Analysis of an adult diabetes mellitus caused by a rare mutation of the gene:A case report

BACKGROUND This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence,featuring a unique mutation in the peroxisome proliferator-activated receptor gamma(PPARG)gene.Data Access Statement:Research data supporting this publication are available from the NN repository at www.NNN.org/download/.CASE SUMMARY The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members.Additionally,high-throughput sequencing was conducted to analyze the PPARG genes of the patient,her siblings,and their offspring.The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy,accompanied by insulin resistance and hypertriglyceridemia.Furthermore,these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns.The results from the gene detection process demonstrated a heterozygous mutation of guanine(G)at position 284 in the coding region of exon 2 of PPARG,which replaced the base adenine(A)(exon2c.284A>Gp.Tyr95Cys).This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein.Notably,both of her siblings harbored a nucleotide heterozygous variation at the same site,and both were diagnosed with diabetes.CONCLUSION The PPARG gene mutation,particularly the p.Tyr95Cys mutation,may represent a newly identified subtype of maturity-onset diabetes of the young.This subtype is characterized by insulin resistance and lipid metabolism disorders.

Interaction between tumor stage and age on survival outcomes of patients with anaplastic thyroid cancer

BACKGROUND Anaplastic thyroid cancer(ATC)is an aggressive,rare malignancy associated with rapid growth and metastasis,and a very poor prognosis.We investigated the clinical characteristics,survival outcomes and independent prognostic factors associated with anaplastic thyroid cancer.AIM To assess to what extent the interaction between age and tumor stage affects mortality.METHODS A total of 622 patients diagnosed with anaplastic thyroid cancer,between 2010 and 2017 were enrolled in our study by retrieving data from the Surveillance,Epidemiology and End Results(SEER)database.We analyzed demographics,clinical characteristics,overall mortality(OM)and cancer specific mortality(CSM)of ATC.Variables with a P value<0.1 were incorporated into the multivariate cox model to determine the independent prognostic factors.Furthermore,we analyzed the interaction between age and tumor stage on mortality.RESULTS In the multivariate analyses,the divorced/separated population had a lower OM[hazard ratio(HR)=0.63,95%CI:0.42-0.94,P<0.05]and CSM(HR=0.61,95%CI:0.40-0.92,P<0.05).OM was higher in tumors with direct extension only(HR=6.26,95%CI:1.29-30.42,P<0.05)and tumors with distant spread(HR=5.73,95%CI:1.34-24.51,P<0.05).CSM was also higher in tumors with direct extension(HR=5.05,95%CI:1.05-24.19,P<0.05)and tumors with distant spread(HR=4.57,95%CI:1.08-19.29,P<0.05).Mortality was not adversely affected by lymph node involvement.OM was lower in patients who received radiation(HR=0.66,95%CI:0.53-0.83,P<0.01),chemotherapy(HR=0.63,95%CI:0.50-0.79,P<0.01)or surgery(HR=0.53,95%CI:0.43-0.66,P<0.01).CSM was also lower in patient who received radiation(HR=0.64,95%CI:0.51-0.81,P<0.01),chemotherapy(HR=0.62,95%CI:0.50-0.78,P<0.01)or surgery(HR=0.51,95%CI:0.41-0.63,P<0.01).There was no significant interaction between age and tumor stage that affected mortality.CONCLUSION In this large US SEER database retrospective study,we found the mortality to be higher in advanced stage tumors with direct extension and distant metastasis.However,patients who received aggressive therapy showed a better overall survival.The aim of our study is to emphasize the importance of detecting ATC at an early stage and provide aggressive therapy to these patients.Since advanced stage ATC is associated with a dismal prognosis,we emphasize the need for randomized control trials and development of novel therapies that will be used to treat ATC.

Analysis of the management and therapeutic performance of diabetes mellitus employing special target

Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantlyby hyperglycemia. The most common causes contributing to the pathophysiologyof diabetes are insufficient insulin secretion, resistance to insulin’stissue-acting effects, or a combination of both. Over the last 30 years, the globalprevalence of diabetes increased from 4% to 6.4%. If no better treatment or cure isfound, this amount might climb to 430 million in the coming years. The major fact-ors of the disease’s deterioration include age, obesity, and a sedentary lifestyle.Finding new therapies to manage diabetes safely and effectively without jeopardizingpatient compliance has always been essential. Among the medicationsavailable to manage DM on this journey are glucagon-like peptide-1 agonists,thiazolidinediones, sulphonyl urease, glinides, biguanides, and insulin-targetingreceptors discovered more than 10 years ago. Despite the extensive preliminarystudies, a few clinical observations suggest this process is still in its early stages.The present review focuses on targets that contribute to insulin regulation andmay be employed as targets in treating diabetes since they may be more efficientand secure than current and traditional treatments.

Physical Activity,Sedentary Behavior,and the Risk of Cardiovascular Disease in Type 2 Diabetes Mellitus Patients:The MIDiab Study

The aim of this study was to explore the associations of moderate-to-vigorous-intensity physical activity(MVPA)time and sedentary(SED)time with a history of cardiovascular disease(CVD)and multifactorial(i.e.,blood pressure(BP),body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),and glycated hemoglobin A1c(HbA1c))control status among type 2 diabetes mellitus(T2DM)patients in China.A cross-sectional analysis of 9152 people with type 2 diabetes from the Multifactorial Intervention on Type 2 Diabetes(MIDiab)study was performed.Patients were grouped according to their self-reported MVPA time(low,<150 min·week−1;moderate,150 to<450 min·week−1;high,≥450 min·week−1)and SED time(low,<4 h·d–1;moderate,4 to<8 h·d–1;high,≥8 h·d–1).Participants who self-reported a history of CVD were identified as having a CVD risk.Odds ratios(ORs)and 95%confidence intervals(CIs)of CVD risk and multifactorial control status associated with MVPA time and SED time were estimated using mixed-effect logistic regression models,adjusting for China’s geographical region characteristics.The participants had a mean±standard deviation(SD)age of(60.87±8.44)years,44.5%were women,and 25.1%had CVD.After adjustment for potential confounding factors,an inverse association between high MVPA time and CVD risk that was independent of SED time was found,whereas this association was not observed in the moderate-MVPA group.A higher MVPA time was more likely to have a positive effect on the control of BMI.Compared with the reference group(i.e.,those with MVPA time≥450 min·week−1 and SED time<4 h·d–1),CVD risk was higher in the low-MVPA group:The OR associated with an SED time<4 h·d–1 was 1.270(95%CI,1.040–1.553)and that associated with an SED time≥8 h·d–1 was 1.499(95%CI,1.149–1.955).We found that a high MVPA time(i.e.,≥450 min·week−1)was associated with lower odds of CVD risk regardless of SED time among patients with T2DM.

Characterization of microRNAs in serum： a novel class of biomarkers for diagnosis of cancer and other diseases

Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.

Increased Risk of Chronic Kidney Diseases in Patients with Metabolic Syndrome:A 3-year Prospective Cohort Study

The relationship of metabolic syndrome(MS)and its components with incident chronic kidney disease(CKD)and rapid decline of estimated glomerular filtration rate(eGFR)was investigated.A total of 10 140 patients participating in the epidemiological study(Risk Evaluation of Cancers in Chinese Diabetic Individuals,REACTION)of risk factors of type 2 diabetes in China were followed up for 3 years,with MS being diagnosed by adult treatment panel IH(ATP IH)combined with waist circumference in Asian population and renal function being evaluated by eGFR<60 mL min^-1(1.73 m^2)^-1 and rapid decline of eGFR≤30%.The results showed that as compared with the non-MS group,the adjusted odds ratios(ORs)of CKD and rapid decline of eGFR were 1.64(OR:1.64;95%CI:1.20-2.25,P<0.05)and 1.23(OR:1.23;95%CI:1.05-1.43,P<0.05)respectively in MS group.With the increase in the number(0,1,2,3 and≥4)of MS components,the prevalence of CKD was 1.42%,1.44%,2.80%,3.42%,and 4.03%(P<0.001),respectively.The ORs of incident CKD were 1.67(OR:1.67;95%CI:1.22-2.27,P<0.05)for high TG,1.50(OR:1.50;95%CI:1.10-2.05,P<0.05)for low HDL-C,and 1.39(OR:1.39;95%CI:1.02-1.91,P<0.05)for hyperglycemia.The risk for developing incident CKD was higher in the group with the highest HOMA-IR than in the group with the lowest HOMA-IR(OR:1.83;95%CI:1.16-2.89,P<0.05).It is suggested that MS is an independent risk factor for incident CKD.The occurrence and development of CKD is closely related to insulin resistance.

Effects of laser photocoagulation on serum angiopoietin-1, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, and soluble angiopoietin receptor Tie-2 levels in type 2 diabetic patients with proliferative diabetic retinopathy

·AIM: To determine the effects of laser photocoagulation on serum levels of angiopoietin-1(Ang-1),angiopoietin-2(Ang-2), soluble angiopoietin receptor Tie-2(Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor(VEGF) in patients with type 2diabetes mellitus(T2DM) and proliferative diabetic retinopathy(PDR). We also explored the role of the Ang/Tie system in PDR.·METHODS:Totally 160patientswithT2 DM, including50 patients with non-diabetic retinopathy(NDR), 58 patients with non-proliferative diabetic retinopathy(NPDR), and52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure.·RESULTS:ThemedianlevelsofAng-2andVEGFinserum were significantly higher in the NPDR group(4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group(2.67 ng/mL and 159.8 pg/mL, respectively, P 【0.01), with the highest level in the PDR group(6.26 ng/mL and531.2 pg/mL, respectively, P 【0.01). The median level of Ang-1 was significantly higher in the NPDR group(10.77ng/mL) compared to the NDR group(9.31 ng/mL) and the PDR groups(9.54 ng/mL)(P 【0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups(1.49 vs 2.69 and 2.90, both P 【0.01). The median level of Tie-2was not significantly different among three groups(P 】0.05).Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups(both P 【0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased(both P 【0.05), whereas serum Ang-1 level and Ang-1/Ang-2ratio were weakly increased(P 】0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group,however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups.·CONCLUSION: Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2 DM patients with PDR.

Association of glycosylated hemoglobin level with lipid ratio and individual lipids in type 2 diabetic patients

Objective:To study the correlation of lipid ratios and individual lipid indexes of patients with type 2 diabetes with glycosylated hemoglobin(HbA_(1c)).Methods:Samples were collected from 128 type 2 diabetic patients(aged 19-90 years;male 72,female 56).The sera were analyzed for HbA_(1c),total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C).According to the HbA_(1e) level,the patients were divided into three groups,group A(HbA_(?)<7%,n=31),group B(7%<HbA_(1c)<10%,n=48),and group C(HbA_(1c)>10%,n=49).The correlation of HbA_(1c)with lipid ratios & individual lipid indexes were analyzed.Results:With the increased level of HbA(1c),LDL-C had a significantly increasing trend(P<0.05);whereas TC went up with the increased HbA(1c),without any significant differences between three groups.There was no significant correlation between HbA_(1c) and TG or HDL-C. With the increased level of HbA_(1c),TC/HDL-C,LDL-C/HDL-C ratios were gradually increased, with significant differences among groups(P<0.05).The lipid ratios,especially LDL-C/HDL-C ratio was more susceptible to impaired lipid metabolism in T2DM patients than individual lipid. Conclusions:LDL-C/HDL-C ratio is helpful in assessing and reducing the risk of cardiovascular disease caused by impaired lipid metabolism in type 2 diabetic patients.

Prevalence and characteristics of MAFLD in Chinese adults aged 40 years or older:A community-based study

Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.

Primary Hyperparathyroidism:A Tale of Two Cities Revisited-New York and Shanghai

In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism （PHPT） changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT con- tinues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.

EFFECTS OF GLIBENCLAMIDE, GLIMEPIRIDE, AND GLICLAZIDE ON ISCHEMIC PRECONDITIONING IN RAT HEART

Objective To compare the influence of different sulfonylureas on the myocardial protection effect of ischemic preconditioning (IPC) in isolated rat hearts, and ATP-sensitive potassium channel current (IKATP) of rat ventricular myocytes. Methods Isolated Langendorff perfused rat hearts were randomly assigned to five groups: (1) control group, (2) IPC group, (3) IPC+glibenclamide (GLB, 10 μmol/L) group, (4) IPC+glimepiride (GLM, 10 μmol/L) group, (5) IPC+gliclazide (GLC, 50 μmol/L) group. IPC was defined as 3 cycles of 5-minute zero-flow global ischemia followed by 5-minute reperfusion. The haemodynamic parameters and the infarct size of each isolated heart were recorded. And the sarcolemmal IKATP of dissociated ventricular myocytes reperfused with 10 μmol/L GLB, 1 μmol/L GLM, and 1 μmol/L GLC was recorded with single-pipette whole-cell voltage clamp under simulated ischemic condition. Results The infarct sizes of rat hearts in IPC (23.7%±1.3%), IPC+GLM (24.6%±1.0%), and IPC+GLC (33.1%±1.3%) groups were all significantly smaller than that in control group (43.3%±1.8%; P<0.01, n=6). The infarct size of rat hearts in IPC+GLB group (40.4%±1.4%) was significantly larger than that in IPC group (P<0.01, n=6). Under simulated ischemic condition, GLB (10 μmol/L) decreased IKATP from 20.65±7.80 to 9.09±0.10 pA/pF (P<0.01, n=6), GLM (1 μmol/L) did not significantly inhibit IKATP (n=6), and GLC (1 μmol/L) decreased IKATP from 16.73±0.97 to 11.18±3.56 pA/pF(P<0.05, n=6). Conclusions GLM has less effect on myocardial protection of IPC than GLB and GLC. Blockage of sarcolemmal ATP-sensitive potassium channels in myocardium might play an important role in diminishing IPC-induced protection of GLM, GLB, and GLC.

Optimal Waist Circumference Cut-off values for Identifying Metabolic Risk Factors in Middle-aged and Elderly Subjects in Shandong Province of China

Objective To study the optimal waist circumference （WC） cut-off values for identifying metabolic risk factors in middle-aged and elderly subjects in Shandong Province of China. Methods A total of 2 873 men and 5 559 women were included in this cross-sectional study. Metabolic syndrome （MetS） was diagnosed according to the definition of Chinese Diabetes Society in 2004. The relation between WC and MetS was analyzed by multivariate logistic regression analysis. The optimal WC cut-off values were identified using the area under the ROC curve and the different diagnostic criteria for central obesity were compared. Results The WC was the risk factor for MetS independent of BMI, blood glucose, blood lipid, and blood pressure. The optimal WC cut-off value was 83.8 cm and 91.1 cm for identifying MetS in women and men, respectively. Compared with 80 cm and 85 cm for women and men, 85 cm and 90 cm had a higher Youden index for identifying all metabolic risk factors and MetS in women and men. Conclusion The appropriate WC cut-off value is 85 cm and 90 cm for identifying central obesity and MetS in women and men in Shandong Province of China.

Peripheral Artery Disease and Risk of Fibrosis Deterioration in Nonalcoholic Fatty Liver Disease:A Prospective Investigation

Objective Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease(NAFLD).Peripheral artery disease(PAD)and liver fibrosis share many common metabolic dysfunctions.We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients.Methods The study recruited 1,610 NAFLD patients aged≥40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015.Fibrosis deterioration was defined as the NAFLD fibrosis score(NFS)status increased to a higher category at the follow-up visit.PAD was defined as an ankle-brachial index of<0.90 or>1.40.Results During an average of 4.3 years’follow-up,618 patients progressed to a higher NFS category.PAD was associated with 92%increased risk of fibrosis deterioration[multivariable-adjusted odds ratio(OR):1.92,95%confidence interval(CI):1.24,2.98].When stratified by baseline NFS status,the OR for progression from low to intermediate or high NFS was 1.74(95%CI:1.02,3.00),and progression from intermediate to high NFS was 2.24(95%CI:1.05,4.80).There was a significant interaction between PAD and insulin resistance(IR)on fibrosis deterioration(P for interaction=0.03).As compared with non-PAD and non-IR,the coexistence of PAD and IR was associated with a 3.85-fold(95%CI:2.06,7.18)increased risk of fibrosis deterioration.Conclusion PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients,especially in those with IR.The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.

Identification of two novel mutations in the GALNT3 gene in a Chinese family with hyperphosphatemic familial tumoral calcinosis

Hyperphosphatemic familial tumoral calcinosis(HFTC) is a rare, autosomal recessive genetic disease.This disease is characterized by the progressive calcification of soft tissues leading to symptoms of pressure and hyperphosphatemia but normal concentrations of serum calcium with or without an elevation of1,25-dihydroxyvitamin D3 levels.HFTC is caused by loss-of-function mutations in the GALNT3, FGF23 or KL genes. Here, we identified two novel mutations in the GALNT3 gene in a Chinese family with HFTC.Identification of a novel genotype in HFTC provides clues for understanding the phenotype–genotype relationships in HFTC and may assist not only in the clinical diagnosis of HFTC but also in the interpretation of the genetic information used for prenatal diagnosis and genetic counseling.

Bilateral inferior petrosal sinus sampling for the treatment of Cushing's disease Data from 52 cases from one institute over an eight-year period

The present study analyzed data from 108 Cushing＇s disease patients, who underwent transsphenoidal surgery in one hospital between January 2003 and April 2010, to investigate the performance value of bilateral inferior petrosal sinus sampling （BIPSS）. Of the 108 patients 52 underwent BIPSS prior to surgery and 56 did not. Results showed that BIPSS accuracy for the diagnosis of Cushing＇s disease was 86.5% （45/52）, and accuracy for adenoma lateralization during surgery was 76.9% （40/52）. In addition, early remission rate was significantly greater compared to patients without BIPSS. Results demonstrated that BIPSS facilitated localization and diagnosis of Cushing＇s disease and helped to predict adenoma lateralization.

Role of ranulas in early diagnosis of Sjögren’s syndrome: A case report

BACKGROUND Although the presentations of Sjögren’s syndrome(SS)are variable,ranging from mild dryness to wider systemic involvement,ranulas as early clinical signs were scarcely reported.Here,we present an adult patient with SS,who developed a unilateral simple ranula and was diagnosed primary SS 3 years later.We also provide a review of cases of SS and ranulas from 1980 to 2020.CASE SUMMARY A 22-year-old girl was found to have a left painless floor-of-mouth lesion 3 years ago,without obvious trauma or inducement.The diagnosis of a unilateral(left)simple ranula was made,and the ranula was surgically treated.Within 3 years after the ranula surgery,she developed acute lymphadenectasis in unilateral parotid twice without inducement,and ultrasonic examination revealed diffuse lesions in bilateral parotids and submandibular glands,which strongly suggested SS.Serologic tests and the unstimulated whole saliva flow rate confirmed the SS diagnosis.CONCLUSION Our study underlines that ranulas are early clinical signs of SS.As early diagnosis and early intervention of SS are important to obtain better outcomes,our findings underline the need for histopathological test after sublingual adenectomy and imaging detection of exocrine glands for the patients with ranulas.

Effects of lipoic acid on the activities of fibrinase, antioxidant enzymes and related factors in patients with type 2 diabetic foot

Objective:To investigate the effects of lipoic acid on the activities of fibrinase, antioxidant enzymes and related factors in patients with type 2 diabetic foot.Methods: 120 patients with type 2 diabetic foot treated in the Department of Endocrinology and Metabolism in our hospital from March 2015 to March 2018 were collected and randomly divided into control group and observation group, 60 cases in each group. The patients in control group were treated with alprostadil, and the patients in observation group were treated with lipoic acid combined with alprostadil. Before and after treatment, the levels of plasminogen activator, fibrinopeptide A, plasminogen activator inhibitor-1, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT), Toll-like receptor 2 (TLR2), Toll-like receptor 9 (TLR9), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-9 (MMP-9) and homocysteine (Hcy) of patients in the two groups were detected and compared.Results: After treatment, the levels of plasminogen activator, SOD, GSH-PX and CAT of patients in the control group and the observation group were significantly increased. The levels of fibrinogen A and plasminogen activator inhibitor -1 of patients in the control group and the observation group were significantly decreased. The changes of the above indexes of patients in the observation group were more obvious than those in the control group (P<0.05). The levels of TLR2, TLR9, VCAM-1, MMP-9 and Hcy in the serum of patients in the control group and the observation group were significantly decreased. The down-regulation of these factors of patients in the observation group was more obvious than that in the control group (P<0.05).Conclusion:Lipoic acid combined with alprostadil in the treatment of type 2 diabetes mellitus disease can significantly enhance the activity of fibrinolytic enzymes and antioxidant capacity, alleviate inflammation, and it has a good clinical effect.

Elevated levels of fructosamine are independently associated with SARS-CoV-2 reinfection:A 12-mo follow-up study

BACKGROUND The association between blood levels of fructosamine(FMN)and recurrent coronavirus disease 2019(COVID-19)is currently unclear.AIM To investigate a prospective relationship between blood levels of FMN and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)reinfection.METHODS A total of 146 Chinese hospitalized patients infected with SARS-CoV-2 were consecutively collectively recruited and followed from January 2020 to May 2021.Diagnosis of COVID-19 and SARS-CoV-2 reinfection was based on the diagnostic criteria and treatment protocol in China.The levels of FMN were determined in blood and divided into tertiles based on their distribution in the cohort of COVID-19 patients.Multivariate-adjusted hazard ratios(HRs)with 95%confidence intervals(CIs)were estimated for SARS-CoV-2 reinfection across the tertiles of FMN levels.A Cox regression model was used to generate the HR for SARS-CoV-2 reinfection in the participants in the top tertile of FMN levels compared with those at the bottom.Disease-free survival was used as the time variable,and relapse was used as the state variable,adjusted for age,gender,influencing factors such as diabetes mellitus,hypertension,and corticosteroid therapy,and clinical indexes such as acute liver failure,acute kidney failure,white blood cell(WBC)count,C-reactive protein,prognostic nutritional index(PNI),and blood lipids.Kaplan-Meier analysis with log-rank tests was used to compare the survival rate between patients with elevated FMN levels(FMN>1.93 mmol/L,the top tertile)and those with nonelevated levels.RESULTS Clinical data for the 146 patients with confirmed COVID-19[age 49(39-55)years;49%males]were analyzed.Eleven patients had SARS-CoV-2 reinfection.The SARS-CoV-2 reinfection rate in patients with elevated FMN levels was significantly higher than that in patients with nonelevated FMN(17%vs 3%;P=0.008)at the end of the 12-mo follow-up.After adjustments for gender,age,diabetes mellitus,hypertension,corticosteroid therapy,WBC count,PNI,indexes of liver and renal function,and blood lipids,patients with nonelevated FMN levels had a lower risk of SARS-CoV-2 reinfection than those with elevated FMN levels(HR=6.249,95%CI:1.377-28.351;P=0.018).Kaplan-Meier analysis showed that the cumulative survival rate of patients infected with SARSCoV-2 was higher in patients with nonelevated FMN levels than in those with elevated FMN levels(97%vs 83%;log rank P=0.002).CONCLUSION Elevated levels of FMN are independently associated with SARS-CoV-2 reinfection,which highlights that patients with elevated FMN should be cautiously monitored after hospital discharge.

Association of Early-Life Famine Exposure with Metabolic Dysfunction-Associated Fatty Liver Disease and Fibrosis in Adulthood

Nonalcoholic fatty liver disease(NAFLD)is known for its insidious onset and chronic nature,which have jeopardized the health and life of 29.2%of adults in China[1].In 2020,metabolic dysfunctionassociated fatty liver disease(MAFLD),a more accurate nomenclature to replace NAFLD,was put forward in an international consensus of experts involving 22 countries[2].In China,at least 300 million people will suffer from MAFLD by 2030,which will be a heavy burden on national health[3].

Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai

Objective This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease(CKD)in Shanghai community residents.Methods We used data from a cohort study of community residents who participated in three examinations in 2008,2009,and 2013,respectively.Fasting plasma glucose(FPG)level,blood pressure(BP),and lipid levels were determined in 2,109 participants at all three visits,and CKD was evaluated between the second and the third visits.Visit-to-visit variabilities in metabolic factors were described by coefficients of variation(CV)at three visits.A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV.CKD was defined as the estimated glomerular filtration rate<60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio≥30 mg/g.Results A total of 200(9.5%)participants had CKD at the third visit.Compared with the lowest quartile of CV,the highest quartile was associated with a 70%increased risk of CKD for FPG[odds ratio,OR=1.70;95%confidence interval(CI)1.06–2.72],62%for systolic BP(OR=1.62,95%CI 1.04–2.50),and 85%for low-density lipoprotein cholesterol(OR=1.85,95%CI 1.23–2.80).Furthermore,the risk of CKD increased significantly with an increasing variability score.Compared with participants with score 0,participants with scores of 1,2,and 3 were associated with 58%(OR=1.58,95%CI 1.08–2.32),121%(OR=2.21,95%CI 1.40–3.49),and 548%(OR=6.48,95%CI 3.18–13.21)higher risks of CKD,respectively.Conclusion The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.