[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.

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.

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.

[Effects of L-threonate on bone resorption by osteoclasts in vitro].

OBJECTIVE: To clarify if calcium L-threonate and sodium L-threonate have inhibitory effects on the bone resorption of rabbit's osteoclasts in vitro. METHODS: This study contained a total of 16 culture groups, including one group as control and 5 groups treated by 5 drugs (calcium D-threonate, sodium L-threonate, alendronate, 17beta-estradiol and calcium gluconate) each at the final concentrations of 10(-9) mol/L, 10(-7) mol/L, 10(-5) mol/L respectively. After 7 days, eight bone slices of every group were stained with toluidine blue and the areas of resorptive pits were analyzed under light microscope; the concentrations of C-telopeptide of type I collagen (CTx or Crosslaps) in culture supernatants were measured by ELISA. RESULTS: (1) The resorption area and the CTx concentration of the Calcium L-threonate groups were reduced significantly as compared with those of control and of Calcium gluconate groups respectively. The resorption area and CTx level of the Sodium L-threonate groups were significantly reduced when compared with those of the control, but the effects of Calcium gluconate groups were not so. (2) The reduction in the resorption area and CTx concentration of Calcium L-threonate group was more than that of Sodium L-threonate group. (3) The reductive effect of the high concentration (10(-5)) group of Calcium L-threonate on the area and CTx level was corresponding to that of 17beta-estradiol at a concentration between 10(-7) and 10(-9). (4) The resorption area was related to the CTx concentration (r=0.876). (5) The CTX level was much more sensitive, precise and stable than the concentration. CONCLUSION: L-threonate, especially calcium L-threonate could inhibit the bone resorption of osteoclasts in vitro, and its effect might be related to the radical of L-threonic acid. The CTx concentration in culture supernatants might be an effective marker quantitatively reflecting the bone resorption by osteoclasts in vitro.