Neuromyelitis optica(NMO)is an autoimmune demyelinating disorder,predominantly characterized by severe optic neuritis,transverse myelitis and the high level of antibodies against aquaporin-4(AQP4)or NMO-immunoglobulin...Neuromyelitis optica(NMO)is an autoimmune demyelinating disorder,predominantly characterized by severe optic neuritis,transverse myelitis and the high level of antibodies against aquaporin-4(AQP4)or NMO-immunoglobulin G(IgG).Researches trying to correlate NMO with specific human leukocyte antigen(HLA)alleles took place in a limited extend in the last few years.Nevertheless,it has become clear that HLAs play a crucial role in the genetic risk of NMO,in the understanding of its pathogenesis and the differential diagnosis mainly from multiple sclerosis(MS),and also from other demyelinating diseases.In this study,we retrieved all the available data in the MEDLINE concerning the distribution of HLA frequencies in NMO and NMO-spectrum diseases,in all available ethnic groups,and compared them with those of MS.The results suggest that,the well-established HLA-DRB1*15:01 allele,associated with MS,plays rather a protective role for NMO.HLA-DRB1*03 allele is highly frequent in the NMO-IgG positive Caucasian patients,while HLA-DPB1*05:01 is the predominant allele in Japanese patients.The HLA-genotype and anti-AQP4 presence are the common immunological components in cases of comorbidity of NMO and other autoimmune diseases.The authors aim to summarize in the critical review the results of these researches worldwide,create a workable table including all this information for an easier reading approach and highlight the importance of these results in therapeutic decision making,using the HLA profile as biomarker in patients’stratification.展开更多
Objective:Cervical cancer caused by persistent high-risk human papillomavirus(hrHPV)infection remains a leading cause of cancer-related mortality in women.As prophylactic HPV vaccines cannot eliminate existing infecti...Objective:Cervical cancer caused by persistent high-risk human papillomavirus(hrHPV)infection remains a leading cause of cancer-related mortality in women.As prophylactic HPV vaccines cannot eliminate existing infections,developing therapeutic vaccines targeting HPV E6/E7 oncoproteins is critical for reversing precancerous lesions.This study aimed to design a novel multiepitope vaccine against HPV16,incorporating newly identified immunodominant epitopes and evaluating the therapeutic efficacy.Methods:The multi-epitope vaccine HSP70-12P was bioinformatically designed to include cytotoxic T lymphocyte(CTL)and helper T lymphocyte(HTL)epitopes from HPV16 E6/E7,which were fused to the C-terminal domain(residues 359±610)of Mycobacterium tuberculosis HSP70 as an adjuvant.Two formulations were used,as follows:(1)protein-based Pro-HSP70-12P;and(2)DNA-based DNA-HSP70-12P.Therapeutic efficacy was evaluated in TC-1 tumor-bearing mouse models.Tumor regression,survival rates,and immune correlates(T cell responses and cytokine profiles)were assessed.Immunodominant epitopes were identified using ELISpot.Results:The Pro-HSP70-12P protein vaccine induced strong immune responses and provided lasting antitumor protection.The vaccine activated cell-mediated immunity and stimulated effector memory T cells in the HPV-16-related tumor mouse model,resulting in strong tumor clearance effects.Pro-HSP70-12P demonstrated superior performance compared to the DNA-HSP70-12P vaccine,achieving complete regression of small tumors(diameter<2 mm)with a single dose and conferring long-lasting protection in TC-1 rechallenge experiments.Three novel immunodominant epitopes were identified(E6-38-45,E6-124-132,and E7-50-57).The E6 epitopes address a critical gap in E6-targeted vaccine design.Conclusions:The multi-epitope protein vaccine,Pro-HSP70-12P,represents a potent therapeutic candidate against HPV-driven malignancies,which has the capacity to induce tumor regression and long-term immunity.These findings support further clinical development.展开更多
Retroviruses have been proven to cause infections and diseases in a series of mammalian hosts but not in dogs.Then,this letter discussed the dog susceptibility to retrovirus infection,encompassing arguments to underst...Retroviruses have been proven to cause infections and diseases in a series of mammalian hosts but not in dogs.Then,this letter discussed the dog susceptibility to retrovirus infection,encompassing arguments to understand why dogs may have not been infected by retroviruses thus far.The potential resistance of retrovirus in dogs enables this provocative short communication to discuss this question,looking at some evolutive aspects.The lineage of canids has shown,throughout its evolutionary history,a smaller accumulation of retroviruses in canid genomes,classifed as endogenous retroviruses.In this context,the genomes of canids seem to ofer obstacles,which have been evolutionarily conserved,in the face of retroviral infection.展开更多
Gastric carcinoma remains a common disease worldwide with a dismal prognosis. Therefore, it represents a very important health problem. It occurs with a high incidence in Asia and is one of the leading causes of cance...Gastric carcinoma remains a common disease worldwide with a dismal prognosis. Therefore, it represents a very important health problem. It occurs with a high incidence in Asia and is one of the leading causes of cancer death in the world. Although the incidence and mortality of gastric carcinoma are decreasing in many countries,gastric cancer still represents the second most frequent malignancies in the world and the fourth in Europe. The 5-year survival rate of gastric carcinoma is low. The etiology and pathogenesis are not yet fully known. The study of gastric cancer is important in clinical medicine as well as in public health. Over the past 15 years,integrated research in molecular pathology has clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of the development and progression of gastric cancer. Gastric cancer, as all cancers, is the end result of the interplay of many risk factors as well as protective factors. Although epidemiological evidence indicates that environmental factors play a major role in gastric carcinogenesis, the role of immunological, genetic, and immunogenetic factors are thought to contribute to the pathogenesis of gastric carcinoma. Among the environmental factors,diet and Helicobacter pylori are more amenable to intervention aimed at the prevention of gastric cancer.The aim of the present paper is to review and include the most recent published evidence to demonstrate that only a multidisciplinary approach will lead to the advancement of the pathogenesis and prevention of gastric cancer. On the immunogenetic research it is clear that evidence is accumulating to suggest that a genetic profile favoring the proinflammatory response increases the risk of gastric carcinoma.展开更多
AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel disea...AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases （IBD）. In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS： We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTG52 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5＇ exonuclease assay （TaqMan）. New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS： Allele 5209G was weakly associated with Crohn＇s disease （odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57）, and allele 8473T with ulcerativecolitis （OR 1.50, 95%CI 1.00-2.27）. The haplotype including both alleles showed a strong association with IBD （OR 13.15, 95%CI 3.17-116.15）. This haplotype, while rare （-0.3%） in the general population, is found more frequently in patients （3.5%）. CONCLUSION： Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.展开更多
AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in pa-tients with dyspepsia. METHODS: Cumulative dental pla...AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in pa-tients with dyspepsia. METHODS: Cumulative dental plaque specimens and gastric biopsies were submitted to histological exami-nation, rapid urease test and polymerase chain reac-tion (PCR) assays to detect the presence of cagA and vacA polymorphisms.RESULTS: Detection of H. pylori from dental plaque and gastric biopsy samples was greater by PCR com-pared to histological examination and the rapid ure-ase test. DNA from H. pylori was detected in 96% of gastric mucosa samples and in 72% of dental plaque samples. Sixty-three (89%) of 71 dental plaque sam-ples that were H. pylori-positive also exhibited identical vacA and cagA genotypes in gastric mucosa. The most common genotype was vacAs1bm1 and cagA positive, either in dental plaque or gastric mucosa. These viru-lent H. pylori isolates were involved in the severity of clinical outcome.CONCLUSION: These pathogenic strains were found simultaneously in dental plaque and gastric mucosa, which suggests that gastric infection is correlated with the presence of H. pylori in the mouth.展开更多
Nonhomologous DNA end joining （NHEJ） is the primary pathway for repair of double-strand DNA breaks in human cells and in multicellular eukaryotes. The causes of double-strand breaks often fragment the DNA at the sit...Nonhomologous DNA end joining （NHEJ） is the primary pathway for repair of double-strand DNA breaks in human cells and in multicellular eukaryotes. The causes of double-strand breaks often fragment the DNA at the site of damage, resulting in the loss of information there. NHEJ does not restore the lost information and may resect additional nucleotides during the repair process. The ability to repair a wide range of overhang and damage configurations reflects the flexibility of the nuclease, polymerases, and ligase of NHEJ. The flexibility of the individual components also explains the large number of ways in which NHEJ can repair any given pair of DNA ends. The loss of information locally at sites of NHEJ repair may contribute to cancer and aging, but the action by NHEJ ensures that entire segments of chromosomes are not lost.展开更多
There is a critical shortage of organs, cells, and corneas from deceased human donors worldwide. There are also shortages of human blood for transfusion. A potential solution to all of these problems is the transplant...There is a critical shortage of organs, cells, and corneas from deceased human donors worldwide. There are also shortages of human blood for transfusion. A potential solution to all of these problems is the transplantation of organs, cells, and corneas from a readily available animal species, such as the pig, and the transfusion of red blood cells from pigs into humans. However, to achieve these ends, major immunologic and other barriers have to be overcome. Considerable progress has been made in this respect by the genetic modification of pigs to protect their tissues from the primate immune response and to correct several molecular incompatibilities that exist between pig and primate. These have included knockout of genes responsible for the expression of major antigenic targets for primate natural anti-pig antibodies, insertion of human complement- and coagulation-regulatory transgenes, and knockdown of swine leukocyte antigens that stimulate the primate＇s adaptive immune response. As a result of these manipulations, the administration of novel immunosuppressive agents, and other innovations, pig hearts have now functioned in baboons for 6-8 months, pig islets have maintained normoglycemia in diabetic monkeys for 〉 1 year, and pig corneas have maintained transparency for several months. Clinical trials of pig islet trans- plantation are already in progress. Future developments will involve further genetic manipulations of the organ- source pig, with most of the genes that are likely to be beneficial already identified.展开更多
AIM： TO investigate the ABH and Lewis antigen expression in erythrocytes, saliva and gastric epithelium, as well as the association between H pylori and the presence of gastric epithelial lesions.METHODS： The distri...AIM： TO investigate the ABH and Lewis antigen expression in erythrocytes, saliva and gastric epithelium, as well as the association between H pylori and the presence of gastric epithelial lesions.METHODS： The distribution of ABH and Lewis blood group antigens in erythrocytes, saliva and gastric mucosa of Hpylori-infected gastric ulcer patients was analyzed. Forty-two patients with gastric ulcer were studied, and fifty healthy individuals were used as control group. The blood group antigens were determined by direct hemagglutination, dot-ELISA and immunohistochemi- cal methods in erythrocytes, saliva and gastric mucosa specimens, respectively. Diagnosis for H pylori infection was performed by conventional optical microscopy and ELISA.RESULTS： A higher seroprevalence of IgG H pylori specific antibodies was observed in gastric ulcer patients （90%） compared to the control group （60%）. We observed a significant increase of phenotypes O, A2 and Lewis b in H pylori-infected patients. The expression of these antigens had progressive alterations in areas of ulcerous lesions and intestinal metaplasia.CONCLUSION： ABH and Lewis blood group antigens are a good indicator for cellular alterations in the gastric epithelium.展开更多
AIM： To study the association between Interleukin-1 （IL-1） and tumor necrosis factor （TNF）-α polymorphisms, infection by Helicobacter pylori （H pylori） and the development of gastrointestinal diseases.METHODS...AIM： To study the association between Interleukin-1 （IL-1） and tumor necrosis factor （TNF）-α polymorphisms, infection by Helicobacter pylori （H pylori） and the development of gastrointestinal diseases.METHODS： Genomic DNA was extracted from the peripheral blood of 177 patients with various gastrointestinal diseases and from 100 healthy volunteers. The polymorphisms in IL-1β and TNF-α genes were analyzed using the polymerase chain reactionrestriction fragment length polymorphism method （PCRRFLP） and those from IL-1RN with PCR. The presence of infection due to H pylori and the presence of the CagA toxin were detected by serology. The histopathological parameters in the gastric biopsies of the patients were according to the Sydney classification.RESULTS： A comparison of the frequencies of the different polymorphisms studied among the patients and the control group demonstrated that the allele IL- 1RN＊2 was more frequent among patients with gastric ulcers and adenocarcinoma. Carriers of the allele IL- RN＊2 and those with reactive serology for anti-CagA IgG had a greater risk of developing peptic ulcer and gastric adenocarcinoma, as well as a higher degree of inflammation and neutrophilic activity in the gastricCONCLUSION： Our results indicate a positive association between IL-1RN gene polymorphism and infection by positive H pylori CagA strains and the development of gastric ulcers and adenocarcinoma.展开更多
Traditional Chinese medicine polysaccharides is a biologically active ingredient that is not easy to be digested.It is fermented by intestinal microflora to promote qualitative and selective changes in the composition...Traditional Chinese medicine polysaccharides is a biologically active ingredient that is not easy to be digested.It is fermented by intestinal microflora to promote qualitative and selective changes in the composition of the intestinal microbiome,which often result in beneficial effects on the health of the host.People call it“prebiotics”.In this review,we systematically summarized the anti-diabetic effect of traditional Chinese medicine polysaccharides.These polysaccharides regulate the metabolism of sugar and lipids by inter-influence with the intestinal microflora,and maintain human health,while improving type 2 diabetes-like symptoms such as high blood glucose,and abnormal glucose and lipid metabolism.展开更多
Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective tissues.The genome of an individual is always influenced...Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective tissues.The genome of an individual is always influenced by parental,embryonic,tissue-specific,and environmental epigenomes and the same must have been the possible reason for invariable inquiries relating to familial,environmental and life style patterns in the preliminary investigations of diabetic complications.Unprecedented methylation of lysine residues of histones and cytosines of CpG islands of promoter DNA impede the transcription of genes and homocysteine is the metabolic key player of methyl groups.Gck and COX7A1 are the 2 examples in the present review to elucidate the epigenetic influence on the onset of diabetes.miRNAs are additional promising cellular components influencing both at transcriptional and translational levels and promoting either in favour or against(i.e.,feed back) TFs,signaling factors and proteins through their pliotropic effects and thus are reported to regulate cellular physiology.miR-124a and miR-9 are primarily endemic to nervous tissue and they are now being exploited in islets for their function in executing exocytosis of insulin,which of course is one of the fundamental canons of diabetes.miR-375 persuades beta cells for glucose-induced insulin gene expression.The current approach to evaluate the constellation of genes and their products involved in diabetes in huge number of samples through GWA studies may unravel intricacies involved in the management of diabetes and its associated consequences.展开更多
AIM To study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease(NAFLD) in db/db mice. METHODS Male diabetic db /db mice(BKS.Cg-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl...AIM To study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease(NAFLD) in db/db mice. METHODS Male diabetic db /db mice(BKS.Cg-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl peptidase 4(DPP4) inhibitor linagliptin(10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. Intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals. We estimated the changes in hepatocytes, sinusoidal cells, liver microvasculature and lymphatic roots. Hepatic staining for lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1) was assessed by immunohistochemistry. RESULTS In 18-wk-old diabetic mice, liver steatosis(predominantly microvesicular and mediovesicular steatosis) was accompanied by dilation of the roots of the lymphatic system, interlobular blood vessels and bile canaliculi. Compared to saline-treated mice, linagliptin-treated mice exhibited a reduction in the mean numeral densities of hepatocytes with lipid droplets(92.4% ± 1.7% vs 64.9% ± 5.8% per field of view, P = 0.0002) and a lower proportion of hepatocytes with a high density of lipid droplets(20.7% ± 3.6% vs 50.4% ± 3.1%, P = 0.0007). We observed heterogeneous hepatocytes and relatively preserved cell structures in the linagliptin group. Dilation of blood and lymphatic vessels, as well as ultrastructural changes in the hepatocyte endoplasmic reticulum and mitochondria, were alleviated by linagliptin treatment. In intact and placebo-treated mice, immunohistochemical staining for LYVE-1 was observed in the endothelial cells of interlobular lymphatic vessels and on the membranes of some endothelial sinusoidal cells. We observed an enlarged LYVE-1 reaction area in linagliptin-treated mice compared to intact and placebo-treated mice. The improvement in the structural parameters of the liver in linagliptin-treated mice was independent to changes in the plasma glucose levels. CONCLUSION The DPP4 inhibitor linagliptin alleviates liver steatosis and structural changes in the hepatic microvasculature and lymphatic roots in a model of NAFLD in diabetic db/db mice.展开更多
AIM： To investigate the single nucleotide polymorphisms （SNPs） in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS： Analyses of CD14 -260C〉T, CARD15/ NOD2...AIM： To investigate the single nucleotide polymorphisms （SNPs） in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS： Analyses of CD14 -260C〉T, CARD15/ NOD2 3020insC, Toll-like receptor （TLR）4 ＋896A〉G, TLR9 -1237T〉C, TLR9＋2848G〉A, and IRAKM ＋ 22148G〉A SNPs were performed in 157 ileal-pouch anal anastomosis （IPAA） patients （79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients） and 224 Italian Caucasian healthy controls. RESULTS： No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLRg-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, odd＇s ratio （OR） = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group （P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3）. There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriershoip of the CD14-260T and TLR9-1237C alleles in the chronic relapsing pouchitis group suggests that these markers identift a subgroup of IPAA patients with a rish of developing chronic or refractory pouchitis.展开更多
AIM To evaluate risk factors for primary sclerosing cholangitis(PSC) recurrence(rPSC) after orthotopic liver transplantation(OLT) in patients with well-preserved colons. METHODS We retrospectively evaluated the medica...AIM To evaluate risk factors for primary sclerosing cholangitis(PSC) recurrence(rPSC) after orthotopic liver transplantation(OLT) in patients with well-preserved colons. METHODS We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with followup of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen(HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical methods.RESULTS Altogether, 31 men and 16 women with a median(range) age of 36(15-68) years at the time of OLT and a median follow-up of 122(60-249) mo were included. rPSC was confirmed in 21/47(44.7%) of patients, a median 63(12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio(HR): 4.02, 95% confidence interval(CI): 1.58-10.98] and history of acute cellular rejection(rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis(r PSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor(r PSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04(rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03(rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07(rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective roles.CONCLUSION De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.展开更多
AIM To investigate the role of tacrolimus intra-patient variability(IPV)in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and an...AIM To investigate the role of tacrolimus intra-patient variability(IPV)in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies(dn DSAs),as well as graft survival during the first 2 years posttransplantation.Between 02/08 and 06/2015,116 patients that received tacrolimus plus mycophenolate mofetil(with or without steroids)were included.RESULTS Twenty-two patients(18.5%)experienced at least one acute-rejection episode(BPAR).Predictive factors for a BPAR were a tacrolimus IPV of>35%[OR=3.0795%CI(1.14-8.24),P=0.03]or>40%[OR=4.16(1.38-12.50),P=0.01],and a tacrolimus trough level of<5 ng/mL[OR=3.68(1.3-10.4),P=0.014].Thirteen patients(11.2%)developed at least one dn DSA during the follow-up.Tacrolimus IPV[coded as a continuous variable:OR=1.1,95%CI(1.0-1.12),P=0.006]of>35%[OR=4.83,95%CI(1.39-16.72),P=0.01]and>40%[OR=9.73,95%CI(2.65-35.76),P=0.001]were identified as predictors to detect dn DSAs.IPV did not impact on patient-or graft-survival rates during the follow-up.CONCLUSION Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver transplantation.展开更多
Nasopharyngeal cancer (NPC) is a rare disease in most parts of the world, except for Southeast Asia, some parts of North Africa and the Arctic. It is mostly seen in people of Chinese origin. In India, NPC is also rare...Nasopharyngeal cancer (NPC) is a rare disease in most parts of the world, except for Southeast Asia, some parts of North Africa and the Arctic. It is mostly seen in people of Chinese origin. In India, NPC is also rare, except for the Hill States of Northeast India, particularly Nagaland, Manipur, and Mizoram. The striking feature of NPC in Northeast India is that the incidence ranges over the complete spectrum from the lowest (as 0.5/100 000 to 2.0/100 000 among Caucasoid) to the highest (as ~20/100 000 among Cantonese/Zhongshan dialect Chinese). The age-adjusted rate of NPC in Kohima district of Nagaland State is 19.4/100 000, which is among the highest recorded rates. By contrast, in Assam, one of the so-called Hill States but not itself a hilly state, NPC is much less common. The Northeastern region is distinguished by a preponderance of the Tibeto-Burman languages and by variable mongoloid features among peoples of the region. The nature of the migratory populations who are presumed to be bearers of the mongoloid risk is unknown, but these NPC occurrence features provide an outstanding opportunity for NPC risk investigation, such as that of the hypothesis of Wee et al. for westward displacement of Chinese aborigines following the last glacial maximum.展开更多
AIM: To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients. METHODS: Thirty seven patients with mild to moderate UC were rando...AIM: To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients. METHODS: Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo (group B). Patients were monitored using the Modified Truelove-Witts Severity Index (MTWSI). The primary endpoint was clinical remission (MTWSI ≤ 2) at 4 wk. Secondary endpoints were clinical response (defined as a reduction from baseline in the MTWSI of ≥ 2 points) and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS: Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine (group A) and mesalamine plus placebo (group B) respectively (OR = 1.71; 95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MTWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) after 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5). Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups. CONCLUSION: In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone), the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.展开更多
文摘Neuromyelitis optica(NMO)is an autoimmune demyelinating disorder,predominantly characterized by severe optic neuritis,transverse myelitis and the high level of antibodies against aquaporin-4(AQP4)or NMO-immunoglobulin G(IgG).Researches trying to correlate NMO with specific human leukocyte antigen(HLA)alleles took place in a limited extend in the last few years.Nevertheless,it has become clear that HLAs play a crucial role in the genetic risk of NMO,in the understanding of its pathogenesis and the differential diagnosis mainly from multiple sclerosis(MS),and also from other demyelinating diseases.In this study,we retrieved all the available data in the MEDLINE concerning the distribution of HLA frequencies in NMO and NMO-spectrum diseases,in all available ethnic groups,and compared them with those of MS.The results suggest that,the well-established HLA-DRB1*15:01 allele,associated with MS,plays rather a protective role for NMO.HLA-DRB1*03 allele is highly frequent in the NMO-IgG positive Caucasian patients,while HLA-DPB1*05:01 is the predominant allele in Japanese patients.The HLA-genotype and anti-AQP4 presence are the common immunological components in cases of comorbidity of NMO and other autoimmune diseases.The authors aim to summarize in the critical review the results of these researches worldwide,create a workable table including all this information for an easier reading approach and highlight the importance of these results in therapeutic decision making,using the HLA profile as biomarker in patients’stratification.
基金supported by Chinese Academy Medical Sciences Innovation Fund for Medical Sciences(Grant No.2021-I2M-1-004)The Yunnan Provincial Science and Technology Department(Grant No.202002AA100009)+3 种基金The Yunnan Province Xingdian Talent Support Program(Grant No.XDYC-CYCX-2023-0074)The Yunnan Provincial Innovation Team of Therapeutic Neutralizing Antibody(Grant No.202405AS350026)Yunnan Fundamental Research Projects(Grant No.202201AS070059)NMPA Key Laboratory for Quality Control and Evaluation of Vaccines and Biological Products。
文摘Objective:Cervical cancer caused by persistent high-risk human papillomavirus(hrHPV)infection remains a leading cause of cancer-related mortality in women.As prophylactic HPV vaccines cannot eliminate existing infections,developing therapeutic vaccines targeting HPV E6/E7 oncoproteins is critical for reversing precancerous lesions.This study aimed to design a novel multiepitope vaccine against HPV16,incorporating newly identified immunodominant epitopes and evaluating the therapeutic efficacy.Methods:The multi-epitope vaccine HSP70-12P was bioinformatically designed to include cytotoxic T lymphocyte(CTL)and helper T lymphocyte(HTL)epitopes from HPV16 E6/E7,which were fused to the C-terminal domain(residues 359±610)of Mycobacterium tuberculosis HSP70 as an adjuvant.Two formulations were used,as follows:(1)protein-based Pro-HSP70-12P;and(2)DNA-based DNA-HSP70-12P.Therapeutic efficacy was evaluated in TC-1 tumor-bearing mouse models.Tumor regression,survival rates,and immune correlates(T cell responses and cytokine profiles)were assessed.Immunodominant epitopes were identified using ELISpot.Results:The Pro-HSP70-12P protein vaccine induced strong immune responses and provided lasting antitumor protection.The vaccine activated cell-mediated immunity and stimulated effector memory T cells in the HPV-16-related tumor mouse model,resulting in strong tumor clearance effects.Pro-HSP70-12P demonstrated superior performance compared to the DNA-HSP70-12P vaccine,achieving complete regression of small tumors(diameter<2 mm)with a single dose and conferring long-lasting protection in TC-1 rechallenge experiments.Three novel immunodominant epitopes were identified(E6-38-45,E6-124-132,and E7-50-57).The E6 epitopes address a critical gap in E6-targeted vaccine design.Conclusions:The multi-epitope protein vaccine,Pro-HSP70-12P,represents a potent therapeutic candidate against HPV-driven malignancies,which has the capacity to induce tumor regression and long-term immunity.These findings support further clinical development.
基金Fapesp 2014/22827–7Ministério da Saúde do BrasilFundação Faculdade de Medicina and CNPq Grant to JC:301275/2019–0.
文摘Retroviruses have been proven to cause infections and diseases in a series of mammalian hosts but not in dogs.Then,this letter discussed the dog susceptibility to retrovirus infection,encompassing arguments to understand why dogs may have not been infected by retroviruses thus far.The potential resistance of retrovirus in dogs enables this provocative short communication to discuss this question,looking at some evolutive aspects.The lineage of canids has shown,throughout its evolutionary history,a smaller accumulation of retroviruses in canid genomes,classifed as endogenous retroviruses.In this context,the genomes of canids seem to ofer obstacles,which have been evolutionarily conserved,in the face of retroviral infection.
基金Supported by the Foundation of Immunogenetics and Cluster I of VU University Medical Center, Amsterdam
文摘Gastric carcinoma remains a common disease worldwide with a dismal prognosis. Therefore, it represents a very important health problem. It occurs with a high incidence in Asia and is one of the leading causes of cancer death in the world. Although the incidence and mortality of gastric carcinoma are decreasing in many countries,gastric cancer still represents the second most frequent malignancies in the world and the fourth in Europe. The 5-year survival rate of gastric carcinoma is low. The etiology and pathogenesis are not yet fully known. The study of gastric cancer is important in clinical medicine as well as in public health. Over the past 15 years,integrated research in molecular pathology has clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of the development and progression of gastric cancer. Gastric cancer, as all cancers, is the end result of the interplay of many risk factors as well as protective factors. Although epidemiological evidence indicates that environmental factors play a major role in gastric carcinogenesis, the role of immunological, genetic, and immunogenetic factors are thought to contribute to the pathogenesis of gastric carcinoma. Among the environmental factors,diet and Helicobacter pylori are more amenable to intervention aimed at the prevention of gastric cancer.The aim of the present paper is to review and include the most recent published evidence to demonstrate that only a multidisciplinary approach will lead to the advancement of the pathogenesis and prevention of gastric cancer. On the immunogenetic research it is clear that evidence is accumulating to suggest that a genetic profile favoring the proinflammatory response increases the risk of gastric carcinoma.
基金Supported by The Grants from the International Agency for Research on Cancer (Special Training Award to DGC)the French Association for Research on Cancer (grant #7478)the Crohn's and Colitis Foundation of America (to ASP)
文摘AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases （IBD）. In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS： We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTG52 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5＇ exonuclease assay （TaqMan）. New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS： Allele 5209G was weakly associated with Crohn＇s disease （odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57）, and allele 8473T with ulcerativecolitis （OR 1.50, 95%CI 1.00-2.27）. The haplotype including both alleles showed a strong association with IBD （OR 13.15, 95%CI 3.17-116.15）. This haplotype, while rare （-0.3%） in the general population, is found more frequently in patients （3.5%）. CONCLUSION： Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.
基金Supported by Coordenao de Aperfeioamento de Pessoal de Nível Superior and Federal University of Pará
文摘AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in pa-tients with dyspepsia. METHODS: Cumulative dental plaque specimens and gastric biopsies were submitted to histological exami-nation, rapid urease test and polymerase chain reac-tion (PCR) assays to detect the presence of cagA and vacA polymorphisms.RESULTS: Detection of H. pylori from dental plaque and gastric biopsy samples was greater by PCR com-pared to histological examination and the rapid ure-ase test. DNA from H. pylori was detected in 96% of gastric mucosa samples and in 72% of dental plaque samples. Sixty-three (89%) of 71 dental plaque sam-ples that were H. pylori-positive also exhibited identical vacA and cagA genotypes in gastric mucosa. The most common genotype was vacAs1bm1 and cagA positive, either in dental plaque or gastric mucosa. These viru-lent H. pylori isolates were involved in the severity of clinical outcome.CONCLUSION: These pathogenic strains were found simultaneously in dental plaque and gastric mucosa, which suggests that gastric infection is correlated with the presence of H. pylori in the mouth.
文摘Nonhomologous DNA end joining （NHEJ） is the primary pathway for repair of double-strand DNA breaks in human cells and in multicellular eukaryotes. The causes of double-strand breaks often fragment the DNA at the site of damage, resulting in the loss of information there. NHEJ does not restore the lost information and may resect additional nucleotides during the repair process. The ability to repair a wide range of overhang and damage configurations reflects the flexibility of the nuclease, polymerases, and ligase of NHEJ. The flexibility of the individual components also explains the large number of ways in which NHEJ can repair any given pair of DNA ends. The loss of information locally at sites of NHEJ repair may contribute to cancer and aging, but the action by NHEJ ensures that entire segments of chromosomes are not lost.
文摘There is a critical shortage of organs, cells, and corneas from deceased human donors worldwide. There are also shortages of human blood for transfusion. A potential solution to all of these problems is the transplantation of organs, cells, and corneas from a readily available animal species, such as the pig, and the transfusion of red blood cells from pigs into humans. However, to achieve these ends, major immunologic and other barriers have to be overcome. Considerable progress has been made in this respect by the genetic modification of pigs to protect their tissues from the primate immune response and to correct several molecular incompatibilities that exist between pig and primate. These have included knockout of genes responsible for the expression of major antigenic targets for primate natural anti-pig antibodies, insertion of human complement- and coagulation-regulatory transgenes, and knockdown of swine leukocyte antigens that stimulate the primate＇s adaptive immune response. As a result of these manipulations, the administration of novel immunosuppressive agents, and other innovations, pig hearts have now functioned in baboons for 6-8 months, pig islets have maintained normoglycemia in diabetic monkeys for 〉 1 year, and pig corneas have maintained transparency for several months. Clinical trials of pig islet trans- plantation are already in progress. Future developments will involve further genetic manipulations of the organ- source pig, with most of the genes that are likely to be beneficial already identified.
基金Supported by the Secretaria Executiva de Ci ncia,Tecnologia e Meio Ambiente-SECTAM Coordena o de Aperfei oamento de Pessoal de Nivel Superior-CAPES.Co-first-authors:Luisa Caricio Martins,Tereza Cristina de Oliveira Corvelo
文摘AIM： TO investigate the ABH and Lewis antigen expression in erythrocytes, saliva and gastric epithelium, as well as the association between H pylori and the presence of gastric epithelial lesions.METHODS： The distribution of ABH and Lewis blood group antigens in erythrocytes, saliva and gastric mucosa of Hpylori-infected gastric ulcer patients was analyzed. Forty-two patients with gastric ulcer were studied, and fifty healthy individuals were used as control group. The blood group antigens were determined by direct hemagglutination, dot-ELISA and immunohistochemi- cal methods in erythrocytes, saliva and gastric mucosa specimens, respectively. Diagnosis for H pylori infection was performed by conventional optical microscopy and ELISA.RESULTS： A higher seroprevalence of IgG H pylori specific antibodies was observed in gastric ulcer patients （90%） compared to the control group （60%）. We observed a significant increase of phenotypes O, A2 and Lewis b in H pylori-infected patients. The expression of these antigens had progressive alterations in areas of ulcerous lesions and intestinal metaplasia.CONCLUSION： ABH and Lewis blood group antigens are a good indicator for cellular alterations in the gastric epithelium.
基金Supported by Secretaria Executiva de Ciência,Tecnologiae Meio Ambiente-SECTAM and Coordenao de Aperfeioamento de Pessoal de Nível Superior-CAPES
文摘AIM： To study the association between Interleukin-1 （IL-1） and tumor necrosis factor （TNF）-α polymorphisms, infection by Helicobacter pylori （H pylori） and the development of gastrointestinal diseases.METHODS： Genomic DNA was extracted from the peripheral blood of 177 patients with various gastrointestinal diseases and from 100 healthy volunteers. The polymorphisms in IL-1β and TNF-α genes were analyzed using the polymerase chain reactionrestriction fragment length polymorphism method （PCRRFLP） and those from IL-1RN with PCR. The presence of infection due to H pylori and the presence of the CagA toxin were detected by serology. The histopathological parameters in the gastric biopsies of the patients were according to the Sydney classification.RESULTS： A comparison of the frequencies of the different polymorphisms studied among the patients and the control group demonstrated that the allele IL- 1RN＊2 was more frequent among patients with gastric ulcers and adenocarcinoma. Carriers of the allele IL- RN＊2 and those with reactive serology for anti-CagA IgG had a greater risk of developing peptic ulcer and gastric adenocarcinoma, as well as a higher degree of inflammation and neutrophilic activity in the gastricCONCLUSION： Our results indicate a positive association between IL-1RN gene polymorphism and infection by positive H pylori CagA strains and the development of gastric ulcers and adenocarcinoma.
基金supported by Heilongjiang Post-doctoral Research Start-up Fund Funding Project in 2017(No.LBH-Q17167)the Outstanding Youth of Project by Natural Science Foundation of Heilongjiang Province of China(No.YQ2019H028).
文摘Traditional Chinese medicine polysaccharides is a biologically active ingredient that is not easy to be digested.It is fermented by intestinal microflora to promote qualitative and selective changes in the composition of the intestinal microbiome,which often result in beneficial effects on the health of the host.People call it“prebiotics”.In this review,we systematically summarized the anti-diabetic effect of traditional Chinese medicine polysaccharides.These polysaccharides regulate the metabolism of sugar and lipids by inter-influence with the intestinal microflora,and maintain human health,while improving type 2 diabetes-like symptoms such as high blood glucose,and abnormal glucose and lipid metabolism.
基金One of the authors(Sreerama Krupanidhi)is grateful to DST,and DBT,New Delhi,India,for providing funds through FIST and BIF programmes respectively during the time of which the present review is conceived.
文摘Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective tissues.The genome of an individual is always influenced by parental,embryonic,tissue-specific,and environmental epigenomes and the same must have been the possible reason for invariable inquiries relating to familial,environmental and life style patterns in the preliminary investigations of diabetic complications.Unprecedented methylation of lysine residues of histones and cytosines of CpG islands of promoter DNA impede the transcription of genes and homocysteine is the metabolic key player of methyl groups.Gck and COX7A1 are the 2 examples in the present review to elucidate the epigenetic influence on the onset of diabetes.miRNAs are additional promising cellular components influencing both at transcriptional and translational levels and promoting either in favour or against(i.e.,feed back) TFs,signaling factors and proteins through their pliotropic effects and thus are reported to regulate cellular physiology.miR-124a and miR-9 are primarily endemic to nervous tissue and they are now being exploited in islets for their function in executing exocytosis of insulin,which of course is one of the fundamental canons of diabetes.miR-375 persuades beta cells for glucose-induced insulin gene expression.The current approach to evaluate the constellation of genes and their products involved in diabetes in huge number of samples through GWA studies may unravel intricacies involved in the management of diabetes and its associated consequences.
基金Supported by Grants from the Russian Ministry of Education and Science,Nos.14.621.21.0010,RFMEFI62114X0010 and14.619.21.0005,RFMEFI61914X0005
文摘AIM To study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease(NAFLD) in db/db mice. METHODS Male diabetic db /db mice(BKS.Cg-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl peptidase 4(DPP4) inhibitor linagliptin(10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. Intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals. We estimated the changes in hepatocytes, sinusoidal cells, liver microvasculature and lymphatic roots. Hepatic staining for lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1) was assessed by immunohistochemistry. RESULTS In 18-wk-old diabetic mice, liver steatosis(predominantly microvesicular and mediovesicular steatosis) was accompanied by dilation of the roots of the lymphatic system, interlobular blood vessels and bile canaliculi. Compared to saline-treated mice, linagliptin-treated mice exhibited a reduction in the mean numeral densities of hepatocytes with lipid droplets(92.4% ± 1.7% vs 64.9% ± 5.8% per field of view, P = 0.0002) and a lower proportion of hepatocytes with a high density of lipid droplets(20.7% ± 3.6% vs 50.4% ± 3.1%, P = 0.0007). We observed heterogeneous hepatocytes and relatively preserved cell structures in the linagliptin group. Dilation of blood and lymphatic vessels, as well as ultrastructural changes in the hepatocyte endoplasmic reticulum and mitochondria, were alleviated by linagliptin treatment. In intact and placebo-treated mice, immunohistochemical staining for LYVE-1 was observed in the endothelial cells of interlobular lymphatic vessels and on the membranes of some endothelial sinusoidal cells. We observed an enlarged LYVE-1 reaction area in linagliptin-treated mice compared to intact and placebo-treated mice. The improvement in the structural parameters of the liver in linagliptin-treated mice was independent to changes in the plasma glucose levels. CONCLUSION The DPP4 inhibitor linagliptin alleviates liver steatosis and structural changes in the hepatic microvasculature and lymphatic roots in a model of NAFLD in diabetic db/db mice.
文摘AIM： To investigate the single nucleotide polymorphisms （SNPs） in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS： Analyses of CD14 -260C〉T, CARD15/ NOD2 3020insC, Toll-like receptor （TLR）4 ＋896A〉G, TLR9 -1237T〉C, TLR9＋2848G〉A, and IRAKM ＋ 22148G〉A SNPs were performed in 157 ileal-pouch anal anastomosis （IPAA） patients （79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients） and 224 Italian Caucasian healthy controls. RESULTS： No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLRg-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, odd＇s ratio （OR） = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group （P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3）. There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriershoip of the CD14-260T and TLR9-1237C alleles in the chronic relapsing pouchitis group suggests that these markers identift a subgroup of IPAA patients with a rish of developing chronic or refractory pouchitis.
基金the Ministry of Health of the Czech Republic,No.15-28064A and No.16-27477A
文摘AIM To evaluate risk factors for primary sclerosing cholangitis(PSC) recurrence(rPSC) after orthotopic liver transplantation(OLT) in patients with well-preserved colons. METHODS We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with followup of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen(HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical methods.RESULTS Altogether, 31 men and 16 women with a median(range) age of 36(15-68) years at the time of OLT and a median follow-up of 122(60-249) mo were included. rPSC was confirmed in 21/47(44.7%) of patients, a median 63(12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio(HR): 4.02, 95% confidence interval(CI): 1.58-10.98] and history of acute cellular rejection(rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis(r PSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor(r PSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04(rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03(rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07(rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective roles.CONCLUSION De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.
文摘AIM To investigate the role of tacrolimus intra-patient variability(IPV)in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies(dn DSAs),as well as graft survival during the first 2 years posttransplantation.Between 02/08 and 06/2015,116 patients that received tacrolimus plus mycophenolate mofetil(with or without steroids)were included.RESULTS Twenty-two patients(18.5%)experienced at least one acute-rejection episode(BPAR).Predictive factors for a BPAR were a tacrolimus IPV of>35%[OR=3.0795%CI(1.14-8.24),P=0.03]or>40%[OR=4.16(1.38-12.50),P=0.01],and a tacrolimus trough level of<5 ng/mL[OR=3.68(1.3-10.4),P=0.014].Thirteen patients(11.2%)developed at least one dn DSA during the follow-up.Tacrolimus IPV[coded as a continuous variable:OR=1.1,95%CI(1.0-1.12),P=0.006]of>35%[OR=4.83,95%CI(1.39-16.72),P=0.01]and>40%[OR=9.73,95%CI(2.65-35.76),P=0.001]were identified as predictors to detect dn DSAs.IPV did not impact on patient-or graft-survival rates during the follow-up.CONCLUSION Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver transplantation.
文摘Nasopharyngeal cancer (NPC) is a rare disease in most parts of the world, except for Southeast Asia, some parts of North Africa and the Arctic. It is mostly seen in people of Chinese origin. In India, NPC is also rare, except for the Hill States of Northeast India, particularly Nagaland, Manipur, and Mizoram. The striking feature of NPC in Northeast India is that the incidence ranges over the complete spectrum from the lowest (as 0.5/100 000 to 2.0/100 000 among Caucasoid) to the highest (as ~20/100 000 among Cantonese/Zhongshan dialect Chinese). The age-adjusted rate of NPC in Kohima district of Nagaland State is 19.4/100 000, which is among the highest recorded rates. By contrast, in Assam, one of the so-called Hill States but not itself a hilly state, NPC is much less common. The Northeastern region is distinguished by a preponderance of the Tibeto-Burman languages and by variable mongoloid features among peoples of the region. The nature of the migratory populations who are presumed to be bearers of the mongoloid risk is unknown, but these NPC occurrence features provide an outstanding opportunity for NPC risk investigation, such as that of the hypothesis of Wee et al. for westward displacement of Chinese aborigines following the last glacial maximum.
基金Direccion General de Investigación, No. SAF2004-06289Contract Art. 83 L.O.U. with Cytochrome, No. UAH 64/2003 and the Instituto de Salud Carlos Ⅲ, No. C03/02
文摘AIM: To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients. METHODS: Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo (group B). Patients were monitored using the Modified Truelove-Witts Severity Index (MTWSI). The primary endpoint was clinical remission (MTWSI ≤ 2) at 4 wk. Secondary endpoints were clinical response (defined as a reduction from baseline in the MTWSI of ≥ 2 points) and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS: Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine (group A) and mesalamine plus placebo (group B) respectively (OR = 1.71; 95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MTWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) after 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5). Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups. CONCLUSION: In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone), the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.
