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Neuroendocrine differentiation (NED) may serve as a prognostic factor in colorectal cancer; however, the prognostic relevance of NED remains controversial. The aim of the present study was to determine whether NED influenced the survival of patients in colorectal cancer while exploring its potential interactions with other clinicopathological features. Patients with primary stage I to IV colorectal adenocarcinoma ranging between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier technique, Cox proportional hazards model, propensity score matching, and stratification analyses were employed in this study. A total of 94,291 patients (including 101 patients with NED and 94,190 patients without NED) were included. In the univariable analyses, NED was found to be correlated with a significantly poorer overall survival (hazard ratio (HR) of death = 3.09, 95% CI 2.42–3.95, P < 0.001) and cancer-specific survival (HR of death = 3.77, 95% CI 2.94–4.83, P < 0.001). Moreover, NED remained independently correlated with overall survival (HR of death = 1.84, 95% CI 1.34–2.51, P < 0.001) and cancer-specific survival (HR of death = 2.01, 95% CI 1.45–2.79, P < 0.001) after adjusting in multivariable and propensity score analyses. Furthermore, further stratification analyses indicated that the influence of NED on survival was not affected by tumor location, differentiation, T stage, and distant metastasis status; however, it was found to be associated with lymph node metastasis. NED is associated with poor survival outcomes among colorectal cancer patients, especially in those with positive lymph nodes.

The clinical characteristics of stage III colon cancer and the prognostic significance of tumor deposits were investigated, to construct a prognostic nomogram.The data of patients were retrieved from the Surveillance, Epidemiology, and End Results database. Patients were randomized to a training or validation cohort. The Kaplan-Meier method was used to analyze survival rates. In the training cohort, a prognostic nomogram was established via Cox regression and then tested in the validation cohort. The accuracy and discrimination of the nomogram were assessed using concordance indices (C-indices) and calibration curves.Of the 9246 patients meeting the inclusion criteria, 1788 (19.3%) had tumor deposits. Patients with tumor deposits only showed similar survival rates to those with lymph node metastases only (P = 0.83). Compared with these, patients with both tumor deposits and lymph node metastases exhibited significantly worse survival (P 0.01). In the multivariate Cox regression analyses, the following were identified as independent prognostic indicators and adopted to formulate the nomogram: tumor deposits, age, ethnicity, T stage, the number of positive regional lymph nodes, grade, and carcinoembryonic antigen. In the training cohort, the calibration curve showed good consistency, and the concordance index of the nomogram for predicting overall survival reaches 0.727 (95% CI: 0.71524-0.73876), superior to the concordance index of the American Joint Committee on Cancer staging system (0.594, 95% CI: 0.58224-0.60576). These results are supported in the validation cohort.Tumor deposits may be an independent prognostic factor for patients with stage III colon cancer after colectomy. The nomogram constructed herein accurately predicted overall survival.

The prediction of mortality for septic acute kidney injury (AKI) has been assessed by a number of potential biomarkers, including long noncoding RNAs (lncRNAs). However, the validation of lncRNAs as biomarkers, particularly for the early stages of septic AKI, is still warranted. Our results indicate that the lncRNA TCONS_00016233 is upregulated in plasma of sepsis-associated non-AKI and AKI patients, but a higher cutoff threshold (9.5 × 105, copy number) provided a sensitivity of 71.9% and specificity of 89.6% for the detection of AKI. The plasma TCONS_00016233 was highly correlated with serum creatinine, tissue inhibitor metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP7), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and urinary TCONS_00016233. Lipopolysaccharide (LPS) induced the expression of lncRNA TCONS_00016233 via the Toll-like receptor 4 (TLR4)/p38 mitogen-activated protein kinase (MAPK) signal pathway in human renal tubular epithelial (HK-2) cells. Furthermore, TCONS_00016233 mediates the LPS-induced HK-2 cell apoptosis and the expression of IL-1β and TNF-α. Mechanistically, TCONS_00016233 acts as a competing endogenous RNA (ceRNA) to prevent microRNA (miR)-22-3p-mediated downregulation of the apoptosis-inducing factor mitochondrion-associated 1 (AIFM1). Finally, overexpression of TCONS_00016233 is capable of aggravating the LPS- and cecal ligation and puncture (CLP)-induced septic AKI by targeting the miR-22-3p/AIFM1 axis. Taken together, our data indicate that TCONS_00016233 may serve as an early diagnosis marker for the septic AKI, possibly acting as a novel therapeutic target for septic AKI.

Blockchain-based cryptocurrencies have received extensive attention recently. Massive data has been stored on permission-less blockchains. The analysis of massive blockchain data can bring huge business values. However, the absence of well-processed up-to-date blockchain datasets impedes big data analytics of blockchain data. To fill this gap, we collect and process the up-to-date on-chain data from Ethereum, which is one of the most popular permission-less blockchains. We name such well-processed Ethereum data as XBlock-ETH, which consists of transactions, smart contracts, and cryptocurrencies (i.e., tokens). However, it is non-trivial to partition and categorize the collected raw Ethereum data to the well-processed datasets since the whole processing procedure requires sophisticated knowledge on software engineering as well as big data analytics. Moreover, we also present basic statistics and exploration for each of the well-processed datasets. Furthermore, we also outline the possible research opportunities based on XBlock-ETH, with the data and code released online.

Introduction Latent autoimmune diabetes in adults (LADA) shows a heterogeneous clinical profile that is dependent on the glutamic acid decaroxylase antibody (GADA) titer. We speculated that LADA patients with a high or low GADA titer may have distinct T-lymphocyte subset profiles and distinct expression patterns of transcription factors involved in T-cell immunomodulation. Methods Patients with LADA (n = 40) and type 2 diabetes (T2DM; n = 14) were recruited to the study, and peripheral blood mononuclear cells were isolated. The proportions of T-lymphocyte subsets (Th1 [T helper type 1], Th2 [T helper type 2], Treg [regulatory T], and Th17 [T helper type 17] cells) were determined by flow cytometry. Real-time polymerase chain reaction (PCR) was performed to estimate mRNA expression levels of the T-cell subtype-enriched transcription factors T-bet (Th1), GATA3 (Th2), transcription factor forkhead box protein 3 (FOXP3) (Treg), and RORC (Th17). Results The frequency of Th1 (as a percentage of total CD4+T cells) was greater in the LADA patients with high-titer GADA than in the LADA patients with low-titer GADA (11.06 ± 1.62 vs. 7.05 ± 0.86, P = 0.030). Compared to the T2DM group, in the low-titer GADA group the frequency of Th1 was significantly reduced (7.05 ± 0.86 vs. 16.75 ± 3.73, P = 0.017) and the frequency of Th17 frequency was signficantly increased (1.11 ± 0.09 vs. 0.74 ± 0.16, P = 0.017). Compared to T2DM patients, in the high-titer GADA group there was a significantly reduced expression of FOXP3 (0.35 ± 0.13 vs. 1.75 ± 0.54, P = 0.002), RORC (0.53 ± 0.19 vs. 2.00 ± 0.77, P = 0.046), and GATA3 (0.74 ± 0.17 vs. 2.31 ± 0.91, P = 0.046). Similarly, the high-titer GADA group expressed reduced levels of FOXP3 and RORC compared to the low-titer GADA group (0.35 ± 0.13 vs. 1.50 ± 0.41, P = 0.027; 0.53 ± 0.19 vs. 1.35 ± 0.21, P = 0.027, respectively). There was a negative correlation between FOXP3 expression level and GADA titer for the entire cohort (r = − 0.0433, P = 0.015) and a stronger negative correlation in LADA patients (r = − 0.606, P = 0.008). Conclusion LADA patients with high-titer GADA express lower levels of T-cell transcription factors, including the Treg transcription factor FOXP3, which may contribute to differences in the clinical profile compared to LADA patients with low-titer GADA. Trial Registration ClinicalTrials.gov identifier, NCT01159847.

Tumor deposits in colon cancer are related to poor prognosis, whereas the prognostic power of tumor deposits in combination with lymph node metastasis (LNM) is controversial. This study aimed to compare the overall survival between LNM alone and LNM in combination with tumor deposits, and to verify whether the number of tumor deposits can be considered LNM in patients with both LNM and tumor deposits in stage III colon cancer by propensity score matching (PSM). Patients carrying resected stage III adenocarcinoma of colon cancer were identified from the Surveillance, Epidemiology, and End Results database (2010–2015). The Kaplan-Meier method, Cox proportional hazard models and PSM were used. On the whole, 23,168 patients (20,451 (88.3%) with only LNM and 2,717 (11.7%) with both LNM and tumor deposits) were selected. After undergoing PSM, patients with both LNM and tumor deposits showed worse overall survival (hazard ratio = 1.33, 95% confidence interval: 1.20–1.47, P < 0.001). After the number of tumor deposits was added with that of positive regional lymph nodes, patients with both LNM and tumor deposits seemed to have prognostic implications similar to those with LNM alone (hazard ratio = 1.02, 95% confidence interval: 0.93–1.12, P = 0.66). The simultaneous presence of LNM and tumor deposits, as compared with the presence of only LNM, had an association with a worse outcome. Tumor deposits should be considered as LNM in patients with both tumor deposits and LNM in stage III colon cancer.

Aim: This study aims to establish and validate an effective nomogram to predict cancer-specific survival (CSS) in elderly patients with stages I–III colon cancer.Methods: The data of elderl...

Aims/Introduction Dipeptidyl peptidase‐4 inhibitor has been proven to improve glycemic control and β‐cell function in latent autoimmune diabetes in adults (LADA). The potential immune modulation mechanism is still unknown. Thus, we tested T‐lymphocyte subsets and expression of relevant transcription factors in LADA patients with sitagliptin intervention for up to 1‐year. Materials and Methods A total of 40 LADA patients were randomly assigned to sitagliptin and/or insulin treatment (SITA group; n = 20) or insulin alone treatment (CONT group; n = 20). Peripheral blood mononuclear cells were isolated at baseline, 6 months and 12 months. The percentage of T‐lymphocyte subsets (T helper 1, T helper 2, T helper 17 and regulatory T cells) tested by flow cytometry, and the messenger ribonucleic acid expression (T box expressed in T cells [T‐BET], GATA binding protein 3 [GATA3], forkhead box protein 3 [FOXP3] and related orphan receptor C [RORC]) tested by real‐time polymerase chain reaction were determined at baseline, 6 months and 12 months. Results The percentage of regulatory T cells in the SITA group was significantly lower than that of the CONT group at baseline. The percentage of T helper 2 cells was higher than that of the CONT group at 6 months and 12 months. At 12 months, the percentage of T helper 17 cells was lower in the SITA group than that of the CONT group. After a 1‐year visit, the messenger ribonucleic acid expression levels of T‐BET expressed in T cells and RORC in the SITA group were significantly lower than at baseline. Whereas that of RORC in the CONT group were significantly lower than that at baseline. Conclusions The data confirmed that sitagliptin altered the phenotype of T cells and downregulated the expression of T‐BET and RORC in LADA patients, and ameliorated glycemic control in LADA patients.

Dipeptidyl peptidase-4 (DPP-4) inhibitors constitute a novel class of anti-diabetic agents confirmed to improve glycemic control and preserve β-cell function in type 2 diabetes. Three major large-scale studies, EXAMINE, SAVOR-TIMI 53, and TECOS, have confirmed the cardiovascular safety profile of DPP-4 inhibitors. Based on these results, DPP-4 inhibitors have gained widespread use in type 2 diabetes treatment. It is currently unknown, however, whether DPP-4 inhibitors have similar therapeutic efficacy against autoimmune diabetes. Several in vitro and in vivo studies have addressed this issue, but the results remain controversial. In this review, we summarize experimental findings and preliminary clinical trial results, and identify potentially effective immune modulation targets of DPP-4 inhibitors for autoimmune diabetes.

Blockchain-based cryptocurrencies and applications have flourished in blockchain research community. Massive data generated from diverse blockchain systems bring not only huge business values but also technological challenges in data analytics of heterogeneous blockchain data. Different from Bitcoin and Ethereum, EOSIO has richer diversity and a higher volume of blockchain data due to its unique architectural design in resource management, consensus scheme and high throughput. Despite its popularity (e.g., 89,800,000 blocks generated till November 14, 2019 since its launch on June 8, 2018), few studies have been made on data analysis of EOSIO. To fill this gap, we collect and process the up-to-date on-chain data from EOSIO. We name these well-processed EOSIO datasets as XBlock-EOS, which consists of 7 well-processed datasets: 1) Block, Transaction and Action, 2) Internal and External EOS Transfer Action, 3) Contract Information, 4) Contract Invocation, 5) Token Action, 6) Account Creation, 7) Resource Management. It is challenging to process and analyze a high volume of raw EOSIO data and establish the mapping from original raw data to the well-grained datasets since it requires substantial efforts in extracting various types of data as well as sophisticated knowledge on software engineering and data analytics. Meanwhile, we present statistics and exploration on these datasets. Moreover, we also outline the possible research opportunities based on XBlock-EOS., Comment: 15 pages, 12 figures, 7 tables

With the development of cloud computing, a great amount of information is stored on cloud, such as Facebook, Twitter, and so on. Single cloud or company is not reliable enough for permanent information storage. Once the cloud or company is in downtime, users could lost their information. Multiple clouds can store the information with more security. However, in JointCloud environment, it is a big problem for multiple clouds or companies to maintain the common rights of information for each user. In this paper, we propose EtherShare, a blockchain-based application in JointCloud environment. EtherShare enables users to share information with permanent storage and open access. It keeps the rights of users through smart contracts to make consensus between multiple clouds. And this application is open source on Github.

Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune-mediated destruction of insulin-producing β cells. Recent studies showed that in addition to malaria, artemisinin and its derivative, artesunate (AS), could alleviate several autoimmune diseases. However, whether AS has a role in the prevention or treatment of T1D is still unknown. Therefore, in this study we administrated AS or DMSO in the drinking water of nonobese diabetic (NOD) mice, a mouse model of T1D. We found that AS administration significantly prevented the incidence of T1D. The frequency of IL-4-producing CD4+ single-positive T cells and CD8+ T cells was significantly elevated, and IFN-γ-producing T cells were reduced in the spleen and pancreatic lymph nodes. In the pancreas, the skewing to IL-4-producing T cells was also observed. In addition, more regulatory T cells were found in the pancreas. mRNA levels of proinflammatory cytokines, including TNF-α and IL-6, were decreased. In addition, AS administration promoted the functional maturity of β cells in vitro. Our findings demonstrate that AS administration can prevent T1D in NOD mice mainly by reducing autoimmune T cells and increasing protective T cells. Our data constitute the first functional study of AS in T1D, which may provide a new rationale for future translational studies.-Li, Z., Shi, X., Liu, J., Shao, F., Huang, G., Zhou, Z., Zheng, P. Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL-4-producing T cells and regulatory T cells.

Background: The prediction of mortality for septic acute kidney injury (AKI) has been assessed by a number of potential biomarkers, including long non-coding RNAs (lncRNAs). However, the validation of lncRNAs as biomarkers, particularly for the early stages of septic AKI, is still warranted. Methods: Human blood and urine samples were collected from healthy volunteers(n =30), sepsis patients with AKI (n =96) and sepsis patients without AKI (n=96) for the LncRNA chip assay, RT-qPCR, and absolute real-time PCR analysis. Human renal tubular epithelial (HK-2) cells and C57B6 mice were used to investigate the role and mechanism of LncRNA. and absolute quantification. Findings: Our results indicate that the lncRNA TCONS_00016233 is upregulated in plasma of sepsis-associated non-AKI and AKI patients, but a higher cutoff threshold (9.5x105, copy number) provided a sensitivity of 71.9% and specificity of 89.6% for the detection of AKI. The plasma TCONS_00016233 was highly correlated with serum creatinine, TIMP-2, IGFBP7, and urinary TCONS_00016233. Furthermore, TCONS_00016233 mediates the LPS induced human renal tubular epithelial (HK-2) cells apoptosis. Mechanistically, TCONS_00016233 acts as a ceRNA to prevent miR-22-3p-mediated down-regulation of apoptosis-inducing factor mitochondrion- associated 1(AIFM1). Finally, overexpression of TCONS_00016233 is capable of aggravating the LPS and CLP-induced septic AKI by targeting miR-22-3p/AIFM1 axis. Interpretation: Taken together, our data indicate that TCONS_00016233 may serve as an early diagnosis marker for the septic AKI, possibly acting as a novel therapeutic target for septic AKI. Funding Statement: National Natural Science Foundation of China (81870475, 81570646, 81770951), Hunan Province Natural Science Foundation (2018JJ2568), and excellent Youth Foundation of Hu’nan Scientific Committee (2017JJ1035) supported this study. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: Research protocol was approved by the Second Xiangya Hospital Review Board, The People’s Republic of China Hospital. Written informed consent was got from all individual participants. Animal experiments were performed in strict accordance with the recommendations of the Institutional Committee for the Care and Use of Laboratory Animals of Second Xiangya Hospital (China).

With the rapid development of economy in China, the pharmaceutical industry rises quickly. Although China’s higher medical vocational education develops fast, there are many problems in the current traditional teaching mode and curriculum system, which cannot meet the needs of students. How to reform the education mode under the background of informatization is becoming the focus of vocational education reform in recent years. In this paper, we discussed the teaching effectiveness of DQP framework, an international advanced talent training system of higher vocational education. We found that by choosing reasonable integration of teaching content, different teaching methods, it is in line with the requirements of the times. It facilitates the establishment of pharmacology curriculum standards, the organization of the compilation of pharmacology textbooks which contains the latest knowledge, the use of student-centered flipped classroom teaching mode to improve students’ autonomous learning ability, etc..

Background The non-obese diabetic (NOD) mouse is a commonly used animal model for studying type 1 diabetes (T1D). The aims of our study were to explore the diabetes-preventive effect in NOD mice and the potential mechanisms of an optimized co-expression DNA vaccine containing GAD65 fragment gene with the IL-10 gene (SGAD65190-315/IL-10). Methods Female NOD mice at the age of 3–4 weeks old were randomly divided into two groups and received intra-muscular injection of either blank pBudCE4.l vector (n = 34) or pBudCE4.l carrying the SGAD65190-315/IL-10 (n = 32). The incidence of diabetes was monitored up to 30 weeks of age. The severity of insulitis, apoptosis rate of β cells and relevant mechanisms were examined. Results Administration with SGAD65190-315/IL-10 blocked the onset of autoimmune diabetes in NOD mice, significantly suppressed islet inflammation, inhibited the apoptosis of islet β cells, induced immune tolerance to autoantigen GAD65 and proinsulin and shifted the Th1/Th2 balance towards Th2. More importantly, the frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the spleen and pancreatic lymph nodes in vaccine-immunized mice were significantly increased, and these Tregs were GAD65-reactive. In addition, Treg depletion by anti-CD25 mAb administration abolished the protective effects of SGAD65190-315/IL-10 on diabetes and insulitis. Moreover, depletion of CD4+CD25+ T cells using magnetic-activated cell sorting impaired the protective effect of SGAD65190-315/IL-10 vaccination on adoptive transfer of diabetes. Conclusions Our data suggested that SGAD65190-315/IL-10 DNA vaccine had protective effects on T1D by upregulating autoantigen-reactive Tregs. Our findings may provide a novel preventive therapy for T1D. Copyright © 2016 John Wiley & Sons, Ltd.

Objective: This study aimed to investigate the prevalence of the newly-identified islet autoantibody, tetraspanin 7 autoantibody (TSPAN7A) in Chinese type 1 diabetes (T1D) and Latent Autoimmune Diabetes in Adults (LADA), and the correlation between TSPAN7A and islet function in LADA patients. Research Design and Methods: Patients with newly onset T1D (n=158), long-lasting T1D (n=157), LADA (n=175), type 2 diabetes (T2D; n=204) and healthy control subjects (n=170) were recruited for the cross sectional study. Another cohort including 46 LADA patients with 3-year follow-up was recruited forthe longitudinal study. TSPAN7A was assayed by luciferase immunoprecipitation system assay. Results: The prevalence of TSPAN7A in newly onset T1D, non-newly onset T1D, T2D, LADA and healthy control subjects were 25.3% (40/158), 10.2% (16/157), 0.5% (1/204), 21.1 (37/175) and 1.2% (2/170), respectively. Out of the 23 patients with newly onset T1D but negative for GADA, IA2 and ZnT8A, 3 patients were positive for TSPAN7A (13.0%) improving the detection of autoantibodies from 81.6% to 83.5% in T1D. In LADA patients, analysis of logistic regression demonstrated that duration (OR=1.77, P=0.026), GADA titer (OR=2.79, P=0.006) and TSPAN7A (OR=2.86, P=0.034) were the risk factors to islet function while BMI was the protection factor (OR=0.35, P=0.001). In the follow-up study, LADA patients with TSPAN7A showed a worse islet function compared those negative for TSPAN7A after 3-year diagnosis. Conclusion: TSPAN7A is a novel diagnostic tool for T1D and LADA. Combination of TSPAN7A with other autoantibodies can improve the diagnosis of T1D. TSPAN7A is negatively correlated with islet function in LADA. Disclosure Z. Zhou: None. X. Shi: None. P. Zheng: None. G. Huang: None. Y. Wang: None. C. Deng: None.

Context: The discrepancies in terms of human leukocyte antigen (HLA)-DRB1-DQA1-DQB1 conferred risks between latent autoimmune diabetes in adults (LADA) and type 1 diabetes (T1D) patients remained almost completely unknown. The goal of the current study is to determine and compare HLA-conferred risks between LADA and T1D. Design: A case-control study was conducted in a representative Chinese data set containing 520 T1D patients, 562 LADA patients, and 1065 controls. The frequencies and odds ratios for HLA susceptible haplotypes and genotypes and for arginine at residue 52 in the DQ-α chain or aspartic acid at residue 57 in the DQ-β chain were analyzed. Results: DRB1*0405-DQA1*03-DQB1*0401 and DRB1*0901-DQA1*03-DQB1*0303 are the major LADA susceptible haplotypes, which also confer comparable risks for T1D (odds ratio 2.02 vs 2.20 and 1.61 vs 2.30, respectively). The strongly associated T1D haplotype DRB1*0301-DQA1*05-DQB1*0201 is also associated with LADA but confers only half of the T1D risk (odds ratio 2.65 vs 4.84). Interestingly, the most susceptible T1D haplotypes, DRB1*0901-DQA1*05-DQB1*0201, DRB1*0301-DQA1*03-DQB1*0201, and DRB1*0301-DQA1*03-DQB1*0303, are not associated with LADA. Genotypes for DR3/DR3, DR3/DR9, and DR9/DR9 are highly associated with T1D susceptibility, whereas only DR9/DR9 confers risk for LADA. DR3/DR3 is the high-risk genotype in Chinese T1D patients, which manifests similar risk as the DR3/DR4 genotype in Caucasians but with a lower frequency. DR9/DR9 is the high risk LADA genotype in Chinese. Alleles with DQ-α arginine at residue 52-positive, DQ-β aspartic acid at residue 57-negative, and their combination formed in cis or trans confer susceptibility to T1D but not to LADA. Conclusion: Our results suggest that LADA risk conferred by HLA-DRB1-DQA1-DQB1 loci in Chinese differs significantly from that of T1D risk. This information would be useful for classifying Asian LADA patients, which should provides novel insight into the understanding of its pathoetiology as well.

Background Recent discoveries from animal models demonstrated that neutrophils can induce type 1 diabetes (T1D) through infiltrating into the islets. However, the evidence of their actions in T1D patients is relatively rare, and the change trend of neutrophil numbers and functions in different subtypes of diabetes has not been investigated. Methods Patients with newly diagnosed T1D (n = 189), latent autoimmune diabetes in adults (LADA) (n = 86), T2D (n = 235), and healthy controls (n = 709) were enrolled. Circulating neutrophil counts were measured, and their correlations with clinical parameters were analysed. Neutrophils were isolated by density gradient centrifugation and magnetic bead cell sorting method. Neutrophil migration rate and chemokine levels in the blood were explored by trans-well and ELISA, respectively. Neutrophil phagocytosis rate, adhesion molecules and chemokine receptors expression were investigated by flow cytometry. Results Compared with controls, neutrophil counts decreased in T1D patients but increased in T2D patients, with no change in LADA patients. The numbers showed a gradual increase trend from T1D, LADA to T2D. In autoimmune diabetes, neutrophil counts were associated with the number and titre of positive autoantibodies against β-cell antigens. No difference was found in neutrophil phagocytosis rate, but neutrophil migration in T1D patients was impaired and associated with CD62L expression, which was related closely to the titre of autoantibody. Conclusions Neutrophil numbers and migration abilities displayed distinct levels in different types of diabetes. In T1D, CD62L seems to play an important role in the migration of neutrophils and β-cell autoimmunity.

Summary Type 1 diabetes (T1D) is an autoimmune disease, which is characterized by the destruction of islet β cells in the pancreas triggered by genetic and environmental factors. In past decades, extensive familial and genome‐wide association studies have revealed more than 50 risk loci in the genome. However, genetic susceptibility cannot explain the increased incidence of T1D worldwide, which is very likely attributed by the growing impact of environmental factors, especially gut microbiome. Recently, the role of gut microbiome in the pathogenesis of T1D has been uncovered by the increasing evidence from both human subjects and animal models, strongly indicating that gut microbiome might be a pivotal hub of T1D‐triggering factors, especially environmental factors. In this review, we summarize the current aetiological and mechanism studies of gut microbiome in T1D. A better understanding of the role of gut microbiome in T1D may provide us with powerful prognostic and therapeutic tools in the near future.

The ligation of programmed cell death-1 (PD-1) to its ligands PD-L1 and PD-L2 counteracts T-cell activation, which is critical in immune tolerance. The persistent high expression of PD-1 and PD-L1 are also observed on tumor-infiltrating lymphocytes and various tumor cells, maintaining the highly suppressive microenvironment in tumor sites and promoting tumor malignancies. The blockade of PD-1 axis with PD-L2 fusion protein or monoclonal antibodies against either PD-1 or PD-L1 has been clinically evaluated in various tumor types. This short review summarizes the progress of PD-1 axis blockade in clinical trials to evaluate its effectiveness in the antitumor immunotherapy.