Objective To compare the discrepancies among results of three commonly used laboratory direct test methods for maximal oxygen uptake(VO2max),explore their linear regression relationships,mutual predictability and comparability.Methods Using a quasi-experimental design of cluster sampling and within-group interaction design,20 male cross-country skiers were tested for VO2max using the Bruce protocol(Method 1),90-second incremental load exercise on power bicycle(Method 2),and 1-minute incremental load exercise on treadmill(Method 3),with an interval of one week.The indepen-dent and dependent variable were the three VO2max test methods and the VO2max,respectively.Results Significant differences were found in the average VO2max of the three test results,with the value mea-sured by Method 1 ranking the first,followed by that assessed by Method 3 and Method 2(P<0.05).Moreover,the frequency of individual differences in the results of the three methods showed that the VO2max of Method 1 was about 6 and 3 ml/min·kg higher than that measured by Method 2 and 3.However,at the same treadmill speed,the average blood lactate evaluated using Method 3 was higher than Method 1,and the speed reached aerobic and anaerobic thresholds about one speed unit(1 km/h)lower than Method 1.Meanwhile,linear regression analyses of the test results between Method 1 and 2,as well as Method 1 and 3 showed that both the regression models and coefficients were statis-tically significant(P<0.001),with the R-squared values of 9.25 and 9.05,respectively.Conclusion The Bruce protocol performs best in assessing the maximum value of the athlete's VO2max phase,whose results have linear regression relationships with the other two methods,and can be used for pre-dicting their results.Moreover,athletes of different events and levels can choose different VO2max test methods accordingly.Lastly,the speed and heart rate ranges corresponding to the aerobic and anaero-bic thresholds can serve as an effective and convenient method to control the training intensity.

The classification of diabetes is undergoing a significant transformation.As advancements in medical technology and a deeper understanding of its etiology,traditional classification methods based on clinical characteristics and insulin dependency are increasingly revealing their limitations.In recent years,the integration of genomic,epigenetic,and metabolomic technologies,combined with the application of big data analytics and machine learning in disease classification,has propelled diabetes classification towards enhanced precision and personalization.These cutting-edge technologies elucidate the intricate pathophysiological mechanisms and exten-sive heterogeneity inherent in diabetes,offering novel methodologies for early diagnosis,individualized treatment,and prognostic evaluation.This paradigm shift not only deepens the comprehension of diabetes complexity but also holds the potential to provide more precise and efficacious therapeutic interventions for patients.Consequently,this marks a historic transition from simplistic,clinically-based classification systems to sophisticated,molecular mechanism-based paradigms in diabetes classification.

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

Type 1 diabetes mellitus (T1DM) is an organ-specific disease characterized by autoimmune damage to pancreatic β cells. Insulin therapy is the most basic and important treatment for T1DM, but insulin therapy cannot fundamentally terminate or improve the main cause of T1DM, namely the disorder of the immune regulation mechanism. With the advancement of science and technology, the continuous development of new insulin and hypoglycemic drugs has provided better means for glycemic control. Pancreas transplantation, islet transplantation, immunotherapy, and cell therapy have provided hope for the prevention or reversal of T1DM. It is of great significance to understand the current situation and future of new technologies for T1DM treatment for the research and management of T1DM patients.

Diabetes is a group of clinical syndromes with multiple causes and pathologies resulting from multiple factors. Different types of diabetes have different intrinsic types and complex clinical phenotypes according to genetics, immunology, metabolism, and clinical characteristics. Latent autoimmune diabetes in adults and ketosis-prone diabetes are the manifestation of clinical heterogeneity among different types of diabetes. High clinical heterogeneity gradually obscures the classic differences between diabetes types and leads to the emergence of new forms of diabetes. The high heterogeneity of diabetes poses challenges to the accurate classification of diabetes mellitus. It has significance in the prediction, prevention, diagnosis, and treatment of the disease for us to have a deep understanding of the clinical consequences of heterogeneity within and between different diabetes types.

Objective:To analyze the clinical features of latent autoimmune diabetes (LADA) in adults among newly diagnosed type 2 diabetes mellitus (T2DM), and to explore whether LADA diagnostic models can be established based on this.Methods:From May 2016 to January 2017, 302 patients with newly diagnosed T2DM in the outpatient and inpatient department of metabolism and endocrinology of Yueyang Central Hospital were analyzed. All of them were tested for glutamic acid decarboxylase antibody (GADA). According to the consensus of the Chinese Medical Association Diabetes Association (CDS) LADA diagnosis and treatment, they were divided into LADA group (18 cases) and T2DM group (284 cases). The general clinical data and clinical biochemical indexes of the two groups were analyzed; Multiple linear regression method was used to evaluate the feasibility of establishing LADA diagnostic model.Results:⑴ Compared with patients in the T2DM group, the patients in the LADA group had a younger age of onset, and " three more and one less" symptoms were more common ( P<0.05); the weight, body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), triglycerides (TG), fasting C peptide (FCP), postprandial 2 h C peptide (2 h-CP), modified islet function index HOMA-islet (CP-DM), and modified insulin resistance index HOMA-IR (CP) in the LADA group were all lower, while high-density lipoprotein cholesterol (HDL-C) and HbA1c were higher ( P<0.05). ⑵ the linear regression method was used to analyze the multicollinearity of patients in LADA group and T2DM group. The biochemical indexes with statistically significant difference were selected as independent variables through correlation analysis, and the GADA value was used as dependent variable. The statistical results showed that the independent variables could not fully meet the conditions of multicollinearity regression analysis. Conclusions:⑴ Related clinical features and glucose metabolism indicators have differential diagnosis significance for LADA, but this study cannot be used for multiple linear regression analysis, and it is difficult to establish a diagnostic model for LADA. ⑵ LADA diagnosis is a comprehensive diagnosis, which should be combined with the results of islet autoantibody and clinical features.

Objective: To evaluate the association between NLRP2(NLR Family Pyrin Domain Containing 2) gene polymorphisms and classical type 1 diabetes mellitus(T1DM) in Chinese Han population. Methods: A case-control study was conducted in 510 classical T1DM patients from the Department of Metabolism and Endocrinology in the Second Xiangya Hospital affiliated to Central South University and 531 healthy controls in this region. The polymorphisms of rs1043673 in NLRP2 gene were analyzed by MassARRAY. Mann-Whitney U test and χ² test were used to compare the differences between patients and controls. Logistic regression analysis and χ² test were performed to compare the distributions of the alleles and genotypes between T1DM patients and controls. Kruskal-Wallis H test was used to compare the clinical characteristics of different genotypes in T1D patients. Results: The differences of the allele and genotype distributions in rs1043673 of NLRP2 gene were not significant between patients and controls. The polymorphisms of rs1043673 were associated with fasting C-peptide(P=0.029), postprandial 2-h C-peptide(P=0.017), and titer of GADA(P=0.043) in T1DM patients. Conclusion The polymorphisms of NLRP2 gene were associated with the characteristics of T1DM patients.

Unnatural amino acid orthogonal translation machinery can insert unnatural amino acids at desired sites of protein through stop codon by means of foreign orthogonal translation system composed of aminoacyl-tRNA synthetase and orthogonal tRNA genes. This new genetic engineering technology is not only a new tool for biochemical researches of proteins, but also an epoch-making technology for the development of new-type live viral vaccines. The mutated virus containing premature termination codon in genes necessary for replication can be propagated in transgenic cells harboring unnatural amino acid orthogonal translation machinery in media with corresponding unnatural amino acid, but it cannot replicate in conventional host cells. This replication-deficient virus is a new-type of live viral vaccine that possesses advantages of high efficacy of traditional attenuated vaccine and high safety of killed vaccine. This article reviews the application and prospect of unnatural amino acid orthogonal translation machinery in the development of novel replication-deficient virus vaccines.
Amino Acids ; genetics ; Amino Acyl-tRNA Synthetases ; Genetic Engineering ; Protein Engineering ; RNA, Transfer ; Viral Vaccines

Fulminant type 1 diabetes (FT1D) is a new subtype of type 1 diabetes mellitus.It has a fulminant onset of symptoms accompanied with disturbance of consciousness or elevated trypsin,severe hyperglycemia,and severe metabolic disorders.It is a critical disease.FT1D in pregnant women,the elderly,and children and adolescents have different clinical manifestations and treatments due to their different physiological aspects in comparison with that in the adults.This article summarizes the characteristics and managements of FT1D in pregnant women,the elderly,and children and adolescents in order to further enhance the understanding of FT1 D.We call on all clinicians to be vigilant and pay attention to the early diagnosis and treatment of FT1 D in special populations.

Objective To investigate the expression levels and significance of hypoxia inducible factor-1 α (HIF-1 α),vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in pathological scar.Methods 73 patients with pathological scar from March 2015 to February 2017 in our hospital were selected,including 42 cases in hypertrophic scar group and 31 cases in keloid group.20 cases of non pathological scar patients and 20 cases of normal plastic surgery were selected as control group.mRNA and protein expression levels of HIF-1,VEGF and MMP-2 in skin tissue of each group were detected by real-time fluorescence quantitative and Western blot,and the clinical significance was analyzed.Results Compared with non pathological scar tissue and normal skin tissue,the mRNA and protein expression levels of HIF-1α,VEGF and MMP-2 in pathological scar tissue were significantly increased,and the differences were statistically significant (P ＜ 0.05).The mRNA and protein expression levels of HIF-1α in keloid group were significantly higher than those in hypertrophic scar group (P ＜ 0.05);there was no significant difference in the expressions of mRNA and protein of VEGF between keloid group and hypertrophic scar group (P ＞ 0.05);the mRNA and protein expression levels of MMP-2 in keloid group were significantly lower than those in hypertrophic scar group (P ＜ 0.05).Pearson correlation analysis showed that there was a significant positive correlation between HIF-1α and VEGF,MMP-2 in pathological scar tissues (r =0.623,0.507,P ＜ 0.05).Conclusions The expressions of HIF-1α,VEGF and MMP-2 in pathological scar tissue is obviously increased,which is closely related to the formation of pathological scar.