[Effects of virtual reality in phase I cardiac rehabilitation training for elderly coronary heart disease patients after percutaneous coronary intervention].

The study aimed to examine the effects of virtual reality (VR) technology-based phase I cardiac rehabilitation (CR) program in elderly coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI). Thirty-six cases of elderly CHD patients who underwent PCI in the First Affiliated Hospital of Chongqing Medical University from June 2022 to April 2023 were recruited by convenience sampling method. The patients were randomly assigned by means of random digital table method to two study groups: control group (n = 18), which received conventional nursing intervention after PCI, and experimental group (n = 18), which received a combined program of conventional nursing intervention together with CR program based on VR technology. The 6 min walk test (6MWT), Simple Physical Performance Battery (SPPB), SF-36 scale, Hospital Anxiety and Depression Scale (HADS) and Impact of Events Scale-Revised (IES-R) were tested before and after rehabilitation. Moreover, the incidence of major adverse cardiovascular events (MACE) was recorded at 3 months after PCI. After VR-based CR, the 6MWT distance and SPPB scores of patients in the experimental group were higher than those in control group (P < 0.05). The HADS scores and IES-R scores of the patients in the experimental group were lower than those in control group (P < 0.01), and the difference in SF-36 scale scores was not statistically significant between two groups (P > 0.05). The incidence of MACE was not significantly different at 3 months after PCI (P > 0.05). These results suggest that VR-based phase I CR program mitigates the degree of PCI postoperative stress, anxiety, and depression in elderly CHD patients, however, enhances the resistance to fatigue and does not increase the risk of adverse cardiac events, suggesting it is a safe intervention.

Association between serum copper level and reproductive health of Women in the United States: a cross-sectional study.

Copper is an indispensable trace element in metabolism. This study aimed to investigate the relationship between copper and reproductive health, and possibly provide new insights for diagnosis and treatment. This study was based on data extracted from the NHANES database (2013-2014 and 2015-2016). The t-test, ANOVA, Chi-square test, multiple linear regression, and restricted cubic spline analysis were used. Serum copper levels were significantly higher in women with gestational diabetes than in those without gestational diabetes (P = 0.0150). Women with higher copper levels and smoking habits tended to deliver overweight babies (P = 0.028). Women with diabetes had higher serum copper and were prone to deliver overweight babies (P = 0.024). Serum copper levels showed a positive relationship with sex hormone-binding globulin (SHBG) levels (P < 0.0001). In this study, serum copper levels were found to be associated with reproductive health in women. Further studies are required to draw causal inferences.

iNOS regulates activation of the NLRP3 inflammasome through the sGC/cGMP/PKG/TACE/TNF-α axis in response to cigarette smoke resulting in aortic endothelial pyroptosis and vascular dysfunction.

BACKGROUND: Cigarette smoke (CS) is associated with vascular injury and dysfunction, which may be mediated by iNOS and NLRP3. However, the exact mechanism is unknown. METHODS: iNOS-knockout and NLRP3-knockout C57BL/6 mice were exposed to air or CS. The vascular structure was examined by hematoxylin-eosin staining. The vascular tension was measured by a vascular reactivity assay. The expression of iNOS, NLRP3, caspase-1p20, IL-1ß and eNOS were measured by western blotting. Human aortic endothelial cells (HAECs) were exposed to L-NIL (iNOS inhibitor), MCC950 (NLRP3 inhibitor), ODQ (sGC inhibitor), KT5823 (PKG inhibitor) or TAPI-1 (TACE/ADAM17 inhibitor) for 1 h prior to cigarette smoke extract (CSE) treatment. The cell viability and lactate dehydrogenase activity were assessed and pyroptosis was determined by scanning electron microscopy. The mRNA expression of TNF-α, and protein expression of iNOS, active-TACE, NLRP3, caspase-1p20, IL-1ß, and eNOS were measured. RESULTS: CS resulted in shrinkage of endothelial cells, impaired aorta relaxation, reduced eNOS expression, and induced expression of iNOS, NLRP3, caspase-1p20 and IL-1ß, which could be prevented by knockdown of iNOS and NLRP3. CSE reduced cell viability, induced LDH release and pyroptosis, and promoted iNOS, NLRP3, caspase-1p20, and IL-1ß expression and reduced eNOS reduction, which could be reversed by inhibition of iNOS or NLRP3 in HAECs. Altogether, activation of the NLRP3 inflammasome by iNOS in CS-exposed HAECs may be mediated by the sGC/cGMP/PKG/TACE/TNF- α pathway. CONCLUSION: These results link iNOS to NLRP3 in CSE-stimulated HAECs through the sGC/cGMP/PKG/TACE/TNF-α pathway. The findings identify a mechanism through which iNOS and NLRP3 contribute to the pathogenesis of CS-induced pyroptosis and impaired aorta relaxation in HAECs.

Phosphorylation of Akt at Thr308 regulates p-eNOS Ser1177 during physiological conditions.

Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) plays a crucial role in maintaining vascular homeostasis. As a hallmark of eNOS activation, phosphorylation of eNOS at Ser1177 induced by activated protein kinase B (PKB/Akt) is pivotal for NO production. The complete activation of Akt requires its phosphorylation of both Thr308 and Ser473. However, which site plays the main role in regulating phosphorylation of eNOS Ser1177 is still controversial. The purpose of the present study is to explore the specific regulatory mechanism of phosphorylated Akt in eNOS activation. Inhibition of Akt Thr308 phosphorylation by a specific inhibitor or by siRNA in vitro led to a decrease in eNOS phosphorylation at Ser1177 and to lower NO concentration in the cell culture medium of HUVECs. However, inhibiting p-Akt Ser473 had no effect on eNOS phosphorylation at Ser1177. Next, we administered mice with inhibitors to downregulate p-Akt Ser473 or Thr308 activity. Along with the inhibition of p-Akt Thr308, vascular p-eNOS Ser1177 protein was simultaneously downregulated in parallel with a decrease in plasma NO concentration. Additionally, we cultured HUVECs at various temperature conditions (37, 22, and 4 °C). The results showed that p-Akt Ser473 was gradually decreased in line with the reduction in temperature, accompanied by increased levels of p-Akt Thr308 and p-eNOS Ser1177. Taken together, our study indicates that the phosphorylation of Akt at Thr308, but not at Ser473, plays a more significant role in regulating p-eNOS Ser1177 levels under physiological conditions.

D-dimer level and long-term outcome in patients with end-stage heart failure secondary to idiopathic dilated cardiomyopathy.

BACKGROUND: Previous studies had demonstrated hemostatic abnormalities in patients with heart failure (HF) and several studies have shown that abnormal coagulation indices, represented by elevated D-dimer, had prognostic significance in patients with compatible or acute decompensated HF. However, the impact of D-dimer on the outcome in patients with end-stage HF remains unclear. METHODS: A total of 244 consecutive patients with end-stage HF due to idiopathic dilated cardiomyopathy (DCM) were prospectively enrolled from February 2011 to September 2014. D-dimer levels were measured and its prognostic value was assessed. Primary endpoint was all-cause mortality during the follow-up period. Secondary endpoints were stroke, bleeding, occurrence of sustained ventricular tachycardia or ventricular fibrillation, and major adverse cardiovascular events (MACE). RESULTS: D-dimer was significantly elevated in the non-survivors (median: 0.8 vs. 1.1 mg/L, P < 0.001). Traditional markers including B-type natriuretic peptide, troponin I, left ventricular ejection fraction, and left ventricular end-diastolic dimension provided limited prognostic value; but the addition of D-dimer refined the risk stratification. The optimal cut-off value of D-dimer to predict all-cause mortality was 0.84 mg/L by receiver operator characteristic analysis. Elevated D-dimer level was independently associated with increased risk of long-term all-cause mortality (HR = 2.315, 95% CI: 1.570-3.414, P < 0.001) and MACE (HR = 1.256, 95% CI: 1.058-1.490, P = 0.009), and the predictive value was independent of age, sex, atrial fibrillation and anticoagulation status. CONCLUSIONS: Elevated D-dimer level was independently associated with poor long-term outcome in patients with end-stage HF secondary to idiopathic DCM, and the predictive value was superior to that of traditional prognostic markers.

The use status of anticoagulation drugs for inpatients with nonvalvular atrial fibrillation in Southwest China.

BACKGROUND: Oral anticoagulants (OACs) are effective for the prophylaxis of stroke in patients with atrial fibrillation (AF). This cross-sectional study aimed to investigate the status of anticoagulation treatment for hospitalized AF patients in Southwest China. METHODS: A total of 4760 hospitalized patients with AF were enrolled from 21 hospitals in Chongqing city from January 1 to December 31, 2013. RESULTS: Among the enrolled patients, 3785 were diagnosed with nonvalvular AF. These patients had a mean age of 74.4±10.1 years. The mean CHADS2 score of all subjects was 2.60±1.34, and 80.7% of the patients had CHADS2 ≥2. The use rate of OACs was only 11.5% for patients with a high risk for stroke (CHADS2 ≥2) and was much lower in patients from the second-level hospitals than in patients from the third-level hospitals (5.8% vs. 16.9%, P<0.001). The leading reason for the underuse of OACs in high-risk patients was physician's nonfeasance. CONCLUSION: This study demonstrated that the underuse of anticoagulation therapy in hospitalized patients with nonvalvular AF was particularly serious in Southwest China, especially in the second-level hospitals. Urgent and effective measures are desperately needed to improve this alarming situation in China.

The -137G/C single nucleotide polymorphism in IL-18 gene promoter contributes to tuberculosis susceptibility in Chinese Han population.

BACKGROUND: Interleukin (IL) -18 is crucial to host defense against mycobacterial infections. Recent studies have indicated IL-18 gene polymorphisms are associated with susceptibility to several clinical diseases. OBJECTIVE: The aim of this study is to investigate the association of IL-18 (-137G/C and -607C/A) gene promoter single nucleotide polymorphisms (SNPs) with susceptibility to tuberculosis (TB), and the effects of those SNPs to its protein producing capacity in Chinese Han population. METHODS: 407 TB patients (including 113 children and 294 adults) and 469 healthy volunteers (including 167 children and 302 adults) from Chinese Han population were enrolled. The IL-18 gene promoter polymorphisms at positions of -137 and -607 were determined by sequence specific primer-polymerase chain reaction (SSP-PCR). The IL-18 levels in the supernatants of PBMCs from 46 healthy volunteers were measured by ELISA. RESULTS: The gene distribution of IL-18 -137G/C and -607C/A showed none difference between adult and pediatric population. The frequency of IL-18 -137GG genotype was significantly higher in total TB group than that in total healthy control group (79.1% V 69.3%, P<0.01), while the frequencies of GC genotype and C allele were conversely lower (19.2% V 27.9%, P<0.01; 11.3% V 16.7%, P<0.01 respectively). The difference of the -137CC genotype distribution between patients and controls was not observed. At the -607C/A polymorphic site, patient and control groups had a very similar gene distribution. Isolated PBMCs with IL-18 -137GC/CC genotype were able to produce a higher level of IL-18 than those with IL-18 -137GG genotype, either spontaneously or in response to PMA plus calcimycin A23187. CONCLUSION: IL-18 -137G/C polymorphism contributed to TB susceptibility in Chinese Han population. Allele G might be a predisposing gene of TB, while allele C probably plays a role in preventing mycobacterium tuberculosis infection by promoting more vigorous protein expression.