Systemic Blood Predictors of Elevated Pulmonary Artery Pressure Assessed by Non-invasive Echocardiography After Acute Exposure to High Altitude: A Prospective Cohort Study.

Aim: Elevated pulmonary artery pressure (ePAP) in response to high-altitude hypoxia is a critical physiopathological factor in the hypoxic adaptation that may lead to high-altitude pulmonary edema in the acute phase or high-altitude pulmonary hypertension in the long term. However, the sea-level predictors of risk factors for altitude-induced ePAP have not been examined. Thus, we aimed to identify the baseline systemic blood predictors of ePAP after acute high-altitude exposure. Materials and Methods: A total of 154 participants were transported to a high altitude 3,700 m from sea level within 2 h. Echocardiography examinations were performed to assess the mean pulmonary artery pressure (mPAP) and hemodynamics at both altitudes. All the individuals underwent blood tests to determine the concentrations of vascular regulatory factors. Univariate and adjusted logistic regression analyses were performed to identify the independent predictors of ePAP and factors related to ePAP. Results: The mPAP increased significantly from sea level to high altitude (19.79 ± 6.53-27.16 ± 7.16 mmHg, p < 0.05). Increased levels of endothelin (ET-1), Ang (1-7), Ang II, and bradykinin were found after high-altitude exposure, while the levels of nitric oxide (NO), prostaglandin E2 (PEG2), and serotonin decreased sharply (all p-values < 0.05). At high altitude, 52.6% of the subjects exhibited ePAP, and the mPAP was closely correlated with the baseline Ang II level (r = 0.170, p = 0.036) and follow-up levels of NO (r = -0.209, p = 0.009), Ang II (r = 0.246, p = 0.002), and Ang (1-7) (r = -0.222, p = 0.006) and the left atrial inner diameter (LAD, r = 0.270, p < 0.001). Both the baseline and follow-up NO and Ang II levels were significantly different between the ePAP and non-ePAP groups. Finally, we identified the baseline Ang II and NO concentrations as two independent predictors of ePAP (p < 0.05). We also found that two vascular regulatory factors with inverse roles, namely, Ang (1-7) and Ang II, at high altitudes were independently associated with ePAP. Additionally, ET-1, NO, PEG2, and LAD were associated with ePAP. Conclusion: The baseline concentrations of Ang II and NO at sea level are two independent predictors of ePAP after acute high-altitude exposure. Furthermore, Ang (1-7) and Ang II combined with ET-1, NO, PEG2, and LAD at high altitudes may contribute to the development of ePAP.

Baseline Ratio of Soluble Fas/FasL Predicts Onset of Pulmonary Hypertension in Elder Patients Undergoing Maintenance Hemodialysis: A Prospective Cohort Study.

Background: Pulmonary hypertension (PH) is one of the most common complications associated with end-stage renal disease (ESRD). Though numerous risk factors have been founded, other risk factors remain unidentified, particularly in patients undergoing maintenance hemodialysis with elder age. Soluble Fas (sFas) and its ligand FasL (sFasL) have been reported in chronic renal disease patients; however, they have not been identified in the PH patients of elder hemodialysis patients. We aimed to determine the roles of sFas/sFasL in onset of PH in elder patients undergoing maintenance hemodialysis with ESRD. Methods: Altogether, 163 patients aged 68.00 ± 10.51 years with ESRD who undergoing maintenance hemodialysis in a prospective cohort and were followed-up for a median of 5.5 years. They underwent echocardiography examinations, liver function assessments, residual renal function, and serum ion examinations, before and after dialysis. Furthermore, levels of sFas and sFasL at baseline had also been measured. We compared demographic data, echocardiographic parameters, liver function, ions, and residual renal function as well as serum sFas and sFasL between the PH and non-PH groups. These parameters were correlated with systolic pulmonary artery pressure (sPAP) using Spearman's correlation. Moreover, univariate and adjusted logistic regression analyses have also been conducted. Results: The incidence of PH in the elder dialysis patients was 39.1%. PH populations were demonstrated with significantly higher end-diastolic internal diameters of the left atrium, left ventricle, right ventricle (RV), and pulmonary artery, as well as the left ventricular posterior wall thickness (LVWP; all p < 0.05). A higher baseline serum sFas and sFasL levels have also been identified ( p < 0.001). They also showed lower fractional shortening and left ventricular ejection fraction (LVEF; p < 0.05). Following dialysis, the post-dialysis serum potassium concentration (K+) was significantly higher in the PH group ( p = 0.013). Furthermore, the adjusted regression identified that ratio of sFas/FasL (OR: 1.587, p = 0.004), RV (OR: 1.184, p = 0.014), LVPW (OR: 1.517, p = 0.007), and post-dialysis K+ (OR: 2.717, p = 0.040) was the independent risk factors for PH while LVEF (OR: 0.875, p = 0.040) protects patients from PH. Conclusion: The baseline ratio of sFas/sFasL, RV, LVPW, and post-dialysis K+ was independent risk factors for PH onset, while LVEF was a protective factor for PH.

Relationship between creatinine to body weight ratios and diabetes mellitus: A Chinese cohort study.

BACKGROUND: Research on the relationship between creatinine to body weight ratios (Cre/BW ratios) and the prevalence of diabetes is still lacking. The intention of this research was to explore the potential relationship between Cre/BW ratio and diabetes prevalence in Chinese adults. METHODS: This retrospective study was conducted on 199 526 patients in the Chinese Rich Healthcare Group from 2010 to 2016. The participants were divided into four groups on the basis of the quartiles of the Cre/BW ratios. Multivariate multiple imputation and dummy variables were used to handle missing values. Multivariate regression analysis was applied to detect the relationship between Cre/BW and diabetes. A smoothing plot was also used to identify whether there were nonlinear relationships. RESULTS: After handling missing values and adjusting for potential confounders, the multivariate Cox regression analysis results showed that Cre/BW was inversely correlated with diabetes risk (hazard ratio [HR]: 0.268; 95% confidence interval [CI]: 0.229-0.314, p < 0.00001). For men, the HR of incident diabetes was 0.255 (95% CI: 0.212-0.307) and for women it was 0.297 (95% CI: 0.218-0.406). Moreover, sensitivity analysis confirmed the stability of the results. Furthermore, the smoothing plot revealed that there was a saturation effect between Cre/BW and the incidence of diabetes. CONCLUSIONS: This study demonstrated that increased Cre/BW is negatively correlated with diabetes in Chinese adults. It also found that Cre/BW has a nonlinear relationship with the incidence of diabetes.

The Prevalence of Pulmonary Hypertension Among Maintenance Dialysis Patients With ESRD and Its Associated Factors: A Retrospective Study.

Aim: To determine the prevalence of pulmonary hypertension (PH) and its associated factors among end-stage renal disease (ESRD) patients who underwent maintenance dialysis. Methods: A total of 491 patients received echocardiography examinations and underwent pulmonary artery systolic pressure (PASP) assessments. A subgroup of 283 patients were subjected to plasma creatinine (Cr) and blood urea nitrogen concentration (BUN) tests, routine blood examinations and electrolyte analysis. First, we compared the differences in echocardiographic, Cr and BUN, blood routine and electrolyte parameters between PH and non-PH groups. The correlations between PASP and the parameters mentioned above were also analyzed. Furthermore, univariate and adjusted logistic regression analyses were performed to identify the independent associated factors. Results: The incidence of PH among ESRD patients who were treated with maintenance dialysis was 34.6%. Most of the echocardiographic parameters, including end-diastolic internal diameters of the left atrium, left ventricle, right atrium, and pulmonary artery, as well as interventricular septum mobility, left ventricular posterior wall mobility, fractional shortening, stroke volume and left ventricle ejection fraction (LVEF), were associated with PH. Furthermore, Mg2+ (p = 0.037) and Cl- (p = 0.043) were significantly associated with PASP. However, after adjustments were made in the regression analysis, only internal diameters of the left atrium, right atrium, and LVEF were independently associated with PH. Conclusion: PH is prevalent, with a relatively high incidence among ESRD patients who undergo maintenance dialysis. The sizes of the left and right atria as well as LVEF were independently associated with PH, but further cohort and basic mechanistic studies are needed to confirm this finding.

New HIV diagnoses in patients with COVID-19: two case reports and a brief literature review.

BACKGROUND: COVID-19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Severe cases developed life-threatening complications, such as respiratory failure, shock, and multiple organs dysfunction. Immunocompromised patients often present atypical presentations of viral infected diseases. CASE PRESENTATION: We report newly diagnosed HIV infections in two patients with COVID-19 in China. In our two cases, both patients with elevated IL-6 received Tocilizumab treatment, but did not present obvious therapeutic effect. CONCLUSIONS: These cases highlight possible co-detection of known immunocompromised diseases such as HIV. The two cases we reported stressed the risk of misdiagnosis, especially during the pandemic of an infectious disease and the importance of extended testing even if in immune-compromised condition the immune state may be ignored.

The Prevalence and Independent Risk Factors of Significant Tricuspid Regurgitation Jets in Maintenance Hemodialysis Patients With ESRD.

BACKGROUND AND AIM: Tricuspid regurgitation (TR) is a frequent complication in various cardiovascular diseases. However, few studies have reported the prevalence of TR especially the moderate to severe or significant TR (ms-TR) maintenance dialysis patients. Thus, we aimed to identify the prevalence of ms-TR and its associated factors. METHODS: A total of 491 maintenance dialysis patients underwent echocardiographic examinations, while a subgroup (n = 283) also received routine blood tests, renal function examinations, and electrolyte analysis. We first compared the differences in abovementioned parameters among groups with various TR areas (TRAs). Finally, univariate and adjusted regression were also used to identify factors that were independently associated with ms-TR. RESULTS: The incidence of TR jets was 62.6%, which included a mildly increased TRA (47.8%), moderately increased TRA (10.4%), and severely increased TRA (3.5%). Most of the cardiac structures and functional parameters, such as the end-diastolic internal diameters of the left atrium (LA), left ventricle (LVDD), right atrium (RA), right ventricle (RV), left ventricular ejection fraction (LVEF), and fractional shortening (FS), were significantly associated with ms-TR. Among serum ions, only total CO2 (TCO2; r = -0.141, p = 0.047) was negatively correlated with TRA. After adjusted, only Na+ [odds ratio (OR): 0.871 0.888, p = 0.048], RA (OR: 1.370, p < 0.001), and FS (OR: 0.887, p < 0.001) were independently associated with ms-TR. CONCLUSION: Tricuspid regurgitation occurs in maintenance hemodialysis patients with ESRD. Na+ FS and RA were independently associated with ms-TR, and these parameters may be potential risk factors/predictors for ms-TR.

Acute Mountain Sickness Is Associated With a High Ratio of Endogenous Testosterone to Estradiol After High-Altitude Exposure at 3,700 m in Young Chinese Men.

Background: A large proportion of populations suffer from acute mountain sickness (AMS) after exposure at high altitude. AMS is closely related with age and gender implying that the sex hormones may play critical roles in AMS. Our observational study aimed to identify the association between the endogenous testosterone (T), estradiol (E2) and AMS. Methods: A total of 113 subjects were recruited in 2012. The participants were evaluated at 500 m and after acute (1 day) and short-term (7 days) high-altitude exposure at 3,700 m. The subjects also completed a case report form questionnaire and underwent blood pressure measurements and an echocardiography examination. The red blood cell (RBC) count, Hb concentration ([Hb]), hematocrit (HCT), E2, T, and erythropoietin (EPO) were measured. Results: Upon acute high-altitude exposure, E2 and EPO were significantly lower in AMS+ group, and T/E2 and stroke volume were higher. On the 1st day, AMS score correlated positively with the T/E2 ratio while it negatively correlated with E2. After 7 days at 3,700 m, the AMS+ subjects had higher erythropoietic parameters: EPO, T, and T/E2 were significantly higher in the AMS+ group. [Hb], RBC count, HCT, EPO, T and T/E2 were also correlated with AMS score. EPO, HCT, and the RBC count were also correlated with T/E2. Regression analyses indicated that T/E2 significantly correlated to AMS score and T/E2 on the 1st day was an independent predictor for AMS on the 7th day. Conclusion: AMS was correlated with T/E2 ratio and EPO. After short-term exposure, higher T/E2 may contribute to AMS together with EPO via erythropoiesis. Furthermore, T/E2 level at high altitude in the early stage was an independent predictor for AMS in the latter stage.

D-4F decreases the expression of Aß protein through up-regulating long non coding RNA sirt1-as in SAMP8 mice.

Cholesterol plays key roles on (Aß) metabolism and production. D-4F is the apolipoprotein A-I mimetic peptide which has been revealed a critical role in regulation cholesterol. We aimed at identifying the effects of D-4F on Aß production in SAMP8 and the underlying mechanisms. METHODS: SAMP8 mice (n = 15) were randomized into three groups for treatment with D-4F given in drinking water: high-dose group (0.5 mg/ml), low-dose group (0.3 mg/ml) and control group (just drinking water). The heart, kidney, liver and brain were obtained from SAMP8 (9 of them included in the analysis). The long non-coding RNA sirt1-as was measured in all tissues. The immunohistochemistry, western blot qRT-PCR were performed to determine the sirt1-as and the relevant proteins or RNAs levels. RESULTS: After treated with D-4F, the sirt1-as has been significantly upregulated in brain, rather than heart, kidney or liver. Specially, sirt1-as was significantly up-regulated by high dose of D-4F in the hippocampus area (p = 0.007) compared with control group. Further analysis revealed that D-4F up-regulates the expression of SIRT1. We also found that D-4F treatment significantly increased the reverse cholesterol transport related proteins liver X receptor α (LXRα) and ATP-binding cassette transporter A1 (ABCA1, p < 0.05). Finally, the amyloid ß-protein (Aß protein) was statistically lower than that in the control group (p < 0.05). CONCLUSION: Our observation indicated that D-4F decreases the expression of Aß protein through up-regulating long non coding RNA sirt1-as and its downstream proteins which may involve in reverse cholesterol transport.

A higher baseline plasma uric acid level is an independent predictor of arterial stiffness: A community-based prospective study.

Hyperuricemia has been demonstrated to be a risk factor for cardiovascular diseases. Though the association between uric acid (UA) and arterial stiffness has been investigated previously in patients with basic diseases, the predictive value of baseline UA level for arterial stiffness has not been conducted. We aimed at identifying the predictive role of UA for arterial stiffness prospectively.A longitudinal follow-up study in a routine health check-up population was performed with an average follow-up of 4.8 years. The demographic information, baseline and follow-up anthropometric parameters, arterial stiffness (pulse-wave velocity, PWV), and biomarker variables including UA have been measured and analyzed.A total of 1447 valid follow-ups were available for the final analysis. Both of the baseline and follow-up UA levels were significantly higher in the arterial stiffness groups than that in the nonarterial stiffness groups (all P values <0.001). The follow-up carotid-femoral PWV [(cf-PWV), r = 0.161, P < 0.001] was strongly correlated with baseline UA. At the follow-up cross-section, cf-PWV was also closely associated with UA (r = 0.101, P < 0.001). Logistic regressions revealed that a higher baseline UA level was an independent predictor of follow-up arterial stiffness assessed by cf-PWV [odds ratio (OR): 1.824; P = 0.046].A higher baseline level of UA is closely related to arterial stiffness and is an independent predictor of arterial stiffening.

Age as a risk factor for acute mountain sickness upon rapid ascent to 3,700 m among young adult Chinese men.

BACKGROUND: The aim of this study was to explore the relationship between age and acute mountain sickness (AMS) when subjects are exposed suddenly to high altitude. METHODS: A total of 856 young adult men were recruited. Before and after acute altitude exposure, the Athens Insomnia Scale score (AISS) was used to evaluate the subjective sleep quality of subjects. AMS was assessed using the Lake Louise scoring system. Heart rate (HR) and arterial oxygen saturation (SaO2) were measured. RESULTS: Results showed that, at 500 m, AISS and insomnia prevalence were higher in older individuals. After acute exposure to altitude, the HR, AISS, and insomnia prevalence increased sharply, and the increase in older individuals was more marked. The opposite trend was observed for SaO2. At 3,700 m, the prevalence of AMS increased with age, as did severe AMS, and AMS symptoms (except gastrointestinal symptoms). Multivariate logistic regression analysis showed that age was a risk factor for AMS (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.13, P<0.05), as well as AISS (adjusted OR 1.39, 95% CI 1.28-1.51, P<0.001). CONCLUSION: The present study is the first to demonstrate that older age is an independent risk factor for AMS upon rapid ascent to high altitude among young adult Chinese men, and pre-existing poor subjective sleep quality may be a contributor to increased AMS prevalence in older subjects.

Relationship between excessive erythrocytosis and acute mountain sickness: a field study.

BACKGROUND: Alterations in hematology, especially erythroid changes, may be involved in acute mountain sickness (AMS) at high altitude. This study aimed to identify the relationship between excessive erythrocytosis and AMS following different durations of high-altitude exposure. METHODS: A total of 692 healthy young Chinese men were recruited for the study in June and July of 2012 and were divided into the following five groups: I) the 24-h group (24 hours after arrival at Lhasa, 3,700 m, n = 261); II) the 7-d group (exposed at Lhasa, 3,700 m for seven days, n = 99); III) the re-exposure group (re-exposed at Yang Bajing, 4,400 m for seven days after >1 year of acclimation at 3,700 m,n = 94); IV) the acclimated group (>1 year of acclimation at 3,700 m, Lhasa, n = 42); and V) the sea-level control (control group, Chengdu, n = 196). Case report forms were used to record the subjects' demographic information and AMS-related symptoms. All of the subjects underwent routine blood tests. RESULTS: The red blood cell (RBC) count fell slightly but was not significant upon acute exposure to high altitude, whereas the hemoglobin concentration ([Hb]) increased significantly. After high-altitude re-exposure, both of the [Hb] and RBC count showed significant increases. The incidence of AMS was 65.1%, 26.3% and 51.1%, respectively in the 24-h, 7-d and re-exposure groups. The [Hb] (P = 0.024) and hematocrit (P = 0.017) were greater in the AMS(+) individuals than in the AMS(-) individuals in 7-d group. A correlation analysis revealed that the [Hb] and hematocrit were closely related with AMS score in 7-d and re-exposure groups, while the RBC showed a correlation with AMS score only in the re-exposure group. The AMS incidence was lowest when the [Hb] was between 140 and 160 g/L in the 24-h and 7-d groups. CONCLUSIONS: AMS is associated with both [Hb] and excessive erythrocytosis. Additionally, our findings indicate the existence of an optimal [Hb] for preventing AMS.

Correlation between blood pressure changes and AMS, sleeping quality and exercise upon high-altitude exposure in young Chinese men.

BACKGROUND: Excessive elevation of arterial blood pressure (BP) at high altitude can be detrimental to our health due to acute mountain sickness (AMS) or some AMS symptoms. This prospective and observational study aimed to elucidate blood pressure changes induced by exposure to high-altitude hypoxia and the relationships of these changes with AMS prevalence, AMS severity, sleep quality and exercise condition in healthy young men. METHODS: A prospective observational study was performed in 931 male young adults exposed to high altitude at 3,700 m (Lhasa) from low altitude (LA, 500 m). Blood pressure measurement and AMS symptom questionnaires were performed at LA and on day 1, 3, 5, and 7 of exposure to high altitude. Lake Louise criteria were used to diagnose AMS. Likewise, the Athens Insomnia Scale (AIS) and the Epworth Sleepiness Scale (ESS) were filled out at LA and on day 1, 3, and 7 of exposure to high altitude. RESULTS: After acute exposure to 3,700 m, diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) rose gradually and continually (P < 0.05). Analysis showed a relationship with AMS for only MABP (P < 0.05) but not for SBP and DBP (P > 0.05). Poor sleeping quality was generally associated with higher SBP or DBP at high altitude, although inconsistent results were obtained at different time (P < 0.05). SBP and Pulse BP increased noticeably after high-altitude exercise (P < 0.05). CONCLUSIONS: Our data demonstrate notable blood pressure changes under exposure to different high-altitude conditions: 1) BP increased over time. 2) Higher BP generally accompanied poor sleeping quality and higher incidence of AMS. 3) SBP and Pulse BP were higher after high-altitude exercise. Therefore, we should put more effort into monitoring BP after exposure to high altitude in order to guard against excessive increases in BP.