention of EGVB concomitant with sarcopenia in patients with cirrhosis. However, its advantage is not prominent for patients with cirrhosis in EGVB without sarcopenia.

Objective To compare the efficacy and safety of tacrolimus with those of cyclosporine in treating idiopathic membranous nephropathy (IMN) via network meta-analysis. Methods Databases including PubMed,Embase,CENTRAL (Cochrane),Wanfang Database,CNKI,and VIP citation database were searched for relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Package Meta 4.5.0 and Gemtc 0.8.1 in R 3.3.1 were used to analyze the included studies. Results In this network meta-analysis,the complete remission rate (RR=0.98,95% CI:0.70-1.40)and the total remission rate (RR=1.00,95% CI:0.90-1.20)of idiopathic membranous nephropathy did not differ significantly between IMN patients treated with cyclosporine A or tacrolimusand,nor did the incidences of hepatic dysfunction(RR=1.40,95% CI:0.52-4.00),infection(RR=0.75,95% CI:0.18-3.10),or gastrointestinal syndrome(RR=2.1,95% CI:0.36-28.00). Conclusion Cyclosporine A seems to have similar effectiveness and safety to tacrolimus in treating IMN.

Objective To investigate the expression changes of the hydrogen sulfide synthases cystathionineγ-lyase (CSE), cystathionineβ-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST), after optic nerve crush (ONC) in rat the retina.Methods The rat model of ONC was established.Rats were divided into normal control, ONC, and sham control groups.Histopathologic changes in retina, the number of retinal ganglion cells (RGC) and retinal thickness of inner part (RTIP) were measured.The changes of CSE, CBS and 3-MST mRNA expression were detected with quantitative real-time PCR.Results The retinal histostructure was normal in normal controls and with minor changes in sham controls, respectively.Compared with sham group, significant retina damages were found in the ONC group:a time-dependent reduction of RGC number and RTIP.Expressions of CSE, CBS and 3-MST mRNA in rat retina were detected in normal control.Compared with normal controls, the expressions of CSE, CBS and 3-MST mRNA did not show any significant changes in the sham controls.Compared with sham controls, CBS mRNA expressions showed a time-dependent increase at 3 d, 7 d and 14 d after crush in the ONC group;CSE mRNA expressions increased to the peak at 3 d and then slightly reduced at 14 d after crush;3-MST mRNA expressions showed the trend of increase at 3 d and 7 d and then enhanced remarkably at 14 d after crush.Conclusion Hydrogen sulfide synthases CSE, CBS and3-MST expressions were up-regulated in rat retina following ONC, which may cause an increase in local endogenous hydrogen sulfide production in the retina and a compensatory protective effect.

The bevacizumab and its glycoforms were analyzed by matrix-assisted laser desorption ionization-time of flight-time of flight-mass spectrometry (MALDI-TOF-MS), sodium dodecyl sulfate polyacrylamide gel electrophoresis ( SDS-PAGE) and short-gun strategy, with the sequence of unique peptide and seventeen glycoforms being characterized. The bevacizumab and its glycopeptides concentrations in mice plasma with different intravenous injection doses of bevacizumab were detected and the concentration-time curves were obtained by parallel reaction monitoring ( PRM) method based on liquid chromatography-tandem mass spectrometry (LC-MS / MS) technique. First, standard curves were created for quantification of mAb in mice plasma, which showed good linearity, with the correlation coefficient (R2 ) value of 0. 998 and the lower limit of quantification of 66 fmol. Detection results of high and low doses of the drug in the mice plasma samples showed that the drug concentration-time curve trend was consistent, e. g. the concentration was decreasing. However, the results of quantitation of seventeen glycoforms demonstrated that the metabolism of different glycoforms was different. The concentrations of most glycoforms increased first, whereas the metabolism afterwards differed by different glycoforms.

OBJECTIVETo explore the effect of Salvianolate on myosin heavy chain (MHC) in cardiomyocytes of congestive heart failure (CHF) rats.

METHODSSixty male SD rats were divided into 6 groups according to random digit table, i.e., the normal control group (NCG), the model group, the Captopril group (CAG), the low dose Salvianolate group (LSG), the high dose Salvianolate group (HSG), the Captopril and high dose Salvianolate group (CSG), 10 in each group. CHF rat model was established with peritoneal injection of adriamycin in all rats except those in the NCG. Equal volume of normal saline was peritoneally injected to rats in the NCG, once per week for 6 successive weeks. Corresponding medication was started from the 5th week of injecting adriamycin. Rats in the CAG were administered with Captopril solution at the daily dose of 10 mg/kg by gastrogavage. Rats in the LSG and the HSG were administered with Salvianolate solution at the daily dose of 24.219 mg/kg and 48.438 mg/kg respectively by gastrogavage. Salvianolate was dissolved in 2 mL 5% glucose solution and administered by peritoneal injection. Rats in the CSG were peritoneally injected with high dose Salvianolate solution and administered with Captopril solution by gastrogavage. Two mL normal saline was peritoneally injected to rats in the model group, once per day for 8 successive weeks. Eight weeks later, the cardiac function and myocardial hypertrophy indices were detected by biological signal collecting and processing system. mRNA expression levels of alpha-MHC and beta-MHC in cardiac muscle were detected by fluorescence quantitative PCR. Expressions of protein kinase C (PKC) in cardiac muscle were detected by Western blot.

RESULTSCompared with the normal control group, heart mass index (HMI) and left ventricular mass index (LVMI) obviously increased in the model group (P < 0.01). Compared with the model group, HMI and LVMI decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). It was more obviously lowered in the CSG group than in the CAG group (P < 0.05). Compared with the NCG, the mRNA expression level of alpha-MHC in cardiac muscle decreased, the mRNA expression level of p-MHC and the expression of PKC in cardiac muscle increased in the model group (P < 0.01). Compared with the model group, the mRNA expression level of alpha-MHC in cardiac muscle was increased, and the mRNA expression level of beta-MHC and the expression of PKC in cardiac muscle were decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). There was statistical difference between the CSG group and the CAG group (P < 0.05).

CONCLUSIONSSalvianolate could up-regulate the mRNA expression level of alpha-MHC, and down-regulate the mRNA expression level of beta-MHC in cardiac muscle. Its mechanism might be related to decreasing the expression of PKC.

Animals ; Captopril ; Doxorubicin ; Drugs, Chinese Herbal ; Heart Failure ; metabolism ; Male ; Myocardium ; Myocytes, Cardiac ; drug effects ; metabolism ; Myosin Heavy Chains ; metabolism ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the efficacy and safety of a phenylalanine-free amino acid-based enteral formula (AA-PKU2) in the treatment of children with phenylketonuria (PKU) aged 1-8 years.

METHODSA prospective, open, self-controlled, multi-center trial was performed, enrolling 121 PKU children (1-8 years in age) consecutively between July, 2009 and May, 2011. Enteral nutrition therapy was administered for 32 weeks. The data on blood phenylalanine (PHE) levels, metal development, weight, height, head circumference, serum nutritional biomarkers (total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), and measurements from routine blood and urine examinations and from renal and hepatic function tests were collected before the therapy and at 8 weeks and 32 weeks after the therapy and were comparatively analyzed.

RESULTSThe mean blood PHE level at 8 and 32 weeks of AA-PKU2 treatment was 353±253 and 361±280 µmol/L respectively, significantly lower than that before the treatment (487±327 µmol/L; P<0.01). The difference in intelligence quotient scores before and after AA-PKU2 treatment was not significant (P>0.05) when assessed by the Gesell tests in children aged 1-4 years but significant (P<0.01) when assessed by WPPSI or WISR-R tests in children over 4 years. The average height, weight and head circumference at 8 and 32 weeks after treatment were significantly increased as compared to these measurements before treatment (P<0.01) with absolute levels similar to those in the control children. In contrast, the mean values of total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol at both time points were not different either from those prior to the treatment or from those in the control children. Mild diarrhea was the adverse events associated with AA-PKU2 treatment, which occurred in 3 (2.5%) cases. All these 3 patients fully recovered without treatment.

CONCLUSIONSThe phenylalanine-free amino acid-based formula, AA-PKU2, is effective and safe in controlling blood PHE levels and improving mental development with adequate nutritional support in PKU.

Child ; Child, Preschool ; Enteral Nutrition ; Female ; Humans ; Infant ; Intelligence ; Male ; Phenylalanine ; blood ; Phenylketonurias ; diet therapy ; psychology ; Prospective Studies

This study was purposed to observe the influence of umbilical cord mesenchymal stem cells (UC-MSC) on the peripheral blood CD4(+)CD25(+)regulatory T cells (Treg), Th17 cells and neutrophils in rats with collagen type II-induced arthritis(CIA), and to explore the regulating effect of UC-MSC transplantation on immunocyte subgroup. The rats wee divided into 3 groups: CIA group (model group), UC-MSC treated group and blank control group. The CIA rats were injected with UC-MSC via tail vein. The percentage of CD4(+)CD25(+) cells in peripheral blood and the expression of NCD11b on neutrophil surface in CIA rates was detected by flow cytometry (FCM), and the serum interleukin-17 (IL-17) was observed by enzyme-linked immunosorbent assay (ELISA). The results showed that the mean fluorescence intensity(MFI) of NCD11b and the level of IL-17 in the model group were significantly higher than those in the blank control group, and the ratio of CD4(+)CD25(+) cells were significantly lower (P < 0.05). The MIF of NCD11b and the level of IL-17 in the UC-MSC treated group were significantly lower than that in the model group (P < 0.05), while the proportion of CD4(+)CD25(+) Treg increased (P < 0.05). Since the fifth week, the above indicators in the UC-MSC group have almostly approached the control group. It is concluded that the UC-MSC can increase peripheral blood Treg proportion in CIA rat, inhibit the secretion of Th17 and the activity of neutrophils, reduce the immune inflammation reaction, decrease the release of proinflammatory factor, and induce immune reconstruction.
Animals ; Arthritis, Experimental ; immunology ; therapy ; Female ; Interleukin-17 ; metabolism ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; Neutrophils ; immunology ; Rats ; Rats, Sprague-Dawley ; Th17 Cells ; immunology ; Umbilical Cord ; cytology

BACKGROUNDThe prevalence of chronic kidney disease (CKD) and prediabetes has increased in China, and at different rates in different locations. Therefore a community-based screening research was conducted in order to determine the prevalence of CKD and prediabetes, and to analyze associated risk factors of CKD and prediabetes in a city of Southern China.

METHODSA total of 7801 community residents aged 18 year and older from 6 communities were screened by a stratified random cluster sampling method. An estimated glomerular filtration rate (eGFR), albuminuria, fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Age-standardized prevalence was calculated by the direct method with the use of data on the population distribution in China in 2006. Multivariate logistic analysis was used to analyze the risk factors of CKD and prediabetes, and association of insulin resistance (IR) with CKD and prediabetes was analyzed.

RESULTSThe age-standardized prevalence of CKD was 12.5%, eGFR < 60 ml×min(-1)×1.73 m(-2) was 2.7% and ACR (albumin to creatinine ratio) > 30 mg/g was 10.3%. The age-standardized prevalence of prediabetes was 12.1%. Logistic regression suggests that IR was a common independent risk factor of CKD and prediabetes. Further analysis show that HOMA-IR was increased with the aggravation of kidney injury and FPG.

CONCLUSIONCKD and prediabetes have become a major public health problem in Zhuhai, Southern China; insulin resistance may be an important risk factor.

Adult ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Prediabetic State ; epidemiology ; Prevalence ; Renal Insufficiency, Chronic ; epidemiology ; Risk Factors ; Surveys and Questionnaires

ObjectiveSLC2A9 is a novel identified urate transporter that affects serum uric acid levels. The present study is aimed to investigate rs7442295 polymorphism in intron 6 of SLC2A9 in a population of Chinese male gout or hypemricaemia subjects. MethodsA total of 268 gout patients and 288 healthy male volunteers were included. Blood pressure, body mass index(BMI), serum uric acid, glucose, lipid,urea and creatine were detected. DNA was purified from peripheral blood and the rs7442295 polymorphism was evaluated using high resolution melting ( HRM ) analysis and direct sequencing. Data were analyzed with t test or chi-square test. Results A/A and A/G genotypes were unambiguously distinguished with HRM technology. The occurrence of the homozygous type (G/G) was completely absent among the study population.The prevalence of the A/A and A/G genotype was 96.2％ and 3.8％ respectively. However, no significant differences of genotype frequencies were found in gout patients and normal subjects(x2=0.003, P=0.82; x2=0.003, P=1.00). But the serum uric acid levels in individuals with the A/G genotype[(293±100) μmol/L]were significantly lower than those with the A/A genotype[(392±133) μmol/L](t=2.426, P＜0.01 ). The A/G genotype frequency was significantly higher in the low-uric acid group than in the high uric-acid group (x2=6.279, P=0.01 ). Genotyping based on HRM was fully concordant with sequencing. Conclusion The polymorphism rs7442295 in SLC2A9 may be a genetic marker to assess risk of hyperuricemia among Chinese male Hart population. HRM is a simple, fast, reliable and close-tube technology for genotyping.

Objective To investigate a new single nucleotid polymorphism (SNP) intron5(+4668C/T) in SLC22A12 in primary gout patients and the association between clinical characteristics and genotypes. Methods One hundred and one primary gout patients and 186 healthy subjects were recruited into this study. Blood pressure, body mass index (BMI) was recorded. Serum uric acid, glucose, lipid and creatinine were detected. DNA was extracted from peripheral blood to amplify the fragment located in intron 5. The genotypes of SLC22A12 can be detected with high-resolution melting (HRM) assay, followed by sequencing analysis. Chi-square test was used for statistical analysis. Results ① A new SNP in intron 5 of SLC22A12 was identi-fied successfully by HRM, which was defined as intron 5 (+4668C/T). CC, CT and TT genotypes were unam-biguously distinguished with HRM technology, which was fully concordant with sequencing. ②The genotypes of CC, CT and TT in male and female groups were 28.1%, 33.7%, 38.2% and 20.0%, 47.1%, 32.9%, respectively.③ However, no significant differences of genotype distribution were found concerning BMI, blood pressure, creatinine, total cholesterol and triglyceride in both male group and female group. But the serum uric acid levels in the CC genotype were significantly higher than those with the CT+TT genotypes. ④ The genotype frequencies of CC and CT+TT in high uric acid group were remarkably different from those in low uric acid group (21.2%, 78.8%,; 35.0%, 65.0%; P<0.05). Conclusion A new SNP has been successfully discovered with HRM technology with simplicity, rapidity and accuracy. T allele of intron 5 (+4668C/T) may be a genetic protective factor for hyperuricemia among Chinese population.