Type 1 diabetes (T1D) is a T cell‑mediated autoimmune disorder characterized by the destruction of insulin‑producing β‑cells. Sialic acid‑binding Ig‑like lectin 15 (Siglec‑15) could inhibit T‑cell activation and suppress immune responses. However, the association between Siglec‑15 expression levels and T1D is largely unknown. Serum concentrations of soluble Siglec‑15 were quantified in a cohort comprising 34 individuals newly diagnosed with T1D and 21 healthy control subjects. A murine mesenchymal stem cell (MSC) line, C3H10 T1/2, was genetically engineered to stably express SIGLEC15 through lentiviral transduction. Non‑obese diabetic (NOD) mice were administered treatments with Siglec15‑expressing MSCs, control MSCs, or phosphate‑buffered saline. The present study evaluated diabetes incidence, blood glucose concentrations, the severity of insulitis and the composition of immune cell populations in the pancreatic lymph nodes and spleens. In the present study, measurement of human serum specimens by ELISA revealed a positive association between new‑onset T1D and soluble Siglec‑15 levels. In NOD mice, treatment with Siglec15‑MSCs resulted in a significant reduction in diabetes incidence, preservation of insulin‑positive islets and mitigation of insulitis. Flow cytometric analysis demonstrated an increase in CD4+effector memory T cells within the pancreatic‑draining lymph nodes of mice treated with Siglec15‑MSCs, while no significant alterations were observed in splenic T cell populations or the frequencies of regulatory T cells. The findings of this study underscore the potential of Siglec‑15‑overexpressing MSCs as a promising cell‑based therapeutic approach for T1D, primarily through the localized modulation of memory T cells within the pancreatic lymph nodes.

Somatostatin analogues (SSAs) are cornerstone treatments for hormone-secreting tumors but can disrupt glucose metabolism. Comparative effects on glycemic parameters between different SSAs and doses remain quantitatively unclear. We searched major databases for RCTs reporting fasting blood glucose (FBG) or glycated hemoglobin (HbA1c) changes with SSA treatment vs. control/active comparator. Frequentist network meta-analysis (NMA) using Stata 17.0 compared effects across SSA types/doses (octreotide, lanreotide, pasireotide 20 mg, 40 mg, 60 mg), expressed as mean differences (MDs) with 95

To comprehensively investigate the dynamic changes and correlations among nutritional parameters, inflammatory, and immune biomarkers for head and neck cancer (HNC) patients during (chemo-)radiotherapy. Body composition measurements, subjective nutritional assessments, and hematological biomarkers were prospectively evaluated at four time points: pre-radiotherapy (T1), mid-radiotherapy (T2), at the completion of radiotherapy (T3), and 1 month afterward (T4). A total of 65 patients completed four follow-ups. Longitudinal analysis revealed statistically significant differences (all P < 0.05) in nutritional, inflammatory, and immune parameters across the four time points (T1–T4). Nutritional parameters including body weight, body mass index, fat-free mass, soft lean mass, skeletal muscle mass, body fat mass, handgrip strength, Nutritional Risk Screening 2002 (NRS2002) score, Patient-Generated Subjective Global Assessment (PG-SGA) score, Karnofsky Performance Status (KPS) score, daily energy intake, daily protein intake, albumin, total protein, prealbumin, hemoglobin, platelet, and red blood cell count all demonstrated significant temporal changes. Similarly, inflammatory/immune biomarkers including white blood cell count, neutrophil count, lymphocyte count, T-lymphocyte count, B-lymphocyte count, C-reactive protein, procalcitonin, interleukin-6, interleukin-10, interferon-γ, and tumor necrosis factor-α showed significant fluctuations during radiotherapy. Spearman’s correlation analysis demonstrated associations among nutritional parameters, inflammatory, and immune biomarkers at T3 (all P < 0.05). Our prospective study demonstrates that patients with HNC experience progressive deterioration in nutritional status (particularly fat-free mass loss) during (chemo-)radiotherapy, which is accompanied by heightened inflammatory responses and diminished immune function. These findings strongly support the integration of multimodal nutritional-inflammatory-immune monitoring protocols into routine oncologic care throughout radiotherapy.

BackgroundThe functional changes in alpha cells in patients with type 1 diabetes (T1D) with different residual beta cell functions remain poorly elucidated. The study aimed to investigate the relationship between glucagon secretion and C-peptide levels and to explore the relationship between glucagon response and glucose increment in respond to a secretagogue in a steamed bread meal tolerance test (BMTT) in T1D.MethodsThe study enrolled 43 adult patients with T1D and 24 healthy control subjects. Patients with T1D who underwent BMTT were divided into two groups based on peak C-peptide levels: C peptide low (CPL; C-peptide < 200 pmol/L; n=14) and high (CPH; C peptide ≥ 200 pmol/L; n=29). Plasma glucose, C-peptide, glucagon levels at 0, 30, 60, 120, and 180 min were measured. The glucagon response to the BMTT was defined by areas under the curve (AUC) as early (AUC0-30), late (AUC30-180), or total (AUC0-180) glucagon.ResultsCompared to healthy individuals, fasting plasma glucagon was lower and postprandial plasma glucagon level was increased in patients with T1D. Glucagon levels after BMTT between the CPL and CPH group showed significant group by time interaction. Peak glucagon and glucagon at 60-180 min, total and late glucagon response were higher in CPL than CPH group, while fasting glucagon and early glucagon response adjusted for glucose were comparable between CPL and CPH group. The higher late glucagon response and late glucagon response adjusted for glucose were associated with lower peak C-peptide in T1D. The higher late glucagon response and lower peak C-peptide were associated with the higher value of ▵glucose at 180 min.ConclusionStimulated C-peptide levels affect the paradoxical increase in postprandial glucagon secretion in patients with T1D, especially late glucagon response. The exaggerated postprandial glucagon secretion further stimulates the elevation of postprandial glucose in patients with T1D.

ObjectiveAbnormal iron metabolism is related to the risk of diabetes, but the underlying mechanism of this association remains uncertain. This study was conducted to evaluate the contributions of systemic iron status to β-cell function and insulin sensitivity of patients with newly diagnosed T2DM.MethodsA total of 162 patients with newly diagnosed T2DM and 162 healthy controls were enrolled in the study. Basic characteristics, biochemical indicators, and iron metabolism biomarkers, including serum iron (SI), ferritin (SF), transferrin (Trf), and transferrin saturation (TS), were collected. All patients underwent a 75 g oral glucose tolerance test. A series of parameters for assessing β-cell function and insulin sensitivity were calculated. The multivariate stepwise linear regression model was used to investigate the contributions of iron metabolism to β-cell function and insulin sensitivity.ResultsCompared with healthy controls, patients with newly diagnosed T2DM had significantly higher levels of SF. Among the diabetic patients, the SI and TS levels were higher, and the percentage of Trf levels below normal values was lower in men than in women. In all diabetic patients, SF was the independent risk factor associated with impaired β-cell function. Further stratification analysis showed that Trf was an independent protective factor for β-cell function in male patients, while SF was an independent risk factor for impaired β-cell function in female patients. However, systemic iron status did not affect insulin sensitivity.ConclusionElevated SF levels and decreased Trf levels had a profound effect on impaired β-cell function in Chinese patients with newly diagnosed T2DM.

Objective The destruction of pancreatic beta cells causes type 1 diabetes mellitus (T1D), an autoimmune disease. Studies have demonstrated that there is heterogeneity in residual beta-cell function in Caucasians; therefore, we aimed to evaluate beta-cell function in Chinese autoimmune T1D patients. Methods beta-cell function was determined using oral glucose tolerance testing or standardized steamed bread meal tolerance test in 446 participants with autoantibody-positive T1D. Clinical factors, such as age onset, sex, duration, body mass index, autoantibodies, other autoimmune diseases, diabetic ketoacidosis, hypoglycemia events, glycosylated hemoglobin, and insulin dose, were retrieved. We also analyzed single nucleotide polymorphism (SNP) data for C-peptides from 144 participants enrolled in the Chinese-T1D genome-wide association study. Results Of 446 T1D patients, 98.5%, 97.4%, 86.9%, and 42.6% of individuals had detectable C-peptide values (>= 0.003 nmol/L) at durations of < 1 year, 1 to 2 years, 3 to 6 years, and >= 7 years, respectively. A total of 60.7% of patients diagnosed at >= 18 years old and 15.8% of those diagnosed at < 18 years had detectable C-peptide after >= 7 years from the diagnosis. Furthermore, the patients diagnosed at >= 18 years old had higher absolute values of stimulated C-peptide (>= 0.2 nmol/L). Diabetic ketoacidosis, hypoglycemia events, and insulin doses were shown to be associated with beta-cell function. SNPs rs1770 and rs55904 were associated with C-peptide levels. Conclusion Our results have indicated that there are high residuals of beta-cell mass in Chinese patients with autoimmune T1D. These findings may aid in the consideration of therapeutic strategies seeking prevention and reversal of beta-cell function among Chinese T1D patients.

Malnutrition is a common complication of cancer patients, and solving nutrition problems is still one of the challenging tasks in clinical practice. The incidence of malnutrition in head and neck cancer patients during the peri-radiotherapeutic period is high, which is not only related to disease-mediated metabolic disorders, complications and psychological factors, but also associated with the toxic and side effects induced by radiotherapy. Malnutrition will reduce the tolerance, accuracy, and therapeutic effects of radiotherapy, which in turn lowers the quality of life and even adversely affects the prognosis of disease. Medical nutrition therapy can improve the nutritional status of the body, ensure smooth progress of radiotherapy, and improve the efficacy of comprehensive cancer treatment. It is necessary and urgent to deliver standardized nutrition therapy and management of head and neck cancer patients during the peri-radiotherapeutic period. Nutritional risk screening, nutritional assessment, and acute radiation injury assessment are required to develop an individualized nutrition treatment plan and make dynamic adjustment. In this article, relevant literature of nutrition therapy for head and neck radiotherapy at home and abroad was summarized, and the standardized nutrition therapy for head and neck cancer patients during the peri-radiotherapeutic period was reviewed.

Objective:To explore whether palmitic acid (PA) can induce ferroptosis in pancreatic beta-cell line MIN6 cells.Methods:Pancreatic beta-cell line MIN6 cells were divided into normal group, PA group (1.0 mmol/L), PA+apoptosis inhibitor (Z-VAD-FMK) group (5 μmol/L), PA+ ferrostain-1(Fer-1) group (5 μmol/L), PA+ necrostatin-1(Nec-1) group (5 μmol/L). Each group was set three parallels. Cell viability was detected by CCK8 method. Cellular ultrastructure was assessed with electron microscopy. FerroOrange was used to detect intracellular Fe 2+. The lipid peroxidation assay kit was used to detect the concentration of malondialdehyde (MDA). Flow cytometry was used to detect intracellular reactive oxygen species (ROS) levels. Real-time quantitative polymerase chain reaction was used to detect the mRNA levels of caspase3, receptor-interacting protein kinase 3 ( RIPK3), acyl-CoA synthetase long-chain family member 4 ( ACSL4), prostaglandin endoperoxidase synthase 2 ( Ptgs2), arachidonate lipoxygenase 15 ( ALOX15), ferritin heavy chain ( FTH), ferritin light chain ( FTL), and glutathione peroxidase 4 ( GPX4). Western blotting was used to detect the proteins levels of cleaved caspase3, RIPK3, ACSL4, ALOX15 and Ptgs2. The t-test was used to compare two groups. Results:Compared with the PA group, cell viability of MIN6 was higher in PA+Z-VAD-FMK group, PA+Fer-1 group or PA+Nec-1 group ( P<0.01). MIN6 cells, which were treated with PA to exhibit the characteristic morphologic features, were associated with apoptosis, necrosis and ferroptosis under electron microscope. Compared with the control group, in PA group, the levels of the cellular intracellular Fe 2+, MDA and total lipid ROS were increased. The mRNA relative expression levels of caspase3, RIPK3, ACSL4, Ptgs2 and ALOX15 were increased. The mRNA relative expression levels of FTH and GPX4 were decreased. The protein relative expression levels of cleaved caspase3, RIPK3, ACSL4, ALOX15 and Ptgs2 were increased (all P<0.01). Compared with the PA group, in PA+Fer-1 group, the levels of cellular intracellular Fe 2+, MDA and total lipid ROS were decreased. The mRNA relative expression levels of ACSL4, Ptgs2 and ALOX15 were decreased. The mRNA relative expression levels of FTH and GPX4 were increased. The protein relative expression levels of ACSL4, ALOX15 and Ptgs2 were decreased (all P<0.01). Conclusion:PA could induce ferroptosis in pancreatic beta-cell line MIN6 cells.

1型糖尿病（T1DM）是一种慢性自身免疫性疾病，以胰岛β细胞进行性破坏为特征。CD4 +和CD8 +记忆T细胞均在T1DM发病中发挥着重要作用，尤其是CD8 +T细胞被认为是介导β细胞破坏的关键T细胞。自身反应性记忆T细胞的持续存在被认为是T1DM慢性炎症持续存在的主要原因。T1DM患者自身反应性T细胞主要是效应记忆细胞。研究发现通过清除或调节自身反应性T细胞可以保护胰岛β细胞功能。在T1DM免疫治疗中涉及记忆T细胞免疫治疗方法包括T细胞清除、清除和抑制动态平衡细胞因子、T细胞表面共刺激因子的阻断、抑制Kv1.3通道等。这些免疫治疗方法对记忆T细胞亚群都会有所影响。

BACKGROUND:Type 1 diabetes (T1D) is a severe and prevalent metabolic disease. Due to its high heredity, an increasing number of genome-wide association studies have been performed, most of which were from hospital-based case-control studies with a relatively small sample size. The association of single nucleotide polymorphisms (SNPs) and T1D has been less studied and is less understood in natural cohorts.AIM:To investigate the significant variants of T1D, which could be potential biomarkers for T1D prediction or even therapy.METHODS:A genome-wide association study (GWAS) of adult T1D was performed in a nested case-control study (785 cases vs 804 controls) from a larger 5-year cohort study in Suzhou, China. Potential harmful or protective SNPs were evaluated for T1D. Subsequent expression and splicing quantitative trait loci (eQTL and sQTL) analyses were carried out to identify target genes modulated by these SNPs.RESULTS:A harmful SNP for T1D, rs3117017 [odds ratio (OR) = 3.202, 95% confidence interval (CI): 2.296-4.466, P = 9.33 × 10-4] and three protective SNPs rs55846421 (0.113, 0.081-0.156, 1.76 × 10-9), rs75836320 (0.283, 0.205-0.392, 1.07 × 10-4), rs362071 (0.568, 0.495-0.651, 1.66 × 10-4) were identified. Twenty-two genes were further identified as potential candidates for T1D onset.CONCLUSION:We identified a potential genetic basis of T1D, both protective and harmful, using a GWAS in a larger nested case-control study of a Chinese population.

Chronic inflammation of autoimmune diseases, including type 1 diabetes (T1D), is mainly mediated by memory T(Tm) cells, predominantly effector memory T (Tem) cells. The roles of the programmed death-1 (PD-1) receptor on lymphocytes have been well studied in tumor and other infection models. However, little is known about the relationship between the expression of PD-1 on CD8+ Tem cells and the pathogenesis of T1D. A total of 52 patients diagnosed with T1D and 39 gender-, age-, and ethnically matched health control individuals were enrolled in this study. Peripheral blood mononuclear cells from these individuals were isolated and analyzed by flow cytometry. We evaluated the frequencies of PD-1+ CD8+ memory T cell subsets from patients' peripheral blood with T1D and the spleen cells of nonobese diabetic (NOD) mice in the present study. We also investigated the effects of blocking PD-1/PD-L1 pathway on islet’s inflammation in NOD mice. Frequencies of PD-1+ CD8+ Tem cells were decreased significantly in PBMC of patients with T1D (40.73 ± 12.72 vs 47.43 ± 15.56, *p < 0.05). The frequencies of PD-1+ CD8+ Tem cells were decreased in patients with T1D who were positive for two or more autoantibodies compared with the patients with one autoantibody (13.46% vs 46.95 ± 12.72%, *p < 0.05). Meanwhile, the frequencies of PD-1+ CD8+ central memory T (Tcm) cells were also significantly decreased in patients with two or more autoantibodies compared with other groups (≥ 2AAb vs HC 33.1 ± 8.92% vs 43.71 ± 11.78%, *p < 0.05; ≥ 2AAb vs AAb—33.1 ± 8.92% vs 41.65 ± 11.2%, *p < 0.05; ≥ 2AAb vs 1AAb 33.1 ± 8.92% vs 48.09 ± 10.58%, ***p < 0.001). The frequencies of PD-1+CD8+ Tem cells were positively correlated with fasting serum C-peptide levels (r = 0.4308, *p < 0.05) and C-peptide levels 2 h after meal in T1D patients (r = 0.5723, **p < 0.01). The frequencies of PD-1+CD8+ Tcm cells were only negatively correlated with the levels of HbA1c (r = − 0.2992, *p < 0.05). Similarly, the frequencies of PD-1+CD8+ Tem were significantly decreased in intervention group (anti-mouse PD-1 mAb) compared with the control group (14.22 ± 6.455% vs 27.69 ± 9.837%, *p < 0.05). Pathologically, CD8, PD-1 and PD-L1 were strongly expressed in the islets of diabetic mice after PD-1 blockade. It is the first report of the expression of PD-1 on CD8+ Tem cells in T1D in the present study. Our observations suggest that the PD-1/PD-L1 signal pathway on CD8+ Tem cells of T1D subjects might identify a new pathway for delaying the occurrence and development by inhibiting autoimmunity.

Objective: It is poorly understood α-cell function changes to respond to the different detectable C-peptide levels in patients with type 1 diabetes (T1D). This study aims to investigate the relationship between glucagon secretion and declining β-cell function in patients with T1D. Methods: Eighty-seven subjects [68, autoimmune type 1 diabetes (T1AD); 4, fulminant type 1 diabetes (FT1D); 15 healthy controls] were enrolled. All participants underwent a 100g steamed bread meal tests (SBMT). T1AD patients were divided into C-peptide negative (CPN), C-peptide middle (CPM) and C-peptide high (CPH) group based on peak C-peptide levels. Both fasting and postprandial of glucose, C-peptide and glucagon were measured. Glucagon among groups were compared by a linear mixed-effects model. The relationship between C-peptide, glucose and glucagon responses was evaluated by regression analysis. Results: At baseline, fasting glucagon concentrations were comparable between CPN, CPM and CPH group (F=0.099, P=0.906). After SBMT, 180min-glucagon in CPN group were higher than in CPM (P=0.004) and in CPH group (P<0.001). The iAUC30-180 of glucagon was lower in CPH than in CPN (P=0.001) and in CPM group (P=0.034), whereas the iAUC0-30 glucagon did not differ among CPN, CPM and CPH group (F=1.246, P=0.295). The same results were observed in iAUC of glucagon/glucose. After adjustment for age, BMI and diabetes duration, the iAUC30-180 glucagon in T1AD was inversely related to peak C-peptide and positively related to peak glucose levels (Radj2=0.315, P<0.001); however, the iAUC0-30 glucagon in T1AD was only positively related to 30min-glucose (Radj2=0.466, P<0.001). Conclusions: This study demonstrates α-cell function in patients with T1D are compromised with different levels of residual C-peptide. Glucose is also a contributor factor for postprandial hyperglucagonemia. Disclosure L. Zhang: None. Y. Shi: None. Y. Huang: None. Q. Hu: None. Y. Qin: None. M. Zhang: None. Funding National Natural Science Foundation of China (81670756, 81974103), Provincial Key Research and Development Foundation of Jiangsu (BE2018748)

IL-2 is one of the earliest cytokines discovered and applied in clinical medicine.At the first time,IL-2 drew much attention because of its ability to stimulate the proliferation of T cells.Posterior studies revealed that IL-2 can shift the balance between Tregs and Teffs by activating downstream signaling through the combination with receptor IL-2R.The shifted balance of Tregs and Teffs could maintain the immune tolerance and thus change the course of immune-mediated diseases.Recently,with further research on biological activity of IL-2,scientists re-evaluate the indications,application dose,security,as well as immunotherapeutic effect of IL-2.