Shi-Zhu Bian

DNMT1-PPARγ pathway in macrophages regulates chronic inflammation and atherosclerosis development in mice.

The DNA methyltransferase-mediated proinflammatory activation of macrophages is causally linked to the development of atherosclerosis (AS). However, the role of DNMT1, a DNA methylation maintenance enzyme, in macrophage polarization and AS development remains obscure. Here, we established transgenic mice with macrophage-specific overexpression of DNMT1 (TgDNMT1) or PPAR-γ (TgPPAR-γ) to investigate their effects on AS progression in ApoE-knockout mice fed an atherogenic diet. Primary macrophages were extracted to study the role of the DNMT1/PPAR-γ pathway in regulating inflammatory cytokine production. We demonstrated that TgDNMT1 significantly increased proinflammatory cytokine production in macrophages and plasma, and it accelerated the progression of AS in the atherogenic diet-treated ApoE-knockout mice. Further, we found that the DNA methylation status of the proximal PPAR-γ promoter was regulated by DNMT1 in macrophages. Notably, additional TgPPAR-γ or pharmacological activation of PPAR-γ effectively prevented TgDNMT1-induced proinflammatory cytokine production in macrophages and AS development in the mouse model. Finally, we demonstrated that elevated DNMT1 was correlated with decreased PPAR-γ, and increased proinflammatory cytokine production in the peripheral blood monocytes isolated from the patients with AS, compared to those of healthy donors. Our findings shed light on a novel strategy for the prevention and therapy of AS.

Principal Component Analysis and Risk Factors for Acute Mountain Sickness upon Acute Exposure at 3700 m.

Objective We aimed to describe the heterogeneity in the clinical presentation of acute mountain sickness (AMS) and to identify its primary risk factors. Methods The participants (n = 163) received case report form questionnaires, and their heart rate (HR), oxygen saturation (SpO2), echocardiographic and transcranial Doppler variables, ability to perform mental and physical work, mood and psychological factors were assessed within 18 to 22 hours after arriving at 3700 m from sea level (500 m) by plane. First, we examined the differences in all variables between the AMS-positive and the AMS-negative groups. Second, an adjusted regression analysis was performed after correlation and principal component analyses. Results The AMS patients had a higher diastolic vertebral artery velocity (Vd; p = 0.018), a higher HR (p = 0.006) and a lower SpO2. The AMS subjects also experienced poorer sleep quality, as quantified using the Athens Insomnia Scale (AIS). Moreover, the AMS population exhibited more negative mood states, including anxiety, depression, hostility, fatigue and confusion. Five principal components focused on diverse aspects were also found to be significant. Additionally, more advanced age (p = 0.007), a higher HR (p = 0.034), a higher Vd (p = 0.014), a higher AIS score (p = 0.030), a decreased pursuit aiming capacity (p = 0.035) and decreased vigor (p = 0.015) were risk factors for AMS. Conclusions Mood states play critical roles in the development of AMS. Furthermore, an elevated HR and Vd, advanced age, elevated AIS sores, insufficient vigor and decreased mental work capacity are independent risk factors for AMS.

Physiological and psychological factors associated with onset of high-altitude headache in Chinese men upon acute high-altitude exposure at 3700 m.

Aim We aimed to identify clinical characteristics and risk factors associated with onset of high-altitude headache (HAH) after acute exposure at 3700 m. Method In two hours, 163 individuals ascended by plane to 3700 m. Demographic information, physiological and psychological measurements, cognitive function, physical work capacity tests and profile of mood states within one week prior to the departure and within 24 hours after arrival were examined. Results HAH patients featured significantly higher vertebral artery diastolic velocity (Vd), heart rate (HR) and pulmonary artery diameter. HAH was also associated with a more negative mood state, including scores for tension anxiety, depression, hostility, fatigue and confusion, as well as lower vigor (all p values <0.05). Furthermore, negative emotions were positively related to HAH severity. HAH slightly decreased cognitive functioning. HR, Vd, lack of vigor, confusion and self-reported anxiety (all p values <0.05) were independent risk factors for HAH. We have identified three independent baseline predictors for HAH including internal diameter of the left ventricle (LVD), Athens Insomnia Scale (AIS) and confusion score. Conclusions Higher HR, Vd, confusion and self-reported anxiety and insufficient vigor were independent risk factors for HAH. Furthermore, higher baseline LVD, AIS and confusion score are independent predictors of HAH.

Analysis of High-altitude Syndrome and the Underlying Gene Polymorphisms Associated with Acute Mountain Sickness after a Rapid Ascent to High-altitude

To investigated the objective indicators and potential genotypes for acute mountain sickness (AMS). 176 male subjects were evaluated for symptoms scores and physiological parameters at 3700 m. EPAS1 gene polymorphisms were explored and verified effects of potential genotypes on pulmonary function by inhaled budesonide. The incidence of AMS was 53.98% (95/176). The individuals who suffered from headache with anxiety and greater changes in heart rate (HR), the forced vital capacity (FVC), and mean flow velocity of basilar artery (Vm-BA), all of which were likely to develop AMS. The rs4953348 polymorphism of EPAS1 gene had a significant correlation with the SaO2 level and AMS, and a significant difference in the AG and GG genotype distribution between the AMS and non-AMS groups. The spirometric parameters were significantly lower, but HR (P = 0.036) and Vm-BA (P = 0.042) significantly higher in the AMS subjects with the G allele than those with the A allele. In summary, changes in HR (≥82 beats/min), FVC (≤4.2 Lt) and Vm-BA (≥43 cm/s) levels may serve as predictors for diagnosing AMS accompanied by high-altitude syndrome. The A allele of rs4953348 is a protective factor for AMS through HR and Vm-BA compensation, while the G allele may contribute to hypoxic pulmonary hypertension in AMS.

A higher baseline somatization score at sea level as an independent predictor of acute mountain sickness

OBJECTIVE The current study aimed to identify the predictive values of psychological factors that are evaluated by the Symptoms Checklist-90 (SCL-90) for acute mountain sickness (AMS). METHODS The subjects (n=285, non-acclimatized young Chinese men), who were recruited in July 2013, completed a case report questionnaire. In addition, their vital signs (heart rate [HR], blood pressure and pulse oxygen saturation) were measured, and their psychological factors were examined using the SCL-90 at sea level. AMS was diagnosed using the Lake Louise self-assessment scoring system in the morning of the second day after their arrival at 3450m. RESULTS Of the nine factors of the SCL-90, the AMS patients (AMS score≥3) were characterized by significantly higher scores for baseline somatization [14.0 (5.0) vs. 13.0 (3.0), p<0.001], obsession-compulsion, depression, anxiety and hostility compared with the non-AMS group (all p values<0.05). Spearmans correlation analyses revealed associations between AMS scores and somatization (r=0.316, p<0.001), depression, anxiety, obsession-compulsion, interpersonal sensitivity, hostility, phobic anxiety, paranoid ideation and psychoticism scores (all p values<0.001). Although all nine factors were associated with AMS in a univariate regression (all p<0.05), a further adjusted logistic regression analysis indicated that only baseline somatization score (odds ratio=1.129, p=0.001) was an independent predictor of AMS. Furthermore, some non-AMS often-occurred symptoms (paresthesia, shortness of breath, reduced activity and tinnitus) were also found to be associated with the baseline SCL-90 scores. CONCLUSION AMS is correlated with the baseline somatization score at sea level, which was measured using the SCL-90. A higher baseline somatization score is also an independent predictor of AMS.

Association between Low Free Triiodothyronine Levels and Poor Prognosis in Patients with Acute ST-Elevation Myocardial Infarction

Background Low free triiodothyronine (fT3) levels are generally associated with poor prognosis in patients with heart diseases, but this is controversial and there is a lack of data about ST-elevation myocardial infarction (STEMI) in Chinese patients. Objective To assess the association between fT3 levels and the prognosis of patients with STEMI. Methods This was a prospective observational study of 699 consecutive patients with STEMI treated at the Xinqiao Hospital between January 1, 2013, and December 31, 2014. The patients were divided into the low fT3 (fT3 < 3.1 pmol/L; n = 179, 27.5%) and normal fT3 (fT3 ≥ 3.1 pmol/L; n = 473, 72.5%) groups according to fT3 levels at admission. Patients were followed up at 1, 3, 6, and 12 months for all-cause death and major adverse cardiac events (MACE). Results During the 1-year follow-up, there were 70 all-cause deaths (39.1%) in the low fT3 group and 40 (8.5%) in the normal fT3 group (P < 0.001). MACE occurred in 105 patients (58.7%) in the low fT3 group and 74 (15.6%) in the normal fT3 group (P < 0.001). Multivariate Cox proportional hazards regression analysis indicated that fT3 levels were independently associated with 30-day and 1-year all-cause death [30-day: hazard ratio (HR) = 0.702, 95% confidence interval (95% CI): 0.501–0.983, P = 0.04; 1-year: HR = 0.557, 95% CI: 0.411–0.755, P < 0.001] and MACE (30-day: HR = 0.719, 95% CI: 0.528–0.979, P = 0.036; 1-year: HR = 0.557, 95% CI: 0.445–0.698, P < 0.001). Conclusion Low fT3 levels were strongly associated with poor prognosis in patients with STEMI. Measurement of fT3 levels may be a valuable and simple way to identify high-risk STEMI patients.