BACKGROUND Müller-Weiss disease(MWD)is an idiopathic foot condition characterized by spontaneous tarsal“scaphoiditis”in adults.Frequently bilateral and affecting females during the 4th-6th decades of life,the p...BACKGROUND Müller-Weiss disease(MWD)is an idiopathic foot condition characterized by spontaneous tarsal“scaphoiditis”in adults.Frequently bilateral and affecting females during the 4th-6th decades of life,the pathogenesis of MWD remains unclear:It has been traditionally considered a spontaneous osteonecrosis of the navicular.The typical presentation of MWD is a long period of subtle discomfort followed by prolonged standing,atraumatic,disabling pain.Currently,there is no gold standard for the treatment of patients with MWD.Most support initial conservative therapy.Operative treatment should be considered for failure of conservative therapies longer than 6 months.The indication for surgery is severity of symptoms rather than severity of deformities.Operative treatment options include core decompression,internal fixation of the tarsal navicular,open or arthroscopic triple fusion,talo-navicular or talo-navicular-cuneiform arthrodesis,and navicular excision with reconstruction of the medial column.CASE SUMMARY In this study,we report four patients affected by MWD.Clinical and radiographic assessment,follow-up and treatment are reported.CONCLUSION As it is frequently misdiagnosed,MWD is challenging for orthopedic surgeons.Early diagnosis and effective treatment are mandatory to avoid sequelae.展开更多
Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental ...Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.展开更多
BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search wa...BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
TMEM16F is involved in many physiological processes such as blood coagulation,cell membrane fusion and bone mineralization.Activation of TMEM16F has been studied in various central nervous system diseases.High TMEM16F...TMEM16F is involved in many physiological processes such as blood coagulation,cell membrane fusion and bone mineralization.Activation of TMEM16F has been studied in various central nervous system diseases.High TMEM16F level has been also found to participate in microglial phagocytosis and transformation.Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer’s disease.However,few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer’s disease.In this study,we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD.We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome.Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice.After TMEM16F knockdown in mice,spatial memory ability was improved,microglia polarization to the M2 phenotype was promoted,NLRP3 inflammasome activation was inhibited,cell apoptosis and Aβplaque deposition in brain tissue were reduced,and brain injury was alleviated.We used amyloid-beta(Aβ_(25-35))to stimulate human microglia to construct microglia models of Alzheimer’s disease.The levels of TMEM16F,inducible nitric oxide synthase(iNOS),proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aβ_(25-35) treated group compared with that in the control group.TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3,reduced the release of proinflammatory factors interleukin-1,interleukin-6 and tumor necrosis factor-α,and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1βand interleukin-18.This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin.Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer’s disease through participating in polarization of microglia and activation of the NLRP3 inflammasome.These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer’s disease treatment.展开更多
N6-methyladenosine(m6A)modification is a reversible process promoted by“writers”,inhibited by“erasers”,and processed by“readers”.During the last decade,increasing emphasis has been placed on the underlying roles...N6-methyladenosine(m6A)modification is a reversible process promoted by“writers”,inhibited by“erasers”,and processed by“readers”.During the last decade,increasing emphasis has been placed on the underlying roles of m6A modification owing to their great importance in biological significance.The abnormal regulation of m6A modification will lead to aberrant cellular behavior and various diseases.Recently,studies have demonstrated that m6A modification is closely associated with the genesis and progression of ocular surface diseases(OSDs).This review focus on the role of m6A modification and research progress in OSDs including fungal keratitis,herpes simplex keratitis,immunerelated keratoconjunctival diseases,pterygium,ocular chemical burns,and Graves’ophthalmopathy,which may provide new insights into and prospective applications for OSDs.展开更多
BACKGROUND Ménétrier’s disease is a rare condition characterized by enlarged gastric folds,usually located in the whole body and fundus of the stomach.This report presents an unusual case of localized M...BACKGROUND Ménétrier’s disease is a rare condition characterized by enlarged gastric folds,usually located in the whole body and fundus of the stomach.This report presents an unusual case of localized Ménétrier’s disease elevated by a submucosal lipoma and thus looking like a polypoid mass and causing an episode of upper gastrointestinal bleeding.The mass was successfully removed with endoscopic submucosal dissection.CASE SUMMARY Esophagogastroduodenoscopy was performed on a 76-year-old male patient after an episode of upper gastrointestinal bleeding,manifesting as fatigue and melena.A large polypoid mass(4 cm×1 cm)with enlarged mucosal folds was found in the body of the stomach,between the lesser curvature and posterior wall.A small ulcer at the distal end of the mass was identified as the source of the bleeding.Biopsy was negative for neoplasia.Computed tomography showed a submucosal lesion beneath the affected mucosa,most likely a lipoma.The mass was removed en bloc with tunneling endoscopic submucosal dissection.Final pathology determined that the mass included Ménétrier’s disease and a submucosal lipoma.The patient was scheduled for follow-up esophagogastroduodenoscopy.CONCLUSION Localized Ménétrier’s disease can coexist with a submucosal lipoma creating a polypoid mass with risk of bleeding.展开更多
目的探讨单核细胞单层实验(monocyte monolayer assay,MMA)是否能够用于IgG抗-M相关胎儿新生儿溶血病(hemolytic disease of fetus and newborn,HDFN)的预测。方法选取8例含有IgG抗-M的孕妇并采集血浆标本,其中有胎儿水肿等严重临床症...目的探讨单核细胞单层实验(monocyte monolayer assay,MMA)是否能够用于IgG抗-M相关胎儿新生儿溶血病(hemolytic disease of fetus and newborn,HDFN)的预测。方法选取8例含有IgG抗-M的孕妇并采集血浆标本,其中有胎儿水肿等严重临床症状及无明显临床症状的各4例;8份血浆用二硫苏糖醇(dithiothreitol,DTT)灭活,与M抗原阳性红细胞孵育致敏后,将致敏红细胞与单核细胞混合进行吞噬试验,同时设立阳性及阴性对照,并计算吞噬率;采用t检验对2组吞噬率进行比较。结果4例发生严重抗-M相关HDFN的孕妇的MMA吞噬率分别为15.37%、13.05%、9.17%和24.50%,均值为15.52%;检出IgG抗-M但未发生HDFN的孕妇,其MMA吞噬率分别为8.74%、11.07%、5.12%和6.23%,均值为7.79%,2组吞噬率无差异(P>0.05)。2组吞噬率分别与阴性对照比较均无差异(P>0.05),但均明显低于阳性对照(P<0.05)。结论IgG抗-M介导单核细胞吞噬的能力较低,提示抗-M导致胎儿水肿的机制可能并非红细胞被吞噬破坏而发生的溶血,因此体外单核细胞单层实验可能不适用于IgG抗-M相关HDFN的预测。对于检出IgG抗-M的孕妇,现仍需通过定期监测胎儿大脑中动脉血流,来判断胎儿宫内贫血情况。展开更多
AIM:To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease(m SES-CD).METHODS:Seventy-six Crohn's disease(CD) patients who underwent transanal double balloon endoscopy(...AIM:To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease(m SES-CD).METHODS:Seventy-six Crohn's disease(CD) patients who underwent transanal double balloon endoscopy(DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new m SES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE,in addition to the activity of four colorectal segments. To compare the usefulness of m SES-CD with SES-CD,we similarly divided the patients into two groups according to total m SES-CD score(low disease activity group,< 4; high disease activity group,≥ 4). The clinical value of m SES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint.RESULTS:Median age of the 76 CD patients was 36 years(range,16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm(range,3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE,of which 62(83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients(2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high m SES-CD scores showed significantly shorter surgeryfree survival than those with low scores(P < 0.05). In contrast,surgery-free survival did not significantly differ between the low and high SES-CD groups(P > 0.05). Multivariate analysis by a Cox proportional hazards model identified m SES-CD as an independent factor for surgery-free survival.CONCLUSION:m SES-CD is useful in evaluating the risk of surgery-free survival in patients with CD.展开更多
Objective: This meta-analysis aims to evaluate the effects of traditional Chinese medicine(TCM) nursing combined with conventional nursing in patients with chronic obstructive pulmonary disease(COPD).Methods: Data wer...Objective: This meta-analysis aims to evaluate the effects of traditional Chinese medicine(TCM) nursing combined with conventional nursing in patients with chronic obstructive pulmonary disease(COPD).Methods: Data were collected from the databases of PubMed, Embase, the Cochrane Library, Web of Science, Google Scholar,China National Knowledge Infrastructure(CNKI), WanFang Data(WF) and VIP Database, including literature regarding the effects of TCM nursing combined with conventional nursing in patients with COPD published before January 2017. The Jadad scale was used to assess the quality of the eligible literature. The weighted mean differences and odds ratios were used to analyze St. George's Respiratory Questionnaire(SGRQ) scores, pulmonary function, hospital stay, and clinical efficacy.Results: Twenty-three randomized controlled trials comprising 3116 cases(TCM nursing combined with the conventional nursing group: 1559; conventional nursing group: 1557) met the inclusion criteria. TCM nursing combined with conventional nursing was associated with a lower SGRQ score, higher forced expiratory volume in 1 second(FEV1) value, higher FEV1/forced vital capacity(FVC) value, higher FEV1% value, higher FEV1 predicted value, shorter hospital stay, and preferable clinical efficacy.Conclusions: TCM nursing combined with conventional nursing emphasized that dialectical nursing can be performed preferably in patients with COPD.展开更多
AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian a...AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.展开更多
The present study was designed to alert the public opinion and policy makers on the supposed enhancing effects of exposure to ambient air particulate matter with aerodynamic diameters < 2.5 mm (PM 2.5 ) on non-alco...The present study was designed to alert the public opinion and policy makers on the supposed enhancing effects of exposure to ambient air particulate matter with aerodynamic diameters < 2.5 mm (PM 2.5 ) on non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western countries. For far too long literature data have been fixated on pulmonary diseases and/or cardiovascular disease, as consequence of particulate exposure, ignoring the link between the explosion of obesity with related syndromes such as NAFLD and air pollution, the worst characteristics of nowadays civilization. In order to delineate a clear picture of this major health problem, further studies should investigate whether and at what extent cigarette smoking and exposure to ambient air PM 2.5 impact the natural history of patients with obesity-related NAFLD,i.e. , development of non alcoholic steatohepatitis, disease characterized by a worse prognosis due its progression towards fibrosis and hepatocarcinoma.展开更多
Objective:To investigate the role of ^(99m)Tc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathicParkinson's disease(PD).Methods:Thirty-eight patients with primary,tentative diagnosis of PD and eighte...Objective:To investigate the role of ^(99m)Tc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathicParkinson's disease(PD).Methods:Thirty-eight patients with primary,tentative diagnosis of PD and eighteen age-matchednormal controls were studied with ^(99m)Tc-TRODAT-1 SPECT imaging.The regions of interests(ROIs)were drawn manually oncerebellum(CB),occipital cortex(OC)and three transverse plane slice-views of striatums,the semiquantitative BG(back-ground)/[(OC+CB)/2]were then calculated.Results:A lower uptake of ^(99m)Tc-TRODAT-1 in striatums were displayed inthirty-six out of thirty-eight PD patients by visual inspection,compared to controls.In twenty-four PD cases with HYS(Hoehn andYahr scale)stage Ⅰ,a greater loss of DAT uptake was found in striatum and its subregions contralateral striatum to the affectedlimbs than in the same regions of the controls,although the striatal uptake was bilaterally reduced.Using Spearman correlationanalysis showed that the reduction of the uptake ratios significantly correlated with the UPDRS in striatum and all its subregions inthe PD group(P<0.05),a similar change was also found in the putamen by using the rating scale of Hoehn and Yahr (P<0.05).However,analysis of variance(ANOVA)did not show any relationship between the decreasing uptake of ^(99m)Tc-TRODAT-1 andincreasing severity of PD patients,although the specific uptake of ^(99m)Tc-TRODAT-1 was continuously decreased in the striatumby visual inspection with the progress of PD from HYS stage Ⅰ to Ⅲ.Conclusion:^(99m)Tc-TRODAT-1 SPECT imaging may serve asa useful method for improving the correct diagnosis of PD.In assessing the role of ^(99m)Tc-TRODAT-1 SPECT in disease severity ofPD,UPDRS can offer a comprehensive index,although the Hoehn and Yahr assessment may be available in part.展开更多
The diagnosis of inflammatory bowel disease(IBD) depends on direct endoscopic visualization of the colonic and ileal mucosa and the histological study of the obtained samples.Radiological and scintigraphic methods are...The diagnosis of inflammatory bowel disease(IBD) depends on direct endoscopic visualization of the colonic and ileal mucosa and the histological study of the obtained samples.Radiological and scintigraphic methods are mainly used as an adjunct to endoscopy.In this review,we focus on the diagnostic potential of nuclear medicine procedures.The value of all radiotracers is described with special reference to those with greater experience and more satisfactory results.Tc-99m hexamethylpropylene amine oxime white blood cells remain a widely acceptable scintigraphic method for the diagnosis of IBD,as well as for the evaluation of disease extension and severity.Recently,pentavalent Tc-99m dimercaptosuccinic acid has been recommended as an accurate variant and a complementary technique to endoscopy for the follow-up and assessment of disease activity.Positron emission tomography alone or with computed tomography using fluorine-18 fluorodeoxyglucose appears to be a promising method of measuring inflammation in IBD patients.展开更多
Objective:To study the clinical value of Technetium-99m sestamibi myocardial perfusion single photon emission computed tomography(SPECT) in diabetes with suspected coronary artery diseases.Methods:Seventy-eight diabet...Objective:To study the clinical value of Technetium-99m sestamibi myocardial perfusion single photon emission computed tomography(SPECT) in diabetes with suspected coronary artery diseases.Methods:Seventy-eight diabetic patients complicated with cardiac symptoms or electrocardiogram(ECG) abnormalities and suspected coronary heart disease hospitalized in the department of endocrinology from January,2008 to December,2008 were investigated.Technetium-99m sestamibi myocardial perfusion SPECT was performed in all patients.Exercise stress test was done in 35 cases(group A).Adenosine stress test was done in 43 cases(group B).Results:The positive rates in the two groups were 54.29%(19/35) and 53.48%(23/43),respectively.There was no statistic difference between the 2 groups(P>0.05).The abnormality rates in male and female groups were 63.04% and 28.13%,respectively(P<0.01).Eighty-six segments of perfusion abnormality were detected in 38 positive patients.Four segments of fixed defect were found in 4 cases.Conclusion:As non-invasive method,myocardial perfusion SPECT can play an important role in the treatment of diabetes with suspected coronary artery disease.展开更多
文摘BACKGROUND Müller-Weiss disease(MWD)is an idiopathic foot condition characterized by spontaneous tarsal“scaphoiditis”in adults.Frequently bilateral and affecting females during the 4th-6th decades of life,the pathogenesis of MWD remains unclear:It has been traditionally considered a spontaneous osteonecrosis of the navicular.The typical presentation of MWD is a long period of subtle discomfort followed by prolonged standing,atraumatic,disabling pain.Currently,there is no gold standard for the treatment of patients with MWD.Most support initial conservative therapy.Operative treatment should be considered for failure of conservative therapies longer than 6 months.The indication for surgery is severity of symptoms rather than severity of deformities.Operative treatment options include core decompression,internal fixation of the tarsal navicular,open or arthroscopic triple fusion,talo-navicular or talo-navicular-cuneiform arthrodesis,and navicular excision with reconstruction of the medial column.CASE SUMMARY In this study,we report four patients affected by MWD.Clinical and radiographic assessment,follow-up and treatment are reported.CONCLUSION As it is frequently misdiagnosed,MWD is challenging for orthopedic surgeons.Early diagnosis and effective treatment are mandatory to avoid sequelae.
基金supported by the National Natural Science Foundation of China,Nos.82071190 and 82371438(to LC)Innovative Strong School Project of Guangdong Medical University,No.4SG21230G(to LC)Scientific Research Foundation of Guangdong Medical University,No.GDMUM2020017(to CL)。
文摘Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.
文摘BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金supported by the National Natural Science Foundation of China,No.82072941(to QHX)Liaoning Province Key R&D Program Guidance Project,No.2020JH2/10300044Science and Technology Plan Project of Shenyang,No.20-205-4-050(both to XHS)。
文摘TMEM16F is involved in many physiological processes such as blood coagulation,cell membrane fusion and bone mineralization.Activation of TMEM16F has been studied in various central nervous system diseases.High TMEM16F level has been also found to participate in microglial phagocytosis and transformation.Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer’s disease.However,few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer’s disease.In this study,we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD.We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome.Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice.After TMEM16F knockdown in mice,spatial memory ability was improved,microglia polarization to the M2 phenotype was promoted,NLRP3 inflammasome activation was inhibited,cell apoptosis and Aβplaque deposition in brain tissue were reduced,and brain injury was alleviated.We used amyloid-beta(Aβ_(25-35))to stimulate human microglia to construct microglia models of Alzheimer’s disease.The levels of TMEM16F,inducible nitric oxide synthase(iNOS),proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aβ_(25-35) treated group compared with that in the control group.TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3,reduced the release of proinflammatory factors interleukin-1,interleukin-6 and tumor necrosis factor-α,and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1βand interleukin-18.This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin.Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer’s disease through participating in polarization of microglia and activation of the NLRP3 inflammasome.These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer’s disease treatment.
基金Supported by Project of Shanghai Science and Technology (No.20ZR1443600)。
文摘N6-methyladenosine(m6A)modification is a reversible process promoted by“writers”,inhibited by“erasers”,and processed by“readers”.During the last decade,increasing emphasis has been placed on the underlying roles of m6A modification owing to their great importance in biological significance.The abnormal regulation of m6A modification will lead to aberrant cellular behavior and various diseases.Recently,studies have demonstrated that m6A modification is closely associated with the genesis and progression of ocular surface diseases(OSDs).This review focus on the role of m6A modification and research progress in OSDs including fungal keratitis,herpes simplex keratitis,immunerelated keratoconjunctival diseases,pterygium,ocular chemical burns,and Graves’ophthalmopathy,which may provide new insights into and prospective applications for OSDs.
文摘BACKGROUND Ménétrier’s disease is a rare condition characterized by enlarged gastric folds,usually located in the whole body and fundus of the stomach.This report presents an unusual case of localized Ménétrier’s disease elevated by a submucosal lipoma and thus looking like a polypoid mass and causing an episode of upper gastrointestinal bleeding.The mass was successfully removed with endoscopic submucosal dissection.CASE SUMMARY Esophagogastroduodenoscopy was performed on a 76-year-old male patient after an episode of upper gastrointestinal bleeding,manifesting as fatigue and melena.A large polypoid mass(4 cm×1 cm)with enlarged mucosal folds was found in the body of the stomach,between the lesser curvature and posterior wall.A small ulcer at the distal end of the mass was identified as the source of the bleeding.Biopsy was negative for neoplasia.Computed tomography showed a submucosal lesion beneath the affected mucosa,most likely a lipoma.The mass was removed en bloc with tunneling endoscopic submucosal dissection.Final pathology determined that the mass included Ménétrier’s disease and a submucosal lipoma.The patient was scheduled for follow-up esophagogastroduodenoscopy.CONCLUSION Localized Ménétrier’s disease can coexist with a submucosal lipoma creating a polypoid mass with risk of bleeding.
文摘目的探讨单核细胞单层实验(monocyte monolayer assay,MMA)是否能够用于IgG抗-M相关胎儿新生儿溶血病(hemolytic disease of fetus and newborn,HDFN)的预测。方法选取8例含有IgG抗-M的孕妇并采集血浆标本,其中有胎儿水肿等严重临床症状及无明显临床症状的各4例;8份血浆用二硫苏糖醇(dithiothreitol,DTT)灭活,与M抗原阳性红细胞孵育致敏后,将致敏红细胞与单核细胞混合进行吞噬试验,同时设立阳性及阴性对照,并计算吞噬率;采用t检验对2组吞噬率进行比较。结果4例发生严重抗-M相关HDFN的孕妇的MMA吞噬率分别为15.37%、13.05%、9.17%和24.50%,均值为15.52%;检出IgG抗-M但未发生HDFN的孕妇,其MMA吞噬率分别为8.74%、11.07%、5.12%和6.23%,均值为7.79%,2组吞噬率无差异(P>0.05)。2组吞噬率分别与阴性对照比较均无差异(P>0.05),但均明显低于阳性对照(P<0.05)。结论IgG抗-M介导单核细胞吞噬的能力较低,提示抗-M导致胎儿水肿的机制可能并非红细胞被吞噬破坏而发生的溶血,因此体外单核细胞单层实验可能不适用于IgG抗-M相关HDFN的预测。对于检出IgG抗-M的孕妇,现仍需通过定期监测胎儿大脑中动脉血流,来判断胎儿宫内贫血情况。
文摘AIM:To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease(m SES-CD).METHODS:Seventy-six Crohn's disease(CD) patients who underwent transanal double balloon endoscopy(DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new m SES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE,in addition to the activity of four colorectal segments. To compare the usefulness of m SES-CD with SES-CD,we similarly divided the patients into two groups according to total m SES-CD score(low disease activity group,< 4; high disease activity group,≥ 4). The clinical value of m SES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint.RESULTS:Median age of the 76 CD patients was 36 years(range,16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm(range,3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE,of which 62(83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients(2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high m SES-CD scores showed significantly shorter surgeryfree survival than those with low scores(P < 0.05). In contrast,surgery-free survival did not significantly differ between the low and high SES-CD groups(P > 0.05). Multivariate analysis by a Cox proportional hazards model identified m SES-CD as an independent factor for surgery-free survival.CONCLUSION:m SES-CD is useful in evaluating the risk of surgery-free survival in patients with CD.
文摘Objective: This meta-analysis aims to evaluate the effects of traditional Chinese medicine(TCM) nursing combined with conventional nursing in patients with chronic obstructive pulmonary disease(COPD).Methods: Data were collected from the databases of PubMed, Embase, the Cochrane Library, Web of Science, Google Scholar,China National Knowledge Infrastructure(CNKI), WanFang Data(WF) and VIP Database, including literature regarding the effects of TCM nursing combined with conventional nursing in patients with COPD published before January 2017. The Jadad scale was used to assess the quality of the eligible literature. The weighted mean differences and odds ratios were used to analyze St. George's Respiratory Questionnaire(SGRQ) scores, pulmonary function, hospital stay, and clinical efficacy.Results: Twenty-three randomized controlled trials comprising 3116 cases(TCM nursing combined with the conventional nursing group: 1559; conventional nursing group: 1557) met the inclusion criteria. TCM nursing combined with conventional nursing was associated with a lower SGRQ score, higher forced expiratory volume in 1 second(FEV1) value, higher FEV1/forced vital capacity(FVC) value, higher FEV1% value, higher FEV1 predicted value, shorter hospital stay, and preferable clinical efficacy.Conclusions: TCM nursing combined with conventional nursing emphasized that dialectical nursing can be performed preferably in patients with COPD.
基金Supported by An unrestricted research grant from Abbott Labora-toriesan OTKA postdoctoral fellowship (PF63953) (to Andrikov-ics H)+2 种基金the Bolyai Janos Postdoctoral Scholarship of the Hungar-ian Academy of Sciences (to Lakatos PL)No. NR/9219-3/2007 of the Internal Grant Agency of the Czech Ministry of Health (to Lukas M)Generation of the Czech IBD as well as control data-bases was enabled by the support of a grant given by the Czech Ministry of Education No. 2B06155
文摘AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.
文摘The present study was designed to alert the public opinion and policy makers on the supposed enhancing effects of exposure to ambient air particulate matter with aerodynamic diameters < 2.5 mm (PM 2.5 ) on non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western countries. For far too long literature data have been fixated on pulmonary diseases and/or cardiovascular disease, as consequence of particulate exposure, ignoring the link between the explosion of obesity with related syndromes such as NAFLD and air pollution, the worst characteristics of nowadays civilization. In order to delineate a clear picture of this major health problem, further studies should investigate whether and at what extent cigarette smoking and exposure to ambient air PM 2.5 impact the natural history of patients with obesity-related NAFLD,i.e. , development of non alcoholic steatohepatitis, disease characterized by a worse prognosis due its progression towards fibrosis and hepatocarcinoma.
文摘Objective:To investigate the role of ^(99m)Tc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathicParkinson's disease(PD).Methods:Thirty-eight patients with primary,tentative diagnosis of PD and eighteen age-matchednormal controls were studied with ^(99m)Tc-TRODAT-1 SPECT imaging.The regions of interests(ROIs)were drawn manually oncerebellum(CB),occipital cortex(OC)and three transverse plane slice-views of striatums,the semiquantitative BG(back-ground)/[(OC+CB)/2]were then calculated.Results:A lower uptake of ^(99m)Tc-TRODAT-1 in striatums were displayed inthirty-six out of thirty-eight PD patients by visual inspection,compared to controls.In twenty-four PD cases with HYS(Hoehn andYahr scale)stage Ⅰ,a greater loss of DAT uptake was found in striatum and its subregions contralateral striatum to the affectedlimbs than in the same regions of the controls,although the striatal uptake was bilaterally reduced.Using Spearman correlationanalysis showed that the reduction of the uptake ratios significantly correlated with the UPDRS in striatum and all its subregions inthe PD group(P<0.05),a similar change was also found in the putamen by using the rating scale of Hoehn and Yahr (P<0.05).However,analysis of variance(ANOVA)did not show any relationship between the decreasing uptake of ^(99m)Tc-TRODAT-1 andincreasing severity of PD patients,although the specific uptake of ^(99m)Tc-TRODAT-1 was continuously decreased in the striatumby visual inspection with the progress of PD from HYS stage Ⅰ to Ⅲ.Conclusion:^(99m)Tc-TRODAT-1 SPECT imaging may serve asa useful method for improving the correct diagnosis of PD.In assessing the role of ^(99m)Tc-TRODAT-1 SPECT in disease severity ofPD,UPDRS can offer a comprehensive index,although the Hoehn and Yahr assessment may be available in part.
文摘The diagnosis of inflammatory bowel disease(IBD) depends on direct endoscopic visualization of the colonic and ileal mucosa and the histological study of the obtained samples.Radiological and scintigraphic methods are mainly used as an adjunct to endoscopy.In this review,we focus on the diagnostic potential of nuclear medicine procedures.The value of all radiotracers is described with special reference to those with greater experience and more satisfactory results.Tc-99m hexamethylpropylene amine oxime white blood cells remain a widely acceptable scintigraphic method for the diagnosis of IBD,as well as for the evaluation of disease extension and severity.Recently,pentavalent Tc-99m dimercaptosuccinic acid has been recommended as an accurate variant and a complementary technique to endoscopy for the follow-up and assessment of disease activity.Positron emission tomography alone or with computed tomography using fluorine-18 fluorodeoxyglucose appears to be a promising method of measuring inflammation in IBD patients.
文摘Objective:To study the clinical value of Technetium-99m sestamibi myocardial perfusion single photon emission computed tomography(SPECT) in diabetes with suspected coronary artery diseases.Methods:Seventy-eight diabetic patients complicated with cardiac symptoms or electrocardiogram(ECG) abnormalities and suspected coronary heart disease hospitalized in the department of endocrinology from January,2008 to December,2008 were investigated.Technetium-99m sestamibi myocardial perfusion SPECT was performed in all patients.Exercise stress test was done in 35 cases(group A).Adenosine stress test was done in 43 cases(group B).Results:The positive rates in the two groups were 54.29%(19/35) and 53.48%(23/43),respectively.There was no statistic difference between the 2 groups(P>0.05).The abnormality rates in male and female groups were 63.04% and 28.13%,respectively(P<0.01).Eighty-six segments of perfusion abnormality were detected in 38 positive patients.Four segments of fixed defect were found in 4 cases.Conclusion:As non-invasive method,myocardial perfusion SPECT can play an important role in the treatment of diabetes with suspected coronary artery disease.