Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
Branchio-oto-renal(BOR)syndrome is an uncommon disorder inherited in an autosomal dominant manner.Its main clinical manifestations include branchial cleft cysts,anterior auricular fistula,hearing impairment,and kidney...Branchio-oto-renal(BOR)syndrome is an uncommon disorder inherited in an autosomal dominant manner.Its main clinical manifestations include branchial cleft cysts,anterior auricular fistula,hearing impairment,and kidney malformations.BOR syndrome is associated with heterozygous pathogenic variants including EYA1,SIX1,and SIX5.The study focused on a 13-year-old Chinese boy who presented with hearing impairment,renal malformations,and bony atresia of the right external auditory canal with microtia.The boy's clinical manifestations met the diagnostic criteria for BOR syndrome.Two of the boy's family members underwent clinical examination.However,neither displayed a phenotype associated with BOR syndrome.The boy and his two relatives provided blood samples for genomic DNA extraction,followed by Sanger sequencing.A novel mutation in the GREB1L gene was identified in the boy,but neither of his family members exhibited the same variant.Identifying a novel mutation in GREB1L offers valuable insights into the genotype-phenotype correlation of BOR syndrome,improving the precision of early diagnosis and promoting the advancement of personalized treatment strategies.展开更多
Background:Transmural heterogeneity of the transient outward potassium current(I_(to))is a major contributor to J-wave syndrome(JWS).However,the underlying molecular mechanisms remain elusive.The present study aimed t...Background:Transmural heterogeneity of the transient outward potassium current(I_(to))is a major contributor to J-wave syndrome(JWS).However,the underlying molecular mechanisms remain elusive.The present study aimed to investigate the role of cardiac injury-related bclaf1-interacting lncRNA(lncCIRBIL)in JWS and to delineate the molecular mechanisms.Methods:Whole-cell patch-clamp techniques were used to record ionic currents and action potentials(APs).Protein and mRNA expression related to I_(to)current were assessed.RNA immunoprecipitation,RNA Pulldown,mRNA stability,and decapping assays were performed to dissect the underlying mechanisms.Results:Plasma lncCIRBIL levels were significantly reduced in JWS patients and cold-induced JWS mice.Knockout of lncCIRBIL increased the incidence of J-wave and the susceptibility to ventricular arrhythmia in mice.In lncCIRBIL-deficient mice,the transmural gradient of Kv4.2 expression and I_(to)current density was markedly enhanced in the right ventricle,but not the left ventricle.In contrast,cardiomyocyte-specific transgenic overexpression of lncCIRBIL produced the opposite effects.In human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the conserved human homologous fragment of lncCIRBIL(hcf-CIRBIL)suppressed I_(to),attenuated the AP notch,and prolonged APD20.Mechanistically,lncCIRBIL directly binds to up-frameshift protein1(UPF1),promoting KCND2 mRNA decay by enhancing its decapping.Conclusions:LncCIRBIL modulates the transmural heterogeneity of KCND2 expression by regulating UPF1-mediated mRNA decay.Inhibition of lncCIRBIL exacerbates JWS by enhancing right ventricular I_(to)heterogeneity,whereas its overexpression exerts protective effects.These findings identify lncCIRBIL as a potential therapeutic target for J-wave syndrome.展开更多
Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role ...Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA,with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin(mTOR)signaling cascade.We uncovered that activation of the mTOR complex 1(mTORC1)within smooth muscle cells,instigated by the oscillatory wall shear stress(OSS)that stems from disturbed flow(DF),is a catalyst for TAA progression.This revelation was corroborated through both an MFS mouse model(Fbn1+/C1039G)and clinical MFS specimens.Crucially,our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS.Therapeutic administration of rapamycin suppresses mTORC1 activity,leading to the attenuation of aberrant SMC behavior,reduced inflammatory infiltration,and restoration of extracellular matrix integrity—collectively decelerating TAA advancement in our mouse model.These insights posit the mTORC1 axis as a strategic target for intervention,offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.展开更多
BACKGROUND Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as RAF1.Mutations in RAF1 are typically...BACKGROUND Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as RAF1.Mutations in RAF1 are typically associated with hypertrophic cardiomyopathy(HCM).However,in this case,the patient exhibited atrial and ventricular septal defects(VSDs).CASE SUMMARY This case report describes an 11-year-old boy diagnosed with Noonan syndrome,in whom genetic testing revealed a c.770C>T(p.Ser257 Leu)mutation in RAF1.The patient presented with intermittent chest discomfort and shortness of breath,symptoms that significantly worsened after physical activity.Clinical evaluation revealed marked growth retardation and multiple physical abnormalities.Electrocardiographic and echocardiographic assessments revealed VSDs,atrial septal defects,and left ventricular outflow tract obstruction.Following multidisciplinary consultation,the patient underwent cardiac surgical intervention,which led to clinical improvement;however,they subsequently developed a third-degree atrioventricular block,necessitating the implantation of a permanent pacemaker.During follow-up,echocardiographic findings demonstrated near-complete resolution of the shunt across the atrial and ventricular septa,significant improvement in left ventricular outflow tract obstruction,and notable reduction in ventricular septal thickness.A genetic mutation at the c.770C>T(p.Ser257 Leu)locus of RAF1 is typically associated with HCM and pulmonary hypertension.However,this patient’s clinical phenotype manifested as HCM,atrial septal defect,and VSD,suggesting that this mutation may involve a different pathophysiological mechanism.CONCLUSION This case confirms the genotype-phenotype heterogeneity of Noonan syndrome and highlights the complex management requirements of RAF1 mutation-associated cardiac pathologies.Early surgical intervention can ameliorate structural defects,but it must be integrated with genetic counseling and lifelong monitoring to optimize patient outcomes.展开更多
BACKGROUND Protein-losing enteropathy(PLE)is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia.Patients with Noonan syndrome may present with disorder of lymph vessel formation.Howe...BACKGROUND Protein-losing enteropathy(PLE)is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia.Patients with Noonan syndrome may present with disorder of lymph vessel formation.However,PLE is rarely reported with Noonan syndrome.CASE SUMMARY A 15-year-old female was hospitalized multiple times for recurrent edema and diarrhea secondary to hypoalbuminemia.Additional manifestations included a ventricular septal defect at birth,intermuscular hemangioma,slightly wide interocular and intermammary distances,and absence of the distal phalanx of the left little finger since birth.Abdominal computed tomography revealed cavernous transformation of the portal vein,and liver biopsy indicated“porto-sinusoidal vascular disease”.Whole exome and Sanger sequencing revealed a heterozygous mutation(exon9:C.850C>T:P.R284C)in leucine zipper-like transcription regulator 1,suggesting Noonan syndrome type 10.Further examinations revealed thoracic duct dysplasia and intestinal lymphangiectasia causing PLE in this patient.A multidisciplinary team decided to address thoracic duct dysplasia with outlet obstruction.Approximately two years after the microsurgical relief of the thoracic duct outlet obstruction,the patient achieved persistent normal serum albumin level without edema or diarrhea.Furthermore,the relevant literatures on Noonan syndrome and PLE were reviewed.CONCLUSION Herein,we reported the first case of PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1(c.850C>T:P.R284C)with newly reported manifestations.This case presented the successful treatment of clinical hypoalbuminemia attributed to thoracic duct dysplasia,intestinal lymphangiectasia and PLE.展开更多
Diarrhea predominant irritable bowel syndrome(IBS-D)have a serious impact on the patient’s quality life due to the lack of safe and effective drugs.The transient receptor potential vanilloid subtype 1(TRPV1)is an ion...Diarrhea predominant irritable bowel syndrome(IBS-D)have a serious impact on the patient’s quality life due to the lack of safe and effective drugs.The transient receptor potential vanilloid subtype 1(TRPV1)is an ion channel receptor implicated in the perception of visceral injury.Recent studies indicated that TRPV1 mediates visceral hypersensitivity in IBS-D patients by enhancing the excitability of intestinal sensory neurons.Consequently,inhibiting the TRPV1 may be a promising option for the treatment of IBS-D.Current research demonstrates that various traditional Chinese medicine(TCM)methods,such as herbal prescriptions,acupuncture,and moxibustion,can reduce visceral sensitivity by regulating TRPV1 expression and its activation sensitization.This suggests that TCM methods may serve as safe and effective options for alleviating IBS-D.Therefore,this article summarizes potential therapeutic strategies of TCM as a regulator of TRPV1 for managing IBS-D.It also provides insights into potential TCM methods and natural phytochemical molecular nuclei for future drug research targeting TRPV1 in IBS-D.展开更多
Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in st...Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in stress-induced intestinal barrier dysfunction.METHODS The colonic mucus Tβ4 levels in IBS patients were determined and their effects on the epithelial barrier were assessed in vitro and in vivo.Specifically,rats genetically deficient in Tβ4(Tβ4^(-/-))or mice deficient in MCs(Kit^(w-sh/w-sh))were used to observe the effects of reintroducing Tβ4 or wild-type peritoneal MCs(wt-PMCs)into these animals.Additionally,the regulatory mechanism underlying Tβ4 secretion in MCs was investigated.RESULTS We demonstrated that high levels of Tβ4 in IBS mucus and intestinal MCs mediate stress-associated disruptive changes to the epithelial barrier.Moreover,Tβ4 treatment of wild-type or MC-deficient Kit^(w-sh/w-sh)mice caused a reduction in tight junction proteins and the interleukin 22 receptor A1(IL22RA1)/Reg3γcascade,but an increase in myosin light chain kinase.Furthermore,Tβ4^(-/-)rats were resistant to stress,though reintroduction of Tβ4 or wt-PMCs restored stress or corticotropin-releasing hormone(CRH)-induced barrier disturbance.Consistently,Tβ4 release from MCs was dependent on the CRH receptor 1,but not degranulation.The effect of Tβ4 was accompanied by IL22RA1/Janus kinase 1(JAK1)/signal transducer and activation of transcription 3(STAT3)pathway inhibition,suggesting a mechanism for physical and immune barrier suppression.CONCLUSION Collectively,these results suggest that Tβ4,which is abundant in IBS mucus and the secretome of MCs,plays a crucial role in the pathogenesis of IBS via IL22RA1/JAK1/STAT3 signaling,with potential implications for diagnostic and therapeutic targeting.展开更多
Sjögren’s syndrome(SS)is an autoimmune disease characterized primarily by oral and periocular dryness.Astragalus-Salvia(AS)and Ophiopogon-Dendrobium(OD)represent two frequently utilized herb pairs in SS treatmen...Sjögren’s syndrome(SS)is an autoimmune disease characterized primarily by oral and periocular dryness.Astragalus-Salvia(AS)and Ophiopogon-Dendrobium(OD)represent two frequently utilized herb pairs in SS treatment.While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms,its underlying mechanism remains unclear.This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic(NOD)/Ltj mice with SS.The study utilized NOD/Ltj mice as SS models,administering AS-OD treatment for 10 weeks at doses of 113.1,226.2,and 339.3 mg·d−1·20 g−1.Results demonstrated that AS-OD improved SS symptoms,evidenced by enhanced salivary flow rate,decreased anti-SSA/Ro and anti-SSB/La antibody levels,increased swimming duration,and reduced lactate(LA)and blood urea nitrogen(BUN)levels in NOD/Ltj mice.AS-OD reduced lymphocyte infiltration,enhanced Aquaporin-5(AQP5)expression in the submandibular gland,decreased inflammatory cytokine levels in the submandibular gland,and reduced the T helper type 17/regulatory T lymphocyte(Th17/Treg)cell ratio in the spleen.Transcriptomic and proteomic analyses indicated AS-OD’s involvement in regulating phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)and Janus kinase 3/signal transducer and activator of transcription 3(JAK1/STAT3)pathways,with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells.Furthermore,AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway.In A-253 cells,AS-OD reduced inflammatory cytokine levels,CXC chemokine ligand 9/10(CXCL9/10),and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway.AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.展开更多
Type 1 diabetes(T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well describ...Type 1 diabetes(T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1 D as a monoglandular disease and the relation to polyglandular autoimmune syndrome(PAS) have also been wellexplored. The incidence of T1 D has steadily increased in most parts of the world, especially in industrialized nations. T1 D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1 D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterialinduced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type Ⅲ, which encompasses T1 D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1 D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome.展开更多
We conducted an analysis of the Kallmann syndrome 1 （KAL-1） genotype in 17 patients with Kallmann syndrome （KS）, 9 patients with normosmic idiopathic hypogonadotropic hypogonadism （nlHH） and 20 age-matched norma...We conducted an analysis of the Kallmann syndrome 1 （KAL-1） genotype in 17 patients with Kallmann syndrome （KS）, 9 patients with normosmic idiopathic hypogonadotropic hypogonadism （nlHH） and 20 age-matched normal men in Northwestern China. To do this, we used multiplex PCR analysis with exon-flanking primers and automated sequencing techniques with peripheral blood DNA samples. Intragenic deletions were found at the KAL-1 locus in two KS patients. One case with an atrial septal defect exhibited an intragenic deletion of exon 6. Another KS patient with cryptorchidism had intragenic deletions of exons 5 and 6. For the nlHH patients, no abnormalities were observed in the exonic and flanking sequences of KAL-1. This report describes two intragenic deletions of KAL-1 in two KS patients and suggests that KAL-1 deletion might be more prevalent in KS patients with other congenital organ abnormalities than those described previously in other series from Northwestern China.展开更多
A number of disparate diseases can lead to pulmonary hypertension(PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an importan...A number of disparate diseases can lead to pulmonary hypertension(PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an important factor adversely impacting the prognosis of PH. Furthermore, metabolic syndrome is associated with vascular diseases including PH. Inflammation plays a significant role both in PH and metabolic syndrome. Adipose tissue modulates lipid and glucose metabolism, and also produces pro-and anti-inflammatory adipokines that modulate vascular function and angiogenesis, suggesting a close functional relationship between the adipose tissue and the vasculature. Both caveolin-1, a cell membrane scaffolding protein and peroxisome proliferator-activated receptor(PPAR) γ, a ligandactivated transcription factor are abundantly expressed in the endothelial cells and adipocytes. Both caveolin-1 and PPARγ modulate proliferative and anti-apoptotic pathways, cell migration, inflammation, vascular homeostasis, and participate in lipid transport, triacylglyceride synthesis and glucose metabolism. Caveolin-1 and PPARγ regulate the production of adipokines and in turn are modulated by them. This review article summarizes the roles and inter-relationships of caveolin-1,PPARγ and adipokines in PH and metabolic syndrome.展开更多
Objective:To explore the relationship between IL-1β.IL-1Ra gene polymorphism and the occurrence of polycystic ovary syndrome(PCOS) infertility.Methods:A total of 59 PCOS infertility cases visiling the reproductive ce...Objective:To explore the relationship between IL-1β.IL-1Ra gene polymorphism and the occurrence of polycystic ovary syndrome(PCOS) infertility.Methods:A total of 59 PCOS infertility cases visiling the reproductive center of our hospital from Mar.2010 to Mar.2012 and 56 healthy women were selected.ELISA method was used lor the detection of IL-1β.IL-1Ra lewis,and the levels of serum supersensitivity C reaction protein(US-CRP).insulin(FINS),follieule-stimulating hormone(FSH) and fasting blood—glucose(FRG) were detected.PCR analysis technology was adopted to detect the gene polymorphism of the.511 site of IL-1βand the second introne of IL- 1Ra.Results:The levels of IL-1β.IL-1Ra.US-CRP.FINS and FBG in blood scrum of patients in PCOS group were significantly higher than those in control group(P【0.05 or P【0.01).The level of FSH in PCOS group was significantly lower than that in control group(P【0.05).The genotypic frequency of T/T.the 511 site of IL-1βin PCOS group was 42.37%.significantly higher than 1250%in control group 【P【0.01).The frequency of T allele was also significantly higher than that in control group(P【0.01).The genotypic frequency ofⅠ/Ⅴ.the second introne of IL-1Ra in PCOS group was 20.34%,signicianlly higher than 3.57%in control group(P【0.05).The frequency of V allele in PCOS group was significantly higher than that in control group(P【0.05).Conclusions: T allele of the 511 site of IL-1βgene and V allele of the second inlrone of IL-1Ra gene might be the genetic basis of the rising of IL-1β.IL-1Ra and US-CRP levels in blood serum of PCOS patients,and are associated with the infertility occurrence of PCOS patients.展开更多
AIM:To describe our patients affected with ectopic biliary tree gastrinoma and review the literature on this topic.METHODS:Between January 1992 and June 2012,28 patients affected by duodenopancreatic endocrine tumors ...AIM:To describe our patients affected with ectopic biliary tree gastrinoma and review the literature on this topic.METHODS:Between January 1992 and June 2012,28 patients affected by duodenopancreatic endocrine tumors in multiple endocrine neoplasia type 1(MEN1)syndrome underwent surgery at our institution.This retrospective review article analyzes our experience regarding seventeen of these patients subjected to duodenopancreatic surgery for Zollinger-Ellison syndrome(ZES).Surgical treatment consisted of duodenopancreatectomy(DP)or total pancreatectomy(TP).Regional lymphadenectomy was always performed.Any hepatic tumoral lesions found were removed during surgery.In MEN1 patients,removal of duodenal lesions can sometimes lead to persistence or recurrence of hypergastrinemia.One possible explanation for this unfavorable outcome could be unrecognized ectopic localization of gastrin-secreting tumors.This study described three cases among the seventeen patients who were found to have an ectopic gastrinoma located in the biliary tree.RESULTS:Seventeen MEN1 patients affected with ZES were analyzed.The mean age was 40 years.Fifteen patients underwent DP and two TP.On histopathological examination,duodeno pancreatic endocrine tumors were found in all 17 patients.Eighty-one gastrinomas were detected in the first three portions of the duodenum.Only one gastrinoma was found in the pancreas.The mean number of gastrinomas per patient was 5(range 1-16).Malignancy was established in 12 patients(70.5%)after lymph node,liver and omental metastases were found.Three patients exhibited biliary tree gastrinomas as well as duodenal gastrinoma(s).In two cases,the ectopic gastrinoma was removed at the same time as pancreatic surgery,while in the third case,the biliary tree gastrinoma was resected one year after DP because of recurrence of ZES.CONCLUSION:These findings suggest the importance of checking for the presence of ectopic gastrinomas in the biliary tree in MEN1 patients undergoing ZES surgery.展开更多
AIM: To report a novel mutation in FBN1 gene in a Chinese consanguineous family with common Marfan syndrome(MFS) phenotype and an unusual bilateral macular degeneration. METHODS: Ophthalmic, cardiovascular and systemi...AIM: To report a novel mutation in FBN1 gene in a Chinese consanguineous family with common Marfan syndrome(MFS) phenotype and an unusual bilateral macular degeneration. METHODS: Ophthalmic, cardiovascular and systemic examinations were performed, and genomic DNA extracted from all living family members. The 24-32 exon mutations of FBN1 gene were screened by Sanger Sequencing in all family members and 100 unrelated healthy Chinese individuals. RESULTS: In the four-generation family, classic MFS phenotypes were observed in all 5 patients, 2 of them had peculiar phenotype of bilateral macular degeneration. Mutation screening in FBN1 identified a heterozygous missense mutation(c.3932 A>G, p.Y1311 C) with co-segregation. This mutation was found with the MFS phenotypes in all 5 patients but not in unaffected members or unrelated controls. CONCLUSION: A Chinese consanguineous MFS family with uncommon bilateral macular degeneration and an unreported c.3932 A>G mutation in FBN1 was identified. Our finding expands the FBN1 mutation spectrum and its possible role in the pathogenesis of Marfan syndrome.展开更多
Cardiovascular death is the leading cause of mortality for patients with type 2 diabetes mellitus. The etiologyof cardiovascular disease in diabetes may be divided into hyperglycemia per se and factors operating throu...Cardiovascular death is the leading cause of mortality for patients with type 2 diabetes mellitus. The etiologyof cardiovascular disease in diabetes may be divided into hyperglycemia per se and factors operating through components of metabolic syndrome(Met S). Hyperglycemia causes direct injury to vascular endothelium and possibly on cardiac myocytes. Met S is a cluster of risk factors like obesity, hyperglycemia, hypertension and dyslipidemia. The incidence of this syndrome is rising globally. Glucagon-like peptide-1 receptor agonists(GLP-1RA) are a group of drugs, which address all components of this syndrome favorably. Experimental evidence suggests that they have favorable actions on myocardium as well. Several compounds belonging to GLP-1RA class are in market now and a large number awaiting their entry. Although, originally this class of drugs emerged as a treatment for type 2 diabetes mellitus, more recent data generated revealed beneficial effects on multiple metabolic parameters. We have studied literature published between 2000 and 2016 to look into effects of GLP-1RA on components of Met S. Results from recently concluded clinical trials suggest that some of the molecules in this class may have favorable effects on cardiovascular outcome.展开更多
AIM： To explore the syndrome differentiation in traditional Chinese medicine （TCM） and gene protein expression in gastric carcinoma METHODS： Preoperative data of gastric cancer cases were collected from the Genera...AIM： To explore the syndrome differentiation in traditional Chinese medicine （TCM） and gene protein expression in gastric carcinoma METHODS： Preoperative data of gastric cancer cases were collected from the General Surgery Department and classified according to the criteria for syndrome differentiation in TCM. E-cadherin （E-cad） and ICAM-1 gene protein expressions were detected in postoperative specimens from these cases by the immunohistochemical EnVision two-step method. RESULTS： The E-cad positive expression rate was 90% in 100 cases of gastric carcinoma. The difference in E-cad expression was significant between the different syndrome differentiation types in TCM （P 〈 0.01）. Further group-group comparison showed that there was a significant difference in E-cad expression between the stagnation of phlegm-damp type and the deficiency in both qi and blood and the deficiency-cold of stomach and spleen types, where E-cad expression was high. There was no significant difference between the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type, where E-cad expression was relatively low. The ICAM-1 positive expression rate was 58%, and there was no statistically significant difference between the two groups （x^2= 8.999, P 〉 0.05）. CONCLUSION： E-cad expression is relatively low in the internal obstruction of stagnant toxin type and the incoordination between liver and stomach type, where tumor development and metastasis may be associated with low E-cad expression, or with low homogeneous adhesiveness between tumor cells.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
文摘Branchio-oto-renal(BOR)syndrome is an uncommon disorder inherited in an autosomal dominant manner.Its main clinical manifestations include branchial cleft cysts,anterior auricular fistula,hearing impairment,and kidney malformations.BOR syndrome is associated with heterozygous pathogenic variants including EYA1,SIX1,and SIX5.The study focused on a 13-year-old Chinese boy who presented with hearing impairment,renal malformations,and bony atresia of the right external auditory canal with microtia.The boy's clinical manifestations met the diagnostic criteria for BOR syndrome.Two of the boy's family members underwent clinical examination.However,neither displayed a phenotype associated with BOR syndrome.The boy and his two relatives provided blood samples for genomic DNA extraction,followed by Sanger sequencing.A novel mutation in the GREB1L gene was identified in the boy,but neither of his family members exhibited the same variant.Identifying a novel mutation in GREB1L offers valuable insights into the genotype-phenotype correlation of BOR syndrome,improving the precision of early diagnosis and promoting the advancement of personalized treatment strategies.
基金supported by National Natural Science Foundation of China(82270320 to Yin D C,82300280 to Jin X X,82070344,81870295 to Pan Z W)HMU Marshal Initiative Funding(HMUMIF-21017 to Pan Z W)Excellent Young Medical Talents Training Fund of the First Affiliated Hospital of Harbin Medical University(No.2024YQ03 to Jin X X).
文摘Background:Transmural heterogeneity of the transient outward potassium current(I_(to))is a major contributor to J-wave syndrome(JWS).However,the underlying molecular mechanisms remain elusive.The present study aimed to investigate the role of cardiac injury-related bclaf1-interacting lncRNA(lncCIRBIL)in JWS and to delineate the molecular mechanisms.Methods:Whole-cell patch-clamp techniques were used to record ionic currents and action potentials(APs).Protein and mRNA expression related to I_(to)current were assessed.RNA immunoprecipitation,RNA Pulldown,mRNA stability,and decapping assays were performed to dissect the underlying mechanisms.Results:Plasma lncCIRBIL levels were significantly reduced in JWS patients and cold-induced JWS mice.Knockout of lncCIRBIL increased the incidence of J-wave and the susceptibility to ventricular arrhythmia in mice.In lncCIRBIL-deficient mice,the transmural gradient of Kv4.2 expression and I_(to)current density was markedly enhanced in the right ventricle,but not the left ventricle.In contrast,cardiomyocyte-specific transgenic overexpression of lncCIRBIL produced the opposite effects.In human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the conserved human homologous fragment of lncCIRBIL(hcf-CIRBIL)suppressed I_(to),attenuated the AP notch,and prolonged APD20.Mechanistically,lncCIRBIL directly binds to up-frameshift protein1(UPF1),promoting KCND2 mRNA decay by enhancing its decapping.Conclusions:LncCIRBIL modulates the transmural heterogeneity of KCND2 expression by regulating UPF1-mediated mRNA decay.Inhibition of lncCIRBIL exacerbates JWS by enhancing right ventricular I_(to)heterogeneity,whereas its overexpression exerts protective effects.These findings identify lncCIRBIL as a potential therapeutic target for J-wave syndrome.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82000429 and 81470574)Young Elite Scientists Sponsorship Program by CAST,China(Program No.:YESS20230395/2023QNRC001)+4 种基金Beijing Nova Program,China(Program No.:20230484308)Youth Elite Program of Beijing Friendship Hospital,China(Program No.:YYQCJH2022-9)Young Elite Scientists Sponsorship Program by BAST,China(Program No.:BYESS2024045)Capital's Funds for Health Improvement and Research,China(Grant No.:CFH2022-4-20217)Chinese Institutes for Medical Research,Beijing(CIMR)Organized Research Project,China(Project No.:CX23YQ07)。
文摘Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA,with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin(mTOR)signaling cascade.We uncovered that activation of the mTOR complex 1(mTORC1)within smooth muscle cells,instigated by the oscillatory wall shear stress(OSS)that stems from disturbed flow(DF),is a catalyst for TAA progression.This revelation was corroborated through both an MFS mouse model(Fbn1+/C1039G)and clinical MFS specimens.Crucially,our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS.Therapeutic administration of rapamycin suppresses mTORC1 activity,leading to the attenuation of aberrant SMC behavior,reduced inflammatory infiltration,and restoration of extracellular matrix integrity—collectively decelerating TAA advancement in our mouse model.These insights posit the mTORC1 axis as a strategic target for intervention,offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.
基金Supported by the Gansu Provincial Science and Technology Plan Project,No.24JRRA886 and No.23JRRA1287Gansu Provincial People’s Hospital:Excellent Doctoral Student Cultivation Program,No.22GSSYD-14.
文摘BACKGROUND Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as RAF1.Mutations in RAF1 are typically associated with hypertrophic cardiomyopathy(HCM).However,in this case,the patient exhibited atrial and ventricular septal defects(VSDs).CASE SUMMARY This case report describes an 11-year-old boy diagnosed with Noonan syndrome,in whom genetic testing revealed a c.770C>T(p.Ser257 Leu)mutation in RAF1.The patient presented with intermittent chest discomfort and shortness of breath,symptoms that significantly worsened after physical activity.Clinical evaluation revealed marked growth retardation and multiple physical abnormalities.Electrocardiographic and echocardiographic assessments revealed VSDs,atrial septal defects,and left ventricular outflow tract obstruction.Following multidisciplinary consultation,the patient underwent cardiac surgical intervention,which led to clinical improvement;however,they subsequently developed a third-degree atrioventricular block,necessitating the implantation of a permanent pacemaker.During follow-up,echocardiographic findings demonstrated near-complete resolution of the shunt across the atrial and ventricular septa,significant improvement in left ventricular outflow tract obstruction,and notable reduction in ventricular septal thickness.A genetic mutation at the c.770C>T(p.Ser257 Leu)locus of RAF1 is typically associated with HCM and pulmonary hypertension.However,this patient’s clinical phenotype manifested as HCM,atrial septal defect,and VSD,suggesting that this mutation may involve a different pathophysiological mechanism.CONCLUSION This case confirms the genotype-phenotype heterogeneity of Noonan syndrome and highlights the complex management requirements of RAF1 mutation-associated cardiac pathologies.Early surgical intervention can ameliorate structural defects,but it must be integrated with genetic counseling and lifelong monitoring to optimize patient outcomes.
基金Supported by the Shandong Provincial Natural Science Foundation of China,No.ZR2023QH015Qingdao Municipal Natural Science Foundation of China,No.23-2-1-134-zyyd-jch.
文摘BACKGROUND Protein-losing enteropathy(PLE)is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia.Patients with Noonan syndrome may present with disorder of lymph vessel formation.However,PLE is rarely reported with Noonan syndrome.CASE SUMMARY A 15-year-old female was hospitalized multiple times for recurrent edema and diarrhea secondary to hypoalbuminemia.Additional manifestations included a ventricular septal defect at birth,intermuscular hemangioma,slightly wide interocular and intermammary distances,and absence of the distal phalanx of the left little finger since birth.Abdominal computed tomography revealed cavernous transformation of the portal vein,and liver biopsy indicated“porto-sinusoidal vascular disease”.Whole exome and Sanger sequencing revealed a heterozygous mutation(exon9:C.850C>T:P.R284C)in leucine zipper-like transcription regulator 1,suggesting Noonan syndrome type 10.Further examinations revealed thoracic duct dysplasia and intestinal lymphangiectasia causing PLE in this patient.A multidisciplinary team decided to address thoracic duct dysplasia with outlet obstruction.Approximately two years after the microsurgical relief of the thoracic duct outlet obstruction,the patient achieved persistent normal serum albumin level without edema or diarrhea.Furthermore,the relevant literatures on Noonan syndrome and PLE were reviewed.CONCLUSION Herein,we reported the first case of PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1(c.850C>T:P.R284C)with newly reported manifestations.This case presented the successful treatment of clinical hypoalbuminemia attributed to thoracic duct dysplasia,intestinal lymphangiectasia and PLE.
基金supported by the Science and Technology Department of Sichuan Province(2023NSFSC1757)the"Xinglin Scholar"Talent Research Promotion Plan of Chengdu University of Traditional Chinese Medicine(grant number MPRC2021020).
文摘Diarrhea predominant irritable bowel syndrome(IBS-D)have a serious impact on the patient’s quality life due to the lack of safe and effective drugs.The transient receptor potential vanilloid subtype 1(TRPV1)is an ion channel receptor implicated in the perception of visceral injury.Recent studies indicated that TRPV1 mediates visceral hypersensitivity in IBS-D patients by enhancing the excitability of intestinal sensory neurons.Consequently,inhibiting the TRPV1 may be a promising option for the treatment of IBS-D.Current research demonstrates that various traditional Chinese medicine(TCM)methods,such as herbal prescriptions,acupuncture,and moxibustion,can reduce visceral sensitivity by regulating TRPV1 expression and its activation sensitization.This suggests that TCM methods may serve as safe and effective options for alleviating IBS-D.Therefore,this article summarizes potential therapeutic strategies of TCM as a regulator of TRPV1 for managing IBS-D.It also provides insights into potential TCM methods and natural phytochemical molecular nuclei for future drug research targeting TRPV1 in IBS-D.
基金Supported by the National Natural Science Foundation of China,No.81270465the Sichuan Science and Technology Program,No.2024NSFSC0631,No.2023JDRC0088,and No.MZGC20240097+4 种基金the Basic Research Cultivation Support Program of Fundamental Research Funds for the Central Universities,No.2682023ZTPY071the Baiqiuen Public Welfare Foundation Program,No.BCF-LX-XH-20221014-12the Third People’s Hospital of Chengdu Clinical Research Program,No.CSY-YN-01-2023-012the Yibin Science and Technology Program,No.2021ZYY009the Chengdu Medical Research Project Foundation,No.2022284.
文摘Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in stress-induced intestinal barrier dysfunction.METHODS The colonic mucus Tβ4 levels in IBS patients were determined and their effects on the epithelial barrier were assessed in vitro and in vivo.Specifically,rats genetically deficient in Tβ4(Tβ4^(-/-))or mice deficient in MCs(Kit^(w-sh/w-sh))were used to observe the effects of reintroducing Tβ4 or wild-type peritoneal MCs(wt-PMCs)into these animals.Additionally,the regulatory mechanism underlying Tβ4 secretion in MCs was investigated.RESULTS We demonstrated that high levels of Tβ4 in IBS mucus and intestinal MCs mediate stress-associated disruptive changes to the epithelial barrier.Moreover,Tβ4 treatment of wild-type or MC-deficient Kit^(w-sh/w-sh)mice caused a reduction in tight junction proteins and the interleukin 22 receptor A1(IL22RA1)/Reg3γcascade,but an increase in myosin light chain kinase.Furthermore,Tβ4^(-/-)rats were resistant to stress,though reintroduction of Tβ4 or wt-PMCs restored stress or corticotropin-releasing hormone(CRH)-induced barrier disturbance.Consistently,Tβ4 release from MCs was dependent on the CRH receptor 1,but not degranulation.The effect of Tβ4 was accompanied by IL22RA1/Janus kinase 1(JAK1)/signal transducer and activation of transcription 3(STAT3)pathway inhibition,suggesting a mechanism for physical and immune barrier suppression.CONCLUSION Collectively,these results suggest that Tβ4,which is abundant in IBS mucus and the secretome of MCs,plays a crucial role in the pathogenesis of IBS via IL22RA1/JAK1/STAT3 signaling,with potential implications for diagnostic and therapeutic targeting.
基金the National Natural Science Foundation of China(No.82074341).
文摘Sjögren’s syndrome(SS)is an autoimmune disease characterized primarily by oral and periocular dryness.Astragalus-Salvia(AS)and Ophiopogon-Dendrobium(OD)represent two frequently utilized herb pairs in SS treatment.While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms,its underlying mechanism remains unclear.This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic(NOD)/Ltj mice with SS.The study utilized NOD/Ltj mice as SS models,administering AS-OD treatment for 10 weeks at doses of 113.1,226.2,and 339.3 mg·d−1·20 g−1.Results demonstrated that AS-OD improved SS symptoms,evidenced by enhanced salivary flow rate,decreased anti-SSA/Ro and anti-SSB/La antibody levels,increased swimming duration,and reduced lactate(LA)and blood urea nitrogen(BUN)levels in NOD/Ltj mice.AS-OD reduced lymphocyte infiltration,enhanced Aquaporin-5(AQP5)expression in the submandibular gland,decreased inflammatory cytokine levels in the submandibular gland,and reduced the T helper type 17/regulatory T lymphocyte(Th17/Treg)cell ratio in the spleen.Transcriptomic and proteomic analyses indicated AS-OD’s involvement in regulating phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)and Janus kinase 3/signal transducer and activator of transcription 3(JAK1/STAT3)pathways,with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells.Furthermore,AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway.In A-253 cells,AS-OD reduced inflammatory cytokine levels,CXC chemokine ligand 9/10(CXCL9/10),and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway.AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
文摘Type 1 diabetes(T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1 D as a monoglandular disease and the relation to polyglandular autoimmune syndrome(PAS) have also been wellexplored. The incidence of T1 D has steadily increased in most parts of the world, especially in industrialized nations. T1 D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1 D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterialinduced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type Ⅲ, which encompasses T1 D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1 D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome.
文摘We conducted an analysis of the Kallmann syndrome 1 （KAL-1） genotype in 17 patients with Kallmann syndrome （KS）, 9 patients with normosmic idiopathic hypogonadotropic hypogonadism （nlHH） and 20 age-matched normal men in Northwestern China. To do this, we used multiplex PCR analysis with exon-flanking primers and automated sequencing techniques with peripheral blood DNA samples. Intragenic deletions were found at the KAL-1 locus in two KS patients. One case with an atrial septal defect exhibited an intragenic deletion of exon 6. Another KS patient with cryptorchidism had intragenic deletions of exons 5 and 6. For the nlHH patients, no abnormalities were observed in the exonic and flanking sequences of KAL-1. This report describes two intragenic deletions of KAL-1 in two KS patients and suggests that KAL-1 deletion might be more prevalent in KS patients with other congenital organ abnormalities than those described previously in other series from Northwestern China.
文摘A number of disparate diseases can lead to pulmonary hypertension(PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an important factor adversely impacting the prognosis of PH. Furthermore, metabolic syndrome is associated with vascular diseases including PH. Inflammation plays a significant role both in PH and metabolic syndrome. Adipose tissue modulates lipid and glucose metabolism, and also produces pro-and anti-inflammatory adipokines that modulate vascular function and angiogenesis, suggesting a close functional relationship between the adipose tissue and the vasculature. Both caveolin-1, a cell membrane scaffolding protein and peroxisome proliferator-activated receptor(PPAR) γ, a ligandactivated transcription factor are abundantly expressed in the endothelial cells and adipocytes. Both caveolin-1 and PPARγ modulate proliferative and anti-apoptotic pathways, cell migration, inflammation, vascular homeostasis, and participate in lipid transport, triacylglyceride synthesis and glucose metabolism. Caveolin-1 and PPARγ regulate the production of adipokines and in turn are modulated by them. This review article summarizes the roles and inter-relationships of caveolin-1,PPARγ and adipokines in PH and metabolic syndrome.
文摘Objective:To explore the relationship between IL-1β.IL-1Ra gene polymorphism and the occurrence of polycystic ovary syndrome(PCOS) infertility.Methods:A total of 59 PCOS infertility cases visiling the reproductive center of our hospital from Mar.2010 to Mar.2012 and 56 healthy women were selected.ELISA method was used lor the detection of IL-1β.IL-1Ra lewis,and the levels of serum supersensitivity C reaction protein(US-CRP).insulin(FINS),follieule-stimulating hormone(FSH) and fasting blood—glucose(FRG) were detected.PCR analysis technology was adopted to detect the gene polymorphism of the.511 site of IL-1βand the second introne of IL- 1Ra.Results:The levels of IL-1β.IL-1Ra.US-CRP.FINS and FBG in blood scrum of patients in PCOS group were significantly higher than those in control group(P【0.05 or P【0.01).The level of FSH in PCOS group was significantly lower than that in control group(P【0.05).The genotypic frequency of T/T.the 511 site of IL-1βin PCOS group was 42.37%.significantly higher than 1250%in control group 【P【0.01).The frequency of T allele was also significantly higher than that in control group(P【0.01).The genotypic frequency ofⅠ/Ⅴ.the second introne of IL-1Ra in PCOS group was 20.34%,signicianlly higher than 3.57%in control group(P【0.05).The frequency of V allele in PCOS group was significantly higher than that in control group(P【0.05).Conclusions: T allele of the 511 site of IL-1βgene and V allele of the second inlrone of IL-1Ra gene might be the genetic basis of the rising of IL-1β.IL-1Ra and US-CRP levels in blood serum of PCOS patients,and are associated with the infertility occurrence of PCOS patients.
文摘AIM:To describe our patients affected with ectopic biliary tree gastrinoma and review the literature on this topic.METHODS:Between January 1992 and June 2012,28 patients affected by duodenopancreatic endocrine tumors in multiple endocrine neoplasia type 1(MEN1)syndrome underwent surgery at our institution.This retrospective review article analyzes our experience regarding seventeen of these patients subjected to duodenopancreatic surgery for Zollinger-Ellison syndrome(ZES).Surgical treatment consisted of duodenopancreatectomy(DP)or total pancreatectomy(TP).Regional lymphadenectomy was always performed.Any hepatic tumoral lesions found were removed during surgery.In MEN1 patients,removal of duodenal lesions can sometimes lead to persistence or recurrence of hypergastrinemia.One possible explanation for this unfavorable outcome could be unrecognized ectopic localization of gastrin-secreting tumors.This study described three cases among the seventeen patients who were found to have an ectopic gastrinoma located in the biliary tree.RESULTS:Seventeen MEN1 patients affected with ZES were analyzed.The mean age was 40 years.Fifteen patients underwent DP and two TP.On histopathological examination,duodeno pancreatic endocrine tumors were found in all 17 patients.Eighty-one gastrinomas were detected in the first three portions of the duodenum.Only one gastrinoma was found in the pancreas.The mean number of gastrinomas per patient was 5(range 1-16).Malignancy was established in 12 patients(70.5%)after lymph node,liver and omental metastases were found.Three patients exhibited biliary tree gastrinomas as well as duodenal gastrinoma(s).In two cases,the ectopic gastrinoma was removed at the same time as pancreatic surgery,while in the third case,the biliary tree gastrinoma was resected one year after DP because of recurrence of ZES.CONCLUSION:These findings suggest the importance of checking for the presence of ectopic gastrinomas in the biliary tree in MEN1 patients undergoing ZES surgery.
基金Supported by National Natural Science Foundation of China(No.81300798)Project supported by the Natural Science Foundation of Hunan Province,China(No.2018JJ3737)Department of Science and Technology,Hunan(No.2015TP2007)
文摘AIM: To report a novel mutation in FBN1 gene in a Chinese consanguineous family with common Marfan syndrome(MFS) phenotype and an unusual bilateral macular degeneration. METHODS: Ophthalmic, cardiovascular and systemic examinations were performed, and genomic DNA extracted from all living family members. The 24-32 exon mutations of FBN1 gene were screened by Sanger Sequencing in all family members and 100 unrelated healthy Chinese individuals. RESULTS: In the four-generation family, classic MFS phenotypes were observed in all 5 patients, 2 of them had peculiar phenotype of bilateral macular degeneration. Mutation screening in FBN1 identified a heterozygous missense mutation(c.3932 A>G, p.Y1311 C) with co-segregation. This mutation was found with the MFS phenotypes in all 5 patients but not in unaffected members or unrelated controls. CONCLUSION: A Chinese consanguineous MFS family with uncommon bilateral macular degeneration and an unreported c.3932 A>G mutation in FBN1 was identified. Our finding expands the FBN1 mutation spectrum and its possible role in the pathogenesis of Marfan syndrome.
文摘Cardiovascular death is the leading cause of mortality for patients with type 2 diabetes mellitus. The etiologyof cardiovascular disease in diabetes may be divided into hyperglycemia per se and factors operating through components of metabolic syndrome(Met S). Hyperglycemia causes direct injury to vascular endothelium and possibly on cardiac myocytes. Met S is a cluster of risk factors like obesity, hyperglycemia, hypertension and dyslipidemia. The incidence of this syndrome is rising globally. Glucagon-like peptide-1 receptor agonists(GLP-1RA) are a group of drugs, which address all components of this syndrome favorably. Experimental evidence suggests that they have favorable actions on myocardium as well. Several compounds belonging to GLP-1RA class are in market now and a large number awaiting their entry. Although, originally this class of drugs emerged as a treatment for type 2 diabetes mellitus, more recent data generated revealed beneficial effects on multiple metabolic parameters. We have studied literature published between 2000 and 2016 to look into effects of GLP-1RA on components of Met S. Results from recently concluded clinical trials suggest that some of the molecules in this class may have favorable effects on cardiovascular outcome.
基金Supported by the National Natural Science Foundation of China,No. 30271626
文摘AIM： To explore the syndrome differentiation in traditional Chinese medicine （TCM） and gene protein expression in gastric carcinoma METHODS： Preoperative data of gastric cancer cases were collected from the General Surgery Department and classified according to the criteria for syndrome differentiation in TCM. E-cadherin （E-cad） and ICAM-1 gene protein expressions were detected in postoperative specimens from these cases by the immunohistochemical EnVision two-step method. RESULTS： The E-cad positive expression rate was 90% in 100 cases of gastric carcinoma. The difference in E-cad expression was significant between the different syndrome differentiation types in TCM （P 〈 0.01）. Further group-group comparison showed that there was a significant difference in E-cad expression between the stagnation of phlegm-damp type and the deficiency in both qi and blood and the deficiency-cold of stomach and spleen types, where E-cad expression was high. There was no significant difference between the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type, where E-cad expression was relatively low. The ICAM-1 positive expression rate was 58%, and there was no statistically significant difference between the two groups （x^2= 8.999, P 〉 0.05）. CONCLUSION： E-cad expression is relatively low in the internal obstruction of stagnant toxin type and the incoordination between liver and stomach type, where tumor development and metastasis may be associated with low E-cad expression, or with low homogeneous adhesiveness between tumor cells.
