Update on evidence-based clinical application of sodium-glucose cotransporter inhibitors: Insight to uncommon cardiovascular disease scenarios in diabetes.

In this paper, we concentrate on updating the clinical research on sodium-glucose cotransporter inhibitors (SGLTis) for patients with type 2 diabetes who have heart failure with a preserved injection fraction, acute heart failure, atrial fibrillation, primary prevention of atherosclerotic cardiovascular disease/cardiovascular disease, and acute myocardial infarction. We searched the data of randomized controlled trials and meta-analyses of SGLTis in patients with diabetes from PubMed between January 1, 2020 and April 6, 2024 for our review. According to our review, certain SGLTis (empagliflozin, dapagliflozin, canagliflozin, and tofogliflozin), but not sodium-glucose cotransporter 1 inhibitor (SGLT1i), exhibit relatively superior clinical safety and effectiveness for treating the abovementioned diseases. Proper utilization of SGLTis in these patients can foster clinical improvement and offer an alternative medication option. However, clinical trials involving SGLTis for certain diseases have relatively small sample sizes, brief intervention durations, and conclusions based on weak evidence, necessitating additional data. These findings are significant and valuable for providing a more comprehensive reference and new possibilities for the clinical utilization and scientific exploration of SGLTis.

An Improved Harris Hawks Optimization Algorithm and Its Application in Grid Map Path Planning.

Aimed at the problems of the Harris Hawks Optimization (HHO) algorithm, including the non-origin symmetric interval update position out-of-bounds rate, low search efficiency, slow convergence speed, and low precision, an Improved Harris Hawks Optimization (IHHO) algorithm is proposed. In this algorithm, a circle map was added to replace the pseudo-random initial population, and the population boundary number was reduced to improve the efficiency of the location update. By introducing a random-oriented strategy, the information exchange between populations was increased and the out-of-bounds position update was reduced. At the same time, the improved sine-trend search strategy was introduced to improve the search performance and reduce the out-of-bound rate. Then, a nonlinear jump strength combining escape energy and jump strength was proposed to improve the convergence accuracy of the algorithm. Finally, the simulation experiment was carried out on the test function and the path planning application of a 2D grid map. The results show that the Improved Harris Hawks Optimization algorithm is more competitive in solving accuracy, convergence speed, and non-origin symmetric interval search efficiency, and verifies the feasibility and effectiveness of the Improved Harris Hawks Optimization in the path planning of a grid map.

[Iodine Nutritional Status and Prevalence of Thyroid Disorders among Adults in Chengdu].

Objective: To investigate the prevalence of thyroid disorders, iodine nutritional status and relevant risk factors among adults in Chengdu city on the basis of two population-based surveys, one conducted between 2016 and 2017 and the other, between 2019 and 2020, and to provide references for making health-related administrative decisions. Methods: Two population-based sampling surveys were conducted. The first one was done between October 2016 and December 2017, using stratified cluster random sampling to select subjects from 2 urban and 2 rural communities in Chengdu. Then, between December 2019 and February 2020, sequential cluster sampling was used to select subjects from communities in the peripheral regions of Longquanyi District, Chengdu. Both surveys covered natural populations of people who were 18 or older and who met the inclusion criteria. In the first survey, questionnaires, physical examination, thyroid ultrasound, and examinations of serum thyroid biochemical markers and urine iodine were performed, while in the second survey, only questionnaire concerning thyroid disorders and physical examination were performed. Statistical analysis of the nutritional status of iodine, the prevalence of thyroid disorders, and potential risk factor was conducted. Results: A total of 1859 subjects were enrolled for the first survey and 16152 for the second. According to the results of the first survey, the median urine iodine concentration was 172.10 µg/L, and the group with adequate or more than adequate iodine accounted for more than 60% of the surveyed population. The prevalence of thyroid disorders was found to be 0.48% for overt hyperthyroidism, 0.43% for subclinical hyperthyroidism, 0.43% for Grave's disease, 1.34% for overt hypothyroidism, 16.62% for subclinical hypothyroidism, 16.73% for positive thyroid antibody, 12.96% for TPOAb positive, 10.06% for TGAb positive, 0.81% for goiter, 14.85% for single nodule, 14.42% for multi-nodules, and 29.26% for thyroid nodules. Excess iodine is a risk factor for subclinical hypothyroidism ( OR=1.50, 95% confidence interval [ CI]: 1.07-2.10, P<0.05), and iodine deficiency is a risk factor for multiple thyroid nodules ( OR=1.45, 95% CI: 1.02-2.05, P<0.05). The total prevalence of hyperthyroidism, hypothyroidism and Hashimoto's thyroiditis in the two surveys was 6.58% and 5.95%, respectively, showing no significant difference. The second survey lacked accurate data on thyroid nodules. Conclusion: The iodine nutritional status of adults in Chengdu in recent years was appropriate. The total prevalence of hyperthyroidism, hypothyroidism and Hashimoto's thyroiditis remained stable, while that of thyroid nodule increased in recent years. We should continue with the implementation of the universal salt iodization policy and reinforce efforts in monitoring. Furthermore, we should make an active effort to look into the etiology of thyroid nodules.

Increasing angiotensin-converting enzyme (ACE) 2/ACE axes ratio alleviates early pulmonary vascular remodeling in a porcine model of acute pulmonary embolism with cardiac arrest.

BACKGROUND: Acute pulmonary embolism (APE) with cardiac arrest (CA) is characterized by high mortality in emergency due to pulmonary arterial hypertension (PAH). This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme (ACE) 2-angiotensin (Ang) (1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor (AT1) axis (ACE2/ACE axes) ratio on pulmonary artery lesion after return of spontaneous circulation (ROSC). METHODS: To establish a porcine massive APE with CA model, autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg (1 mmHg=0.133 kPa). Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation. Pigs were divided into four groups of five pigs each: control group, APE-CA group, ROSC-saline group, and ROSC-captopril group, to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril. RESULTS: Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells. Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor (VEGF) in the APE-CA group compared with the control group. Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC. Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X (Bax) ratio and decreasing cleaved caspase-3 expression. CONCLUSION: Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.

Changes of fibrinolytic system in thrombolytic resuscitation of pulmonary thromboembolism-induced cardiac arrest model.

The objective of this study is to explore the changes in the coagulation and fibrinolysis system in an animal model with pulmonary embolism after cardiopulmonary bypass and to provide a theoretical basis for clinical practice. An animal model of cardiac arrest due to pulmonary embolism was established for venous thrombus (10-15 mL) in the left external jugular vein of 21 pigs. Computed tomography (CT) pulmonary arteriography was performed after the recovery of the underlying state, cardiac arrest state and spontaneous circulation, and then thrombolysis and cardiopulmonary resuscitation (recombinant tissue plasminogen activator [t-PA] 50 mg) were performed immediately. The changes of tissue factor (TF), tissue factor pathway inhibitor (TFPI), t-PA and plasminogen activator inhibitor-1 (PAI-1) in the blood were detected by ELISA. The blood samples were collected immediately, 1, 2, 4 and 6 hours after the recovery of spontaneous circulation. Data from animals that were successfully resuscitated at different time points were compared using a repeated measures one-way analysis of variance. Seventeen pigs had cardiac arrest after 10 to 15 mL of thrombus injection, and the other four had cardiac arrest after 5 to 8 mL of additional thrombus. Nine pigs survived 6 hours of cardiopulmonary resuscitation. CT pulmonary angiogram showed pulmonary artery obstruction. TF levels were increased compared with basal status, but there was no statistical difference (P > .05). TFPI levels were higher at 1, 2, 4 and 6 hours after recovery of spontaneous circulation compared with basal state (P < .05); t-PA levels were higher at cardiac arrest, and immediately after recovery of spontaneous circulation compared with basal state. There was a statistical difference in PAI-1 level at 1, 2, 4 and 6 hours after recovery of spontaneous circulation (P < .05). There was no statistical difference in PAI-1 level at each stage compared with basal state (P > .05). TFPI has a certain influence on the coagulation and thrombosis regulation of the body, and the increase in fibrinolytic activity has a positive promoting effect on the thrombolysis. It provided the theoretical basis of clinical treatment of thrombotic diseases.

Efficacy and Safety of Dulaglutide Monotherapy Compared to Glimepiride in Oral Antihyperglycemic Medication-Naïve Chinese patients with Type 2 Diabetes: A Post Hoc Analysis of AWARD-CHN1.

INTRODUCTION: Glucagon-like peptide (GLP)-1 receptor agonists are glucose-lowering agents associated with weight loss, cardiovascular benefits, and low hypoglycemic risk and are recommended by recent guidelines as first-line therapy for some patients with type 2 diabetes (T2D). This post hoc analysis of the AWARD-CHN1 study compared the efficacy and safety of once-weekly dulaglutide with glimepiride in oral antihyperglycemic medication (OAM)-naïve Chinese patients with T2D. METHODS: AWARD-CHN1 was a phase 3, double-blind study with 737 patients randomized 1:1:1 to once-weekly dulaglutide (1.5 or 0.75 mg) or glimepiride (1-3 mg/day). This is a post hoc analysis of AWARD-CHN1 based on mixed-model repeated measures using a modified intent-to-treat analysis set with only the OAM-naïve Chinese population. RESULTS: There were 264 OAM-naïve Chinese patients included in this analysis (dulaglutide 1.5 mg, n = 87; dulaglutide 0.75 mg, n = 90; glimepiride, n = 87). A greater glycated hemoglobin (HbA1c) reduction from baseline was observed with dulaglutide 1.5 mg and 0.75 mg compared to glimepiride (- 2.02% and - 1.84% vs - 1.37%, respectively; both P < 0.001). Significantly more patients in dulaglutide 1.5 mg and 0.75 mg groups achieved HbA1c targets < 7.0% compared to glimepiride (86.2% and 81.1% vs 65.5%; P = 0.002 and P = 0.026, respectively). Beta cell function was significantly increased for dulaglutide groups compared to glimepiride. Mean body weight was significantly reduced for dulaglutide 1.5 mg and 0.75 mg compared to glimepiride (- 1.40 kg and - 0.96 kg vs + 0.73 kg, respectively; both P < 0.001). Through 26 weeks, 7.9%, 4.2%, and 18.2% of patients reported hypoglycemia, and 40.4%, 23.2%, and 8.0% of patients reported at least one gastrointestinal treatment emergent adverse event, in dulaglutide 1.5 mg, 0.75 mg, and glimepiride groups, respectively. CONCLUSIONS: In this post hoc analysis, dulaglutide was effective in reducing both HbA1c and weight with favorable tolerability and safety profile, which is consistent with results seen in larger international dulaglutide monotherapy studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01644500.

Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model.

Acute pulmonary embolism (APE) with cardiac arrest (CA) is associated with a high mortality rate. Even upon return of the spontaneous circulation (ROSC), APE­CA survivors are prone to myocardial cell apoptosis, a key cellular mechanism that induces heart failure. A recent study by our group discovered a post­resuscitation imbalance in the serum angiotensin­converting enzyme (ACE)2/ACE axis of the renin­angiotensin system (RAS), as well as regressive cardiac function in a porcine model of APE­CA. However, it has remained elusive how this imbalance in the ACE2/ACE axis affects myocardial cell apoptosis. In the present study, western blot and immunohistochemical analyses demonstrated that the RAS was only activated in the left myocardium, as evidenced by a decreased ACE2/ACE ratio following APE­CA and ROSC, but not the right myocardium. Ultrastructural analysis confirmed myocardial apoptosis in the left and right myocardium. Furthermore, B­cell lymphoma 2 (Bcl­2)­associated X protein (Bax) and caspase­3 levels were elevated and Bcl­2 levels were decreased in the left myocardium following APE­CA and ROSC. Treatment with the ACE inhibitor captopril for 30 min after initiation of ROSC prevented the increase in Bax and the decrease in Bcl­2 in the left myocardium compared with that in saline­treated pigs. Captopril also inhibited the activation of extracellular signal­regulated kinase (ERK)1/2 in the left myocardium. The results of the present study suggest that an imbalance in the ACE2/ACE axis has an important role in myocardial apoptosis following APE­CA, which may be attributed to decreased ERK1/2 activation. In addition, it was indicated that captopril prevents apoptosis in the left myocardium after ROSC.

Association between ACE2/ACE balance and pneumocyte apoptosis in a porcine model of acute pulmonary thromboembolism with cardiac arrest.

Acute pulmonary embolism (APE) is frequently reported in patients with cardiac arrest (CA) in emergency care. Pneumocyte apoptosis is commonly observed in the lungs following an APE. An important pathological mechanism evoking apoptosis during a lipopolysaccharide­induced acute lung injury is the angiotensin­converting enzyme 2 (ACE2)/ACE imbalance. The present study uses a porcine model to examine the anti­apoptotic effects of captopril on APE­CA and the return of spontaneous circulation (ROSC). Pigs were randomly assigned into four groups: Control, APE­CA, ROSC­saline, and ROSC­captopril. Surviving pigs were euthanized at 6 h and lungs were isolated for analysis using several biochemical assays. Compared with the control group, the ACE2/ACE ratio was lower in the APE­CA and ROSC pigs. In addition, APE­CA pigs had higher Bcl­2­associated X protein (Bax) and cleaved caspase­3 levels, and lower B­cell lymphoma­2 (Bcl­2) level compared to control pigs. Captopril treatment reduced lung apoptosis, as demonstrated by lower TUNEL­positive cells, higher Bcl­2, and lower cleaved caspase­3 protein levels in the lung. Notably, the ACE2/ACE ratio was positively correlated with Bcl­2 protein levels and Bcl­2/Bax ratio. In conclusion, captopril has a protective effect against lung apoptosis following ROSC and that maintaining the balance of the ACE2/ACE axis is important for inhibiting pulmonary apoptosis during APE.

[Changes in expressions of sRNA SpR19 and its potential target GroEL in Streptococcus mutans strains with different cariogenicity cultured under different pH conditions].

OBJECTIVE: To investigate the changes in the expression level of sRNA SpR19 and its potential target protein GroEL in clinical isolates of Streptococcus mutans with different cariogenicity exposed to different pH conditions and explore the possibility of using these molecules as biomarkers for assessing the cariogenicity of the bacteria. METHODS: The total RNAs were extracted from the clinical isolates of Streptococcus mutans with high (strain 17) and low cariogenicity (strain 5) for high-throughput sequencing for profiling of the differentially expressed sRNAs. The candidate sRNA, SpR19, was selected for further study on the basis of bioinformatics analysis considering the role of its potential target in the cariogenic process. The differential expression levels of SpR19 in the strains exposed to both pH5.5 and pH7 culture conditions were verified by quantitative real-time PCR. The expression of the potential target of SpR19, GroEL, was also investigated at both the protein and mRNA level using Western blotting and quantitative real-time PCR. RESULTS: Bioinformatic analysis suggested multiple potential target sites of SpR19 both in GroEL mRNA and in the upstream and downstream inter-genic regions. Under different pH conditions, the highly cariogenic strain 17 expressed consistently low levels of SpR19 as compared with the strain 5 with a low cariogenicity; GroEL showed a reverse expression pattern in the 2 strains. An inverse correlation was found between the expressions of SpR19 and GroEL. CONCLUSION: The highly cariogenic strain 17 expressed low levels of SpR19 and high levels of GroEL in both acidic and neutral culture conditions. SpR19 may negatively regulate the cariogenicity of Streptococcus mutants by targeting at GroEL.

Variations of Postresuscitation Lung Function after Thrombolysis Therapy in a Cardiac Arrest Porcine Model Caused by Pulmonary Thromboembolism.

BACKGROUND: Study of lung function in survivor from cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) was rare. The aim of this study was to investigate the variations of postresuscitation lung function after thrombolysis treatment in a CA porcine model caused by PTE. METHODS: After 2 min of untreated CA, pigs of 10-12 weeks with a weight of 30 ± 2 kg (n = 24) were treated with recombinant human tissue plasminogen activator (50 mg). Cardiopulmonary resuscitation (CPR) and ventilation were initiated after drug administration. Pulmonary function and arterial blood gas parameters were measured at baseline, return of spontaneous circulation (ROSC) immediately, and 1 h, 2 h, 4 h, and 6 h after ROSC. RESULTS: The dynamic lung compliance decreased significantly at ROSC immediately and 1 h after ROSC compared to baseline (21.86 ± 2.00 vs. 26.72 ± 2.20 ml/mmHg and 20.38 ± 1.31 vs. 26.72 ± 2.20 ml/mmHg, respectively; P < 0.05; 1 mmHg = 0.133 kPa). Compared with baseline, airway resistance increased significantly at ROSC immediately and 1 h after ROSC (P < 0.05). Respiratory index also increased after ROSC and showed significant differences among baseline, ROSC immediately, and 2 h after ROSC (P < 0.05). Oxygen delivery decreased at ROSC immediately compared to baseline (P < 0.05). The oxygenation index decreased significantly at any time after ROSC compared to baseline (P < 0.05). Extravascular lung water index and pulmonary vascular permeability index (PVPI) showed significant differences at ROSC immediately compared to baseline and 1 h after ROSC (P < 0.05); PVPI at ROSC immediately was also different from 6 h after ROSC (P < 0.05). Ventilation/perfusion ratios increased after ROSC (P < 0.05). Histopathology showed fibrin effusion, bleeding in alveoli, and hemagglutination in pulmonary artery. CONCLUSIONS: Lung function remains abnormal even after CPR with thrombolysis therapy; it is essential to continue anticoagulation and symptomatic treatment after ROSC.

Captopril improves postresuscitation hemodynamics protective against pulmonary embolism by activating the ACE2/Ang-(1-7)/Mas axis.

Acute pulmonary embolism (APE) has a very high mortality rate, especially at cardiac arrest and even after the return of spontaneous circulation (ROSC). This study investigated the protective effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on postresuscitation hemodynamics, in a porcine model of cardiac arrest established by APE. Twenty-nine Beijing Landrace pigs were infused with an autologous thrombus leading to cardiac arrest and subjected to standard cardiopulmonary resuscitation and thrombolysis. Ten resuscitated pigs were randomly and equally apportioned to receive either captopril (22.22 mg/kg) infusion or the same volume saline, 30 min after ROSC. Hemodynamic changes and ACE-Ang II-angiotensin II type 1 receptor (AT1R) and ACE2/Ang-(1-7)/Mas receptor axis levels were determined. APE was associated with a decline in mean arterial pressure and a dramatic increase in pulmonary artery pressure and mean right ventricular pressure. After ROSC, captopril infusion was associated with significantly lower mean right ventricular pressure and systemic and pulmonary vascular resistance, faster heart rate, and higher Ang-(1-7) levels, ACE2/ACE, and Ang-(1-7)/Ang II, compared with the saline infusion. The ACE2/Ang-(1-7)/Mas pathway correlated negatively with external vascular lung water and pulmonary vascular permeability and positively with the right cardiac index. In conclusion, in a pig model of APE leading to cardiac arrest, captopril infusion was associated with less mean right ventricular pressure overload after resuscitation, compared with saline infusion. The reduction in systemic and pulmonary vascular resistance associated with captopril may be by inhibiting the ACE-Ang II-AT1R axis and activating the ACE2/Ang-(1-7)/Mas axis.

Study of Cardiac Arrest Caused by Acute Pulmonary Thromboembolism and Thrombolytic Resuscitation in a Porcine Model.

BACKGROUND: The success rate of resuscitation in cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) is low. Furthermore, there are no large animal models that simulate clinical CA. The aim of this study was to establish a porcine CA model caused by PTE and to investigate the pathophysiology of CA and postresuscitation. METHODS: This model was induced in castrated male pigs (30 ± 2 kg; n = 21) by injecting thrombi (10-15 ml) via the left external jugular vein. Computed tomographic pulmonary angiography (CTPA) was performed at baseline, CA, and return of spontaneous circulation (ROSC). After CTPA during CA, cardiopulmonary resuscitation (CPR) with thrombolysis (recombinant tissue plasminogen activator 50 mg) was initiated. Hemodynamic, respiratory, and blood gas data were monitored. Cardiac troponins T, cardiac troponin I, creatine kinase-MB, myoglobin, and brain natriuretic peptide (BNP) were measured by enzyme-linked immunosorbent assay. Data were compared between baseline and CA with paired-sample t-test and compared among different time points for survival animals with repeated measures analysis of variance. RESULTS: Seventeen animals achieved CA after emboli injection, while four achieved CA after 5-8 ml more thrombi. Nine animals survived 6 h after CPR. CTPA showed obstruction of the pulmonary arteries. Mean aortic pressure data showed occurrence of CA caused by PTE (Z = -2.803, P = 0.002). The maximal rate of mean increase of left ventricular pressure (dp/dtmax) was statistically decreased (t = 6.315, P = 0.000, variation coefficient = 0.25), and end-tidal carbon dioxide partial pressure (PetCO2) decreased to the lowest value (t = 27.240, P = 0.000). After ROSC (n = 9), heart rate (HR) and mean right ventricular pressure (MRVP) remained different versus baseline until 2 h after ROSC (HR, P = 0.036; MRVP, P = 0.027). Myoglobin was statistically increased from CA to 1 h after ROSC (P = 0.036, 0.026, 0.009, respectively), and BNP was increased from 2 h to 6 h after ROSC (P = 0.012, 0.014, 0.039, respectively). CONCLUSIONS: We established a porcine model of CA caused by PTE. The dp/dtmaxand PetCO2may be important for the occurrence of CA, while MRVP may be more important in postresuscitation.

[Epidemiology Study and Risk Factors Analysis of Hyperuricemia in Tibetan Monks of Sichuan Province].

OBJECTIVE: To investigate the prevalence and risk factors of hyperuricemia (HUA) in Tibetan monks of Sichuan province. METHODS: 755 adult Tibetan monks (more than 18 years old) in Ganzi Tibetan Autonomous Prefecture of Sichuan Province were included in this study for health examination. Residents of Kangding City who received health examination were selected as controls. We measured the height, body mass, waist circumference, hip circumference, blood pressure and detected liver and renal function, serum lipid and blood routine exam. Then HUA prevalence in different genders and ages, and risk factors of HUA were analyzed. RESULTS: The serum uric acid (SUA) level of Tibetan monks was (318. 03±107. 70) µmol/L with the total HUA prevalence of 21. 46%. The prevalence of male was higher than that of female (25. 44% vs. 19. 02%, P<0. 05). The overall HUA prevalence of residents in Kangding City was 30. 70%, which was higher than that of the monks (P<0. 01). Prevalence of HUA in male monks was lower than the entire male population (25. 44% vs. 41. 65%) and male Tibetan ones (25. 44% vs. 32. 23%) in Kangding city. Among female population, however, we found that the HUA prevalence of monk (19. 02%) was higher than that of overall female population (14. 07%) and Tibetan residents (14. 72%) in Kangding (P<0. 05). Peak prevalence of HUA in Tibetan monks was between 30 and 40 years old. Gender, waist circumference, waist-to-height ratio (WHtR), fasting plasma glucose (FPG), serum creatinine (SCr), hemoglobin (Hb) levels and the consumption of meat were all independent risk factors for the occurrence of HUA in Tibetan monks according to Logistic regression analysis. CONCLUSION: The prevalence of HUA in male Tibetan monks is lower than that of local urban Tibetan population, but the result in female monks is opposite. Gender, waist circumference, WHtR, FPG, SCr, Hb levels and the consumption of meat were all independent risk factors for HUA.

The association between thyroid autoantibodies in serum and abnormal function and structure of the thyroid.

OBJECTIVES: To evaluate the association between thyroid autoantibodies and abnormalities in thyroid function and structure, and to investigate any risk factors. METHODS: A cross-sectional survey was undertaken in Chengdu residents ≥ 18 years with no previous thyroid disease. The study participants provided demographic and clinical data. Thyroid function and serum concentrations of the thyroid autoantibodies antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) were measured. RESULTS: A total of 1334 subjects were included in this study. The prevalence of TPOAb and TgAb positivity was significantly higher in female than in male subjects. The prevalence of thyroid autoantibodies in those with subclinical hypothyroidism and clinical hyper- and hypothyroidism was significantly greater than in euthyroid subjects. The concentration of TPOAb and TgAb in subjects with both TPOAb and TgAb was significantly higher than in those who exhibited only one type of thyroid autoantibody. Using multivariate logistic regression analysis, female sex, thyroid volume, thyroid hypo- and heteroechogenicity were found to be risk factors for the presence of autoantibodies. CONCLUSIONS: Thyroid autoantibodies were common in the general population. Women with thyroid enlargement, hypoechogenicity and heteroechogenicity might benefit from routine screening for thyroid autoantibodies and thyroid function.

Randomized, double blinded, placebo-controlled trial to evaluate the efficacy and safety of tolvaptan in Chinese patients with hyponatremia caused by SIADH.

To study the effect of tolvaptan on non-acute, non-hypovolemic hyponatremia in inappropriate secretion of antidiuretic hormone (SIADH) syndrome in Chinese patients. Hyponatremic SIADH patients received placebo (N = 18) or tolvaptan (N = 19) at an initial dose of 15 mg/day with further titration to 30 mg/day and 60 mg/day based on serum sodium concentrations. Randomized, double-blind, placebo-controlled trial. Primary endpoint was the change of the serum sodium from baseline to days 4 and 7. Analysis of covariance (ANCOVA) was used for statistical analysis. At day 4, average daily changes in serum sodium levels from baseline was 1.9 ± 2.9 mmol/L (1.9 ± 2.9 mEq/L) in the placebo group and 8.1 ± 3.6 mmol/L (8.1 ± 3.6 mEq/L) in the tolvaptan group; at day 7, the values were 2.5 ± 3.9 mmol/L (2.5 ± 3.9 mEq/L) and 8.6 ± 3.9 mmol/L (8.6 ± 3.9 mmEq/L) for the placebo and tolvaptan groups (ANCOVA, P < 0.001). At days 4 and 7, daily urine output and proportions of patients with normalized serum sodium were significantly superior in the tolvaptan group. The most common adverse events occurring in the tolvaptan group were dry mouth and thirst. Tolvaptan demonstrated superiority to placebo in the treatment of Chinese SIADH patients with hyponatremia by elevating serum sodium concentration with acceptable safety profile.

Interpretation of Chinese Society of Endocrinology consensus statement on hyperglycemia management target in adult inpatients in China.

Hyperglycemia of inpatients will increase the incidence of complications, mortality and medical cost, meanwhile prolong the course of hospitalization. A consensus on hyperglycemia management target in adult inpatients is proposed by experts of the Chinese Society of Endocrinology in order to control hyperglycemia of inpatients safely and effectively. Individualization is emphasized in this consensus. Different stratified glycemic targets should be established according to different patients and conditions. Target blood glucose control is unnecessary for diabetic patients during hospital stay. Glycemic decrement should generally not be quick. Hypoglycemia should be avoided as much as possible, and for overweight and obesity individuals, weight gain should be avoided as much as possible also. At the same time, the risks of infection and hyperglycemic crisis must also be avoided due to loose glycemic control.

Stratifying and tailoring HbA1c control targets for adults with Type 2 diabetes: interpretation of the consensus proposed by the Chinese Society of Endocrinology.

Glycemic control is an important goal of treatment to delay the progression of and complications associated with diabetes, but controversies exist regarding individual HbA1c control targets for different patients. With the aim of optimizing outcomes and minimizing adverse events, a preliminary consensus on HbA1c control targets for adults with Type 2 diabetes has been proposed by the Chinese Society of Endocrinology (CSE). Instead of recommending a general standard value for all patients, the CSE suggests that a relatively reasonable stratified and tailored target for individual patients should take into consideration both clinical status and social factors. Principles governing the establishment of a glycemic control target include safety, feasibility, scientific evidence, and customized care, of which the most important factor is safety. In addition to controlling plasma glucose, equal consideration should be given to other vascular disease risk factors.

Activation of PPARδ promotes mitochondrial energy metabolism and decreases basal insulin secretion in palmitate-treated ß-cells.

The peroxisome proliferator-activated receptor δ (PPARδ) regulates the expression of genes involved in cellular lipid and cell energy metabolism in many metabolically active tissues, such as liver, muscle, and fat, and plays a role in the cellular response to stress and environmental stimuli. The particular role of PPARδ in insulin-secreting ß-cells, however, is not well understood; we recently identified the cell-specific role of PPARδ on mitochondrial energy metabolism and insulin secretion in lipotoxic ß-cells. After treatment of HIT-T15 cells, a syrian hamster pancreatic ß-cell line, with high concentrations of palmitate and/or the specific PPARδ agonist GW501516, we detected the gene expression changes for transcripts, such as peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1α), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (mtTFA), the protein levels of the mitochondria uncoupling protein 2 (UCP2), mitochondrial morphology, the insulin secretion capacity and ATP/ADP ratio. Our results show that GW501516 treatment promoted generation of mitochondrial ATP, as well as expression levels of PGC-1α, NRF-1 and mtTFA, decreased basal insulin secretion, but had no effect on glucose-stimulated insulin secretion (GSIS), increased amounts of UCP2 and changed ATP-to-ADP ratio, improved mitochondrial morphology in palmitate-treated ß-cells. GW501516-induced activation of PPARδ enhanced mitochondrial energy metabolism, but also promoted a concomitant mitochondrial uncoupling and resulted in decreased basal insulin secretion and restricted GSIS; this observation indicated the possible action of a protective mechanism responding to the alleviation of excessive lipid load and basal insulin secretion in lipotoxic ß-cells.

Severe insulin allergy after percutaneous transluminal coronary angioplasty.

BACKGROUND: Insulin therapy is essential for type 1 and inadequately controlled type 2 diabetic patients. Insulin allergies have become less common since the introduction of highly purified human recombinant insulin. There are rare reports of severe insulin allergic reactions after percutaneous transluminal coronary angioplasty (PTCA) in patients with type 2 diabetes who had no previous allergic reactions. To better understand the causes and presentation of this rare acute reaction, we present the following observed case. CASE SUMMARY: A 63-year-old Chinese man (height, 172 cm; weight, 68.5 kg) with a 17-year history of type 2 diabetes and hypertension was first admitted to the West China Hospital, Sichuan University, Sichuan, People's Republic of China, for uncontrolled type 2 diabetes. He used regular human insulin, neutral protamine Hagedorn insulin, or premixed insulin without any allergic reactions. Four months later, PTCA was performed because of an acute myocardial infarction. The patient was administered 50 mg of protamine after active abdominal bleeding due to a right external iliac artery rupture. Three months later, recurrent raised, pruritic erythema occurred at the insulin injection site immediately after injection. Four weeks later, he experienced an attack of generalized urticaria at multiple previous injection sites (abdomen, upper arms, thighs) after injecting premixed insulin. It was accompanied by dizziness and palpitations. During the following 3 months, the symptoms recurred 3 times; one time, the patient reported losing consciousness for 2 to 3 minutes. The results of a skin prick test found that he was allergic to human recombinant insulin and insulin lispro. The allergy was resolved by changing his treatment regimen from insulin to oral hypoglycemic agents. A Naranjo score of 10 suggested a definite relationship (score >or=9) between the adverse drug reaction and the insulin administration. CONCLUSIONS: We present a definite case of allergy associated with insulin and insulin lispro administration. The patient had not experienced anaphylactic reactions prior to PTCA and protamine administration.