Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow aff...Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow affects the course of IBD.It appears that H.pylori infection influences IBD through changes in the diversity of the gut microbiota,and hence in local chemical characteristics,and alteration in the pattern of gut immune response.The gut immune response appears to be modulated by H.pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair.Therefore,a T helper 2(Th2)/macrophage M2 response is stimulated,while the Th1/macrophage M1 response is suppressed.The immunomodulation appears to be associated with intrinsic factors of the bacteria,such as virulence factors-such oncogenic protein cytotoxin-associated antigen A,proteins such H.pylori neutrophil-activating protein,but also with microenvironmental changes that favor permanence of H.pylori in the stomach.These changes include the increase of gastric mucosal pH by urease activity,and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium.Furthermore,there is a causal relationship between H.pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.展开更多
BACKGROUND Helicobacter pylori(H.pylori)has characteristics of family cluster infection;however,its family-based infection status,related factors,and transmission pattern in central China,a high-risk area for H.pylori...BACKGROUND Helicobacter pylori(H.pylori)has characteristics of family cluster infection;however,its family-based infection status,related factors,and transmission pattern in central China,a high-risk area for H.pylori infection and gastric cancer,have not been evaluated.We investigated family-based H.pylori infection in healthy households to understand its infection status,related factors,and patterns of transmission for related disease prevention.AIM To investigate family-based H.pylori infection status,related factors,and patterns of transmission in healthy households for related disease prevention.METHODS Blood samples and survey questionnaires were collected from 282 families including 772 individuals.The recruited families were from 10 selected communities in the greater Zhengzhou area with different living standards,and the family members’general data,H.pylori infection status,related factors,and transmission pattern were analyzed.H.pylori infection was confirmed primarily by serum H.pylori antibody arrays;if patients previously underwent H.pylori eradication therapy,an additional 13C-urea breath test was performed to obtain their current infection status.Serum gastrin and pepsinogens(PGs)were also analyzed.RESULTS Among the 772 individuals examined,H.pylori infection rate was 54.27%.These infected individuals were from 246 families,accounting for 87.23%of all 282 families examined,and 34.55%of these families were infected by the same strains.In 27.24%of infected families,all members were infected,and 68.66%of them were infected with type I strains.Among the 244 families that included both husband and wife,spouse co-infection rate was 34.84%,and in only 17.21%of these spouses,none were infected.The infection rate increased with duration of marriage,but annual household income,history of smoking,history of alcohol consumption,dining location,presence of gastrointestinal symptoms,and family history of gastric disease or GC did not affect infection rates;however,individuals who had a higher education level showed lower infection rates.The levels of gastrin-17,PGI,and PGII were significantly higher,and PGI/II ratio was significantly lower in H.pylori-infected groups than in H.pylori-negative groups.CONCLUSION In our study sample from the general public of central China,H.pylori infection rate was 54.27%,but in 87.23%of healthy households,there was at least 1 H.pylori-infected person;in 27.24%of these infected families,all members were infected.Type I H.pylori was the dominant strain in this area.Individuals with a higher education level showed significantly lower infection rates;no other variables affected infection rates.展开更多
Helicobacter pylori (H.pylori) infects approximately 50% of the world population.The multiple gastrointestinal and extra-gastrointestinal diseases caused by H.pylori infection pose a major healthcare threat to familie...Helicobacter pylori (H.pylori) infects approximately 50% of the world population.The multiple gastrointestinal and extra-gastrointestinal diseases caused by H.pylori infection pose a major healthcare threat to families and societies;it is also a heavy economic and healthcare burden for countries that having high infection rates.Eradication of H.pylori is recommended for all infected individuals.Traditionally,"test and treat"and"screen and treat"strategies are available for various infected populations.However,clinical practice has noticed that these strategies have some shortfalls and may need refinement,mostly due to the fact that they are not easily manageable,and are affected by patient compliance,selection of treatment population and cost-benefit estimations.Furthermore,it is difficult to control infections from the source,therefore,development of additional,compensative strategies are encouraged to solve the above problems and facilitate bacteria eradication.H.pylori infection is a family-based disease,but few studies have been performed in a whole family-based approach to curb its intra-familial transmission and the development of related diseases.In this work,a third,novel whole family-based H.pylori eradication strategy is introduced.This approach screens,identifies,treats and follows up on all H.pylori-infected individuals in entire families to control H.pylori infection among family members,and reduce its long-term complications.This strategy is high-risk population-oriented,and able to reduce H.pylori spread among family members.It also has good patient-family compliance and,importantly,is practical for both high and low H.pylori-infected communities.Future efforts in these areas will be critical to initiate and establish healthcare policies and management strategies to reduce H.pylori-induced disease burden for society.展开更多
INTRODUCTIONIncreasing data has demonstrated that Helicobacterpylori(H.pylori),a spiral gram negativebacterium,colonized in human stomach,can causetype B gastritis,is strongly associated withgastric and duodenal ulcer...INTRODUCTIONIncreasing data has demonstrated that Helicobacterpylori(H.pylori),a spiral gram negativebacterium,colonized in human stomach,can causetype B gastritis,is strongly associated withgastric and duodenal ulceration,and has beenimplicated in the causation of gastric carcinomaand mucosa-associated lymphoid tissue(MALT)lymphomas.It has been reported that there展开更多
BACKGROUND Pediatric enteritis is one of the infectious diseases in the digestive system that causes a variety of digestive problems,including diarrhea,vomiting,and bellyache in children.Clinically,Helicobacter pylori...BACKGROUND Pediatric enteritis is one of the infectious diseases in the digestive system that causes a variety of digestive problems,including diarrhea,vomiting,and bellyache in children.Clinically,Helicobacter pylori(H.pylori)infection is one of the common factors to cause pediatric enteritis.It has been demonstrated that aberrant expression of microRNAs(miRNAs)is found in gastrointestinal diseases caused by H.pylori,and we discovered a significant increase of miR-32-5p in H.pylori-related pediatric enteritis.However,the exact role of miR-32-5p in it is still unknown.AIM To investigate the role of aberrant miR-32-5p in pediatric enteritis induced by H.pylori.METHODS MiR-32-5p expression was detected by quantitative real time-polymerase chain reaction.The biological role of miR-32-5p in H.pylori-treated intestinal epithelial cells was evaluated by Cell Counting Kit-8 assay and flow cytometry.The potential target of miR-32-5p was predicted with TargetScanHuman and verified by luciferase assay.The downstream mechanism of miR-32-5p was explored by using molecular biology methods.RESULTS We found that miR-32-5p was overexpressed in serum of H.pylori-induced pediatric enteritis.Further investigation revealed that H.pylori infection promoted the death of intestinal epithelial cells,and increased miR-32-5p expression.Moreover,miR-32-5p mimic further facilitated apoptosis and inflammatory cytokine secretion of intestinal epithelial cells.Further exploration revealed that SMAD family member 6(SMAD6)was the direct target of miR-32-5p,and SMAD6 overexpression partially rescued cell damage induced by H.pylori.The following experiments showed that miR-32-5p/SMAD6 participated in the apoptosis of intestinal epithelial cells induced by transforming growth factor-β-activated kinase 1(TAK1)-p38 activation under H.pylori infection.CONCLUSION Our work uncovered the crucial role of aberrant expression of miR-32-5p in H.pylori–related pediatric enteritis,and suggested that the TAK1-p38 pathway is involved in it.展开更多
Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection.Hence,the global emergence of metronidazole resistance in Hp poses a maj...Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection.Hence,the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals.Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H.pylori.However,metronidazole resistance can also arise in H.pylori strains expressing functional RdxA protein,suggesting that there are other mechanisms that may confer resistance to this drug.Methods:We performed whole-genome sequencing on 121 H.pylori clinical strains,among which 73 were metronidazoleresistant.Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed.Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H.pylori.Results:Resistance due to RdxA truncation was identified in 34%of metronidazole-resistant strains.Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance.These sites included R16H/C in RdxA,D85N in the inner-membrane protein RclC(HP0565),V265I in a biotin carboxylase protein(HP0370)and A51V/T in a putative threonylcarbamoyl–AMP synthase(HP0918).Conclusions:Our approach identified new potential mechanisms for metronidazole resistance in H.pylori that merit further investigation.展开更多
Gastric B-cell lymphoma of the mucosa associated lym-phoid tissue(MALT) lymphoma is one of the most com-mon forms of extranodal lymphoma.In addition to in-fection with Helicobacter pylori(H.pylori),the presence of an ...Gastric B-cell lymphoma of the mucosa associated lym-phoid tissue(MALT) lymphoma is one of the most com-mon forms of extranodal lymphoma.In addition to in-fection with Helicobacter pylori(H.pylori),the presence of an underlying autoimmune disease has also been associated with MALT lymphoma development.To date,no familial predisposition for MALT lymphomas has been reported as opposed to other types of lymphoma.A 65-year-old woman was admitted at our institution in 1998 with a diagnosis of H.pylori positive gastric MALT lymphoma and the presence of chronic autoim-mune thyroiditis was established on further work-up.H.pylori eradication did not result in regression of the lymphoma and RT-PCR showed the presence of the t(11;18)(q21;q21) translocation.About 1.5 years after H.pylori eradication,chemotherapy with cladribine resulted in complete remission.Due to lymphoma re-currence 13 mo later,radiotherapy to the stomach(46 Gy) resulted in minimal residual disease without further progression.The patient developed a second malig-nancy(Epstein-Bar virus-associated anaplastic large cell lymphoma in the mediastinum) in 2004 which initially responded to two courses of chemotherapy,but she re-fused further therapy and died of progressive lympho-ma in 2006.In 2008,her 55 years old daughter with a long standing Sj gren's syndrome was diagnosed with MALT lymphoma of the right parotid,but no evidence of gastric involvement or H.pylori infection was found.Currently,she is alive without therapy and undergoing regular check-ups.To our knowledge,this is the first report of MALT lymphoma in a f irst-degree relative of a patient with gastric MALT lymphoma in the context of two autoimmune diseases without a clearly established familial background.展开更多
目的探讨残留样蛋白质家族成员4(VGLL4)基因单核苷酸多态性(SNP)与幽门螺杆菌(H.pylori)感染的关系。方法选取450例体检者的血液样本,采用ELISA法将样本分为幽门螺杆菌阴性组(n=220)和幽门螺杆菌阳性组(n=230)。采用聚合酶链式反应-限...目的探讨残留样蛋白质家族成员4(VGLL4)基因单核苷酸多态性(SNP)与幽门螺杆菌(H.pylori)感染的关系。方法选取450例体检者的血液样本,采用ELISA法将样本分为幽门螺杆菌阴性组(n=220)和幽门螺杆菌阳性组(n=230)。采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术对VGLL4 SNP rs1803489、rs7617620、rs13078528位点进行基因分型。结果内蒙古包头地区汉族人群中VGLL4基因SNP rs1803489、rs7617620、rs13078528与幽门螺杆菌感染没有关联。结论在内蒙古包头地区的汉族人群中VGLL4基因SNP rs1803489、rs7617620、rs13078528在幽门螺杆菌感染中不起主要作用。展开更多
文摘Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow affects the course of IBD.It appears that H.pylori infection influences IBD through changes in the diversity of the gut microbiota,and hence in local chemical characteristics,and alteration in the pattern of gut immune response.The gut immune response appears to be modulated by H.pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair.Therefore,a T helper 2(Th2)/macrophage M2 response is stimulated,while the Th1/macrophage M1 response is suppressed.The immunomodulation appears to be associated with intrinsic factors of the bacteria,such as virulence factors-such oncogenic protein cytotoxin-associated antigen A,proteins such H.pylori neutrophil-activating protein,but also with microenvironmental changes that favor permanence of H.pylori in the stomach.These changes include the increase of gastric mucosal pH by urease activity,and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium.Furthermore,there is a causal relationship between H.pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.
基金National Natural Science Foundation of China,No.U1604174Henan Provincial Government-Health and Family Planning Commission,No.20170123 and No.SBGJ202002004Henan Provincial Government-Health and Family Planning Commission Research Innovative Talents Project,No.51282
文摘BACKGROUND Helicobacter pylori(H.pylori)has characteristics of family cluster infection;however,its family-based infection status,related factors,and transmission pattern in central China,a high-risk area for H.pylori infection and gastric cancer,have not been evaluated.We investigated family-based H.pylori infection in healthy households to understand its infection status,related factors,and patterns of transmission for related disease prevention.AIM To investigate family-based H.pylori infection status,related factors,and patterns of transmission in healthy households for related disease prevention.METHODS Blood samples and survey questionnaires were collected from 282 families including 772 individuals.The recruited families were from 10 selected communities in the greater Zhengzhou area with different living standards,and the family members’general data,H.pylori infection status,related factors,and transmission pattern were analyzed.H.pylori infection was confirmed primarily by serum H.pylori antibody arrays;if patients previously underwent H.pylori eradication therapy,an additional 13C-urea breath test was performed to obtain their current infection status.Serum gastrin and pepsinogens(PGs)were also analyzed.RESULTS Among the 772 individuals examined,H.pylori infection rate was 54.27%.These infected individuals were from 246 families,accounting for 87.23%of all 282 families examined,and 34.55%of these families were infected by the same strains.In 27.24%of infected families,all members were infected,and 68.66%of them were infected with type I strains.Among the 244 families that included both husband and wife,spouse co-infection rate was 34.84%,and in only 17.21%of these spouses,none were infected.The infection rate increased with duration of marriage,but annual household income,history of smoking,history of alcohol consumption,dining location,presence of gastrointestinal symptoms,and family history of gastric disease or GC did not affect infection rates;however,individuals who had a higher education level showed lower infection rates.The levels of gastrin-17,PGI,and PGII were significantly higher,and PGI/II ratio was significantly lower in H.pylori-infected groups than in H.pylori-negative groups.CONCLUSION In our study sample from the general public of central China,H.pylori infection rate was 54.27%,but in 87.23%of healthy households,there was at least 1 H.pylori-infected person;in 27.24%of these infected families,all members were infected.Type I H.pylori was the dominant strain in this area.Individuals with a higher education level showed significantly lower infection rates;no other variables affected infection rates.
基金Supported by grants to SZD from Henan Provincial GovernmentScience and Technology Bureau,No.142300410050Henan Provincial Government-Health and Family Planning Commission,No.20170123+1 种基金Henan Provincial Innovative Talents Projects of 2016and 2017National Natural Science Foundation of China,No.U1604174
文摘Helicobacter pylori (H.pylori) infects approximately 50% of the world population.The multiple gastrointestinal and extra-gastrointestinal diseases caused by H.pylori infection pose a major healthcare threat to families and societies;it is also a heavy economic and healthcare burden for countries that having high infection rates.Eradication of H.pylori is recommended for all infected individuals.Traditionally,"test and treat"and"screen and treat"strategies are available for various infected populations.However,clinical practice has noticed that these strategies have some shortfalls and may need refinement,mostly due to the fact that they are not easily manageable,and are affected by patient compliance,selection of treatment population and cost-benefit estimations.Furthermore,it is difficult to control infections from the source,therefore,development of additional,compensative strategies are encouraged to solve the above problems and facilitate bacteria eradication.H.pylori infection is a family-based disease,but few studies have been performed in a whole family-based approach to curb its intra-familial transmission and the development of related diseases.In this work,a third,novel whole family-based H.pylori eradication strategy is introduced.This approach screens,identifies,treats and follows up on all H.pylori-infected individuals in entire families to control H.pylori infection among family members,and reduce its long-term complications.This strategy is high-risk population-oriented,and able to reduce H.pylori spread among family members.It also has good patient-family compliance and,importantly,is practical for both high and low H.pylori-infected communities.Future efforts in these areas will be critical to initiate and establish healthcare policies and management strategies to reduce H.pylori-induced disease burden for society.
文摘INTRODUCTIONIncreasing data has demonstrated that Helicobacterpylori(H.pylori),a spiral gram negativebacterium,colonized in human stomach,can causetype B gastritis,is strongly associated withgastric and duodenal ulceration,and has beenimplicated in the causation of gastric carcinomaand mucosa-associated lymphoid tissue(MALT)lymphomas.It has been reported that there
文摘BACKGROUND Pediatric enteritis is one of the infectious diseases in the digestive system that causes a variety of digestive problems,including diarrhea,vomiting,and bellyache in children.Clinically,Helicobacter pylori(H.pylori)infection is one of the common factors to cause pediatric enteritis.It has been demonstrated that aberrant expression of microRNAs(miRNAs)is found in gastrointestinal diseases caused by H.pylori,and we discovered a significant increase of miR-32-5p in H.pylori-related pediatric enteritis.However,the exact role of miR-32-5p in it is still unknown.AIM To investigate the role of aberrant miR-32-5p in pediatric enteritis induced by H.pylori.METHODS MiR-32-5p expression was detected by quantitative real time-polymerase chain reaction.The biological role of miR-32-5p in H.pylori-treated intestinal epithelial cells was evaluated by Cell Counting Kit-8 assay and flow cytometry.The potential target of miR-32-5p was predicted with TargetScanHuman and verified by luciferase assay.The downstream mechanism of miR-32-5p was explored by using molecular biology methods.RESULTS We found that miR-32-5p was overexpressed in serum of H.pylori-induced pediatric enteritis.Further investigation revealed that H.pylori infection promoted the death of intestinal epithelial cells,and increased miR-32-5p expression.Moreover,miR-32-5p mimic further facilitated apoptosis and inflammatory cytokine secretion of intestinal epithelial cells.Further exploration revealed that SMAD family member 6(SMAD6)was the direct target of miR-32-5p,and SMAD6 overexpression partially rescued cell damage induced by H.pylori.The following experiments showed that miR-32-5p/SMAD6 participated in the apoptosis of intestinal epithelial cells induced by transforming growth factor-β-activated kinase 1(TAK1)-p38 activation under H.pylori infection.CONCLUSION Our work uncovered the crucial role of aberrant expression of miR-32-5p in H.pylori–related pediatric enteritis,and suggested that the TAK1-p38 pathway is involved in it.
基金This project was supported by ShenZhen’s Sanming Project(Grant No:SZSM201510050)University of Malaya-Ministry of Education(UM-MoE)High Impact Research(HIR)grant(reference UM.C/625/1/HIR/MoE/CHAN13/3,Account No.H-50001-A000030)a National Health and Medical Research Council(NHMRC)Sir McFarlane Burnett Fellowship grant(572723)to B.J.M.,the Vice Chancellor of the University of Western Australia,and the Western Australian Department of Commerce and Department of Health.A.W.D.was supported by an Early Career Research Fellowship from the NHMRC(APP1073250).
文摘Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection.Hence,the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals.Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H.pylori.However,metronidazole resistance can also arise in H.pylori strains expressing functional RdxA protein,suggesting that there are other mechanisms that may confer resistance to this drug.Methods:We performed whole-genome sequencing on 121 H.pylori clinical strains,among which 73 were metronidazoleresistant.Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed.Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H.pylori.Results:Resistance due to RdxA truncation was identified in 34%of metronidazole-resistant strains.Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance.These sites included R16H/C in RdxA,D85N in the inner-membrane protein RclC(HP0565),V265I in a biotin carboxylase protein(HP0370)and A51V/T in a putative threonylcarbamoyl–AMP synthase(HP0918).Conclusions:Our approach identified new potential mechanisms for metronidazole resistance in H.pylori that merit further investigation.
文摘Gastric B-cell lymphoma of the mucosa associated lym-phoid tissue(MALT) lymphoma is one of the most com-mon forms of extranodal lymphoma.In addition to in-fection with Helicobacter pylori(H.pylori),the presence of an underlying autoimmune disease has also been associated with MALT lymphoma development.To date,no familial predisposition for MALT lymphomas has been reported as opposed to other types of lymphoma.A 65-year-old woman was admitted at our institution in 1998 with a diagnosis of H.pylori positive gastric MALT lymphoma and the presence of chronic autoim-mune thyroiditis was established on further work-up.H.pylori eradication did not result in regression of the lymphoma and RT-PCR showed the presence of the t(11;18)(q21;q21) translocation.About 1.5 years after H.pylori eradication,chemotherapy with cladribine resulted in complete remission.Due to lymphoma re-currence 13 mo later,radiotherapy to the stomach(46 Gy) resulted in minimal residual disease without further progression.The patient developed a second malig-nancy(Epstein-Bar virus-associated anaplastic large cell lymphoma in the mediastinum) in 2004 which initially responded to two courses of chemotherapy,but she re-fused further therapy and died of progressive lympho-ma in 2006.In 2008,her 55 years old daughter with a long standing Sj gren's syndrome was diagnosed with MALT lymphoma of the right parotid,but no evidence of gastric involvement or H.pylori infection was found.Currently,she is alive without therapy and undergoing regular check-ups.To our knowledge,this is the first report of MALT lymphoma in a f irst-degree relative of a patient with gastric MALT lymphoma in the context of two autoimmune diseases without a clearly established familial background.
文摘目的探讨残留样蛋白质家族成员4(VGLL4)基因单核苷酸多态性(SNP)与幽门螺杆菌(H.pylori)感染的关系。方法选取450例体检者的血液样本,采用ELISA法将样本分为幽门螺杆菌阴性组(n=220)和幽门螺杆菌阳性组(n=230)。采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术对VGLL4 SNP rs1803489、rs7617620、rs13078528位点进行基因分型。结果内蒙古包头地区汉族人群中VGLL4基因SNP rs1803489、rs7617620、rs13078528与幽门螺杆菌感染没有关联。结论在内蒙古包头地区的汉族人群中VGLL4基因SNP rs1803489、rs7617620、rs13078528在幽门螺杆菌感染中不起主要作用。
