Aim To investigate the effects of acid sphingomyelinase(ASMase)on high-fat induced nonalcoholic fatty liver disease in mice and its regulation of PPARα- PGC-1α pathway. Methods ASMase knockout mice based on C57BL/6 background were constructed. Closed group heterozygotes were obtained through hybridized with wild-type mice(ASMase+/-),together with the littermate WT mice were prepared for NAFLD model in this study. The experiment was divided into four groups:WT+Chow:the WT mice were fed with normal diet for 12 weeks; WT+HFD:the WT mice were fed with high-fat diet for 12 weeks; ASMase+/-+Chow:the ASMase+/- mice were fed with normal diet for 12 weeks; ASMase+/- +HFD:the ASMase+/- mice were fed with high fat diet for 12 weeks. Biochemical method was used to detect serum TC,TG and liver TC,TG contents and liver function such as ALT and AST. Oil red staining,HE staining,Masson staining and Sirius red staining were performed to detect liver lipid accumulation,hepatocyte morphology and liver fibrosis. AmplexTM red sphingomyelinase kit was applied to detect ASMase activity. Western blot was performed to detect protein expressions of ASMase,PPARα,PGC-1α and CPT1. Results WT+HFD group displayed hypercholesterolemia and liver dysfunction. Levels of liver triglyceride(TG)were significantly higher than those in WT+Chow group(P<0.05 or P<0.01). Meanwhile,the hepatocytes showed marked steatosis,balloon-like changes,and fibrosis. Protein expression and activity of ASMase in liver increased significantly(P<0.01 or P<0.001),whereas CPT1,PPARα and PGC-1α expressions were not statistically significant compared with matched control group. Heterozygously ASMase-deficient mice reduced the elevated liver TG induced by HFD,as well as improving balloon-like changes and liver fibrosis. Furthermore,the expressions of PPARα,PGC-1α and CPT1 were up-regulated in ASMase+/- +HFD mice compared with WT+Chow group.Conclusions ASMase promotes hepatic steatosis and fibrosis,which may be related to its inhibition of PPARα-PGC-1α pathway.

Aged ; Comorbidity ; Cytoreduction Surgical Procedures ; Diagnosis ; Drug Therapy ; Female ; Follow-Up Studies ; Humans ; Methods ; Neoadjuvant Therapy ; Ovarian Neoplasms ; Patient Preference ; Proportional Hazards Models ; Prospective Studies

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objeetive As to the high incidence of arteriovenous fistula(AVF) stenosis,surgical operation will result in the exhaustion of vascular resources in patients,while percutaneous transluminal angioplasty(PTA) can maintain vascular resources for ostomy.However,there is still no clear definition between the choices of PTA and surgical resection.The aim of this study was to compare the efficacy of PTA and surgical resection followed by reconstruction for the treatment of arteriovenous fistula stenosis in order to find appropriate treatment.Methods Retrospective analysis had been done on 46 hemodialysis patients with arteriovenous fistula stenosis in Nanjing BenQ hospital from January 2015 to March 2017,which included 22 cases treated with PTA (PTA group) and 24 cases treated with surgical operation (operation group).Comparison was made in general clinical situation,patency rate at six months after surgery,over patency time and adverse reactions to surgery between the two groups.Results The number of stenoses in PTA group was bigger than that in operation group and the difference was of statistic significance (2.78±1.43 vs 1.67±0.71,P＜0.05).There was no significant difference in patency rate between the two groups (P =0.828).There were 57 venous stenoses in PTA group,among which 12 stenoses were anastomotic (21.05％) with 79.3％ average stenosis degree and 43 stenoses were at venous outflow tract of fistula (75.44％) with 84.26 average stenosis degree.In PTA group,3 patients had hematoma brachial puncture position and recovered by self-absorption without special treatment.In operation group,1 patient had mild blood oozing and recovered after treatment;4 patients recovered gradually from mild swelling on the back of the hand of the operation side.No difference was found in adverse reactions between two groups (P＞0.05).Conclusion PTA treatment is preferred for multiple stenoses(n ≥ 3),which ensures better preservation of vascular resources at a comparable patency rate.

Objective To investigate the antibacterial resistance in nationwide's tietiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 18 hospitals and the minimal inhibitory concentrations (MICs) were tested using agar dilution method recommended by Clinical and Laboratory Standards Institute (CLSI) in central laboratory.The susceptibilities of isolates to antimicrobial agents were determined by using CLSI or European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2017 guideline.Results A total of 4333 pathogenic isolates from 18 tertiary hospitals in 18 cities nationwide over the period from July 2015 to June 2016 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase (ESBLs) phenotype rates of 59.4％ and 27.5％,respectively;decreased by 7 to 10 percentage points comparing the last time.Carbapenems,amikacin,moxalactam,β-lactam/β-lactamase inhibitor combinations,tigecycline,and fosfomycin displayed desirable antibacterial activity against Enterbacteriaceae,but a significant increasing of carbapenems resistance Klebsiella pneumoniae were noted.For non-fermenting Gram-negative isolates,resistance rate of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipennnem were 29.5％ and 69.8％ and multidrug-resistant (MDR) detection rate were 35.6％ and 78.3％,extensively drug-resistant (XDR) were 10.2％ and 72.5％,respectively.Klebsiella pneumoniae isolated from children were more resistant to β-lactam than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion Though the decline of ESBLs detection rate,carbapenem non-susceptible Klebsiella pneumoniae rates continued to increase,which should be paid more attention.

Objective To investigate the gram-positive coccus resistance in nationwide's tietiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 18 hospitals and the minimal inhibitory concentrations (MICs) were tested using agar/broth dilution method recommended by Clinical and Laboratory Standards Institute (CLSI) in central laboratory.The susceptibilities of isolates to antimicrobial agents were determined by using CLSI or European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2017 guideline.Results A total of 2301 Gram-positive cocci isolated from 18 hospitals in 18 cities nationwide were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus (MRSA) and methicillin resistant Stapylococcus epidermidis (MRSE) were 39.9％ and 86.6％ respectively.No vancomycin insensitive Staphylococcus was detected.Staphylococcus aureus were 100％ susceptibile to linezolid and teicoplanin,but resistant or insensitive for drugs other than vancomycin were observed among Coagulase Negative Staphylococci (CoNS).Antibiotic resistance rate of Enterococcus faecalis and Enterococcusfaecium to ampicillin were 4.5％ and 85.1％.The detectation rate of vancomycin resistant Enterococcus(VRE) was 2.1％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 7.8％,showing slight increase than last time.The prevalence of penicillin nonsusceptible Streptococcus pneumoniae (PNSSP) was 6.6％ based on non-meningitis and parenteral administration criterion;while for cases of oral penicillin,the rate was 70.0％,was as flat as last time.There were no significant differenees of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis Enterococcus faecalis and Enterococcus faecium among various groups such as different department,age,or specimen source.Conclusion Compared with past surveillance result,VRE detection ratio was steady,while MRSA detection ratio decreased.The emergence of resistance and non-susceptible strains to new antibiotics such as linezolid,tigecycline and daptomycin should be payed more attention.

Objective:To carry out preoperative nutritional risk screening for inpatient to understand their nutritional risk status,and to explore the relationship between postoperative nutritional support and related clinical outcomes.Methods:A total of 378 patients in the Third Ward of Department of General Surgery,the Second Affiliated Hospital of Shantou University,completed NRS 2002 scoring within 48 h after admission.The patients with NRS scores more than 3 points were judged to have nutritional risk,and they were divided into nutrition support group (114 cases) and non-nutrition support group (60 cases) according to whether or not to accept the nutrition support.According to the doctor's advice,the data of nutrition support were obtained,the related clinical outcomes were recorded twice a week,and the relationship between them was analyzed.The influencing factors of hospitalization costs and infectious complications were analyzed.Results:Among the 378 inpatients,the nutritional risk rate was 50.53％.Of the 174 patients enrolled in the cohort study,the nutritional support rate was 65.52％ (114/174).The difference of hospitalization time between the nutrition support group and the non-nutrition support group was statistically significant (P=0.028).There was no significant difference between the two groups in the hospitalization costs.The incidence of infectious complications (P=0.034) and the total complication rate (P=0.012) in the nutrition support group were lower than those in the non-nutrition support group.Disease score and nutrition support were the influencing factors of the incidence of infectious complications (P＜0.10).Hospitalization days,disease score and nutrition score were the influencing factors of hospitalization costs (P＜0.10).Conclusions:General surgery patients have higher nutrition risks,and nutrition support can reduce infectious complications,total complications and shorten hospital stay.NRS 2002 has a superior ability of predicting clinical outcomes.

Objective To investigate the effect of 15-Deoxy-△(12,14)-prostaglandin J2 (15 d-PGJ2) on the expression of macrophage migration inhibitory factor (MIF) and its underlying mechanism in J774A.1. Methods The murine monocyte/macrophage cell line J774A.1 were divided into six groups:lipopolysaccharide (LPS) group,incubated with 1 μg/ml LPS for 1 h;normal control group,incubated with PBS for 1 h;negative control group,incubated with 5 μmol/L 15 d-PGJ2 for 1 h;15 d-PGJ2 group,incubated with 5 μmol/L 15 d-PGJ2 for 1 h followed by 1 μg/ml LPS for 1 h;GW9662 group,incubated with 5 μmol/L 15 d-PGJ2 for 1 h following GW9662 10 μmol/L for 1 h,and then incubated with 1 μg/ml LPS for 1 h;and Vehicle group,control of GW9662,GW9662 was replaced by its solvent DMSO. The expression of MIF was detected via immunofluorescence and agarose gel electrophoresis. RT-qPCR and Western blotting were used to test whether 15 d-PGJ2 could regulate mRNA and protein expression of MIF in J774A.1 upon LPS challenge. The effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist GW9662 on the regulation of MIF by 15 d-PGJ2 was observed. The effects of 15 d-PGJ2 on the nuclear translocation of PPAR-γ upon LPS challenge were detected via high content screening analysis. Results MIF DNA and protein expressions were detected in J774A.1. MIF mRNA expression was up-regulated (1.75±0.09,P=0.037) when challenged with LPS and 15 d-PGJ2 inhibited its upregulation (0.84±0.08,P=0.026) in J774A.1. The protein level was consistent with the mRNA level. PPAR-γ antagonist GW9662 reversed the effect of 15 d-PGJ2 (mRNA,1.48±0.06,P=0.016;protein,1.28). Furthermore,nuclear translocation of PPAR-γ was regulated by 15 d-PGJ2 in J774A.1 upon LPS challenge(1.39±0.02 vs. 1.01±0.03,P=0.003). Conclusion 15 d-PGJ2 may down-regulate the MIF expression in J774A.1 in a PPAR-γ-dependent manner.
Anilides ; pharmacology ; Animals ; Cell Line ; Intramolecular Oxidoreductases ; metabolism ; Lipopolysaccharides ; Macrophage Migration-Inhibitory Factors ; metabolism ; Mice ; Monocytes ; drug effects ; PPAR gamma ; antagonists & inhibitors ; Prostaglandin D2 ; analogs & derivatives ; pharmacology

Objective To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients. Methods Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy. Results Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy. Conclusion In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.

Objective To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients. Methods Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy. Results Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy. Conclusion In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.