A cohort study of hospitalized adult dengue patients with fatality in Taiwan: The elderly and febrile characteristics matter for prognosis

Objective:To identify the febrile characteristics and clinical presentations associated with fatality in hospitalized adult patients with dengue virus(DENV)infections.Methods:A total of 289 adult hospitalized patients with laboratoryconfirmed DENV infections were examined,of which 22 were fatal and 267 were non-fatal.A comparison of the clinical and laboratory characteristics was retrospectively conducted of the deceased and surviving individuals.Multivariate logistic regression and receiver operating characteristic curve analysis were performed to identify predictors of fatality.Results:Fatal patients exhibited significantly more comorbidities,particularly renal and cardiac comorbidities,and they were,in general,older than control individuals(P<0.0001).The results of logistic regression analysis showed that febrile duration of less than four days before arriving in the Emergency Department(OR=5.34;95%CI:1.39–20.6),episode of hypotension in the Emergency Department(OR=6.95;95%CI:2.40–20.1),and comorbidity with congestive heart failure(OR=11.26;95%CI:2.31–54.79)were all significantly associated with inpatient fatality due to DENV infection.The ROC curve analysis indicated that the final prognostic model yielded an area under the curve of 0.87(95%CI:0.79–0.97)for fatality.Conclusions:The aforementioned clinical findings may help clinicians predict fatality among adult inpatients with DENV infection.

Seronegative spondyloarthropathy-associated inflammatory bowel disease

Seronegative spondyloarthropathy(SpA)usually starts in the third decade of life with negative rheumatoid factor,human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis,dactylitis,enthesitis and extra-articular manifestations(EAMs).Cases can be classified as ankylosing spondylitis,psoriatic arthritis,reactive arthritis,enteropathic arthritis,or juvenileonset spondyloarthritis.Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease(IBD),with shared genetic and immunopathogenic mechanisms.IBD is a common EAM in SpA patients,while extraintestinal manifestations in IBD patients mostly affect the joints.Although individual protocols are available for the management of each disease,the standard therapeutic guidelines of SpA-associated IBD patients remain to be established.Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA,whereas their use is controversial in IBD due to associated disease flares.Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy.Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD,and a drug of choice for treating SpA-associated IBD.Janus kinase inhibitors,approved for treating SpA and ulcerative colitis,are promising therapeutics in SpA coexistent with ulcerative colitis.A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.

Role of antidiabetic agents in type 2 diabetes patients with chronic kidney disease

Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling,resulting in glucose uptake defect,and an increased blood sugar level.Pancreatic beta cells thus enhance insulin production to compensate.This situation may cause further beta cell dysfunction and failure,which can lead diabetes mellitus(DM).Insulin resistance is thus an important cause of the development of type 2 DM.Insulin resistance has also been found to have a strong relationship with cardiovascular disease and is common in chronic kidney disease(CKD)patients.The mechanisms of insulin resistance in CKD are complex and multifactorial.They include physical inactivity,inflammation and oxidative stress,metabolic acidosis,vitamin D deficiency,adipose tissue dysfun-ction,uremic toxins,and renin-angiotensin-aldosterone system activation.Currently,available anti-diabetic agents,such as biguanides,sulfonylureas,thiazolidinediones,alfa-glucosidase inhibitors,glucagon-like peptide-1-based agents,and sodium-glucose co-transporter-2 inhibitors,have different effects on insulin resistance.In this short review,we describe the potential mechanisms of insulin resistance in CKD patients.We also review the interaction of currently available anti-diabetic medications with insulin resistance.

Long-term quality-of-care score for predicting the occurrence of acute myocardial infarction in patients with type 2 diabetes mellitus

BACKGROUND Cardiovascular disease(CVD)is the leading cause of death globally,and diabetes mellitus(DM)is a well-established risk factor.Among the risk factors for CVD,DM is a major modifiable factor.In the fatal CVD outcomes,acute myocardial infarction(AMI)is the most common cause of death.AIM To develop a long-term quality-of-care score for predicting the occurrence of AMI among patients with type 2 DM on the basis of the hypothesis that good quality of care can reduce the risk of AMI in patients with DM.METHODS Using Taiwan’s Longitudinal Cohort of Diabetes Patients Database and the medical charts of a medical center,we identified incident patients diagnosed with type 2 DM from 1999 to 2003 and followed them until 2011.We constructed a summary quality-of-care score(with values ranging from 0 to 8)with process indicators(frequencies of HbA1c and lipid profile testing and urine,foot and retinal examinations),intermediate outcome indicators(low-density lipoprotein,blood pressure and HbA1c),and co-morbidity of hypertension.The associations between the score and the incidence of AMI were evaluated using Cox regression models.RESULTS A total of 7351 patients who had sufficient information to calculate the score were enrolled.In comparison with participants who had scores≤1,those with scores between 2 and 4 had a lower risk of developing AMI[adjusted hazard ratio(AHR)=0.71;95% confidence interval(95%CI):0.55-0.90],and those with scores≥5 had an even lower risk(AHR=0.37;95%CI:0.21-0.66).CONCLUSION Good quality of care can reduce the risk of AMI in patients with type 2 DM.The quality-of-care score developed in this study had a significant association with the risk of AMI and thus can be applied to guiding the care for these patients.

Entrapment neuropathy of common peroneal nerve by fabella:A case report

BACKGROUND Neuropathy of the common peroneal nerve caused by compression by a fabella is an extremely rare form of compression neuropathy.Involving both the superficial and deep peroneal nerves,it usually manifests as either impaired sensation from the lower lateral leg to the top of the foot or drop foot,or as a combination of both.CASE SUMMARY We report the case of a 58-year-old Asian female who presented with inversion of the right foot during the stance phase of gait without sensory complaints related to the lower leg.Electrodiagnostic testing revealed the neuropathy of the common peroneal nerve at the level of the knee,exclusively affecting the muscular branch of the superficial peroneal nerve.A neuromuscular ultrasound disclosed swelling of the right common peroneal nerve just before it crossed over a large fabella as well as atrophy and fatty infiltration of the right peroneus longus and peroneus brevis muscles.Surgical excision of the fabella and neurolysis were performed.Subsequently,the strength of the right foot evertors improved,but the unsteady gait with occasional falls persisted for nine months after the surgery.Therefore,another procedure was performed to transfer the split posterior tibialis tendon to the peroneus brevis in order to correct the gait.CONCLUSION This is the first case of neuropathy of the common peroneal nerve caused by compression by a fabella affecting exclusively the muscular branch of the superficial peroneal nerve.Clinicians should be aware of this unusual peripheral neuropathy while evaluating and treating patients with gait disturbance.

Reduced risk of dementia in patients with type 2 diabetes mellitus using Chinese herbal medicine:A nested case-control study

BACKGROUND Dementia is a prevalent condition in type 2 diabetes mellitus(T2DM)patients.While Chinese herbal medicine(CHM)is often employed as complementary therapy for glycemic control,its effect in controlling likelihood of dementia has not yet been fully elucidated.AIM To compare the risk of dementia between T2DM patients with and without CHM treatment.METHODS We undertook a nested case-control study and obtained data on patients 20-70 years of age who received medical care for T2DM between 2001 and 2010 from the National Health Insurance Research database in Taiwan.Cases,defined as those with dementia that occurred at least one year after the diagnosis of T2DM,were randomly matched to controls without dementia from the study cohort at a 1:1 ratio.We applied conditional logistic regression to explore the associations between CHM treatment and dementia.RESULTS A total of 11699 dementia cases were matched to 11699 non-dementia controls.We found that adding CHM to conventional care was related to a lower risk of dementia[adjusted odds ratio(OR)=0.51],and high-intensity CHM treatment was associated with an adjusted OR of 0.22.CONCLUSION This study shows that the cumulative CHM exposure was inversely associated with dementia risk in an exposureresponse manner,implying that CHM treatment may be embraced as a disease management approach for diabetic patients to prevent dementia.

miR-106b promotes cancer progression in hepatitis B virusassociated hepatocellular carcinoma

AIM: To investigate the effect of mi R-106 b on tumor progression in hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC).METHODS: A total of 120 patients who underwent liver resection for HCC at National Cheng Kung University Hospital were enrolled in the present study. Micro RNA(mi RNA) array was first used to screen the mi RNA expression profiles in HCC patients. The clinical records were retrospectively analyzed, and correlations with the mi RNA expression profiles were evaluated. The m RNA expression levels of the mi R-106b-25 cluster(mi R-106 b, mi R-93 and mi R-25), and MCM7 in tumor and non-tumor samples were quantitated using quantitative real-time reverse transcription-polymerase chain reaction(q-RT-PCR) analysis, and correlations in the levels of mi R-106 b, mi R-93 and mi R-25 expression were calculated. Kaplan-Meier overall and diseasefree survival rates of HBV-associated HCC patients were analyzed using the log-rank test based on mi R-106 b expression. The comparison of the mi R-106 b expression levels in patients with different clinical outcomes was analyzed using Mann-Whitney U tests. Furthermore, a hepatitis B virus X protein(HBx) expression plasmid was transfected into Huh7 and Hep 3B cells. The expression levels of the mi R-106b-25 cluster and MCM7 in HBx-expressing Huh7 and Hep 3B cells were detected using q-RT-PCR. RESULTS: mi RNA array screening showed that mi R-106 b and its cluster, mi R-93 and mi R-25 were upregulated in HCC patients(P < 0.01). The value of mi R-106 b expression in HBV-associated HCC patients was significantly higher than that in HCV-(P < 0.05) or non-B/non-C-(P < 0.001) associated HCC patients. The expression of the mi R-106b-25 cluster was significantly higher in tumor tissue(P < 0.001) and associated with the host gene, MCM7, in clinical specimens from HBVassociated HCC patients. Furthermore, the expression levels of mi R-106 b, mi R-93 and mi R-25 were positively correlated in HBV-associated HCC tissues(mi R-106 vs mi R-93, r = 0.75; mi R-93 vs mi R-25, r = 0.69; mi R-106 b vs mi R-25, r = 0.33). The overall and diseasefree survival curves showed that high-mi R-106 b expression was correlated with the poor prognosis of HBV-associated HCC. HCC differentiation was significantly correlated with mi R-106 b expression(P < 0.05). Lower mi R-106 b expression levels resulted in the well differentiation of HCC. Moreover, the expression of the mi R106b-25 cluster and MCM7 was up-regulated in Huh7 and Hep 3B cells after transfection with the HBx expression plasmid.CONCLUSION: The data obtained in the present study suggests that HBx enhances mi R-106 b transcription to promote tumor progression in HBV-associated HCC.

Clinical utility of hepatitis B surface antigen kinetics in treatment-na?ve chronic hepatitis B patients during longterm entecavir therapy

AIM To investigate the utility of hepatitis B surface antigen(HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.METHODS This retrospective study included treatment-na?ve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen(HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, oneyear and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies.RESULTS A total of 211 patients were enrolled. The median treatment time was 5.24(2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen(HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients(cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients(cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels.CONCLUSION Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.

Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine

AIM: To investigate the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing ETV vs LAM in nucleos(t)ide-naive, HBe Agpositive patients. Patients received ETV(0.5 mg daily) or LAM(100 mg daily) for a minimum of 52 wk. Patients were eligible to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare changes in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear regression analyses to assess associations of baseline levels and on-treatment changes of ccc DNA with other baseline factors [sex,age, serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV genotype], or ontreatment factors(changes from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demographics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in significantly greater reductions in hepatic HBV ccc DNA [-0.9 log10 copies/human genome equivalent(HGEq) vs-0.7 log10 copies/HGEq; P = 0.0033] and total hepatic DNA levels(-2.1 log10 copies/HGEq vs-1.6 log10 copies/HGEq; P < 0.0001) than LAM. Virologic, biochemical, and histologic response rates at week 48 were also greater with ETV than with LAM. Baseline HBV ccc DNA levels were positively associated with baseline levels of serum HBV DNA and total hepatic HBV DNA, and negatively associated with HBV genotype F. On-treatment changes in HBV ccc DNA levels were negatively associated with baseline levels of serum HBV DNA and baseline ALT, and were positively associated with on-treatment changes in the levels of serum HBV DNA, total hepatic HBV DNA levels, and ALT, change in Knodell necroinflammatory score, and HBe Ag loss.CONCLUSION: Forty-eight weeks of ETV resulted in greater reductions in ccc DNA and total hepatic HBV DNA than LAM, but long-term therapy may be needed for ccc DNA elimination.

Autoimmune liver diseases in systemic rheumatic diseases

Systemic rheumatic diseases(SRDs)are chronic,inflammatory,autoimmune disorders with the presence of autoantibodies that may affect any organ or system.Liver dysfunction in SRDs can be associated with prescribed drugs,viral hepatitis,alternative hepatic comorbidities and coexisting autoimmune liver diseases(AILDs),requiring an exclusion of secondary conditions before considering liver involvement.The patterns of overlap diseases depend predominantly on genetic determinants with common susceptible loci widely distributing in both disorders.In AILDs,it is important to identify the overlapping SRDs at an early stage since such a coexistence may influence the disease course and prognosis.Commonly co-occurring SRDs in AILDs are Sjögren syndrome(SS),rheumatoid arthritis(RA)or systemic lupus erythematosus(SLE)in autoimmune hepatitis(AIH),and SS,RA or systemic sclerosis in primary biliary cholangitis.Owing to different disease complications and therapies,it is imperative to differentiate between SLE liver involvement and SLE-AIH overlap disease.Therapeutic options can be personalized to control coexisting conditions of liver autoimmunity and rheumatic manifestations in AILD-SRD overlap diseases.The collaboration between hepatologists and rheumatologists can lead to significant advances in managing such a complex scenario.In this review,we provide a comprehensive overview on coexisting AILDs in different SRDs and the therapeutic approach in managing these overlap diseases.

Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence

AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma(HCC) recurrence for up to 3 year following curative resection. METHODS: A total of 143 patients(83.1% of the 172 participants in the phase Ⅱ study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase Ⅱ trial. Safety parameters and the following efficacy endpoints were investigated:(1) time to recurrence;(2) diseasefree survival; and(3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group:(1) the recurrence-free rate increased from 50% to 63%, and(2) time to recurrence at the 36 th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate(11 out of 54 patients). Additionally, subgroup analyses of patients with(1) multiple tumors or a single tumor ≥ 2 cm; and(2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage(56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.

Depletion of CD4^+CD25^+ regulatory T cells can promote local immunity to suppress tumor growth in benzo[a]pyrene-induced forestomach carcinoma

AIM: To elucidate the distribution of CD4+CD25+ regulatory T cells (Tregs) in different lymphoid tissues and its local enhancement on tumor growth before and after depletion of CD4+CD25+ Tregs. METHODS: Female ICR mice were gavaged with benzo[a]pyrene (BaP) to induce forestomach carcinoma. CD4+CD25+ Tregs were intraperitoneally depleted with monoclonal antibody PC61. These mice were divided into BaP-only, BaP + IgG, BaP + PC61, and control groups. The forestomach of mice was dissected for histological analysis, and tunnel test was performed for apoptosis of tumor cells. CD4+CD25+ Tregs were sorted from different lymphoid tissues and expression of Foxp3, IL-10, and chemokine receptors was analyzed by flow cytometry, semi-quantitative and real-time polymerase chain reaction. RESULTS: The mice gavaged with only BaP showed increased forestomach papilloma and carcinoma at wk 16 and 32. The proportion of CD4+CD25+ Tregs was significantly higher in peri-stomach regionallymph nodes than in other lymphoid tissues. These CD4+CD25+ Tregs in regional lymph nodes expressed higher levels of Foxp3 and IL-10, enriched in the CD62L-subset, and CCR1 and CCR5 chemokine receptors. In mice gavaged with BaP + PC61, the number of tumor nodules and tumor volume decreased significantly with massive infiltrating cells and apoptosis of tumor cells. In the draining regional lymph nodes, the number of CD4+CD25+ Tregs also decreased significantly. CONCLUSION: Inducible and activated CD4+CD25+ Tregs in the draining regional lymph nodes suppress host local immunity during tumor growth. Depletion of CD4+CD25+ Tregs can promote host local immunity to suppress tumor growth.

Progesterone receptor membrane component 1 as a potential prognostic biomarker for hepatocellular carcinoma

AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1(PGRMC1) and PGRMC2 in hepatocellular carcinoma(HCC). METHODS We performed immunohistochemical staining to evaluate the estrogen receptor(ER), progesterone receptor(PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data(n = 373) from The Cancer Genome Atlas(TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients. We knocked down or overexpressed PGRMC1 in HCC cell lines to evaluate its biological significance in HCC cell proliferation, differentiation, migration, and invasion. RESULTS We found that few HCC cases expressed ER(5.6%) and PR(4.5%). In contrast, most HCC cases expressed PGRMC1(89.9%) and PGRMC2(100%). PGRMC1 and PGRMC2 exhibited significantly lower expression in tumor tissue than in non-tumor tissue(P < 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression(P = 0.004), poorer tumor differentiation(P = 0.045) and liver capsule penetration(P = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival(P = 0.002, HR = 2.384,CI: 1.377-4.128) in our cases, as well as in the TCGA cohort(P < 0.001, HR = 2.857, CI: 1.781-4.584). The expression of PGRMC2 did not relate to patient outcome. PGRMC1 knockdown promoted a poorly differentiated phenotype and proliferation of HCC cells in vitro, while PGRMC1 overexpression caused the opposite effects.CONCLUSION PGRMC1 is a non-classical hormonal receptor that negatively regulates hepatocarcinogenesis. PGRMC1 down-regulation is associated with progression of HCC and is a poor prognostic indicator.

Routine defunctioning stoma after chemoradiation and total mesorectal excision:A single-surgeon experience

AIM:To investigate the 10-year results of treating low rectal cancer by a single surgeon in one institution.METHODS:From Oct 1998 to Feb 2009,we prospectively followed a total of 62 patients with cT2-4 low rectal cancer with lower tumor margins measuring at 3 to 6 cm above the anal verge.All patients received neoadjuvant chemoradiation(CRT) for 6 wk.Among them,85% of the patients received 225 mg/m2/d 5-fluorouracil using a portable infusion pump.The whole pelvis received a total dose of 45 Gy of irradiation in 25 fractions over 5 wk.The interval from CRT completion to surgical intervention was planned to be approximately 6-8 wk.Total mesorectal excision(TME) and routine defunctioning stoma construction were performed by one surgeon.The distal resection margin,circumferential resection margin,tumor regression grade(TRG) and other parameters were recorded.We used TRG to evaluate the tumor response after neoadjuvant CRT.We evaluated anal function outcomes using the Memorial Sloan-Kettering Cancer Center anal function scores after closure of the defunctioning stoma.RESULTS:The median distance from the lower margin of rectal cancer to the anal verge was 5 cm:6 cm in 9 patients,5 cm in 32 patients,4 cm in 10 patients,and 3 cm in 11 patients.Before receiving neoadjuvant CRT,45 patients(72.6%) had a cT3-4 tumor,and 21(33.9%) patients had a cN1-2 lymph node status.After CRT,30 patients(48.4%) had a greater than 50% clinical reduction in tumor size.The final pathology reports revealed that 33 patients(53.2%) had a ypT3-4 tumor and 12(19.4%) patients had ypN1-2 lymph node involvement.All patients completed the entire course of neoadjuvant CRT.Most patients developed only Grade 1-2 toxicities during CRT.Thirteen patients(21%) achieved a pathologic complete response.Few post-operative complications occurred.Nearly 90% of the defunctioning stomas were closed within 6 mo.The local recurrence rate was 3.2%.Pathologic lymph node involvement was the only prognostic factor predicting disease recurrence(36.5% vs 76.5%,P = 0.006).Nearly 90% of patients recovered sphincter function within 2 year after closure of the defunctioning stoma.CONCLUSION:Neoadjuvant CRT followed by TME,combined with routine defunctioning stoma construction and high-volume surgeon experience,can provide excellent surgical quality and good local disease control.

Characterization of flgK gene and FlgK protein required for H pylori Colonization-from cloning to clinical relevance

瞄准：在 H 描绘 flgK 和它的蛋白质产品的角色。pylori 殖民。方法：克隆方法的 PCR 识别了 flgK 基因。isogenic flgK 异种被基因代替构造并且由南部的污点分析和 PCR 分析证实了。recombinant FlgK 蛋白质(r-FlgK ) 被净化。电子显微镜学(他们) 被使用表明 H 的毛虫。pylori。在试管内活动性测试在半固体媒介被估计。H 的密度。有野类型的紧张或它的 flgK 异种的 pylori 殖民与 r-FlgK 与或没有免疫前在 BALB/c 老鼠之中被作比较。对 r-FlgK 的血清学的回答与 H 的不同密度为 70 个临床的病人被分析。pylori 殖民。结果：从十二指肠溃疡紧张， flgK 基因被克隆，它包含了 1821 bp，与到出版序列的 95.7% 身份。没有毛虫为变异的紧张在他们下面被观察，它有活动性的损失。H。pylori 密度在异种接种的 BALB/c 老鼠是更低的或与有与 unimmunized 相比的 r-FlgK 的免疫前，老鼠或老鼠由野类型的紧张(P【0.05 ) 接种。在 H。感染 pylori 的病人，对 r-FlgK 的血清学的回答在效价是一致地低的。结论：flgK 编码的 FlgK 为毛虫形成和 H 是重要的。pylori 活动性。在到 r-FlgK 的 FlgK 或提高的血清学的回答的缺乏能防碍 H。pylori 殖民。H 的 FlgK。pylori 能是为种痘的一个新奇目标。

Human hepatitis viruses-associated cutaneous and systemic vasculitis

Human hepatitis viruses(HHVs)include hepatitis A virus,hepatitis B virus(HBV),hepatitis C virus(HCV),hepatitis delta virus,and hepatitis E virus and can cause liver inflammation in their common human host.Usually,HHV is rapidly cleared by the immune system,following acute HHV invasion.The morbidities associated with hepatitis A virus and hepatitis E virus infection occur shortly after their intrusion,in the acute stage.Nevertheless,the viral infectious process can persist for a long period of time,especially in HBV and HCV infection,leading to chronic hepatitis and further progressing to hepatic cirrhosis and liver cancer.HHV infection brings about complications in other organs,and both acute and chronic hepatitis have been associated with clinical presentations outside the liver.Vascular involvement with cutaneous and systemic vasculitis is a well-known extrahepatic presentation;moreover,there is growing evidence for a possible causal relationship between viral pathogens and vasculitis.Except for hepatitis delta virus,other HHVs have participated in the etiopathogenesis of cutaneous and systemic vasculitis via different mechanisms,including direct viral invasion of vascular endothelial cells,immune complex-mediated vessel wall damage,and autoimmune responses with stimulation of autoreactive B-cells and impaired regulatory T-cells.Cryoglobulinemic vasculitis and polyarteritis nodosa are recognized for their association with chronic HHV infection.Although therapeutic guidelines for HHV-associated vasculitis have not yet been established,antiviral therapy should be initiated in HBV and HCV-related systemic vasculitis in addition to the use of corticosteroids.Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations.

Use of carbon dioxide as negative contrast agent for magnetic resonance cholangiopancreatography

AIM: To evaluate the effects of using CO2 as negative contrast agent in decreasing the overlapping on the pancreaticobiliary system from intestinal fluids.METHODS:We evaluated the magnetic resonance cholangiopancreatography(MRCP) images in 117 patients divided into two groups(group 1,without taking gas producing crystals to produce CO2,n=64;group 2,with CO2,n=53)in a 1.5T unit using MRCP sequence.Anatomic locations of intestinal fluids distribution,overlapping with common bile duct(CBD)and pancreatic duct(PD),were evaluated.RESULTS:In the group with CO2,the decrease in distribution of intestinal fluids was significant in the gastric antrum(P=0.001)and duodenal bulb(P<0.001),but not in the gastric fundus and body and in the second portion of the duodenum(P=1.000,P=0.171,and P=0.584 respectively).In the group with CO2,the decrease in overlapping with CBD was significant(P< 0.001),but the decrease in overlapping with PD was not (P=0.106).CONCLUSION:MRCP with carbon dioxide as negative contrast agent would decrease intestinal fluids in the gastric antrum and duodenal bulb,thereby decreasing overlapping with the CBD.

Anti-and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis,psoriatic arthritis and ankylosing spondylitis

In addition toβ-cell failure with inadequate insulin secretion,the crucial mechanism leading to establishment of diabetes mellitus(DM)is the resistance of target cells to insulin,i.e.insulin resistance(IR),indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor,downstream to the substrates of insulin action.IR is a common feature of most metabolic disorders,particularly type II DM as well as some cases of type I DM.A variety of human inammatory disorders with increased levels of proinflammatory cytokines,including tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β,have been reported to be associated with an increased risk of IR.Autoimmunemediated arthritis conditions,including rheumatoid arthritis(RA),psoriatic arthritis(PsA)and ankylosing spondylitis(AS),with the involvement of proinflammatory cytokines as their central pathogenesis,have been demonstrated to be associated with IR,especially during the active disease state.There is an increasing trend towards using biologic agents and small molecule-targeted drugs to treat such disorders.In this review,we focus on the effects of anti-TNF-α-and non-TNF-α-targeted therapies on IR in patients with RA,PsA and AS.Anti-TNF-αtherapy,IL-1 blockade,IL-6 antagonist,Janus kinase inhibitor and phosphodiesterase type 4 blocker can reduce IR and improve diabetic hyper-glycemia in autoimmune-mediated arthritis.

Features associated with progression of small pancreatic cystic lesions: A retrospective study

AIM: To investigate the progression rate of small pancreatic cystic lesions and identify characteristics associated with their progression.METHODS: Patients with pancreatic cystic lesions with at least 1-year of follow-up were evaluated retrospectively. We excluded patients with cysts larger than 3 cm or with features that were a concern for malignancy. In total, 135 patients were evaluated. The interval progression of the cysts was examined. Characteristics were compared between patients with and without progression.RESULTS: The pancreatic cysts ranged from 3 to 29 mm. The mean follow-up period was 4.5 ± 2.3 years and the mean progression rate was 1.0 ± 1.3 mm/year. Ninety patients showed interval progression and were divided into two groups; the minimal-change group(n = 41), who had cyst progression at less than 1 mm/year, and the progression group(n = 49), who had a progression rate of more than 1 mm/year. Compared with the cysts without progression, the lesions of the progression group were more frequently associated with tubular cyst, septation or a prominent pancreatic duct(P < 0.05). The odds ratio for progression was 5.318 for septation and 4.582 for tubular cysts.CONCLUSION: Small pancreatic cysts progress slowly. Lesions with tubular shape, septa, or prominent pancreatic duct were more likely to progress, and required further diagnostic intervention or shorter surveillance interval.

Spinal giant cell-rich osteosarcoma-diagnostic dilemma and treatment strategy:A case report

BACKGROUND Giant cell-rich osteosarcoma(GCRO) is a rare histological variant of osteosarcoma. Spinal GCROs are extremely rare, with challenging diagnosis and management. Herein, we present a case of spinal GCRO at T2, which was not diagnosed in initial biopsy but after T2 corpectomy. We detailed the clinical course, management strategy, and outcome after a 4-year follow-up.CASE SUMMARY A 17-year-old female patient presented with back pain followed by ascending paresthesia. Spinal computed tomography(CT) and magnetic resonance imaging(MRI) revealed a collapsed T2 vertebra with an enhancing osteolytic mass. CTguided biopsy showed inconclusive morphology. Pathology from T2 corpectomy revealed GCRO. The patient subsequently received neoadjuvant chemotherapy followed by salvage operation of T2 costotransversectomy with grossly-total resection adjuvant chemoradiation. Upon treatment completion, she had complete GCRO remission. The 4-year follow-up spinal MRI showed no tumor recurrence.CONCLUSION Spinal GCRO poses unique challenges in obtaining sufficient tissue diagnosis and complete surgical removal. However, long-term local control of spinal GCRO is possible following complete resection and adjuvant chemoradiation.