Inflammatory bowel disease:A proposal to facilitate the achievement of an unequivocal diagnosis

Following the international guidelines criteria an adequate"diagnostic conclusion"of inflammatory bowel disease(IBD)can be achieved only if clinical,endoscopic and laboratory findings,together with sample technical adequacy and unequivocal histomorphological signs of the disease are available.Thus,a conclusive diagnosis requires a complex combination of clinical, endoscopic and histological data.A considerable number of endoscopic biopsies obtained from IBD patients do not meet the above-mentioned requirements.The aim of the present proposal is to introduce a binary system of evaluation in the"diagnostic conclusion"of the histopathological report that will help to simplify the clinical decisions and consequent patient management.In patients with no history of disease,the pathologist should classify the biopsies in"Diagnostic",when the criteria established by the international guidelines are satisfied and"not diagnostic"when one or more of the above-mentioned criteria are not met. The term"not diagnostic"should replace"highly suggestive"and"probable".This new terminology could avoid ambiguous expressions that encourage the clinician to classify the patient as affected by IBD without fulfilling all of the requirements for an accurate diagnostic approach.

Significance of combined detection of serum 25(OH)D3, hsa-miR-17-5p and HCV-RNA in the diagnosis of hepatitis C disease

Objective: Significance of combined detection of serum 25(OH)D3, hsa-miR-17-5p and HCV-RNA in diagnosis of hepatitis C disease. Methods: A total of 52 patients with benign ovarian tumor resection were selected from April 2016 to April 2018 in our hospital. We paid attention to the implementation of perioperative nursing intervention, and observed the prognosis and the occurrence of adverse reactions. Results: The expression of hsa-mir-17-5p in the observation group was significantly higher than that in the control group, the expression of 25(OH)D3 was lower than that in the control group, the expression of hsa-mir-17-5p in the HCV-RNA positive group was higher than that in the HCV-RNA negative group, and the expression of 25(OH) D3 was lower than that in the HCV-RNA negative group. The expression of HCV-RNA in the observation group was positively and negatively correlated with the expression of 25(OH) D3 and hsa-mir-17-5p in the 25(OH)D3 and the critical values of serum 25 (OH)D3, hsa-mir-17-5p and HCV-RNA were 24.23 ug/L, 1.89 relative expression and 1.22 × 103 IU/mL, respectively. The area of AUC detected by hsa-miR-17-5p+ 25 (OH) D3+25(OH)D3 is larger than that detected separately. Conclusion: The combined detection of serum 25(OH)D3, hsa-mir-17-5p and HCV-RNA has high diagnostic efficiency and sensitivity for hepatitis C. It is suggested that they be used in clinical practice.

Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis

BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.

Association of Catalase Genotype with Oxidative Stress in the Predication of Colorectal Cancer:Modification by Epidemiological Factors

Objective This paper aims to assess the interaction between common variations in catalase（CAT） polymorphic gene and environmental factors for antioxidant defense enzyme in modulating individual susceptibility to colorectal cancer（CRC）.Methods A case-control study with 880 colorectal cancer cases and 848 controls was conducted to investigate whether variations in the catalase（CAT） gene,one of the genes involved in scavenging oxidative stress,influenced susceptibility to CRC.Results The interaction between life style and genotypes as well as with their effects on colorectal cancer was deduced from the present study.Significant difference（P=0.01） was identified in the distribution of CAT genotype between the colorectal cancer cases and the controls.The CRC cases had significantly lower mean activity than the controls（P〈0.01）.Correlation analyses revealed statistically significant correlations between CAT activity and CAT genotype（P〈0.01）.Conclusion The risk of CRC was associated with smoking,low vegetable consumption,high pork and poultry consumptions,and low or high BMI.This is the first study reporting an association of polymorphism CAT-21A〉T with colorectal cancer.Low CAT activity was associated with an increased risk of CRC;however,no evidence was found to support an association between CAT-21A〉T polymorphism and CRC risk.

The therapeutic effect of CORM-3 on acute liver failure induced by lipopolysaccharide/D- galactosamine in mice

BACKGROUND： Acute liver failure （ALF） is a severe and life- threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releas- ing molecule （CORM-3） has been shown to have anti-inflam- matory effect. The present study was to investigate the effect of CORM-3 on ALF and elucidate its underlying mechanism. METHODS： ALF was induced by a combination of LPS/D-GalN in mice which were treated with CORM-3 or inactive CORM-3 （iCORM-3）. The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activi- ties （ALT and AST） and total bilirubin （TBiL）. Serum levels of inflammatory cytokines （TNF-α, IL-6, IL-1β and IL-10） and liver immunohistochemistry of NF-KB-p65 were determined; the expression of inflammatory mediators such as iNOS, COX-2 and TLR4 was measured using Western blotting. RESULTS： The pretreatment with CORM-3 significantly improved the liver histology and the survival rate of mice compared with the controls; CORM-3 also decreased the levels of ALT, AST and TBiL. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines （TNF-α, IL-6 and IL-1β） and increased the anti-in- flammatory cytokine （IL-10） productions in ALF mice. More- over, CORM-3 significantly reduced the increased expression of iNOS and TLR4 in liver tissues and inhibited the nudear ex- pression of NF-KB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An iCORM-3 failed to prevent acute liver damage induced by LPS/D-GalN. CONCLUSION： These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions.

Elevated serum values of procollagen Ⅲ peptide (PIIIP)in patients with ulcerative colitis who will develop pseudopolyps

AIM: To assess the impact of procollagen Ⅲ peptide as a marker of collagenesis in the development of pseudopolyps in patients with ulcerative colitis.METHODS: Development of pseudopolyps was monitored in 25 patients with ulcerative colitis classified according to Powell-Tuck index as mild (n=12) or moderate (n=13) form of disease. Patients with a mild form of disease were treated with oral mesalazine medication (2-4 g/day) and local mesalazine preparation (suppository). Patients with a moderate form of disease received oral mesalazine medication (2-4 g/day), local mesalazine preparation(suppository) and local methylprednisolone at an initial dose of 60 rag/day, followed by dose tapering. How many significant variables (previously determined by analysis of variance) were elevated in the groups with and without pseudopolyp developement was observed. ROC analysis for calculation of new index was made.RESULTS: Serum values of procollagen Ⅲ peptide (PⅢP), C-reactive protein (CRP) and C4 complement component (C4)were statistically significantly lower in the group of patients flee from pseudopolyp development bhan bhose who developed one or more pseudopolyps (0.45±0.12 vs 1.42±0.70,P<0.0027; 7.6±4.7 vs 17.8±9.17, P<0.035, and 0.46±0.11 vs 0.34±0.16, P<0.068, respectively) at endoscopic conrtrols with patohistologically samples during 13 months. There were no statistically significant differences in the values of C3, ceruloplasmin and IgM between the two groups (P>0.05).Discrimination function analysis yielded highest standardized cannon coefficients for PⅢP (0.876), CRP (0.104), C3 (-0.534) and C4 (0.184) (P<0.036). The elevation in two of three laboratory variables (PⅢP, CRP and C4) reached sensitivity of 93 % and specificity of 90 % in the development of pseudopolyps.CONCLUSION: It is proposed that an increase in two of the three laboratory parameters (PⅢP, CRP and C4) could improve the accuracy of prediction of the development of pseudopolyps. When using PⅢP, CRP and C4 on decision making, the positive predictive value and accuracy were 90 % and 92 %, respectively.

Correlation of ischemic ophthalmopathy with lacunar infarction

AIM:To investigate the correlation of ischemic ophthalmopathy(IO)with lacunar infarction(LI),an ischemic lesions in the cerebrovascular system.METHODS:Totally 204 cases of IO without any nervous system symptom and previously diagnosed LI served as the observational group.All 204 cases without IO,nervous system symptoms and previous LI served as the control group.Age and sex between the two groups matched well.LI was diagnosed by magnetic resonance imaging(MRI)and the results of the two groups were statistically analyzed and compared.RESULTS:IO included 174 eyes of 156 patients with non-arteritis anterior ischemic optic neuropathy(NAION),42 eyes of 36 patients with central retinal artery occlusion(CRAO)or branch retinal artery occlusion(BRAO)and 12 eyes of 12 patients with ocular ischemia syndrome(OIS).The detection rate of LI(72.54%)in IO group was obviously higher than that(15.68%)in the control group(P<0.001).IO was positively correlated with LI(r=0.573,P<0.05).In addition,most infarction sites located in the basal ganglia(67.57%),which were not the vital areas of cerebrum and not easy to be found due to their small size.The majority of those first visited IO patients(72.54%)without nervous system symptom and previously diagnosed LI had already suffered from LI.CONCLUSION:According to our studies,there is a positive correlation between IO and LI.IO can be used as an important predictor for the present of LI,especially obvious signs of the patient.

Plasma Vitamin D Levels And Vitamin D Receptor Polymorphisms Are Associated with Survival of Non-small Cell Lung Cancer

Objective：Vitamin D and its receptor（VDR） involve in multiple cellular processes and play an important role in the initiation and progression of malignancy.Thus we hypothesized that plasma vitamin D levels and single nucleotide polymorphisms（SNPs） in VDR may be of prognostic significance in non-small cell lung cancer（NSCLC）.Methods：We examined plasma 25-hydroxyvitamin D [25（OH）D] levels in 87 patients diagnosed with NSCLC using enzyme-linked immunosorbent assay（ELISA） and genotyped seven potentially functional SNPs in VDR in 568 NSCLC patients on Illumina Golden Gate platform.Results：Patients with higher plasma 25（OH）D levels had worse survival than patients with lower ones（P for trend = 0.048）.The SNPs of rs1544410 and rs739837 were independently associated with NSCLC survival（adjusted HR = 1.61,95% CIs = 1.06-2.45 for rs739837 AA vs AC/CC and adjusted HR = 1.51,95% CIs = 1.06-2.16 for rs1544410 AG/AA vs GG）.A joint effect was observed between rs1544410 and rs739837 and the risk of death elevated as the number of unfavourable genotypes patients carried increased（P for trend = 0.003）.There were no significant associations between VDR polymorphisms and plasma 25（OH）D levels.Conclusion：Our findings indicate that plasma 25（OH）D levels and genetic variants of VDR may serve as prognostic markers for NSCLC in this Chinese population.

Effect of cagE gene on Helicobacter pylori-associated gastritis and levels of interleukin-8

Objective: To investigate the status of cagE gene of Helicobacter pylori(H. pylori) isolated from patients with various gastrointestinal diseases and its relationship with the pathological inflammation grade and levels of IL 8 in the gastric mucosa and IL 8 secretion in gastric epithelial cells stimulated by H. pylori . Methods: cagE was amplified by polymerase chain reaction (PCR) in 145 clinical isolates. The inflammation grade of gastric mucosa was evaluated pathologically. IL 8 levels of gastric mucosa and IL 8 concentration of the supernatant of the cocultured SGC 7 901 cells and H. pylori was assayed by enzyme linked immunosorbent assay (ELISA). Results: cagE was positive in 79.3% of all the H. pylori strains. The mean score of the cagE positive gastritis in the antrum and corpus was (1.865±0.335) and (1.759±0.310). Meanwhile, the cagE negative grade was (1.689±0.294), (1.608±0.284). There was no significant difference ( P >0 05). The mean levels of IL 8 in cagE positive group in antrum and corpus were (390.6±101.4) pg/mg and (368.6±91.2) pg/mg; and cagE negative group were (328.6±102.8) pg/mg and (332.6±96.7) pg/mg. IL 8 in SGC7901 cells induced by cagE positive and negative group averaged (789.5±146.7) pg/ml and (757.6±136.4) pg/ml. There was still no significant difference( P >0.05). Conclusion: Positive rate of cagE is very high in Chinese patients regardless of the clinical outcome. And there was no direct relationship between cagE gene and the inflammation grade and IL 8 levels of H. pylori infected gastric mucosa and IL 8 secretion in gastric epithelial cells stimulated by H. pylori .

Induction of cyclooxygenase-2 by insulin in cultured rat vascular smooth muscle cells

To evaluate cyclooxygenase-2 (COX-2) expression induced by insulin in cultured rat vascularmuscle smooth cells (VSMCs). Methods: The rat VSMCs were isolated and cultured in 60 mm plates, pre-treated with in-sulin 10, 100, 500, 1 000 mU/L for 6 h, and 100 mU/L for 3, 6, 12, and 24 h, respectively. RT-PCR was performed tomeasure COX-2 mRNA induction, and Western-blot was used to measure protein expression. In regard to the COX-2 enzymeactivity, after stimulation for a specified duration, the culture medium was collected; Prostaglandin E2 (PGE2) released byVSMCs was measured with an EIA kit. Results: Three hours after insulin (100 mU/L) stimulation, the induction of COX-2mRNA was detectable and increased with the time and dosage of insulin. Insulin induced COX-2 protein expression occurredin a time- and dose-dependent manner. In rat VSMCs, COX-2 induced by insulin resulted in PGE2 production, which wasincreased with insulin action. Conclusion: Insulin could induce COX-2 expression and PGE2 production in VSMCs in time-and dose-dependent manners.

Gene polymorphism of alpha-2 macroglobulin in patients with Parkinson's disease

Objective:To explore the relationship between polymorphism of α2-macroglobulin(A2M) gene and Parkinson’s disease(PD)in Han Nationality in Shanghai.Methods:The distributions of A2M gene polymorphism (a Val1000Ile in exon24, V/I)were detected in 66 PD patients and 120 healthy controls using polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) method. Results:The I allelic frequency in A2M exon24 gene of PD patients(90.9%) was significantly lower than that of the healthy controls(96.3%)(OR=0.39,P=0.033),so was the I/I genotype(OR=0.32,P=0.015), especially in the patients more than 60 years old(OR=0.31,P=0.04).Conclusion:The I allele in exon24 of A2M gene might inhibit the onset of PD in Han Nationality in Shanghai.

Metagenomic next-generation sequencing for pleural effusions induced by viral pleurisy:A case report

BACKGROUND Viral pleurisy is a viral infected disease with exudative pleural effusions.It is one of the causes for pleural effusions.Because of the difficult etiology diagnosis,clinically pleural effusions tend to be misdiagnosed as tuberculous pleurisy or idiopathic pleural effusion.Here,we report a case of pleural effusion secondary to viral pleurisy which is driven by infection with epstein-barr virus.Viral infection was identified by metagenomic next-generation sequencing(mNGS).CASE SUMMARY A 40-year-old male with a history of dermatomyositis,rheumatoid arthritis,and secondary interstitial pneumonia was administered with long-term oral prednisone.He presented with fever and chest pain after exposure to cold,accompanied by generalized sore and weakness,night sweat,occasional cough,and few sputums.The computed tomography scan showed bilateral pleural effusions and atelectasis of the partial right lower lobe was revealed.The pleural fluids were found to be yellow and slightly turbid after pleural catheterization.Thoracoscopy showed fibrous adhesion and auto-pleurodesis.Combining the results in pleural fluid analysis and mNGS,the patient was diagnosed as viral pleuritis.After receiving Aciclovir,the symptoms and signs of the patient were relieved.CONCLUSION Viral infection should be considered in cases of idiopathic pleural effusion unexplained by routine examination.mNGS is helpful for diagnosis.

Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/IL-8 axis

Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involvement of NETs in glioma progression remain largely unknown.This study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor microenvironment.Methods:Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically evaluated.The effects of NETs on glioma cell progression were studied in a co-culture system.In vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of gliomas.Results:Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade glioma.NETs induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and invasion.NETs overproduction promoted glioma cell proliferation,migration,and invasion.Furthermore,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in vitro.In addition,NETs stimulated the NF-κB signaling pathway,thus promoting IL-8 secretion in glioblastoma.Subsequently,IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in TINs.Conclusions:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 axis.Targeting NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.

Isolation,identification,and antifungal susceptibility test for Kodamaea ohmeri:a case report on endocarditis

A 43-year-old man with a history of rheumatoid heart disease developed endocarditis.Blood culture showed endocarditis was caused by Kodamaea ohmeri and the susceptibility test showed the yeast species were susceptible to itraconazole,amphotericin B,and voriconazole,but susceptible-dose dependent to fluconazole,and resistant to 5-flucytosine.Treated with surgery and anti-fungi agents,the patient recovered from endocarditis.This is the first case of K.ohmeri fungemia found in Chinese from mainland.More and more evidence indicate that K.ohmeri is an important opportunistic pathogen for human beings.

CUL4B facilitates HBV replication by promoting HBx stabilization

Objective:Hepatitis B virus(HBV)infection is a major public health problem worldwide.However,the regulatory mechanisms underlying HBV replication remain unclear.Cullin 4 B-RING ubiquitin E3 ligase(CRL4 B)is involved in regulating diverse physiological and pathophysiological processes.In our study,we aimed to explain the role of CUL4 B in HBV infection.Methods:Cul4 b transgenic mice or conditional knockout mice,as well as liver cell lines with CUL4 B overexpression or knockdown,were used to assess the role of CUL4 B in HBV replication.Immunoprecipitation assays and immunofluorescence staining were performed to study the interaction between CUL4 B and HBx.Cycloheximide chase assays and in vivo ubiquitination assays were performed to evaluate the half-life and the ubiquitination status of HBx.Results:The hydrodynamics-based hepatitis B model in Cul4 b transgenic or conditional knockout mice indicated that CUL4 B promoted HBV replication(P<0.05).Moreover,the overexpression or knockdown system in human liver cell lines validated that CUL4 B increased HBV replication in an HBx-dependent manner.Importantly,immunoprecipitation assays and immunofluorescence staining showed an interaction between CUL4 B and HBx.Furthermore,CUL4 B upregulated HBx protein levels by inhibiting HBx ubiquitination and proteasomal degradation(P<0.05).Finally,a positive correlation between CUL4 B expression and HBV pg RNA level was observed in liver tissues from HBV-positive patients and HBV transgenic mice.Conclusions:CUL4 B enhances HBV replication by interacting with HBx and disrupting its ubiquitin-dependent proteasomal degradation.CUL4 B may therefore be a potential target for anti-HBV therapy.

Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8^(+ ) T lymphocytes in human non-small cell lung cancer

T-cell tolerance is an important mechanism for tumor escape,but the molecular pathways involved in T-cell tolerance remain poorly understood.It remains unknown whether the inhibitory immunoreceptor programmed death-1(PD-1)plays a role in conditions of human non-small cell lung cancer(NSCLC).In this study,we detected PD-1 expression on CD81 T cells from healthy control peripheral blood mononuclear cells(PBMCs)and the PBMCs of NSCLC patients as well as NSCLC tissues.Results showed that tumor-infiltrating CD81 T cells had increased PD-1 expression and impaired immune function,including reducing cytokine production capability and impairing capacity to proliferate.Blockade of the PD-1/PD-L1 pathway by the PD-L1-specific antibody partially restored cytokine production and cell proliferation.These data provide direct evidence that the PD-1/PD-L1 pathway is involved in CD81 T-cell dysfunction in NSCLC patients.Moreover,blocking this pathway provides a potential therapy target in lung cancer.