Associations between 25 hydroxyvitamin D concentration and spontaneous abortion.

BACKGROUND: Spontaneous abortion is a common complication of pregnancy that can lead to adverse physical and psychological outcomes for women. Vitamin D is reported to be associated with reproductive functions, whereas its casual effects on abortion remains unclear. MATERIALS AND METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between serum 25 hydroxyvitamin D [25(OH)D] concentration and the risk of spontaneous abortion. GWAS summary data of 25(OH)D were used as exposure, and data of spontaneous abortion was considered as outcome. A retrospective study was additionally conducted to verify the MR results. RESULTS: MR estimates showed that a higher 25(OH)D level was potentially associated with decreased risk of spontaneous abortion (IVW, OR = 0.98, 95%CI = 0.90-1.06; MR Egger, OR = 0.94, 95%CI = 0.84-1.05; Weighted median, OR = 0.93, 95%CI = 0.82-1.06; Weighted mode, OR = 0.93, 95%CI = 0.84-1.03), though the P-value was not statistically significant. The retrospective study also produced consistent result of Vitamin D's protective role to spontaneous abortion. The P-value was very close to statistical significance (P = 0.053). CONCLUSIONS: This study reports the potential protective role of serum 25(OH)D concentration to spontaneous abortion, suggesting that increased vitamin D levels may decrease the risk of abortion. Further larger prospective studies and/or even randomized controlled trials are needed to confirm causal relationship between vitamin D and abortion.

Comparison of Chromosomal Microarray Analysis and Noninvasive Prenatal Testing in Pregnant Women with Fetal Ultrasonic Soft Markers.

Objective: This study aimed to assess the utility of chromosomal microarray analysis (CMA) and noninvasive prenatal testing (NIPT) in detecting clinically significant chromosomal abnormalities among fetuses presenting ultrasonic soft markers (USMs). Methods: A retrospective observational study, spanning from January 1, 2019, to September 30, 2022, enrolled 539 singleton pregnant women with fetal USMs at our center. Of these, 418 cases (77.6%) underwent NIPT, while 121 cases (22.4%) opted for invasive prenatal diagnosis post-appropriate genetic counseling. Cases with high-risk NIPT results proceeded to invasive prenatal diagnosis, where conventional karyotyping and CMA were concurrently performed. Further stratification was done based on the number of USMs, classifying cases into single-USM and multiple-USM groups. Results: Of the 24 cases (4.5%) exhibiting abnormal findings, 17 presented numerical chromosomal abnormalities, 2 featured clinically significant copy number variations (CNVs), 3 showed variants of unknown significance (VOUS), 1 displayed LOH, and 1 exhibited chromosome nine inversion. Notably, 18 cases (75%) theoretically detectable by karyotyping (eg, sizes above 10Mb) and 16 cases (66.7%) detectable by NIPT for five common aneuploidies were identified. Six submicroscopic findings (25%) were exclusively detectable by CMA. The predominant clinically relevant aberrations were observed in the thickened nuchal-translucency (TNT) group (9/35, 25.7%), followed by the multiple soft markers group (3/32, 9.3%). In the NIPT group, the false positive rate was 1.22%, and the false negative rate was 0%. Conclusion: The prevalence of chromosome aneuploidy exceeded that of submicroscopic chromosomal imbalance in pregnant women with fetal USMs. NIPT demonstrated efficacy, particularly for soft markers like echogenic intracardiac focus. However, for those with TNT and multiple soft markers, invasive prenatal diagnosis, including CMA testing, is recommended as the primary investigative approach.

Hyperuricemia is associated with an increased prevalence of ventricular tachycardia and fibrillation in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention.

BACKGROUND: Little is known about the association between hyperuricemia and ventricular tachycardia and fibrillation (VT/VF) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). METHODS: The data from a cohort of STEMI patients undergoing PPCI at our center from January 2013 to December 2018 were retrospectively analyzed. The endpoint of the study was the occurrence of VT/VF, including (1) non-sustained ventricular tachycardia (nsVT) on Holter monitoring; (2) sustained ventricular tachycardia (SVT)/VF on cardiac monitoring. RESULTS: Of the 634 patients included in the study, 147 (23.2%) of them had hyperuricemia. The occurrence of VT/VF after PPCI was significantly higher in patients with hyperuricemia (19.0 vs. 9.4%, p = 0.001) compared with those without hyperuricemia. Hyperuricemia was associated with a significantly higher risk of VF/VT (odds ratio (OR) 2.11; 95% CI 1.11-4.03; p = 0.024). The strength of this association remained statistically after adjustments for age, sex, history of hypertension, estimated glomerular filtration rate, hypersensitive C reactive protein, plasma natrium, peak troponin I, fasting glucose, B-type natriuretic peptides and VT/VF in PPCI (adjusted odds ratio 2.73; 95% CI 1.19-6.27; p = 0.018). CONCLUSIONS: There is a significant association between hyperuricemia and increased prevalence of VT/VF in STEMI patients after PPCI, independently of multiple risk factors and potential confounders.

STMN1 and MKI67 Are Upregulated in Uterine Leiomyosarcoma and Are Potential Biomarkers for its Diagnosis.

BACKGROUND The aim of this study was to investigate STMN1 and MKI67 expression in uterine leiomyosarcoma and their potential roles as biomarkers for diagnosis. MATERIAL AND METHODS The expression of STMN1 and MKI67 mRNA in uterine leiomyosarcoma were investigated in TCGA database. The overall survival (OS) and disease-free survival (DFS) were compared between high and low expression groups. Seventy-two patients who received hysterectomy were included and divided into 4 groups: uterine normal smooth muscle tissue (UNSM=30), uterine leiomyoma (UL=30), uterine cellular leiomyoma (UCL=24), and uterine leiomyosarcoma (ULS=18). The STMN1 and MKI67 protein expression of the 4 groups were examined by immunohistochemistry (IHC) assay. RESULTS The expression level of STMN1 mRNA in cancer tissue was significantly higher than those of normal uterine smooth muscle tissue. The high and low expression of STMN1 and mki67 gene mRNA was not related to the patients' OS and DFS (P>0.05). The positive rate of STMN1 protein in uterine leiomyosarcoma was 100.00%, which was significantly higher than that of the other 3 groups (χ²=11.72, P=0.008). And the positive rate of KIM67 protein in uterine leiomyosarcoma was 77.78%, which was also significantly higher than that of the other 3 groups (χ²=48.89, P=0.000). The diagnostic sensitivity and specificity were 77.78%, 90.74% for STMN1 combined MKI67 with the positive predictive value and negative predictive value of 73.68% and 92.45%, respectively. CONCLUSIONS STMN1 and MKI67 were upregulated in uterine leiomyosarcoma and act as potential biomarkers for uterine leiomyosarcoma diagnosis.

Decorin promotes apoptosis and autophagy via suppressing c-Met in HTR-8 trophoblasts.

Decorin (DCN) regulates a vast array of cellular processes including proliferation, migration, apoptosis, and autophagy, and its aberrant expression has been associated with poor extravillous trophoblasts (EVT) invasion of the uterus, which underlies the occurrence of preeclampsia (PE) and intrauterine growth restriction (IUGR). In this study, we aim to elucidate the molecular mechanism of how the DCN regulates the cell functions through the use of trophoblast cell line, HTR-8. Using a series of cell function assays, including CCK8, RTCA, transwell, scratch-wound assay, and Annexin V staining, we found that DCN suppressed proliferation and invasion, while promoted autophagy and apoptosis of HTR-8 in a dose-dependent manner. Transient stimulation of DCN have increased the activity of c-Met and its downstream effectors - Akt, FAK and m-TOR. However, a prolonged exposure to DCN have significantly downregulated the expression of c-Met, leading to suppression of its downstream effectors. Lentivirus that overexpressed c-Met targeting shRNA was used to knockdown c-Met expression and crizotinib was used to selectively inhibit the kinase activity of c-Met in HTR-8 cells. A combination of DCN and c-Met knockdown/inhibition have reduced the proliferation and invasion in HTR-8 cells; however, DCN-induced autophagy and apoptosis were not synergistically enhanced by c-Met inhibition. In conclusion, DCN promotes autophagy and apoptosis predominantly through downregulating c-Met/Akt/mTOR activity in human trophoblasts.

Low-density lipoprotein cholesterol levels are positively associated with the risk of endobronchial biopsy-induced refractory hemorrhage in patients with lung cancer.

BACKGROUND: Lipoprotein concentrations have been associated with the major risk of bleeding events. However, whether plasma levels of LDL-C are associated with the risk of biopsy-related endobronchial hemorrhage remain elusive. Therefore, the present study was initiated to investigate the explicit association of low-density lipoprotein cholesterol (LDL-C) with endobronchial biopsy (EBB)-induced refractory hemorrhage in patients with lung cancer. METHODS: This retrospective study included a total of 659 consecutive patients with lung cancer who had undergone EBB at a tertiary hospital between January 2014 and April 2018. Using multiple regression analysis, the association between LDL-C and the risk of EBB-induced refractory hemorrhage was assessed after adjusting for potential confounding factors. RESULTS: A significant proportion (13.8%, 91/659) of the patients experienced refractory hemorrhage following EBB. In multivariate regression analysis, higher plasma LDL-C concentrations were associated with increased risk of EBB-induced refractory hemorrhage in patients with lung cancer after adjusting for potential confounders (P < 0.05). Using the lowest quartile of plasma LDL-C as the reference group, the odds ratio (95% confidence interval) of Q2, Q3, and Q4 were 2.32 (1.07, 5.03), 2.37 (0.94, 5.95), and 3.65 (1.16, 11.51), respectively (P for trend < 0.05). Moreover, this association was noticeably more pronounced in male patients with lung cancer in the subgroup analysis (P < 0.05). CONCLUSIONS: Plasma LDL-C was positively correlated with the increased risk of EBB-induced refractory hemorrhage in patients with lung cancer; predominantly, the associated risk was more pronounced in male patients with lung cancer.

Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Platelet Reactivity and Early Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention and Treated With Aspirin and Clopidogrel.

BACKGROUND: The genetic determinants of response to clopidogrel and aspirin are incompletely characterized. Recently, PEAR1 (platelet endothelial aggregation receptor-1) rs12041331 polymorphism has been shown to influence the platelet reactivity, but its impact on cardiovascular outcomes remains unclear in patients treated with antiplatelet agents. METHODS AND RESULTS: In this prospective cohort study, 2439 Chinese patients with acute coronary syndrome or stable coronary artery disease undergoing coronary stent implantation and receiving clopidogrel and aspirin were consecutively recruited. Their platelet reactivity was determined by light transmission aggregometry at 5 and 30 days after coronary intervention. Genotyping was performed using an improved multiplex ligation detection reaction technique. All patients completed a 30-day follow-up for clinical outcomes. Genotyping for PEAR1 showed 768 (38.3%) GG homozygotes, 941 (46.9%) GA heterozygotes, and 298 (14.8%) AA homozygotes. The 30-day incidence of major adverse cardiovascular events, the composite of cardiovascular death, nonfatal myocardial infarction, and ischemic stroke were significantly higher in AA homozygotes than in non-AA homozygotes (adjusted hazard ratio, 2.78; 95% CI, 1.13-6.82; P=0.026), irrespective of CYP2C19*2 loss-of-function polymorphism and known outcome predictors including age, sex, smoking, and diabetes mellitus. The ADP-induced platelet aggregation was significantly lower in AA homozygotes than that in GG homozygotes at both time points, although no significant difference was found for the arachidonic acid-induced platelet aggregation among the 3 groups. CONCLUSIONS: About 15% of Chinese patients undergoing coronary stent implantation were AA homozygotes for PEAR1 rs12041331. These patients had ≈3-fold increase in short-term major adverse cardiovascular events risk compared with non-AA homozygotes, and the adverse clinical outcome is unlikely to be mediated by suboptimal pharmacological response to aspirin or clopidogrel. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01968499.

Synergistic increase in cardiovascular risk in diabetes mellitus with nonalcoholic fatty liver disease: a meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been linked to an increased risk of cardiovascular disease (CVD). To explore the impact of diabetes mellitus (DM) as a cardiovascular risk factor, this meta-analysis quantitatively assessed the association of NAFLD and CVD in diabetic patients. METHODS: PubMed, EMBASE, and the Cochrane Library database were analyzed until the end of March 2017. Original studies analyzing the association between NAFLD and cardiovascular risk factors in the diabetic population were included. The available data related to outcome were extracted for the effect estimate using a random-effects model. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Of the 770 initially identified studies, 11 studies involving 8346 patients were finally included. The Newcastle-Ottawa Quality Assessment Scale scores suggested that the studies included were of high quality. The pooled effects estimate showed that diabetic patients with NAFLD showed a two times increased risk for CVD compared with patients without NAFLD (odds ratio=2.20, 95% confidence interval: 1.67-2.90). Subgroup analysis also yielded a markedly increased risk, with odds ratio (95% confidence interval) values of 2.28 (1.61-3.23) and 1.90 (1.48-2.45) in cross-sectional and cohort studies, respectively. CONCLUSION: This is the first meta-analysis investigating the relationship between NAFLD and CVD independent of the impact of DM. Our findings suggested that NAFLD increases the risk of CVD in populations with comparable DM profiles. Diabetic patients diagnosed with NAFLD might benefit from a more early cardiovascular risk assessment, thereby reducing CVD morbidity and mortality.

Effects of rosuvastatin and atorvastatin on nonsustained ventricular tachycardia in patients with ST-elevation myocardial infarction: a retrospective analysis.

BACKGROUND/AIMS: Early and intensive atorvastatin treatment can decrease nonsustained ventricular tachycardia (nsVT) in patients with ST-segment elevation myocardial infarction (STEMI). The objective of this study was to compare the effects of hydrophilic rosuvastatin and lipophilic atorvastatin on nsVT in STEMI patients treated with primary percutaneous coronary intervention (PCI). METHODS: The data from a cohort of patients undergoing primary PCI at Jinhua Municipal Central Hospital from January 1, 2013 through June 30, 2016 were analyzed. The patients were divided into the rosuvastatin group and the atorvastatin group based on which kind of statins that they had received. The endpoint of the study was the occurrence of nsVT on either electrocardiogram monitoring or Holter monitoring. RESULTS: A total of 301 patients were enrolled in the study (rosuvastatin group: n = 103; atorvastatin group: n = 198). The baseline and procedural characteristics were similar between the two groups, except that total ischemic time in the rosuvastatin group was markedly longer than that in the atorvastatin group (8 (5-16) h vs. 6 (4-12) h; P = 0.001). The administration of rosuvastatin was significantly associated with lower occurrence of nsVT than that of atorvastatin (9.71 vs. 19.70%; P = 0.026). Multivariable logistic regression analysis suggested that the independent predictors of nsVT included rosuvastatin (odds ratio (OR) 0.397, 95% confidence interval (CI) 0.176-0.894), current smoking (OR 2.307, 95% CI 1.011-5.262), and left ventricular ejection fraction (LVEF) (OR 1.060, 95% CI 1.023-1.098). CONCLUSIONS: The effects of rosuvastatin on nsVT might be better than that of atorvastatin in STEMI patients undergoing primary PCI.

Clinical effect of postconditioning in ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the clinical effect of postconditioning on patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS: Randomized controlled trials were identified by searching relevant databases published up to April 2nd, 2014. A meta-analysis of eligible studies was performed by Stata 12.0 and Review Manager 5.2 with a fixed-effect model. RESULTS: Ten studies providing adverse cardiac events in a total of 1346 STEMI patients treated with primary PCI were identified. The occurrence of heart failure was significantly reduced in patients treated with postconditioning compared with usual care (risk ratio (RR) 0.533; 95% confidence intervals (CI) 0.368-0.770), whereas non-fatal reinfarction slightly increased in the postconditioning group (RR 2.746; 95% CI 1.007-7.488). No significant difference in total major adverse cardiac events (MACEs) was observed between the two groups (RR 0.876; 95% CI 0.671-1.144). CONCLUSIONS: Postconditioning in STEMI patients undergoing primary PCI significantly reduces the risk of heart failure, but fails to decrease the incidence of total MACEs and the risk of non-fatal reinfarction.

Acylated iridoids from the roots of Valeriana officinalis var. latifolia.

Phytochemical investigation of the roots of Valeriana officinalis var. latifolia resulted in the isolation and characterization of six new acylated iridoids, (5S,7S,8S,9S)-7-hydroxy-8-isovaleroyloxy-Δ4,¹¹-dihyronepetalactone (1), (5S,7S,8S,9S)-7-hydroxy-10-isovaleroyloxy-Δ4,¹¹-dihyronepetalactone (2), (5S,8S,9S)-10-isovaleroyloxy-Δ4,¹¹-dihyronepetalactone (3), (5S,6S,8S,9R)-6-isovaleroyloxy-Δ4,¹¹-1,3-diol (4), (5S,6S,8S,9R)-1,3-isovaleroxy-Δ4,11-1,3-diol (5), and (5S,6S,8S,9R)-3-isovaleroxy-6-isovaleroyloxy-Δ4,¹¹-1,3-diol (6). Their structures were determined mainly by 1D and 2D NMR spectroscopic techniques. We also report herein for the first time the single crystal X-ray structure of compound 1. In addition, the cytotoxic activities of compounds 1-6 were evaluated against A549 (human lung adenocarcinoma), HCT116 (human colon carcinoma), SK-BR-3 (human breast carcinoma), and HepG2 (human hepatoma) cell lines. Compound 6 showed weak cell growth inhibition of A549, HCT116, SK-BR-3, and HepG2 cells.