BACKGROUND: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear. METHODS: In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress. RESULTS: Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment. CONCLUSION Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.
Rats ; Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Insulin Resistance ; Insulin ; Insulin-Secreting Cells/metabolism* ; Apoptosis ; Stress, Physiological ; Transcription Factors/metabolism* ; Palmitates/pharmacology* ; Obesity/metabolism*

OBJECTIVES: Programmed death 1 (PD-1) associated fulminant type 1 diabetes (PFD) is a rare acute and critical in internal medicine, and its clinical characteristics are still unclear. This study aims to analyze the clinical characteristics of PFD patients to improve clinical diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data of 10 patients with PFD admitted to the Second Xiangya Hospital of Central South University, combined with the data of 66 patients reported in the relevant literature, analyzed and summarized their clinical and immunological characteristics, and compared the patients with PFD with different islet autoantibody status. RESULTS: Combined with our hospital and literature data, a total of 76 patients with PFD were reported, with the age of (60.9±12.1) years old, 60.0% male and body mass index of (22.1±5.2) kg/m2. In 76 patients, the most common tumors were lung cancer (43.4%) and melanoma (22.4%). Among PD-1 inhibitors, the most common drugs are nivolumab (37.5%) and pembrolizumab (38.9%). 82.2% of PFD patients developed diabetes ketoacidosis. The median onset time from PD-1 related inhibitor treatment to hyperglycemia was 95 (36.0, 164.5) d, and the median treatment cycle before the onset of diabetes was 6 (2.3, 8.0) cycles. 26% (19/73) of PFD patients had positive islet autoantibodies, and the proportion of ketoacidosis in the positive group was significantly higher than that in the negative group (100.0% vs 75.0%, P<0.05). The onset time and infusion times of diabetes after PD-1 inhibitor treatment in the autoantibody positive group were significantly lower than those in the autoantibody negative group (28.5 d vs 120.0 d; 2 cycles vs 7 cycles, both P<0.001). CONCLUSIONS After initiation of tumor immunotherapy, it is necessary to be alert to the occurrence of adverse reactions of PFD, and the onset of PFD with islet autoantibody positive is faster and more serious than that of patients with autoantibodies negative. Detection of islet autoantibodies and blood glucose before and after treatment with PD-1 inhibitors is of great value for early warning and prediction of PFD.
Humans ; Male ; Middle Aged ; Aged ; Female ; Diabetes Mellitus, Type 1 ; Programmed Cell Death 1 Receptor ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Ketosis ; Autoantibodies

Objective: To establish and evaluate a multiplex PCR method for rapid identification of Mycobacterium species in order to provide an approach for rapid diagnosis of pathogens causing tuberculosis. Methods: Four genes including 16S rRNA, Rv0577, RD9 and mtbk_20680 were selected to establish the multiplex PCR method. Specific primers were designed and the reaction system and conditions were optimized. The sensitivity and specificity of the multiplex PCR method were evaluated through identifying Mycobacterium africanum (M.africanum), Mycobacterium bovis (M.bovis), M. bovis BCG, seven common non-tuberculosis Mycobacterium (NTM), seven reference species of common respiratory bacteria and 93 clinical strains of Mycobacterium tuberculosis (MTB) isolated from patients with tuberculosis in Gansu Province of China. Results: The fragments of 16S rRNA, Rv0577, RD9 and mtbk_20680 genes were 543 bp, 786 bp, 369 bp and 231 bp in length, respectively. MTB strains of the Beijing genotype were positive for all of the four genes, while the non-Beijing genotype strains were negative for mtbk_20680. M. africanum, M. bovis and M. bovis BCG strains were negative for 16S rRNA and Rv0577. NTM strains only carried 16S rRNA and none of four genes were detected in the seven species of respiratory bacteria. Among the 93 clinical MTB strains, 80 (86.02%) belonged to the Beijing genotype and the other 13 (13.98%) were non-Beijing genotype strains. The specificity of the multiplex PCR method was 100%. Conclusions The established multiplex PCR method could accurately distinguish Mycobacterium, Mycobacterium tuberculosis complex (MTBC), NTM, MTB, and Beijing and non-Beijing genotype MTB with high sensitivity and specificity.

Vitamin D plays an important role in the progress of aging,especially in controlling and improving the age-related diseases.The mechanism is associated with apoptosis,oxidative stress and telomere loss.This article summarized the related progress in relationship between the deficiency of vitamin D and aging during the recent ten years in order to offer new ideas for anti-aging role of vitamin D.

Humans ; Lymphoma, Non-Hodgkin ; diagnosis ; Pleural Effusion

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Male ; Middle Aged ; Paraquat ; poisoning ; urine ; Prognosis ; Young Adult

Objective To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVETM study.Methods Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study.Data on demographics,medical history,glycemic profile and treatment regimen at baseline were collected by physicians.Results A total of 3272 patients [female 42％,male 58％,mean age (56.2 ± 10.8) years] were included in the study.Their BMI was (25.3 ± 3.3) kg/m2.The duration of diabetes was 4.0 (0.1-27.0) years,and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0(0.0-20.2) years.The proportions of subjects with diabetic macro-and micro-vascular complications were 15.8％ (515 cases) and 27.1％ (866 cases),respectively.The hemoglobin Al c (HbAl c) at baseline was (8.33 ± 1.70) ％,and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L.Conclusions A large proportion of patients with type 2 diabetes remain in poor glycemic control,and the prevalence of diabetic complications is high,which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.

It is for estimating the laboratory statistics from the view of clinical medicine objectively,completely and appropriately that we establish ＜ Laboratory Sciences and Clinical Medicine ＞ which fits the requirement for the modern medical laboratory specialists. In this selective course, we use problem-based learning ( PBL ) teaching method which is different from the traditional one, stimulating students to participate in the study actively and passionately,training them to think in a scientific way and to analyse and solve the problem in a rational way. As a result, it works well which makes us believe it is worth popularizing.

For the reform and development of clinical laboratory education, based on the previous course reform, Laboratory Medicine College of Chongqing Medical University has put the leading teachers'responsibility system of laboratory medicine course into practice. In the recent 3 years, the course is better organized.The students are more interested in the course and they communicate more with teachers than ever before. The effect of the course is obvious. The leading teachers' responsibility system in laboratory medicine course should be promoted.

Traditional 2D cell culture technology is widely used in cell culture field, but it lacks the formation of 3D matrix scaffold and lacks specific cytokines in vivo.Cells in 3D cell culture system are similar to cells in vivo for gene expression and cell activity. The article focuses on the application of three-dimensional cell culture technology in cancer research, including the construction of tumor microenvironment,tumor biological behavior, tumor angiogenesis, drug resistance and so on and provides a reference for cancer research workers.