Mechanism of Action of the Plateau-Adapted Gene PPARA in COPD.

Chronic obstructive pulmonary disease (COPD) is a complex respiratory disorder influenced by various factors and involving multiple genes. Respiratory dysfunction in COPD patients leads to hypoxia, resulting in limited oxygen uptake. Peroxisome proliferator-activated receptor alpha (PPARA) is a plateau-adapted gene that regulates respiratory function in populations adapted to high-altitude areas through multiple pathways. Interestingly, PPARA expression is higher in long-term inhabiting Tibetan populations that have adapted to the plateau environment. However, in patients with COPD, the expression of PPARA is downregulated, leading to dysregulation of the hypoxia-inducible factor pathway. Moreover, abnormal PPARA expression in lung epithelial cells triggers inflammatory responses, oxidative stress, and disrupted lipid metabolism, thereby exacerbating disease progression. Thus, this paper explored the mechanism underlying the role of plateau-adapted PPARA in COPD, providing essential theoretical insights into the treatment and prevention of COPD in high-altitude regions.

GSTP1 rs4147581 C>G and NLRP3 rs3806265 T>C as Risk Factors for Chronic Obstructive Pulmonary Disease: A Case-Control Study.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory ailment influenced by a blend of genetic and environmental factors. Inflammatory response and an imbalance in oxidative-antioxidant mechanisms constitute the primary pathogenesis of COPD. Glutathione S-transferase P1(GSTP1) plays a pivotal role as an antioxidant enzyme in regulating oxidative-antioxidant responses in the pulmonary system. The activation of the NOD-like receptor thermal protein domain (NLRP3) inflammatory vesicle can trigger an inflammatory response. Several investigations have implicated GSTP1 and NLRP3 in the progression of COPD; nonetheless, there remains debate regarding this mechanism. Methods: Employing a case-control study design, 312 individuals diagnosed with COPD and 314 healthy controls were recruited from Gansu Province to evaluate the correlation between GSTP1 (rs4147581C>G and rs1695A>G) and NLRP3 (rs3806265T>C and rs10754558G>C) polymorphisms and the susceptibility to COPD. Results: The presence of the GSTP1 rs4147581G allele substantially elevated the susceptibility to COPD (CGvs.CC:OR=3.11,95% CI=1.961-4.935, P<0.001;GGvs.CC:OR=2.065,95% CI=1.273-3.350, P=0.003; CG+GGvs.CC:OR=2.594,95% CI=1.718-3.916, P<0.001). Similarly, the NLRP3rs3806265T allele significantly increased the susceptibility to COPD (TC:TT:OR=0.432,95% CI=0.296-0.630; TC+CCvs.TT:OR=2.132,95% CI=1.479-3.074, P<0.001). However, no statistically significant association was discerned between the rs1695A>G and rs10754558G>C polymorphisms and COPD susceptibility (P>0.05). Conclusion: In summary, this study ascertained that the GSTP1 rs4147581C>G polymorphism is associated with increased COPD susceptibility, with the G allele elevating the risk of COPD. Similarly, the NLRP3 rs3806265T>C polymorphism is linked to elevated COPD susceptibility, with the T allele heightening the risk of COPD.

A Case-Control Study of the Associations between EGLN1 Gene Polymorphisms and COPD.

BACKGROUND: Environmental and genetic factors are jointly involved in the development of chronic obstructive pulmonary disease (COPD). The EGLN1 gene is a major factor in upstream regulation of the hypoxia-inducible pathway. EGLN1 negatively regulates the hypoxia-inducible factors HIF-lα and HIF-2α by regulating the concentration of oxygen, mainly in a hypoxic environment. Hypoxia is a common physiologic condition during the progression of COPD, and several studies have identified genetic variants in EGLN1 as a key factor in the adaptation to hypoxic environments. However, it is still unclear whether there is an association between EGLN1 variants and the risk of developing COPD. METHODS: A case-control study was conducted in the Gannan Tibetan Autonomous Prefecture, Gansu Province. A total of 292 COPD patients and 297 healthy controls were enrolled to assess the association of EGLN1 single nucleotide polymorphisms (SNPs) (rs41303095 A>G, rs480902 C>T, rs12097901 C>G, rs2153364 G>A) with COPD susceptibility. RESULTS: The EGLN1 rs41303095 A>G, rs480902 C>T, rs12097901 C>G, and rs2153364 G>A polymorphisms were not associated with COPD susceptibility (p > 0.05). CONCLUSIONS: The EGLN1 rs41303095 A>G, rs480902 C>T, rs12097901 C>G and rs2153364 G>A polymorphisms were found in this study not to be associated with susceptibility to COPD in Gannan Tibetans.

Assessing Left Ventricular Systolic Function in Patients with Pregnancy-Induced Hypertension Using Three-Dimensional Speckle Tracking Technology.

Objective: This study investigates the clinical utility of three-dimensional speckle tracking technology in assessing left ventricular systolic function in pregnancy-induced hypertension syndrome (PIH). Methods: We retrospectively enrolled 70 patients with diagnosed PIH treated at our institution between July 2019 and August 2021 as the study group. A total of 70 healthy pregnant women undergoing routine antenatal examinations at the same institution during the same period were included in the control group. Two-dimensional conventional echocardiography measured left ventricular parameters in both groups. Three-dimensional speckle tracking technology analyzed Left Ventricular Global Longitudinal Peak Strain (LVGLS), Left Ventricular Global Radial Peak Strain (LVGRS), and Left Ventricular Global Circumferential Peak Strain (LVGCS). Differences in left ventricular systolic function and pregnancy outcomes were compared. Results: In the study group, LVEDD, LVPWTd, and IVSTd (47.67±4.88, 10.68±1.21, 11.24±1.03) exceeded those in the control group (45.21±5.65, 8.17±0.98, 8.91±0.37). LVEF (62.12±5.63) was lower than the control group (65.25±5.17) (all P < .05). LVGLS, LVGCS, and LVGAS in the study group (-15.66±1.07, -20.17±2.89, -23.17±3.43) were higher than the control group (-20.14±1.27, -25.17±1.36, -37.68±3.29), while LVGRS (30.29±3.61) was lower than the control group (34.18±4.08) (all P < .05). The study group had 72.86% natural deliveries and 27.14% cesarean sections; the control group had 31.43% natural deliveries and 68.57% cesarean sections (all P < .05). Weeks of delivery and birth weight in the study group (36.87±1.23, 2.71±0.41) were lower than the control group (38.96±1.54, 3.41±0.78) (both P < .05). Conclusions: Compared to traditional methods, three-dimensional speckle tracking technology more sensitively detects left ventricular strain and rotation in PIH patients. It holds clinical relevance in early left ventricular dysfunction detection, effectively mitigating adverse pregnancy outcomes and warranting clinical adoption and application.

Association between transabdominal uterine artery Doppler and small-for-gestational-age: a systematic review and meta-analysis.

BACKGROUND: The association between uterine artery Doppler (UtA) measurements and small for gestational age (SGA) has not been quantitatively analyzed throughout the whole pregnancy. This systematic review and meta-analysis aims to comprehensively explore the association between UtA measurements and SGA in the first, second, and third trimesters. METHODS: Studies were searched from Pubmed, Embase, Cochrane Library, and Web of Science. Weighted mean difference (WMD), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were used as the effect size. Heterogeneity of all effect sizes was tested and quantified using I2 statistics. Sensitivity analysis was conducted for all outcomes, and publication bias was evaluated using Begg's test. RESULTS: A total of 41 studies were finally included in our meta-analysis. In the first trimester, mean PI was significantly higher in the SGA group than the non-SGA group (WMD: 0.31, 95%CI: 0.19-0.44). In the second trimester, odds of notch presence (OR: 2.54, 95%CI: 2.10-3.08), mean PI (WMD: 0.21, 95%CI: 0.12-0.30), and mean RI (WMD: 0.05, 95%CI: 0.05-0.06) were higher in the SGA group. Also, abnormal UtA measurements were associated with the increased odds of SGA (all P < 0.05). In the third trimester, PI z-score (WMD: 0.62, 95%CI: 0.33-0.91) and PI MoM (WMD: 0.08, 95%CI: 0.06-0.09) showed a significant increase in the SGA group. The odds of SGA were higher in the women with mean PI > 95% (OR: 6.03, 95%CI: 3.24-11.24). CONCLUSIONS: Abnormal UtA measurements were associated with high odds of SGA, suggesting that UtA might be an adjunctive screening method for SGA in the whole pregnancy.

Combined diagnosis of ultrasonic elastography and BI-RADS classification increases diagnostic value in female patients with breast neoplasms.

OBJECTIVE: This study was designed to investigate the clinical value of ultrasonic elastography combined with the Breast Imaging Reporting and Data System (BI-RADS) classification in patients with breast neoplasms. METHODS: A retrospective observational study was conducted on 89 patients with breast neoplasms hospitalized from June 2017 to June 2018. All the enrolled patients had received ultrasound examinations. The diagnostic value of ultrasonic elastography, BI-RADS classification, and the combined diagnosis for breast neoplasms was analyzed. RESULTS: The postoperative pathological examination showed 51 cases of benign lesions and 38 cases of malignant lesions among the 89 cases. The detection of the focal zone revealed 75 benign and 44 malignant lesions. Ultrasonic elastography misdiagnosed 8 malignant lesions as benign and 17 benign lesions as malignant; BI-RADS classification misdiagnosed 7 malignant lesions as benign and 15 benign lesions as malignant; The combined diagnosis misdiagnosed 2 malignant lesions as benign and 4 benign lesions as malignant. The sensitivity of the combined diagnosis was higher than that of ultrasonic elastography (P<0.05). The specificity and positive- and negative predictive values of the combined diagnosis were all higher than those of ultrasonic elastography and BI-RADS classification (all P<0.05). CONCLUSION: Ultrasonic elastography combined with BI-RADS classification has high clinical application value in the diagnosis of breast neoplasms, especially the sensitivity to benign and malignant lesions. And compared with the mono-detection of either ultrasonic elastography or BI-RADS classification, the combined detection yields significantly higher diagnostic accuracy.

3D-STI evaluation of the effect of dexrazoxane on the mechanical properties of right ventricular myocardium in breast cancer patients treated with pirarubicin.

BACKGROUND: Observation indexes used to evaluate the effect of dexrazoxane-anthracycline combinations in breast cancer often only take into account the clinical symptoms, or left ventricular ejection fraction (LVEF), biomarkers [such as creatine kinase MB (CK-MB), brain natriuretic peptide (BNP) and cardiac troponin T (cTnT)], or tumor recurrence rate, improvement of autonomic nerve function or economic benefits. This study aimed to evaluate the effect of dexrazoxane on the changes of mechanical properties of right ventricular myocardium in patients who underwent pirarubicin chemotherapy with three-dimensional speckle-tracking imaging (3D-STI). METHODS: A total of 64 breast cancer post-operation patients who received pirarubicin chemotherapy were randomly divided into two groups: the experimental group (with dexrazoxane added) and the control group (without dexrazoxane). The mechanical properties of the right ventricular myocardium were monitored by 3D-STI before and after chemotherapy. The levels of serum hypersensitive troponin I (hs-cTnI) and N-terminal B-type pro-natriuretic peptide (NT-proBNP) as well as conventional echocardiographic parameters were also measured. RESULTS: After chemotherapy, right ventricular global longitudinal strain (RVGLS) and right ventricular global area strain (RVGAS) were significantly reduced in both groups (P<0.05). There was a significant difference between the two groups (P<0.05). CONCLUSIONS: Dexrazoxane can alleviate the toxicity of pirarubicin in the right ventricular myocardium. 3D-STI is a potential new method for early and accurate evaluation of the mechanical properties and functional changes of the right ventricular myocardium.

Scutellarin Exerts Anti-Inflammatory Effects in Activated Microglia/Brain Macrophage in Cerebral Ischemia and in Activated BV-2 Microglia Through Regulation of MAPKs Signaling Pathway.

BACKGROUND: Scutellarin, an herbal compound, can effectively suppress the inflammatory response in activated microglia/brain macrophage(AM/BM) in experimentally induced cerebral ischemia; however, the underlying mechanism for this has not been fully clarified. We sought to elucidate if scutellarin would exert its anti-inflammatory effects on AM/BM through the MAPKs pathway. MATERIALS AND METHODS: Western blot and immunofluorescence labeling were used to determine the expression of the MAPKs pathway in AM/BM in rats subjected to middle cerebral artery occlusion (MCAO) also in lipopolysaccharide (LPS)-activated BV-2 microglia in vitro. Furthermore, expression of p-p38 along with that of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta(IL-1ß), and inducible nitric oxide synthase (iNOS) in LPS-activated microglia subjected to pretreatment with p38 inhibitor SB203580, p38 activator sc-201214, scutellarin, or a combination of them was evaluated. FINDINGS: Scutellarin markedly attenuated the expression of p-p38, p-JNK in AM/BM in MCAO rats and in vitro. Conversely, p-ERK1/2 expression level was significantly increased by scutellarin. Meanwhile, scutellarin suppressed the expression of proinflammatory mediators including iNOS, TNF-α, and IL-1ß in AM/BM. More importantly, SB203580 suppressed p-p38 protein expression level in LPS-activated BV-2 microglia that was coupled with decreased expression of proinflammatory mediators (TNF-α, iNOS) in LPS-activated BV-2 microglia. However, p38 activator sc-201214 increased expression of proinflammatory mediators TNF-α, iNOS, and IL-1ß. Interestingly, the decreased expression of both proinflammatory markers by p38 MAPK inhibitor and increased expression of proinflammatory markers by p38 MAPK activator were compatible with that in BV-2-activated microglia pretreated with scutellarin. CONCLUSIONS: The results suggest that scutellarin down-regulates the expression of proinflammatory mediators in AM/BM through suppressing the p-JNK and p-p38 MAPKs. Of note, the anti-inflammatory effect of p38 MAPK inhibitor and scutellarin is comparable. Besides, p38 MAPKs activator reverses the effect of scutellarin. Additionally, scutellarin increases p-ERK1/2 expression that may be neuroprotective.

Detection of coronary artery disease in diabetic hypertensive patients using conventional transthoratic echocardiography at rest.

To investigate the usefulness of conventional transthoratic echocardiography in identifying coronary artery disease (CAD) in diabetic hypertensive patients, transthoratic echocardiography and coronary angiography were performed in 122 diabetic hypertensive patients with suspected CAD. Correlation analysis, multivariate analysis and receiver operating characteristic curve (ROC) analysis were done. Diabetic hypertensive patients with CAD had significantly smaller coronary sinus diameter (Dcs), less velocity time integral (VTI), less coronary sinus flow (Flow) and less Flow divided by left ventricular mass (Flow/LVM) at rest versus normal participants (P < 0.01) and diabetic hypertensive patients without CAD (P < 0.05). The VTI, Dcs, Flow, LVM and Flow/LVM all showed significant correlations with the maximal percent stenosis of the coronary artery lesions (P < 0.05). However, only Flow showed statistically significant correlations with the maximal percent stenosis of the coronary artery lesions (P < 0.01) when multiple stepwise regression analysis was performed. For predicting CAD (angiographically proven, >50%) in diabetic hypertensive patients, the area under the ROC (AUC) was 0.92 for Flow, and a cut-off of <220 ml/min had a 93.2% sensitivity, 87.9% specificity and 91.3% accuracy. For predicting a >70% coronary artery stenosis, the AUC was 0.88 for Flow, and a cut-off of <147 ml/min had an 89.5% sensitivity, 87.4% specificity and 88.5% accuracy. Conventional transthoratic echocardiography can effectively and sensitively detect the CAD in diabetic hypertensive patients at rest. The reduced coronary sinus flow is a sensitive and specific predictor of CAD in diabetic hypertensive patients.