Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central ne...Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomy...BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.展开更多
ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a ...ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a promising indicator for identifying individuals with excessive glycosylation,facilitating personalized evaluation and prediction of diabetic complications.However,the factors influencing the HGI in patients with type 1 diabetes(T1D)remain unclear.Autoimmune destruction of pancreaticβcells is central in T1D pathogenesis,yet insulin resistance can also be a feature of patients with T1D and their coexistence is called“double diabetes”(DD).However,knowledge regarding the relationship between DD features and the HGI in T1D is limited.AIM To assess the association between the HGI and DD features in adults with T1D.METHODS A total of 83 patients with T1D were recruited for this cross-sectional study.Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI.DD features included a family history of type 2 diabetes,overweight/obesity/central adiposity,hypertension,atherogenic dyslipidemia,an abnormal percentage of body fat(PBF)and/or visceral fat area(VFA)and decreased estimated insulin sensitivity.Skin autofluorescence of advanced glycation end products(SAF-AGEs),diabetic complications,and DD features were assessed,and their association with the HGI was analyzed.RESULTS A discrepancy was observed between HbA1c and GMI among patients with T1D and DD.A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy(P=0.030),particularly retinopathy(P=0.031).Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI,compared with those without DD features(adjusted odds ratio=8.12;95%confidence interval:1.52-43.47).Specifically,an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI.Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI.CONCLUSION In patients with T1D,DD features are associated with a higher HGI,which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90%of cases.A minority of wild-type GISTs are associated wit...BACKGROUND Gastrointestinal stromal tumors(GISTs)are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90%of cases.A minority of wild-type GISTs are associated with neurofibromatosis type 1(NF1),an autosomal dominant genetic disease resulting from pathogenic mutations in the NF1 gene,which encodes the neurofibromin protein.NF1 patients often exhibit multi-system involvement,with café-au-lait macules and neurofibromas being characteristic symptoms.GISTs are a rare complication of NF1,with the tumors most frequently occurring in the small intestine(90%of cases),while occurrences in the stomach are rare.CASE SUMMARY A 51-year-old woman presented to the emergency department with complaints of dizziness,fatigue,chest tightness,and dark stools.Initial examination revealed a red blood cell count of 1.99×1012/L and a hemoglobin level of 43 g/L.She underwent blood transfusions and fluid replacement to stabilize her condition.Further investigations identified typical café-au-lait macules on her trunk,limbs,and face,along with neurofibromas.Endoscopy showed coffee-colored fluid in the gastric cavity,a large submucosal elevation with an exudative covering,and ulcer formation on the gastric fundus.Exploratory laparoscopy confirmed the tumor’s origin in the gastric fundus,and resection of the giant GIST was performed.Pathological analysis revealed a necrotic GIST measuring 18 cm×14 cm,classified as high-risk,with approximately 5 mitotic figures per 10 high-power fields and no tumor at the margins.Immunohistochemistry results were CD117(+),delay of germination 1(+),CD34(+),and succinate dehydrogenase complex iron sulfur subunit B intact expression.Genetic testing using next-generation sequencing confirmed an NF1 gene mutation.The patient underwent successful tumor resection and was discharged home with postoperative regorafenib therapy.A follow-up at one year showed no recurrence.CONCLUSION Given the diversity of clinical symptoms associated with NF1 and the complexity of NF1-related GISTs,surgical resection with complete tumor removal remains the preferred treatment option.However,the absence of a standardized treatment protocol for adjuvant therapy presents numerous challenges for clinicians.展开更多
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,im...Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.展开更多
In this article,we review the study by Jin et al,which examined the role of intestinal glucagon-like peptide-1(GLP-1)in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus(T1DM).With ...In this article,we review the study by Jin et al,which examined the role of intestinal glucagon-like peptide-1(GLP-1)in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus(T1DM).With the global rise of T1DM,there is an increased burden on society and healthcare systems.Due to insulin therapy and islet dysfunction,T1DM patients are highly vulnerable to severe hypoglycemia,a leading cause of mortality.In healthy individuals,counterregulatory mechanisms restore blood glucose during hypoglycemia,but repeated episodes impair these responses.Jin et al demonstrated that overexpression of GLP-1 attenuates the sympathetic-adrenal reflex and disrupts the secretion of counterregulatory hormones such as glucagon during hypoglycemia,leading to counterregulatory dysfunction.These findings highlight the critical role of GLP-1 in the impaired counterregulatory response to hypoglycemia in T1DM patients and provide new insights into the potential application of GLP-1-related therapies in T1DM patients.展开更多
Objective This study aimed to investigate possible serum 25-hydroxyvitamin D[25(OH)D]cutoffs for the associations between 25(OH)D and Bone turnover markers(BTMs),and how GC gene variation influences such cutoffs in Ch...Objective This study aimed to investigate possible serum 25-hydroxyvitamin D[25(OH)D]cutoffs for the associations between 25(OH)D and Bone turnover markers(BTMs),and how GC gene variation influences such cutoffs in Chinese women of childbearing age.Methods In total,1,505 non-pregnant or non-lactating women(18–45 years)were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance.Serum 25(OH)D,osteocalcin(OC),procollagen type 1 N-terminal propeptide(P1NP),β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide(β-CTX),and single nucleotide polymorphisms were determined.Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds.Results The median serum 25(OH)D was 16.63(11.96–22.55)ng/mL and the prevalence of low serum 25(OH)D(<12 ng/mL)was 25.2%.Women with the lowest 25(OH)D had the highestβ-CTX.After adjustment for the confounders,25(OH)D cutoffs for OC[14.04(12.84–15.23)ng/mL],β-CTX[13.94(12.49–15.39)ng/mL],and P1NP[13.87(12.37–15.37)ng/mL]in the whole population,cutoffs for OC[12.30(10.68–13.91)ng/mL],β-CTX[12.23(10.22–14.23)ng/mL],and P1NP[11.85(10.40–13.31)ng/mL]in women with the GC rs2282679 G allele,and cutoffs for OC[12.75(11.81–13.68)ng/mL],β-CTX[13.05(11.78–14.32)ng/mL],and P1NP[12.81(11.57–14.06)ng/mL]in women with the GC rs2282679 T allele,were observed.Below these cutoffs,BTMs were negatively associated with 25(OH)D,while above these cutoffs,BTMs plateaued.Conclusion In Chinese women of childbearing age,there were thresholds effect of serum 25(OH)D concentrations on BTMs.The results indicated that serum 25(OH)D concentrations<13.87 ng/mL in this population had adverse influences on maintaining bone remodeling.BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.展开更多
A recent nationwide cohort study reported an increased incidence and altered seasonality of type 1 diabetes mellitus(T1DM)during the coronavirus disease 2019(COVID-19)pandemic.The study found that new-onset T1DM cases...A recent nationwide cohort study reported an increased incidence and altered seasonality of type 1 diabetes mellitus(T1DM)during the coronavirus disease 2019(COVID-19)pandemic.The study found that new-onset T1DM cases were significantly higher during the pandemic than in prior years,and the typical winter peak in T1DM diagnoses was blunted.This occurred alongside markedly reduced circulation of other respiratory viruses under lockdown measures.Carmon et al noted weak positive correlations between T1DM incidence and certain viruses(e.g.,influenza and respiratory syncytial virus),suggesting that reduced exposure to common infections-and possibly severe acute respiratory syndrome coronavirus 2 infection itself-might have contributed to the rise in T1DM.To highlight key methodological limitations of that study,which may affect the interpretation of the findings.We reviewed the study design and data of Carmon et al and discussed potential biases,including ecological inference,confounding factors,delayed diagnoses,lack of COVID-19-stratified analysis,and biases in viral surveillance data,supported by recent literature.The association observed by Carmon et al is at risk of ecological fallacy due to the absence of individual infection linkage.Uncontrolled confounders(healthcare access,socioeconomic changes)and not stratifying by COVID-19 infection status limit causal inference.Pandemic-related diagnostic delays likely inflated apparent T1DM incidence,as evidenced by higher rates of diabetic ketoacidosis in new cases.Biases in virological testing data(reduced testing and non-representative sampling)complicate conclusions about“reduced”viral circulation.The pandemic’s impact on T1DM incidence is important but requires cautious interpretation.Future studies should employ individual-level analyses,adjust for confounders,distinguish true incidence increases from diagnostic delays,stratify by infection status,and use comprehensive viral exposure data to draw more robust conclusions.展开更多
This study reviews the anti-inflammatory potential of cannabidiol(CBD)in the management of type 1 diabetes(T1D).A comprehensive search was conducted across PubMed,Scopus,and ScienceDirect databases using the terms“ty...This study reviews the anti-inflammatory potential of cannabidiol(CBD)in the management of type 1 diabetes(T1D).A comprehensive search was conducted across PubMed,Scopus,and ScienceDirect databases using the terms“type 1 diabetes”,“cannabidiol”,“anti-inflammatory effect”,and“CBD”.Articles published between 2005 and 2025 were screened,and studies involving animal models that examined CBD as a therapeutic intervention for T1D and reported on its antiinflammatory effects were included.Of the 62 retrieved articles,only 6 met the predefined inclusion criteria.Although limited in number,the available studies show promising outcomes.CBD demonstrates potential as an adjuvant therapy for T1D due to its immunomodulatory and anti-inflammatory actions.Nonetheless,further research is required to establish safe and effective clinical application protocols.展开更多
BACKGROUND Type 1 diabetes is an autoimmune disease leading to insulin deficiency,and it is mainly diagnosed in young adults.One of the major acute complications of type 1 diabetes is diabetic ketoacidosis(DKA),which ...BACKGROUND Type 1 diabetes is an autoimmune disease leading to insulin deficiency,and it is mainly diagnosed in young adults.One of the major acute complications of type 1 diabetes is diabetic ketoacidosis(DKA),which is a metabolic emergency that can be triggered by stress,infection,or poor blood glucose control.The association of DKA with conditions such as acute pancreatitis and malaria is rare and therefore represents a major diagnostic and therapeutic challenge.CASE SUMMARY A 20-year-old female was admitted to the emergency room for abdominal pelvic pain,fever,asthenia,polyuria,and polydipsia with a progressive deterioration of her state of consciousness.At admission,she was in a mild coma(Glasgow score:9),had a fever of 38.5°C,and had hyperglycemia(6 g/dL).The tests revealed severe DKA,hypertriglyceridemia,hyperamylasemia,and hyperlipasemia as well as malaria parasite density.The computed tomography scan confirmed acute stage E pancreatitis.The diagnosis was that of inaugural ketoacidosis of type 1 diabetes unbalanced by pancreatitis and malaria.Treatment included insulin therapy,rehydration,and antimalarial and analgesic treatment.After 10 days,the outcome was favorable with a normalization of the blood sugar,and an endocrine follow-up was recommend.CONCLUSION Rapid and multidisciplinary management of DKA,pancreatitis,and malaria led to a favorable and stable prognosis.展开更多
BACKGROUND Akkermansia muciniphila(A.muciniphila)has been shown to have positive effects on various metabolic diseases and partially prevent the onset of spontaneous type 1 diabetes mellitus(T1DM)in nonobese diabetic ...BACKGROUND Akkermansia muciniphila(A.muciniphila)has been shown to have positive effects on various metabolic diseases and partially prevent the onset of spontaneous type 1 diabetes mellitus(T1DM)in nonobese diabetic mice;however,its therapeutic efficacy in T1DM mice that have already developed T1DM remains unclear.AIM To assess the effects of A.muciniphila intervention on the intestinal barrier,immune parameters[regulatory T(Tregs)cells/T helper 1 cells balance,signal transducer and activator of transcription 1(STAT1)/nuclear factor kappa-B(NF-κB)signal]and intestinal flora in a streptozotocin(STZ)-induced mouse model of T1DM.METHODS Thirty male C57BL/6 mice were randomized into three groups(n=10 for each):Normal control(NC group),STZ-induced T1DM(STZ group),and A.muciniphilatreated T1DM(A.muciniphila group).T1DM was induced with STZ(50 mg/kg/day intraperitoneally,5 days).Body weight,blood glucose,and water intake were monitored weekly.T1DM was modelled in all STZ-and A.muciniphila-treated mice(random blood glucose>16.7 mmol/L).A.muciniphila group mice received oral A.muciniphila(5×10^(7) colony-forming units/mouse)for 3 days.Following sacrifice,pancreatic histopathology,cytokines in splenic tissue,colonic zonula occludens-1(ZO-1)/zonulin expression,cluster of differentiation(CD)4^(+)/CD8^(+)T-cell ratios,forkhead box P3(FoxP3^(+))Tregs,STAT1/NF-κB p65 signaling,and gut microbiota composition were analyzed.RESULTS Compared with STZ group alone,A.muciniphila group did not affect metabolic parameters.Histopathologically,STZ group and A.muciniphila group pancreatic islet cells underwent vacuolar degeneration and necrosis,exhibiting reduced counts and significantly decreased insulin positivity(P<0.05 vs NC),with no intergroup differences.Flow cytometry and enzyme-linked immunosorbent assay revealed elevated tumor necrosis factoralpha(TNF-α),transforming growth factor-beta(TGF-β),and zonulin levels and decreased ZO-1 expression in STZ vs NC mice(P<0.05).Compared with STZ alone,A.muciniphila group reduced TNF-α,TGF-β,and zonulin levels while increasing the CD4^(+)/CD8^(+)ratio,FoxP3^(+)Tregs,interleukin-4,and ZO-1(P<0.05).Colonic NF-κB p65 expression was higher in STZ vs NC mice(P<0.05),with no significant A.muciniphila group/NC difference after the intervention of A.muciniphila.The expression of NF-κB p65 in A.muciniphila group was lower than that in STZ group.STAT1 expression was lower in A.muciniphila vs STZ mice(P<0.05).16S sequencing revealed reduced Actinobacteria abundance in A.muciniphila vs STZ mice(P<0.05).CONCLUSION Short-term intervention with A.muciniphila has shown positive effects on immune response parameters,exemplified by Treg-mediated restoration of immune tolerance,which may be associated with intestinal barrier enhancement and the decreased abundance of intestinal Actinobacteria.展开更多
BACKGROUND Type 1 diabetes mellitus(T1DM)is an autoimmune disease with a multifactorial pathogenesis.Viral infections have been proposed as contributing triggers,supported by the disease’s seasonal pattern,which typi...BACKGROUND Type 1 diabetes mellitus(T1DM)is an autoimmune disease with a multifactorial pathogenesis.Viral infections have been proposed as contributing triggers,supported by the disease’s seasonal pattern,which typically shows higher incidence in autumn and winter.The coronavirus disease 2019(COVID-19)pandemic and associated lockdowns created a unique context to examine the incidence and seasonality of T1DM during a period characterized by reduced circulation of common viral infections.AIM To investigate the incidence and seasonality of T1DM before and during COVID-19 pandemic in relation to global viral infection rates.METHODS This population-based retrospective study utilized a nationwide computerized database.Extracted data included the number of new T1DM cases over the 8 years preceding and during the COVID-19 pandemic,demographic characteristics of affected individuals,and nationwide respiratory virus polymerase chain reaction data from weekly nasal wash sample collections.RESULTS A total of 2176 patients were diagnosed with new-onset T1DM during the prepandemic period,compared to 348 cases during the pandemic.In the same periods,33727 respiratory virus-positive polymerase chain reaction results from nasal wash samples were recorded pre-pandemic,compared to 2603 during the pandemic.Additionally,363399 positive COVID-19 cases were reported during the pandemic period.Seasonality analysis revealed a higher rate of new-onset T1DM cases and a weaker seasonal pattern during the pandemic.Trend analysis showed a consistent increase in T1DM incidence prior to COVID-19,with a more variable trend observed during the pandemic.Correlation analysis between T1DM incidence and respiratory viruses demonstrated a weak correlation between T1DM incidence and a few respiratory viruses.CONCLUSION The observed increase in new-onset T1DM cases and the disruption of its typical seasonal pattern during the COVID-19 pandemic suggest a potential association between respiratory virus exposure and the development of T1DM.展开更多
In this manuscript,we comment on a recent publication by Yuan et al.This article provides a detailed scientific diagnostic process for a multiple endocrine neo-plasia type 1 patient,thus offering strong guidance for c...In this manuscript,we comment on a recent publication by Yuan et al.This article provides a detailed scientific diagnostic process for a multiple endocrine neo-plasia type 1 patient,thus offering strong guidance for clinical practice.However,we believe that the authors should also provide information on the patient's long-term prognosis.展开更多
Background: Plexiform neurofibromas(PNF) are highly vascular tumors with the potential for significant growth.Surgical removal of giant PNF is often challenging because of intraoperative hemorrhage.This study proposed...Background: Plexiform neurofibromas(PNF) are highly vascular tumors with the potential for significant growth.Surgical removal of giant PNF is often challenging because of intraoperative hemorrhage.This study proposed and evaluated an innovative surgical approach involving FENCY ligation and the role of preoperative embolization in the resection of giant PNF.Methods: This was a retrospective,interventional,and sequential case series conducted in a plastic and reconstructive surgery unit.We summarized all patients with PNF who underwent resection at our center between2019 and 2024.Surgical case notes from 11 patients with giant PNF who underwent FENCY ligation were reviewed,including three patients who received preoperative embolization.All patients participated in structured telephone interviews.Patient demographics,surgical safety,postoperative recovery,and patient satisfaction were evaluated.Results: Among 456 patients with 494 PNF who underwent surgical resection,we categorized the procedures into median,large,and giant PNF subgroups.To illustrate comprehensive perioperative and surgical approaches,we analyzed seven female and four male patients with giant PNF.The median maximum tumor diameter at the time of surgery was 30.4 cm(range,11.5–55.6 cm).Most PNF were located on the face(63.6%),followed by the back(18.2%),buttocks(18.2%),upper limbs(9.1%),and neck(9.1%).The median intraoperative hemorrhage volume was 366 m L(range,10–2 034 m L),And the median hospital stay was 17 days(range,14–33 days).The mean follow-up duration was 2.5 years(range,0.4–5.5 years).No severe complications were observed,except for one case of infection.Conclusion: PNF resection,particularly giant PNF resection,is a high-risk treatment option.Comprehensive evaluation,perioperative preparation,and surgical techniques are required to ensure efficacy and safety.FENCY ligation and preoperative embolization can be used to resect giant PNF in multiple complex regions with satisfactory outcomes.展开更多
基金supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil(CNPq)(312286/2023-6,307201/2023-6,and Instituto Nacional Saude Cerebral INSC,No.406020/2022-1)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(CAPES)Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro-FAPERJ(E-26/010.002260/2019,E-26/010.001652/2019,E-26/010.101036/2018,E-26/202.774/2018,E-26/210.240/2020,E-26/211.138/2021,26/210.823/2021,E-26/211.325/2021,E-26/210.779/2021,E-26/201.086/2022,E-26/210.312/2022,E-26/203.262/2023,E-26/200.195/2023)(to LEBS)。
文摘Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
基金Supported by the University of Louisville-China Pediatric Research Exchange Program(Cai L,Tan Y,Huang J,and Keller B,no salary support)University of Louisville Executive Vice President for Research and Innovation Internal Grant(Huang J and Cai L)University of Louisville School of Medicine Basic Grant(Huang J and Cai L).
文摘BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.
基金Supported by the National Key R D Program of China,No.2022YFC2010102Natural Science Foundation of Hunan Province,No.2021JC0003+1 种基金National Natural Science Foundation of China,No.82070812the Sinocare Diabetes Foundation,No.LYF2022039.
文摘ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a promising indicator for identifying individuals with excessive glycosylation,facilitating personalized evaluation and prediction of diabetic complications.However,the factors influencing the HGI in patients with type 1 diabetes(T1D)remain unclear.Autoimmune destruction of pancreaticβcells is central in T1D pathogenesis,yet insulin resistance can also be a feature of patients with T1D and their coexistence is called“double diabetes”(DD).However,knowledge regarding the relationship between DD features and the HGI in T1D is limited.AIM To assess the association between the HGI and DD features in adults with T1D.METHODS A total of 83 patients with T1D were recruited for this cross-sectional study.Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI.DD features included a family history of type 2 diabetes,overweight/obesity/central adiposity,hypertension,atherogenic dyslipidemia,an abnormal percentage of body fat(PBF)and/or visceral fat area(VFA)and decreased estimated insulin sensitivity.Skin autofluorescence of advanced glycation end products(SAF-AGEs),diabetic complications,and DD features were assessed,and their association with the HGI was analyzed.RESULTS A discrepancy was observed between HbA1c and GMI among patients with T1D and DD.A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy(P=0.030),particularly retinopathy(P=0.031).Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI,compared with those without DD features(adjusted odds ratio=8.12;95%confidence interval:1.52-43.47).Specifically,an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI.Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI.CONCLUSION In patients with T1D,DD features are associated with a higher HGI,which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90%of cases.A minority of wild-type GISTs are associated with neurofibromatosis type 1(NF1),an autosomal dominant genetic disease resulting from pathogenic mutations in the NF1 gene,which encodes the neurofibromin protein.NF1 patients often exhibit multi-system involvement,with café-au-lait macules and neurofibromas being characteristic symptoms.GISTs are a rare complication of NF1,with the tumors most frequently occurring in the small intestine(90%of cases),while occurrences in the stomach are rare.CASE SUMMARY A 51-year-old woman presented to the emergency department with complaints of dizziness,fatigue,chest tightness,and dark stools.Initial examination revealed a red blood cell count of 1.99×1012/L and a hemoglobin level of 43 g/L.She underwent blood transfusions and fluid replacement to stabilize her condition.Further investigations identified typical café-au-lait macules on her trunk,limbs,and face,along with neurofibromas.Endoscopy showed coffee-colored fluid in the gastric cavity,a large submucosal elevation with an exudative covering,and ulcer formation on the gastric fundus.Exploratory laparoscopy confirmed the tumor’s origin in the gastric fundus,and resection of the giant GIST was performed.Pathological analysis revealed a necrotic GIST measuring 18 cm×14 cm,classified as high-risk,with approximately 5 mitotic figures per 10 high-power fields and no tumor at the margins.Immunohistochemistry results were CD117(+),delay of germination 1(+),CD34(+),and succinate dehydrogenase complex iron sulfur subunit B intact expression.Genetic testing using next-generation sequencing confirmed an NF1 gene mutation.The patient underwent successful tumor resection and was discharged home with postoperative regorafenib therapy.A follow-up at one year showed no recurrence.CONCLUSION Given the diversity of clinical symptoms associated with NF1 and the complexity of NF1-related GISTs,surgical resection with complete tumor removal remains the preferred treatment option.However,the absence of a standardized treatment protocol for adjuvant therapy presents numerous challenges for clinicians.
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
文摘Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.
基金Supported by the National Natural Science Foundation of China,No.82400966Guangdong Basic and Applied Basic Research Foundation,No.2021A1515111025Science and Technology Projects in Guangzhou,No.2024A04J5170.
文摘In this article,we review the study by Jin et al,which examined the role of intestinal glucagon-like peptide-1(GLP-1)in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus(T1DM).With the global rise of T1DM,there is an increased burden on society and healthcare systems.Due to insulin therapy and islet dysfunction,T1DM patients are highly vulnerable to severe hypoglycemia,a leading cause of mortality.In healthy individuals,counterregulatory mechanisms restore blood glucose during hypoglycemia,but repeated episodes impair these responses.Jin et al demonstrated that overexpression of GLP-1 attenuates the sympathetic-adrenal reflex and disrupts the secretion of counterregulatory hormones such as glucagon during hypoglycemia,leading to counterregulatory dysfunction.These findings highlight the critical role of GLP-1 in the impaired counterregulatory response to hypoglycemia in T1DM patients and provide new insights into the potential application of GLP-1-related therapies in T1DM patients.
基金funded by the National Natural Science Foundation of China(No.81872627and No.82473611)the National Financial Projects ‘Assessment and Application of Nutrients Requirement and Food Environment for Chinese Residents’(No.102393220020070000013)。
文摘Objective This study aimed to investigate possible serum 25-hydroxyvitamin D[25(OH)D]cutoffs for the associations between 25(OH)D and Bone turnover markers(BTMs),and how GC gene variation influences such cutoffs in Chinese women of childbearing age.Methods In total,1,505 non-pregnant or non-lactating women(18–45 years)were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance.Serum 25(OH)D,osteocalcin(OC),procollagen type 1 N-terminal propeptide(P1NP),β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide(β-CTX),and single nucleotide polymorphisms were determined.Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds.Results The median serum 25(OH)D was 16.63(11.96–22.55)ng/mL and the prevalence of low serum 25(OH)D(<12 ng/mL)was 25.2%.Women with the lowest 25(OH)D had the highestβ-CTX.After adjustment for the confounders,25(OH)D cutoffs for OC[14.04(12.84–15.23)ng/mL],β-CTX[13.94(12.49–15.39)ng/mL],and P1NP[13.87(12.37–15.37)ng/mL]in the whole population,cutoffs for OC[12.30(10.68–13.91)ng/mL],β-CTX[12.23(10.22–14.23)ng/mL],and P1NP[11.85(10.40–13.31)ng/mL]in women with the GC rs2282679 G allele,and cutoffs for OC[12.75(11.81–13.68)ng/mL],β-CTX[13.05(11.78–14.32)ng/mL],and P1NP[12.81(11.57–14.06)ng/mL]in women with the GC rs2282679 T allele,were observed.Below these cutoffs,BTMs were negatively associated with 25(OH)D,while above these cutoffs,BTMs plateaued.Conclusion In Chinese women of childbearing age,there were thresholds effect of serum 25(OH)D concentrations on BTMs.The results indicated that serum 25(OH)D concentrations<13.87 ng/mL in this population had adverse influences on maintaining bone remodeling.BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
文摘A recent nationwide cohort study reported an increased incidence and altered seasonality of type 1 diabetes mellitus(T1DM)during the coronavirus disease 2019(COVID-19)pandemic.The study found that new-onset T1DM cases were significantly higher during the pandemic than in prior years,and the typical winter peak in T1DM diagnoses was blunted.This occurred alongside markedly reduced circulation of other respiratory viruses under lockdown measures.Carmon et al noted weak positive correlations between T1DM incidence and certain viruses(e.g.,influenza and respiratory syncytial virus),suggesting that reduced exposure to common infections-and possibly severe acute respiratory syndrome coronavirus 2 infection itself-might have contributed to the rise in T1DM.To highlight key methodological limitations of that study,which may affect the interpretation of the findings.We reviewed the study design and data of Carmon et al and discussed potential biases,including ecological inference,confounding factors,delayed diagnoses,lack of COVID-19-stratified analysis,and biases in viral surveillance data,supported by recent literature.The association observed by Carmon et al is at risk of ecological fallacy due to the absence of individual infection linkage.Uncontrolled confounders(healthcare access,socioeconomic changes)and not stratifying by COVID-19 infection status limit causal inference.Pandemic-related diagnostic delays likely inflated apparent T1DM incidence,as evidenced by higher rates of diabetic ketoacidosis in new cases.Biases in virological testing data(reduced testing and non-representative sampling)complicate conclusions about“reduced”viral circulation.The pandemic’s impact on T1DM incidence is important but requires cautious interpretation.Future studies should employ individual-level analyses,adjust for confounders,distinguish true incidence increases from diagnostic delays,stratify by infection status,and use comprehensive viral exposure data to draw more robust conclusions.
文摘This study reviews the anti-inflammatory potential of cannabidiol(CBD)in the management of type 1 diabetes(T1D).A comprehensive search was conducted across PubMed,Scopus,and ScienceDirect databases using the terms“type 1 diabetes”,“cannabidiol”,“anti-inflammatory effect”,and“CBD”.Articles published between 2005 and 2025 were screened,and studies involving animal models that examined CBD as a therapeutic intervention for T1D and reported on its antiinflammatory effects were included.Of the 62 retrieved articles,only 6 met the predefined inclusion criteria.Although limited in number,the available studies show promising outcomes.CBD demonstrates potential as an adjuvant therapy for T1D due to its immunomodulatory and anti-inflammatory actions.Nonetheless,further research is required to establish safe and effective clinical application protocols.
文摘BACKGROUND Type 1 diabetes is an autoimmune disease leading to insulin deficiency,and it is mainly diagnosed in young adults.One of the major acute complications of type 1 diabetes is diabetic ketoacidosis(DKA),which is a metabolic emergency that can be triggered by stress,infection,or poor blood glucose control.The association of DKA with conditions such as acute pancreatitis and malaria is rare and therefore represents a major diagnostic and therapeutic challenge.CASE SUMMARY A 20-year-old female was admitted to the emergency room for abdominal pelvic pain,fever,asthenia,polyuria,and polydipsia with a progressive deterioration of her state of consciousness.At admission,she was in a mild coma(Glasgow score:9),had a fever of 38.5°C,and had hyperglycemia(6 g/dL).The tests revealed severe DKA,hypertriglyceridemia,hyperamylasemia,and hyperlipasemia as well as malaria parasite density.The computed tomography scan confirmed acute stage E pancreatitis.The diagnosis was that of inaugural ketoacidosis of type 1 diabetes unbalanced by pancreatitis and malaria.Treatment included insulin therapy,rehydration,and antimalarial and analgesic treatment.After 10 days,the outcome was favorable with a normalization of the blood sugar,and an endocrine follow-up was recommend.CONCLUSION Rapid and multidisciplinary management of DKA,pancreatitis,and malaria led to a favorable and stable prognosis.
文摘BACKGROUND Akkermansia muciniphila(A.muciniphila)has been shown to have positive effects on various metabolic diseases and partially prevent the onset of spontaneous type 1 diabetes mellitus(T1DM)in nonobese diabetic mice;however,its therapeutic efficacy in T1DM mice that have already developed T1DM remains unclear.AIM To assess the effects of A.muciniphila intervention on the intestinal barrier,immune parameters[regulatory T(Tregs)cells/T helper 1 cells balance,signal transducer and activator of transcription 1(STAT1)/nuclear factor kappa-B(NF-κB)signal]and intestinal flora in a streptozotocin(STZ)-induced mouse model of T1DM.METHODS Thirty male C57BL/6 mice were randomized into three groups(n=10 for each):Normal control(NC group),STZ-induced T1DM(STZ group),and A.muciniphilatreated T1DM(A.muciniphila group).T1DM was induced with STZ(50 mg/kg/day intraperitoneally,5 days).Body weight,blood glucose,and water intake were monitored weekly.T1DM was modelled in all STZ-and A.muciniphila-treated mice(random blood glucose>16.7 mmol/L).A.muciniphila group mice received oral A.muciniphila(5×10^(7) colony-forming units/mouse)for 3 days.Following sacrifice,pancreatic histopathology,cytokines in splenic tissue,colonic zonula occludens-1(ZO-1)/zonulin expression,cluster of differentiation(CD)4^(+)/CD8^(+)T-cell ratios,forkhead box P3(FoxP3^(+))Tregs,STAT1/NF-κB p65 signaling,and gut microbiota composition were analyzed.RESULTS Compared with STZ group alone,A.muciniphila group did not affect metabolic parameters.Histopathologically,STZ group and A.muciniphila group pancreatic islet cells underwent vacuolar degeneration and necrosis,exhibiting reduced counts and significantly decreased insulin positivity(P<0.05 vs NC),with no intergroup differences.Flow cytometry and enzyme-linked immunosorbent assay revealed elevated tumor necrosis factoralpha(TNF-α),transforming growth factor-beta(TGF-β),and zonulin levels and decreased ZO-1 expression in STZ vs NC mice(P<0.05).Compared with STZ alone,A.muciniphila group reduced TNF-α,TGF-β,and zonulin levels while increasing the CD4^(+)/CD8^(+)ratio,FoxP3^(+)Tregs,interleukin-4,and ZO-1(P<0.05).Colonic NF-κB p65 expression was higher in STZ vs NC mice(P<0.05),with no significant A.muciniphila group/NC difference after the intervention of A.muciniphila.The expression of NF-κB p65 in A.muciniphila group was lower than that in STZ group.STAT1 expression was lower in A.muciniphila vs STZ mice(P<0.05).16S sequencing revealed reduced Actinobacteria abundance in A.muciniphila vs STZ mice(P<0.05).CONCLUSION Short-term intervention with A.muciniphila has shown positive effects on immune response parameters,exemplified by Treg-mediated restoration of immune tolerance,which may be associated with intestinal barrier enhancement and the decreased abundance of intestinal Actinobacteria.
文摘BACKGROUND Type 1 diabetes mellitus(T1DM)is an autoimmune disease with a multifactorial pathogenesis.Viral infections have been proposed as contributing triggers,supported by the disease’s seasonal pattern,which typically shows higher incidence in autumn and winter.The coronavirus disease 2019(COVID-19)pandemic and associated lockdowns created a unique context to examine the incidence and seasonality of T1DM during a period characterized by reduced circulation of common viral infections.AIM To investigate the incidence and seasonality of T1DM before and during COVID-19 pandemic in relation to global viral infection rates.METHODS This population-based retrospective study utilized a nationwide computerized database.Extracted data included the number of new T1DM cases over the 8 years preceding and during the COVID-19 pandemic,demographic characteristics of affected individuals,and nationwide respiratory virus polymerase chain reaction data from weekly nasal wash sample collections.RESULTS A total of 2176 patients were diagnosed with new-onset T1DM during the prepandemic period,compared to 348 cases during the pandemic.In the same periods,33727 respiratory virus-positive polymerase chain reaction results from nasal wash samples were recorded pre-pandemic,compared to 2603 during the pandemic.Additionally,363399 positive COVID-19 cases were reported during the pandemic period.Seasonality analysis revealed a higher rate of new-onset T1DM cases and a weaker seasonal pattern during the pandemic.Trend analysis showed a consistent increase in T1DM incidence prior to COVID-19,with a more variable trend observed during the pandemic.Correlation analysis between T1DM incidence and respiratory viruses demonstrated a weak correlation between T1DM incidence and a few respiratory viruses.CONCLUSION The observed increase in new-onset T1DM cases and the disruption of its typical seasonal pattern during the COVID-19 pandemic suggest a potential association between respiratory virus exposure and the development of T1DM.
基金Supported by National Natural Science Foundation of China,No.821706751·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,No.ZYJC21011.
文摘In this manuscript,we comment on a recent publication by Yuan et al.This article provides a detailed scientific diagnostic process for a multiple endocrine neo-plasia type 1 patient,thus offering strong guidance for clinical practice.However,we believe that the authors should also provide information on the patient's long-term prognosis.
基金supported by grants from the National Natural Science Foundation of China (grant nos.82472579,82172228,and 82202470)Shanghai Plastic Surgery Research Center of Shanghai Priority Research Center (grant no.2023ZZ02023)+2 种基金Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by the Science and Technology Commission of Shanghai Municipality (grant no.22MC1940300)Project of Biobank (grant no.YBKA202204) from Shanghai Ninth People’s Hospital of Shanghai Jiao Tong University School of MedicineCross-Disciplinary Research Fund of Shanghai Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine (grant no.JYJC202407)。
文摘Background: Plexiform neurofibromas(PNF) are highly vascular tumors with the potential for significant growth.Surgical removal of giant PNF is often challenging because of intraoperative hemorrhage.This study proposed and evaluated an innovative surgical approach involving FENCY ligation and the role of preoperative embolization in the resection of giant PNF.Methods: This was a retrospective,interventional,and sequential case series conducted in a plastic and reconstructive surgery unit.We summarized all patients with PNF who underwent resection at our center between2019 and 2024.Surgical case notes from 11 patients with giant PNF who underwent FENCY ligation were reviewed,including three patients who received preoperative embolization.All patients participated in structured telephone interviews.Patient demographics,surgical safety,postoperative recovery,and patient satisfaction were evaluated.Results: Among 456 patients with 494 PNF who underwent surgical resection,we categorized the procedures into median,large,and giant PNF subgroups.To illustrate comprehensive perioperative and surgical approaches,we analyzed seven female and four male patients with giant PNF.The median maximum tumor diameter at the time of surgery was 30.4 cm(range,11.5–55.6 cm).Most PNF were located on the face(63.6%),followed by the back(18.2%),buttocks(18.2%),upper limbs(9.1%),and neck(9.1%).The median intraoperative hemorrhage volume was 366 m L(range,10–2 034 m L),And the median hospital stay was 17 days(range,14–33 days).The mean follow-up duration was 2.5 years(range,0.4–5.5 years).No severe complications were observed,except for one case of infection.Conclusion: PNF resection,particularly giant PNF resection,is a high-risk treatment option.Comprehensive evaluation,perioperative preparation,and surgical techniques are required to ensure efficacy and safety.FENCY ligation and preoperative embolization can be used to resect giant PNF in multiple complex regions with satisfactory outcomes.
