Serum klotho associated with thyroid hormone in adults: A population-based cross-sectional research.

BACKGROUND AND STUDY AIM: The klotho protein, a multifunctional protein, has been shown to be associated with a wide range of endocrine diseases and has been linked to thyroid tumourigenesis. However, the relationship between serum klotho levels and thyroid hormones remains poorly understood. This study aimed to explore the correlation between serum klotho levels and thyroid hormones. METHODS: Data was obtained from the NHANES cycles 2007-2008, 2009-2010, and 2011-2012. A total of 4674 participants were recruited for this study. Statistical analysis was using multiple linear regression analyses, and restricted cubic spline plots (RCS) to investigate the association between serum klotho levels and serum levels of thyroid hormones. RESULTS: In the unadjusted covariate model, ln(klotho) significantly positively correlated with tT3, tT4, fT3, tT4/fT4, and tT3/fT3 (all P<0.01) and negatively correlated with TSH, tT4/tT3, and fT4/fT3 (all P<0.05). Furthermore, tT3, tT4, fT3and tT3/fT3 (P < 0.05) were still significant in the adjusted model. And it is worth noting that there is an approximately L-shaped nonlinear relationship between ln(klotho) and fT3,tT3 with a cut-off point of 6.697 (P-non-linear < 0.05). The stratification analysis showed gender and iodine level differences in the relationship between serum Klotho levels and thyroid hormones. CONCLUSION: There is an L-shaped nonlinear relationship between ln(klotho) and fT3, tT3, suggesting that klotho could be involved in the physiological regulation of thyroid function.

Microbiological Distribution, Antimicrobial Susceptibility and Risk Factors of Polymicrobial Infections in Diabetic Foot.

BACKGROUND: Diabetic foot infection (DFI) leads to poor prognosis and polymicrobial infections are usually the main cause. The study is to explore the microbiological distribution, antimicrobial drug susceptibility, and risk factors of polymicrobial infections in hospitalized patients with DFI. METHODS: This retrospective study included 160 patients with DFI in Wagner's grades 2, 3, and 4. Deep necrotic tissue was used to acquire specimens for microbiological culture. VITEK-2 system and MALDI-TOF mass spectrometry were used to identify the bacterial isolates. The Kirby Bauer method was used for drug susceptibility tests. RESULTS: A total of 202 pathogens were isolated. The proportion of gram-negative bacilli (GNB, 62.4%, 126 of 202) was higher than that of gram-positive cocci (GPC, 37.6%, 76 of 202). The most prevalent GPC was Staphylococcus aureus in every Wagner grade, while the most common GNB varied in different Wagner grades. Linezolid was the most effective antibiotic for GPC in different Wagner grades. Imipenem was the most effective antibiotic for GNB in Wagner grade 2. Amikacin was the most effective antibiotic for GNB in Wagner grades 3 and 4. Polymicrobial infections existed only in Wagner grades 3 and 4 and increased the risk of amputation (p < 0.01). History of antibiotics, duration of diabetic foot, CRP, and lower extremity arterial disease were the independent risk factors of polymicrobial infections (p < 0.05). CONCLUSIONS: Clinicians should adjust the antibiotic as needed based on the results of drug susceptibility and clinical treatment effect among different Wagner grades. Particular attention should be given to the treatment of polymicrobial infections.

Chloroform associated with bone mineral density and bone mineral content in adults: A population-based cross-sectional research.

BACKGROUND: Bone mineral density is an important indicator of osteoporosis, and its variation with volatile organic compounds exposure has rarely been studied. However, the relationship between chloroform (an essential volatile organic compounds component) and bone mineral density remains unclear. Consequently, we aimed to explore the relationship between chloroform alone and bone mineral density or bone mineral content. METHODS: Herein, 2,553 individuals aged 18 and above from the National Health and Nutrition Examination Surveys (NHANES) in 2009-2010, 2013-2014, and 2017-2020, were included. We employed two independent t-tests and multi-linear regression models to statistically assess the relationship between chloroform exposure and BMD/BMC in the spine and femoral area. RESULTS: A "V"-shaped correlation between chloroform exposure and bone mineral density or bone mineral content (BMD/BMC) was observed in the unadjusted model, particularly in the Ward's triangle and femoral neck as a whole. A negative correlation was specifically observed for the Ward's triangle BMD/BMC and L4 BMD/BMC. On the other hand, in the adjusted model, a dominantly negative correlation between the L4 BMC and chloroform exposure was observed over a range of exposure levels. The subgroup analysis revealed a negative correlation between chloroform concentrations and BMC in the femur and spine, especially in women and the 65-80 age population. CONCLUSION: Our study revealed a "V" shaped correlation between chloroform and BMD/BMC of the femur and spine in U.S. adults. This finding highlights the fact that prolonged exposure to chloroform may cause the changes in BMD/BMC.

Evaluation of a new low-cost negative pressure wound therapy in the treatment of diabetic foot ulcers.

OBJECTIVE: To investigate the effectiveness of a new and low-cost negative pressure wound therapy (LC-NPWT) in the treatment of diabetic foot ulcers (DFUs). METHOD: In this retrospective cohort study, patients from our inpatient clinic with Wagner grade 3 DFUs were given LC-NPWT or conventional wound dressings. The primary outcome was the wound healing rates. Complete wound healing, defined as complete re-epithelialisation of the wound, was recorded during the two months of follow-up. The definition of complete epidermis of the wound was that the skin was closed (100% re-epithelialisation), with no drainage or dressing. The secondary outcomes were the number of inpatient days and surgical procedures, and outcomes after hospital discharge. The wound score from the Bates-Jensen wound assessment tool and the levels of the inflammation factors procalcitonin (PCT), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were compared between the two groups. The Kaplan-Meier survival estimate was used to examine the cumulative wound healing rate. RESULTS: The study cohort comprised 41 patients. The two-month wound healing rate was higher in patients in the LC-NPWT group than in the control group (15/21 (71.4%) versus 8/20 (40.0%), respectively; p=0.043). At the end of the two-month follow-up period, the cumulative wound healing rate was higher in the LC-NPWT group than in the control group (p=0.032). Patients in the LC-NPWT group had fewer inpatient days (19.3±3.84 versus 25.05±4.81; p<0.001) and shorter duration of antibiotic use (32.14±3.89 days versus 36.10±5.80 days; p=0.014) than those who received conventional wound dressings. There were significant improvements in mean wound score between the LC-NPWT group and the control group (p<0.001). After one week of treatment, the blood levels of PCT (0.03±0.30ng/ml versus 0.07±0.08ng/ml; p=0.039), CRP (14.55±13.40mg/l versus 24.71±18.10mg/l; p=0.047) and ESR (42.05±29.29mm/h versus 61.65±22.42mm/h; p=0.021) were lower in patients who received LC-NPWT than those who received conventional wound dressings. CONCLUSION: LC-NPWT is effective in the treatment of DFUs and provides a cheaper alternative for patients with DFUs that could potentially alleviate the economic distress these patients endure.

Association between serum heavy metal levels and diabetic retinopathy in NHANES 2011-2020.

The present study utilized the National Health and Nutrition Examination Survey (NHANES) database to examine the relationship between serum levels of heavy metals and Diabetic retinopathy (DR) in individuals aged over 30 years with type 2 diabetes mellitus (T2DM) in the United States. A cross-sectional analysis was conducted on 1583 individuals with T2DM from the NHANES 2011-2020, including 331 individuals in the DR group and 1252 individuals in the non-DR group. We collected data on serum levels of heavy metals, DR, and serum albumin for descriptive statistics, linear regression, and logistical regression analysis. After adjusting for age, gender, race and other factors, there was no statistically significant association between blood cadmium, selenium, mercury, or lead and DR. However, serum manganese (Mn) and DR had a significant negative association (ß = - 0.2045, 95% CI = - 0.3484, - 0.0606). Serum albumin partially modulated the indirect influence of serum Mn on the incidence of DR, accounting for 12.80% of the association between serum Mn and DR. There was a negative association between serum Mn levels and the prevalence of DR in people with T2DM. Mn intake at least in this study has a little influence on the onset and development of DR.

Relationship between body fat ratio and inflammatory markers in a Chinese population of adult male smokers.

Objective: To explore the correlation between changes in the body fat ratio (BFR) and peripheral blood inflammatory markers according to smoking status in the adult Chinese male population. Methods: A total of 865 participants (aged 20-70 years) were included. All participants underwent a physical health examination at Xiguzhou Central Hospital between October 2015 and July 2016, including measurements of body mass index (BMI), BFR, white blood cell [WBC] count, and neutrophil-lymphocyte ratio [NLR]. Results: WBCs count and NLR were significantly higher in adult male smokers than in non-smokers (P = 0.00). According to the BFR stratification analysis, WBC count and NLR significantly increased in accordance with BFR (P = 0.00). This finding remained significant after adjusting for relevant confounding factors (P < 0.05). Two-factor stratified analysis of smoking status and BFR showed that WBC count and NLR in the smoking population were higher than in nonsmokers, regardless of BFR. The interaction model showed that BFR and smoking status affected WBC count and NLR changes (P < 0.05). A significant positive correlation was found between WBC count, NLR, and BFR in adult male smokers; however, there was no significant correlation with BMI. There was an interaction between smoking and BFR, both of which synergistically affected changes in inflammatory markers, including WBC count and NLR. Conclusion: WBC count and NLR of smokers with a high BFR were significantly higher than those of nonsmokers with a low BFR. It is important to provide evidence-based medical evidence for social tobacco control and to reduce BFR.

Fanconi syndrome induced by the long-term use of tenofovir disoproxil fumarate: a case report and literature review.

We present the case of a woman of 50 years of age who experienced widespread bone pain along with digestive symptoms, including nausea and vomiting. She had been prescribed tenofovir disoproxil fumarate (TDF) tablets for the treatment of hepatitis B. Laboratory testing revealed low circulating phosphorus and potassium concentrations and acidosis. A whole-body bone scan revealed abnormal bone metabolism. Rheumatologic and urologic conditions were ruled out, and therefore TDF-induced Fanconi syndrome (FS) and related bone pain was diagnosed. After the TDF was discontinued, the patient's symptoms and laboratory indices significantly improved. In this manuscript, we highlight the clinical manifestations of and laboratory test results associated with FS and summarize the cases of TDF-induced FS reported on PubMed between 2013 and 2022 to improve understanding of FS.

Epidemiological and transcriptome data identify potential key genes involved in iron overload for type 2 diabetes.

BACKGROUND: Many previous studies have reported the association between iron overload (IO) and type 2 diabetes mellitus (T2DM). However, the underlying molecular mechanism is not clear. METHODS: Epidemiological data from the National Health and Nutrition Examination Survey 2017-2018 (NHANES) was used to systematically explore the association between IO and diabetes. Furthermore, transcriptome data from Gene Expression Omnibus (GEO) were analyzed using bioinformatics methods to explore the underlying functional mechanisms at the molecular level. RESULTS: Data from NHANES showed a "W" shape relationship between serum iron (frozen) and the risk of diabetes (P < 0.001) as well as a "∧" shape correlation between serum unsaturated iron binding capacity (UIBC) and the risk of diabetes (P = 0.007). Furthermore, the serum iron (frozen) was positively associated with fasting plasma glucose and HOMAB (P < 0.05), and UIBC was positively associated with fasting insulin (P < 0.05). Transcriptome data showed that two IO-related genes [Transferrin receptor (TFRC) and Solute carrier family-11 member-2 (SLC11A2)] were down-regulated in T2DM. The correlation analysis showed that expression levels of TFRC and SLC11A2 were significantly and positively correlated with genes involved in insulin secretion (P < 0.05). Protein-protein interaction network analysis showed that TFRC and SLC11A2 interacted with four key genes, including VAMP2, HIF1A, SLC2A1, and RAB11FIP2. CONCLUSION: We found that IO status was associated with increased FPG and aggravated HOMAB, and two IO-related genes (TFRC and SLC11A2) might induce the occurrence of T2DM by influencing insulin secretion, which provides potential therapeutic targets for T2DM patients.

Effectiveness of Negative Pressure Wound Therapy of Diabetic Foot Ulcers Using Periplaneta Americana (Kangfuxin Liquid) Irrigation.

This study was to evaluate the efficacy of Periplaneta Americana (Kangfuxin Liquid) relative to normal saline when applied in negative-pressure wound therapy (NPWT) with instillation for facilitating diabetic foot ulcers (DFUs) healing. Eighty patients with Wagner grades 3 or 4 DFUs were enrolled in this retrospective study. Based on the treatment type, patients were equally assigned to either (i) an NPWT with Kangfuxin liquid instillation group (NPWT-K) or (ii) an NPWT with normal saline instillation group (NPWT-I). The primary study outcome was the wound healing rate and Kaplan-Meier survival estimate was used to examine the cumulative wound healing rate, while the secondary outcomes were the amputation rate, inpatient days, duration of antibiotic treatments, reinfection rate, new ulcer formation rate, readmission rate, and changes in the inflammatory markers (such as ESR, CRP, and PCT) and serum growth factors (including VEGF, EGF, and bFGF). The 12-week wound healing rate (31 of 40[77.5%] vs 22 of 40[55.0%], P = .033) and the cumulative wound healing rate was higher in the NPWT-K group than in the NPWT-I group (P = .004). The wound healing time was shorter in the NPWT-K group (55 days [95% CI 50-60]) than in the NPWT-K group (64 days [95% CI 59-69], P = .016). Patients who received NPWT-K had fewer inpatient days and duration of antibiotic treatment and faced lower reinfection and readmission rates (P < .05). After 1 week of treatment, the ESR, CRP, and PCT levels in the blood were lower in the NPWT-K group than in the NPWT-I group (P < .05), while the VEGF, EGF, and bFGF levels in the NPWT-K group were higher than those in the NPWT-I group (P < .001). The present study showed that NPWT with Kangfuxin liquid instillation was effective and showed significantly accelerated DFUs healing. Thus, Kangfuxin liquid is an effective instillation solution for use in the treatment of DFUs with NPWT.

Association between serum gamma glutamyl transferase and fasting blood glucose in Chinese people: A 6-year follow-up study.

AIMS/INTRODUCTION: In this study, we aimed to investigate the relationships between gamma-glutamyl transferase (GGT) and fasting blood glucose (FBG) during a 6-year follow-up study of participants, and to determine whether GGT is a risk factor for FBG. MATERIALS AND METHODS: A total of 1,369 individuals from the health examination survey in the urban area of Xuzhou, central China, were followed up for 6 years. The patients were divided into four groups based on their baseline GGT levels (in quartiles). The one-way analysis of variance (anova) method was used to compare the differences between the variables and baseline. The relationship between GGT and FBG levels was investigated using repeated measurements anova. RESULTS: The grouping of baseline GGT levels affected the changes in blood glucose during the 6-year follow-up study. In the GGT quartile subgroups, the annual mean increase in FBG levels showed a positive relationship with baseline GGT levels. This trend was even more aggregated in the highest baseline GGT group. Interactions among time course, baseline FBG and GGT groups in different participants together affected the change of FBG levels during the follow-up period. The repeated measures anova suggested that different baseline GGT groups were still significantly associated with increased FBG levels. GGT is a risk factor that affects FBG levels(P < 0.001). CONCLUSIONS: The annual mean increase in FBG levels showed a positive relationship with baseline GGT levels. Higher baseline GGT levels resulted in a faster annual mean increase in FBG. Thus, GGT can be used for the early detection of FBG-related disorders of glucose metabolism for clinical application.

Evaluation of the healing potential of short-term ozone therapy for the treatment of diabetic foot ulcers.

Background: The availability of research on short-term ozone therapy for diabetic foot ulcers (DFUs) is limited, and even when it is accessible, it mainly comprises of basic analysis conducted during long-term ozone therapy. This study was to evaluate the efficacy of short-term ozone therapy in promoting wound healing in DFUs. Methods: A retrospective analysis was conducted on 89 patients with type 2 diabetes complicated by DFUs. The patients were divided into two groups: ozone therapy group (n=41) and control group (n=48). Wound condition, change of bacterial types, changes in inflammatory indicators (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and procalcitonin [PCT]), vascular endothelial growth factor (VEGF), cytokines [Interleukin 6 (IL-6) and tumor necrosis factor-α(TNF-α)], and oxidative stress levels (superoxide dismutase [SOD], malondialdehyde [MDA], and total antioxidant capacity [T-AOC]) were observed pre-treatment and after 1 week. After a 12-week of follow-up, wound healing rate, amputation rate, inpatient day, duration of antibiotics, reinfection rate, incidence of new ulcers, readmission rate, and reoperation rate, and cumulative wound healing rate using Kaplan-Meier curves were assessed. Results: After 1 week of treatment, the ozone therapy group showed higher VEGF, SOD, and T-AOC levels compared to the control group (P<0.05), while CRP, PCT, ESR, IL-6, TNF-α, MDA levels and bacterial types were lower (P<0.05). The ozone therapy group had a higher wound healing rate after a 12-week follow-up (P<0.05). Kaplan-Meier curves indicated a higher cumulative wound healing rate in the ozone therapy group (P<0.05). Additionally, the ozone therapy group had lower inpatient day, duration of antibiotics, reinfection rate, and readmission rate compared to the control group (P<0.05). Conclusion: Short-term ozone therapy is effective in promoting wound healing in DFUs by reducing inflammation, increasing growth factor levels, improving oxidative stress status, shortening healing time, and improving long-term prognosis. These findings suggest the potential of short-term ozone therapy as a valuable treatment modality for DFUs.

Decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus.

The discovery of a large number of small pulmonary nodules and early diagnosis of lung cancer in the diabetic patients prompt us to re-examine the relationship between diabetes and the occurrence and development of lung cancer. The aim of this study was to explore the underlying metabolites changes in diabetes with NSCLC or benign nodule patients, and further to investigate the association of serum IGF-1 level and differentially expressed metabolites (DEMs). An untargeted metabolomics method was used to detect the changes of metabolism in diabetic patients with NSCLC on the platform of HR-MS. Serum level of IGF-1 was measured by ELISA. The patients were divided to three groups, DM, DLB (nodule), and DLC (cancer). we have identified numerous DEMs, which include amino acid, choline, and fatty acid derivatives. Further analysis of the involved metabolic pathways suggested that linoleate metabolism, tryptophan metabolism, histidine metabolism, putative anti-Inflammatory metabolites formation from EPA, and arachidonic acid metabolism were considered to be the most significant metabolic pathways between groups. Networks analysis suggested that a series of metabolites were associated with serum IGF-1among the three groups, which can be divided into 6 categories. Nine metabolites have been identified as the main DEMs among the DLC, DLB, and DM groups. In conclusion, metabolomics is a powerful and promising tool for the cancer risk evaluation in diabetic patients. Our results suggest that decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus.

Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was -1.07% (-1.19%, -0.95%) in the dorzagliatin group and -0.50% (-0.68%, -0.32%) in the placebo group (estimated treatment difference, -0.57%; 95% confidence interval: -0.79%, -0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile.

Lifestyle in adulthood can modify the causal relationship between BMI and islet function: using Mendelian randomization analysis.

BACKGROUND: Body mass index was intimately associated with islet function, which was affected by various confounding factors. Among all methods of statistical analysis, Mendelian randomization best ruled out bias to find the causal relationship. In the present study, we explored the relationship between 13 East Asian body mass index-related genes reported previously and islet function using the Mendelian randomization method. METHODS: A total of 2892 participants residing in northern China were enrolled. Anthropological information, such as sex, age, drinking status, smoking status, weight, height and blood pressure, was recorded for all participants. Fasting glucose and insulin were detected, and the insulin sensitivity index was calculated. 13 single nucleotide polymorphismss in East Asian body mass index -related genes were analysed with the ABI7900HT system. RESULTS: Five genetic locus mutations, CDKAL1, MAP2K5, BDNF, FTO and SEC16B, were found to be associated with body mass index and were used to estimate the genetic risk score. We found that the genetic risk score was negatively associated with the insulin sensitivity index. Even after adjusted of confounding factors, the relationship showed statistical significance. A subsequent interaction effect analysis suggested that the negative relationship between the genetic risk score and insulin sensitivity index no longer existed in the nondrinking population, and smokers had a stronger negative relationship than nonsmokers. CONCLUSION: We found a negative causal relationship between body mass index-related genetic locus mutations and insulin resistance, which might be increased by acquired lifestyle factors, such as drinking and smoking status.

A meta-analysis of circulating microRNAs in the diagnosis of papillary thyroid carcinoma.

BACKGROUND: Aim of this meta-analysis was to evaluate the overall diagnostic value of circulating mini miRNAs for papillary thyroid carcinoma (PTC) and to find the possible molecular marker with higher diagnostic value for PTC. METHODS: We searched the Pubmed, Cochrane and Embase database until June 2020. We selected relevant literatures associated with the diagnosis of PTC with circulating miRNAs. The number of cases in experimental group and the control group, sensitivity and specificity could be extracted from the literatures. RESULTS: We got 9 literatures including 2114 cases of PTC. Comprehensive sensitivity was 0.79, comprehensive specificity was 0.82, positive likelihood ratio was 4.3, negative likelihood ratio was 0.26, diagnostic advantage ratio was 16. The summary receiver operating characteristic curve was drawn and the Area Under the Curve was 0.87. CONCLUSIONS: Circulating microRNAs may be promising molecular markers for the diagnosis of papillary thyroid carcinoma. Combined detection of certain serum microRNAs can improve the diagnostic accuracy of papillary thyroid carcinoma. Especially MiR-222 and miR-146b may be prime candidates for the diagnosis of PTC in Asian population.

Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study.

AIMS/HYPOTHESIS: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes. METHODS: In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 µg) for 12 weeks. The primary endpoint was the change in HbA1c from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA1c < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug. RESULTS: We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 µg, 150 µg and 200 µg groups). At the end of 12 weeks, mean differences in HbA1c in the treatment groups were -7.76 mmol/mol (95% CI -9.23, -4.63, p < 0.001) (-0.72%, 95% CI -1.01, -0.43), -12.89 mmol/mol (95% CI -16.05, -9.72, p < 0.001) (-1.18%, 95% CI -1.47, -0.89) and -11.14 mmol/mol (95% CI -14.19, -7.97, p <0 .001) (-1.02%, 95% CI -1.30, -0.73) in the 75 µg, 150 µg and 200 µg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA1c. Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death. CONCLUSIONS/INTERPRETATION: All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03520972 FUNDING: The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.

Interaction between the rs9356744 polymorphism and metabolic risk factors in relation to type 2 diabetes mellitus: The Cardiometabolic Risk in Chinese (CRC) Study.

The understanding of the genetic basis of type 2 diabetes mellitus (T2DM) has progressed rapidly, but the interactions among common genetic variants and metabolic risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and metabolic environments on the risk of T2DM. Obesity is emerging as an independent risk factor for T2DM and arterial stiffness. Here, we examined the effect of the rs9356744 polymorphism in the body mass index (BMI) gene CDKAL1 on the risk of T2DM in East Asians and particularly assessed the interactions between this polymorphism and other metabolic risk factors. A total of 1975 subjects in whom the rs9356744 polymorphism had been detected in the CDKAL1 gene were enrolled in this study. The height, weight, blood pressure and relevant markers, including glucose, lipids, liver and renal function, of the participants were successfully measured. Pulse wave velocity (PWV) was measured using an automatic wave form analyzer. At baseline, we found a significant association between BMI and rs9356744 genotypes (CC, CT, TT) (P = 0.048). After adjusting for confounding factors, including sex, age and BMI, participants carrying the T allele of rs9356744 showed a lower incidence of T2DM. Further adjustment for blood pressure and lipids did not appreciably change the results (P = 0.019, 0.009, 0.015, respectively). We found significant interactions between the rs9356744 polymorphism and high-density lipoprotein (HDL), serum uric acid (SUA) and carotid-femoral pulse wave velocity (cf-PWV) in relation to T2DM incidence (P for interaction = 0.007, 0.002, 0.004, respectively), especially in the group with the lowest SUA level and the group with the highest HDL and cf-PWV levels (P for trend = 0.006, 0.008, 0.018, respectively). Furthermore, we found a significant interaction between the rs9356744 polymorphism and cf-PWV in relation to the level of 2-h plasma glucose in the oral glucose tolerance test (OGTT) (P for interaction = 0.0341). In summary, the T allele of rs9356744 was an independent protective factor for T2DM. There were significant interactions between rs9356744 and HDL, SUA, and cf-PWV in relation to T2DM risk.

MALDI-TOF MS Based Bacterial Antibiotics Resistance Finger Print for Diabetic Pedopathy.

Diabetes mellitus has become a major global health issue. Currently, the use of antibiotics remains the best foundational strategy in the control of diabetic foot infections. However, the lack of accurate identification of pathogens and the empirical use of antibiotics at early stages of infection represents a non-targeted treatment approach with a poor curative effect that may increase the of bacterial drug resistance. Therefore, the timely identification of drug resistant bacteria is the key to increasing the efficacy of treatments for diabetic foot infections. The traditional identification method is based on bacterial morphology, cell physiology, and biochemistry. Despite the simplicity and low costs associated with this method, it is time-consuming and has limited clinical value, which delays early diagnosis and treatment. In the recent years, MALDI-TOF MS has emerged as a promising new technology in the field of clinical microbial identification. In this study, we developed a strategy for the identification of drug resistance in the diagnosis of diabetic foot infections using a combination of macro-proteomics and MALDI MS analysis. The macro-proteomics result was utilized to determine the differential proteins in the resistance group and the corresponding peptide fragments were used as the finger print in a MALDI MS analysis. This strategy was successfully used in the research of drug resistance in patients with diabetic foot infections and achieved several biomarkers that could be used as a finger print for 4 different drugs, including ceftazidime, piperacillin, levofloxacin, and tetracycline. This method can quickly confirm the drug resistance of clinical diabetic foot infections, which can help aid in the early treatment of patients.