Oligodendrocytes in central nervous system diseases:the effect of cytokine regulation

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

Caliper-based precise positioning of the target(CALIPPOT)for transcranial magnetic stimulation without neuronavigation system

To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for investigating precisely where and when a specific cortical region contributes to a specific cognitive function.1 A more important usage of TMS is the treatment of brain disorders by repetitive TMS(rTMS).

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease:A multicenter cross-sectional study in China

Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.

Oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor of the femur: A case report

BACKGROUND Oncogenic osteomalacia caused by phosphaturic mesenchymal tumors is very difficult to detect.We report a case of tumor-induced osteomalacia caused by a phosphaturic mesenchymal tumor of the left femur in a middle-aged woman after medical imaging and biopsy.CASE SUMMARY A 57-year-old woman presented with progressive bone pain for five years.She was diagnosed with hypophosphatemic osteomalacia,as her laboratory data showed low serum phosphorus and low serum calcium.Her knee joint radiography revealed an osteolytic lesion of the left femur.A computed tomography scan showed mixed density shadows in the left femur.Magnetic resonance imaging of the left femur showed the presence of an oval area with a hypointense signal in T1-weighted magnetic resonance imaging(MRI)and highlow mixed signal in T2-weighted MRI.Biopsy samples revealed the presence of short spindle cells,vascularization,and characteristics of phosphaturic mesenchymal tumors.Tumor resection was performed,and the clinical presentations and laboratory abnormalities were reversed.CONCLUSION Diagnosis of oncogenic osteomalacia is difficult due to the varieties and localization of source tumors and absence of pathognomonic biomedical signs.Our case highlights the importance of a combination of medical imaging and biopsy in the diagnosis of oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor.

The Wnt-dependent and Wnt-independent functions of BCL9 in development,tumorigenesis,and immunity:Implications in therapeutic opportunities

B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin signaling.However,increasing evidences indicate that BCL9 also plays multiple Wnt-independent roles.Herein,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological processes.Moreover,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.

Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis:A case report

BACKGROUND Granulomatosis with polyangiitis(GPA)is one of the most prevalent forms of the antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis.GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis.The diagnosis of GPA depends on clinical presentation,serological evidence of a positive ANCA,and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation.Cytoplasmic ANCA(c-ANCA)is positive in 65%-75% of GPA patients,accompanied by proteinase 3(PR3),the main target antigen of c-ANCA,another 5% of GPA patients had negative ANCA.CASE SUMMARY The patient,a 52-year-old male,presented with unexplained nasal congestion,tinnitus,and hearing loss.After a duration of 4 months experiencing these symptoms,the patient subsequently developed fever and headache.The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis,and the ANCA results were negative.The anti-infective therapy proved to be ineffective,but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day.However,after continuous use of methylprednisolone tablets for 3 months,the patient experienced a recurrence of fever accompanied by right-sided migraine,positive c-ANCA and PR3,and increased total protein in cerebrospinal fluid.The and cyclophosphamide 0.8 g monthly,the patient experienced alleviation of fever and headache.Additionally,the ANCA levels became negative and there has been no recurrence.CONCLUSION For GPA patients with negative ANCA,there is a potential for early missed diagnosis.The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

Combined Effects of Chronic Obstructive Pulmonary Disease and Depression on Spatial Memory in Old Rats

Objective To investigate the combined effects of chronic obstructive pulmonary disease(COPD)and depression on spatial memory in old rats,aiming to better understand the comorbidity of the two diseases in geriatric patients.Methods The SD rats were assigned into five groups:adult control group(n=6),elderly control group(n=6),elderly COPD group(n=6),elderly depression group(n=6)and elderly COPD with depression group(n=6).Smoking and chronic unpredictable mild stress(CUMS)with solitary support were used to induce COPD model,depression model,respectively,and the both were applied for the comorbidity model.Learning and memory deficits were assessed by Morris water maze(MWM)test.The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in serum and hippocampus tissue were determined by Xanthinoxidase method and Thiobarbituric acid reaction(TBAR)method,respectively.Results The results of pulmonary histology,lung function,open-field test and sucrose consumption demonstrated the comorbidity models of COPD and depression in elderly rats were successfully established using smoking and CUMS with solitary support.Compared with the elderly control group,the group of COPD with depression had obviously longer time of latency and longer travel distance to reach the platform in MWM test(LSD-t=-10.116,P=0.000;LSD-t=-6.448,P=0.000).The SOD activity in serum and hippocampus decreased significantly(LSD-t=2.629,P=0.014;LSD-t=2.215,P=0.044)and the MDA content in serum and hippocampus increased significantly(LSD-t=-2.140,P=0.042;LSD-t=-2.070,P=0.049)in elderly COPD with depression group.Conclusions COPD in comorbidity of depression could induce spatial memory deficit in old rats.The mechanisms might be related to the overloaded and free radical metabolic imbalance.These results suggest a potential therapeutic target for comorbidity of COPD and depression in geriatric patients.

Preparation, characterization, pharmacokinetics and anticancer effects of PEGylated β-elemene liposomes

Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.

Centralized isolation of Helicobacter pylori from multiple centers and transport condition influences

AIM:To evaluate the efficacy of centralized culture and possible influencing factors.METHODS:From January 2010 to July 2012,66452 patients with suspected Helicobacter pylori(H.pylori) infection from 26 hospitals in Zhejiang and Jiangsu Provinces in China underwent gastrointestinal endoscopy.Gastric mucosal biopsies were taken from the antrum for culture.These biopsies were transported under natural environmental temperature to the central laboratory in Hangzhou city and divided into three groups based on their transport time:5,24 and 48 h.The culture results were reported after 72 h and the positive culture rates were analyzed by a χ2 test.An additional 5736 biopsies from H.pylori-positive patients(5646 rapid urease test-positive and 90 14C-urease breath test-positive) were also cultured for quality control in the central laboratory setting.RESULTS:The positive culture rate was 31.66%(21036/66452) for the patient samples and 71.72%(4114/5736) for the H.pylori-positive quality control specimens.In the 5 h transport group,the positiveculture rate was 30.99%(3865/12471),and 32.84%(14960/45553) in the 24 h transport group.In contrast,the positive culture rate declined significantly in the 48 h transport group(26.25%; P < 0.001).During transportation,the average natural temperature increased from 4.67 to 29.14℃,while the positive culture rate declined from 36.67%(1462/3987) to 24.12%(1799/7459).When the temperature exceeded 24℃,the positive culture rate decreased significantly,especially in the 48 h transport group(23.17%).CONCLUSION:Transportation of specimens within 24 h and below 24℃ is reasonable and acceptable for centralized culture of multicenter H.pylori samples.

Ectopic pregnancy implanted under the diaphragm: A rare case report

BACKGROUND Abdominal pregnancy is a rare type of ectopic pregnancy.We describe here a case of ectopic pregnancy implanted under the surface of the diaphragm,presenting the particular features of imaging findings from ultrasound,computed tomography(CT)and magnetic resonance imaging(MRI).CASE SUMMARY A 30-year-old woman presented with complaint of intermittent abdominal pain,that had begun 5 d earlier.She had no current or abnormal vaginal bleeding,and her serum human chorionic gonadotropin level(13372.08 IU/L)indicated pregnancy.Vaginal ultrasound showed a mixed echogenic mass in the right ovary.CT(plain)scan showed a curved high density mass beneath the subhepatic space.MRI scan showed a curved mixed signal,with restricted diffusion beneath the subhepatic space.Abdominal ultrasound demonstrated a mixed echogenic mass in the right lobe of the liver near the apex of the diaphragm,with a visible yolk sac and germ cell region with a bud.Subsequent laparoscopy visualized a dark red mass under the right diaphragm,which was resected completely.Histopathological examination of the resected mass confirmed an ectopic pregnancy.The recovery was swift and uneventful,and the patient was discharged to home.CONCLUSION Ectopic pregnancy should be in the differential diagnostic workup(via multiple imaging modalities)of childbearing woman with unexplained abdominal pain.

Laparoscopic-assisted endoscopic full-thickness resection of a large gastric schwannoma: A case report

BACKGROUND Schwannomas,also known as neurinomas,are benign tumors derived from Schwann cells.Gastrointestinal schwannomas are rare and are most frequently reported in the stomach.They are usually asymptomatic and are difficult to diagnose preoperatively;however,endoscopy and imaging modalities can provide beneficial preliminary diagnostic data.There are various surgical options for management.Here,we present a case of a large gastric schwannoma(GS)managed by combined laparoscopic and endoscopic surgery.CASE SUMMARY A 28-year-old woman presented with a 2-mo history of epigastric discomfort and a feeling of abdominal fullness.On upper gastrointestinal endoscopy and endoscopic ultrasonography,a hypoechogenic submucosal mass was detected in the gastric antrum:It emerged from the muscularis propria and projected intraluminally.Computed tomography showed a nodular lesion(4 cm×3.5 cm),which exhibited uniform enhancement,on the gastric antrum wall.Based on these findings,a preliminary diagnosis of gastrointestinal stromal tumor was established,with schwannoma as a differential.Considering the large tumor size,we planned to perform endoscopic resection and to convert to laparoscopic treatment,if necessary.Eventually,the patient underwent combined laparoscopic and gastroscopic surgery.Immunohistochemically,the resected specimen showed positivity for S-100 and negativity for desmin,DOG-1,α-smooth muscle actin,CD34,CD117,and p53.The Ki-67 index was 3%,and a final diagnosis of GS was established.CONCLUSION Combined laparoscopic and endoscopic surgery is a minimally invasive and effective treatment option for large GSs.

Successful treatment of infantile hepatitis B with lamivudine: A case report

BACKGROUND How to treat infantile hepatitis B virus(HBV)infection remains a controversial issue.The nucleoside analogue lamivudine(LAM)has been approved to treat children(2 to 17 years old)with chronic hepatitis B.Here,we aimed to investigate the benefit of LAM treatment in infantile hepatitis B.CASE SUMMARY A 4-mo-old infant born to a hepatitis B surface antigen(HBsAg)-positive woman was found to be infected by HBV during a health checkup.Liver chemistry and HBV seromarker tests showed alanine aminotransferase of 106 U/L,HBsAg of 685.2 cut-off index,hepatitis B“e”antigen of 1454.0 cut-off index,and HBV DNA of>1.0×10^(9) IU/mL.LAM treatment(20 mg/d)was initiated,and after 19 mo,serum HBsAg was entirely cleared and hepatitis B surface antibody was present.The patient received LAM treatment for 2 years in total and has been followed for 3 years.During this period,serum hepatitis B surface antibody has been persistently positive,and serum HBV DNA was undetectable.CONCLUSION Early treatment of infantile hepatitis B with LAM could be safe and effective。

Clinical distribution and molecular profiling on postoperative colorectal cancer patients with different traditional Chinese medicine syndromes

Background:Traditional Chinese medicine(TCM)syndrome,also named syndrome,are comprehensive and integral analyses of clinical information which helps to guide different individualized treatment prescriptions.Methods:Thirty healthy controls and 80 colorectal cancer(CRC)patients(including 33 Spleen Qi Deficiency syndrome,23 Dampness Heat syndrome,17 Blood Stasis syndrome and 7 other syndrome)were enrolled into this study.Human mRNAs were extracted from peripheral blood mononuclear cells.The gene expression for CRC patients with different TCM syndrome was determined by microarray and qRT-PCR.Results:Spleen Qi Deficiency,Dampness Heat and Blood Stasis were the most common syndromes in CRC patients.There is a significant difference was found in mRNA expression levels(especially for PIK3CA,STAT3,SOX9 and KDM5C)among Spleen Qi Deficiency,Dampness Heat and Blood Stasis syndrome groups.The higher mRNA levels of JNK1,TP53,MLH1,MSH6,PMS2,SOCS3,TCF7L2,FAM123B,PSAP,FBXW7,SALL4 and the lower expression of inflammatory cytokine IL-6 were found in Spleen Qi Deficiency group but not other syndrome types.The higher mRNA levels of KRAS,MUC16,EGFR,GRASP65,PIK3CA,MAPK7,CD24,STAT3,SLC11A1,Bcl-2,TXNDC17 and some inflammatory cytokines(IL-6,IL-23,TNF-a,CXCR4)were found in Dampness Heat group but not other syndrome types.Blood Stasis syndrome showed higher expression of SOX9,MLH1,MSH6,KDM5C,PCDH11X,PSAP and SALL4,and lower mRNA levels of PIK3CA,CD24,STAT3,CXCR4,TXNDC17 and TP53.The CRC patients with Dampness Heat syndrome might have a poor prognosis than other syndrome types.Conclusion:The identification of syndrome conditions had different impacts on CRC prognosis,and which might be related with different mRNA expression levels.Some oncogenes and pro-inflammatory cytokines were highly expressed in Dampness Heat group but not other syndrome types,suggesting that the CRC patients with Dampness Heat syndrome might have a poor prognosis.Our results prelimitarily uncovered the molecular basis of syndrome differences in CRC prognosis,a better understanding for TCM treatment of CRC.

Research progress on circulating tumor cells of hepatocellular carcinoma

Circulating tumor cells(CTCs)are the cells released from the primary tumor and found in the peripheral blood,which can colonize and develop at a distance through blood circulation.At present,the commonly used separation and detection methods of CTCs are mainly divided into physical methods,biological methods,and microfluidic chip-based methods.Monitoring CTC count and cell phenotype is of great significance for early screening and diagnosis of hepatocellular carcinoma(HCC).Moreover,the CTC count and cell phenotype are related to assessing the clinical efficacy of the treatment of HCC and the clinical stage of HCC patients.The CTCs count is also closely related to the overall survival,progression-free survival,and postoperative recurrence of patients with HCC.

Effects of endogenous L-cystathionine on enzymatic assays of serum homocysteine in samples from renal dialysis patients

Homocysteine (Hcy) is a thiol-containing amino acid produced by the intracellular demethylation of methionine.Approximately 80% of circulating Hcy in the blood is protein bound by disulfide linkage.The remaining unbound Hcy combines by oxidation either with itself to form the dimer homocystine or with cysteine to form the mixed disulfide cysteine-Hcy.

Diagnostic and Prognostic Value of Survivin in Pleural Effusion

Background: Survivin is an inhibitor of apoptosis that may be a novel diagnostic and prognostic marker of cancer. Our study is to investigate the diagnostic and prognostic value of survivin for pleural effusions. Methods: Sixty-five pleural effusion patients were enrolled prospectively. Pleural effusion samples were examined for survivin level by ELISA. Pleural effusions were divided into three groups: Group I, malignant pleural effusion (MPE) (n = 36);Group II, tuberculous pleurisy (TPE) (n = 18);and Group III, transudative pleural effusion (n = 11). The accuracy of diagnosis and the correlation between survivin level and survival in malignant pleural effusions (MPE) were analyzed. Results: Survivin level was 320.50 ± 228.24 pg/ml in MPE, 328.35 ± 146.79 pg/ml in TPE and 318.87 ± 208.39 pg/ml in transudative pleural effusion respectively. ROC curves for MPE versus TPE were analyzed, area under the ROC curve was 0.419, and for the cutoff value of 254.85 pg/ml sensitivity was 44.4% and specificity 55.6%. Survivin had no discriminative power in differentiating exudative effusions of MPE from non-MPE (p = 0.648). There was no correlation between survivin level and age, sex. However, statistically significant difference was found between primary lung carcinoma (238.66 ± 48.19 pg/ml) and extra-pulmonary metastatic carcinomas (435.09 ± 320.62 pg/ml) according to survivin level (p = 0.033). Survivin levels can distinguish patients who had poor prognosis (median survival 96 days) and those who had good prognosis (median survival 206 days) in MPE. Conclusion: survivin levels detected with ELISA had no discriminative power in differentiating exudative effusions included MPE and TPE. However, over-expression of survivin correlates with poor prognosis in cancer patients. Our results suggest that survivin may be a potential prognostic marker in MPE.

Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide(LPS)-induced inflammatory response

Although microRNA-155(miR-155)is considered a pro-inflammatory mediator,cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells.In this study,we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide(LPS)stimulation;223 genes were down-regulated and 85 genes were up-regulated,including suppressor of cytokine signaling 1(SOCS1)and transforming growth factor-β-activated kinase 1-binding protein 2(TAB2),two well-known genes involved in miR-155-mediated regulation of the Toll-like receptor 4(TLR4)signaling pathway.We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation,and as a proinflammatory mediator by down-regulating SOCS1 in the later stage.Meanwhile,overexpression of TAB23'untranslated region(UTR)in macrophages promoted the development of endotoxin tolerance by competing for binding with miR-155,which resulted in an elevated expression level of SOCS1 protein.These findings provide new insights for understanding the regulatory mechanisms in fine-tuning of LPS-induced innate immune response.

An ATF24 peptide-functionalized β-elemene-nanostructured lipid carrier combined with cisplatin for bladder cancer treatment

Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-Lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin(DDP)for bladder cancer treatment.Methods:The liposomes were prepared by ethanol injection and high-pressure microjet homogenization.The liposomes were characterized,and the drug content,entrapment efficiency,andin vitro release were studied.The targeting efficiency was investigated using confocal microscopy,ultra-fast liquid chromatography,and an orthotopic bladder cancer model.The effects of ATF24-PEG-Lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8(CCK-8)assay,a colony formation assay,and cell apoptosis and cell cycle analyses.The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model.Results:ATF24-PEG-Lipo-β-E had small and uniform sizes(~79 nm),high drug loading capacity(~5.24 mg/mL),high entrapment efficiency(98.37±0.95%),and exhibited sustained drug release behavior.ATF24-PEG-Lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol(PEG)ylatedβ-elemene liposomes(PEG-Lipo-β-E).DDP,combined with ATF24-PEG-Lipo-β-E,exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase,and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways.Furthermore,thein vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors,using the combined strategy.Conclusions:The present study provided an effective strategy for the targeted delivery ofβ-elemene(β-E)to bladder cancer,and a combined strategy for bladder cancer treatment.

Gut microbiota dysbiosis in Chinese children with type 1 diabetes mellitus:An observational study

BACKGROUND Gut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus(T1DM).However,the alterations in the gut microbiota and their correlation with fasting blood glucose(FBG)in Chinese children with T1DM remain unclear.AIM To investigate alterations in the gut microbiota in Chinese children with T1DM and their associations with clinical indicators.METHODS Samples from 51 children with T1DM and 47 age-matched and gender-matched healthy controls were obtained,to explore the structural and functional alterations in the fecal microbiota.The V3-V4 regions of the 16S rRNA gene were sequenced on a MiSeq instrument,and the association with FBG were analyzed.RESULTS We found that the bacterial diversity was significantly increased in the T1DMassociated fecal microbiota,and changes in the microbial composition were observed at different taxonomic levels.The T1DM-reduced differential taxa,such as Bacteroides vulgatus ATCC8482,Bacteroides ovatus,Bacteroides xylanisolvens,and Flavonifractor plautii,were negatively correlated with FBG,while the T1DMenriched taxa,such as Blautia,Eubacterium hallii group,Anaerostipes hadrus,and Dorea longicatena,were positively correlated with FBG.Bacteroides vulgatus ATCC8482,Bacteroides ovatus,the Eubacterium hallii group,and Anaerostipes hadrus,either alone or in combination,could be used as noninvasive diagnostic biomarkers to discriminate children with T1DM from healthy controls.In addition,the functional changes in the T1DM-associated fecal microbiota also suggest that these fecal microbes were associated with altered functions and metabolic activities,such as glycan biosynthesis and metabolism and lipid metabolism,which might play vital roles in the pathogenesis and development of T1DM.CONCLUSION Our present comprehensive investigation of the T1DM-associated fecal microbiota provides novel insights into the pathogenesis of the disease and sheds light on the diagnosis and treatment of T1DM.

Idiopathic multicentric Castleman disease with pulmonary and cutaneous lesions treated with tocilizumab:A case report

BACKGROUND Human herpes virus-8(HHV-8)-negative,idiopathic multicentric Castleman disease(iMCD)is a rare and life-threatening disorder driven by proinflammatory cytokines,which is still poorly understood.Pulmonary parenchyma lesion is a rare condition in iMCD,which mainly manifests as lymphocytic interstitial pneumonia and is an indicator of severe iMCD.Cutaneous lesion is also very rare and mainly occurs in Asians.There have been few reports of iMCD patients with both skin and lung parenchyma involvement.CASE SUMMARY We present a Chinese man who complained about a 3-year history of intermittent dry cough and a 2-year history of diffuse reddish-brown maculopapules.Laboratory examination revealed polyclonal hypergammaglobulinemia and hypercytokinemia including interleukin 6.Chest computed tomography revealed small patchy shadows with ground-glass nodules scattered in two lobes and mediastinal lymphadenopathy.The pathological result of the lymph node was consistent with the plasma cell type of Castleman disease.As serum human immunodeficiency virus test and HHV-8 staining of the lymph node were negative,the patient was finally diagnosed with HHV-8 negative i MCD.He was treated with tocilizumab at an intravenous(i.v.)dose of 8 mg/kg every 2 wk combined with methylprednisolone at an i.v.dose of 80 mg/d initially with gradual dose tapering.Partial remission was achieved 9 mo later.CONCLUSION i MCD with lung parenchyma and skin involvement is a rare condition that requires clinicians'attention and awareness for early diagnosis.