ObjectivesWe aimed to evaluate the relation of total homocysteine (tHcy) concentrations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels, and examine the possible modifiers in the association among a general population of Chinese adults.DesignA cross-sectional study.SettingThe study was conducted within 21 communities in Lianyungang of Jiangsu province, China.ParticipantsA total of 26 648 participants aged ≥35 years and with no antihypertensive drug use were included in the final analysis.ResultsOverall, there was a positive association between tHcy concentrations and SBP (per 5 μmol/L tHcy increase: adjusted β=0.45 mm Hg; 95% CI 0.29 to 0.61) or DBP levels (per 5 μmol/L tHcy increase: adjusted β=0.47 mm Hg; 95% CI 0.35 to 0.59). Compared with participants with tHcy <10 μmol/L, significantly higher SBP levels were found in those with tHcy concentrations of 10 to <15 (adjusted β=0.80 mm Hg; 95% CI 0.32 to 1.28) and ≥15 µmol/L (adjusted β=1.79 mm Hg; 95% CI 1.20 to 2.37; p for trend <0.001). Consistently, significantly higher DBP levels were found in participants with tHcy concentrations of 10 to <15 (adjusted β=0.86 mm Hg; 95% CI 0.49 to 1.22) and ≥15 µmol/L (adjusted β=2.01 mm Hg; 95% CI 1.57 to 2.46; p for trend <0.001), respectively as compared with those with <10 μmol/L. Furthermore, a stronger association between tHcy and SBP (p for interaction=0.009) or DBP (p for interaction=0.067) was found in current alcohol drinkers.ConclusionSerum tHcy concentrations were positively associated with both SBP and DBP levels in a general Chinese adult population. The association was stronger in current alcohol drinkers.

This study examined urban–rural differences in the association of access to healthcare with self-assessed health and quality of life (QOL) among old adults with chronic diseases (CDs) in China. The data of 5796 older adults (≥60) with self-reported CDs were collected from the Study on Global Ageing and Adult Health in China, including indicators of self-assessed health and QOL and information on access to healthcare. Associations of access to healthcare with self-assessed health and QOL at the 10th, 50th, and 90th conditional quantiles were determined after controlling individual and household factors, showing that urban patients who received healthcare within two weeks gave higher ratings on self-assessed health scores at the 10th and 50th quantiles. In rural areas, one-year and two-week access to healthcare was found to be associated with QOL scores at the 10th and 90th quantiles, respectively. Marginal effects of using needed health service decreased with a growth in QOL and self-assessed health scores in both urban and rural locations despite these effects being significant across the whole distribution. Overall, access to healthcare affects the self-assessed health and QOL of the elderly with CDs in China, especially in patients with poor health, though differently for urban and rural patients. Policy actions targeted at vulnerable and rural populations should give priority to reducing barriers to seeking health services.

Background and Objective: Poly (A) binding protein cytoplasmic 1 (PABPC1) plays a crucial role in the regulation of RNA polyadenylation, translation initiation, and mRNA stability and may be involved in tumorigenesis. Herein, we set out to identify the prognostic value of PABPC1 expression in esophageal squamous cell carcinoma (ESCC). Methods: Using quantitative real-time PCR (qRT-PCR) and immunohistochemical analysis, the present study investigated mRNA and protein expressions of PABPC1 in 231 ESCCs and their paired adjacent normal epithelial tissues. Results: We observed a reduction in the average mRNA expression of PABPC1 in ESCC tissue specimen, but the mRNA expression of PABPC1 was significantly higher (P<0.001) in ESCC tissues with high PABPC1 expression and lower (P=0.033) in tissues with low PABPC1 expression. In immunohistochemical analysis, positive expression of the PABPC1 protein was identified in 179 ESCC tissue specimens (179/231, 77.5%), while the percentage of ESCC tissue specimens with high expression of PABPC1 was found to be 41.1% (95/231). PABPC1 expression was found to be significantly correlated with lymph node metastasis (LNM) (P=0.011), pathological stage (P=0.021), tumor recurrence (P<0.001), and the outcome (P<0.001) of patients with ESCC. High expression of PABPC1 was associated with poor overall survival (OS) of ESCC patients (P<0.001) among all pathological stages, particularly in the early stages (pStage-I and -II), and identified to be an independent prognostic factor for OS of patients with ESCC in multivariate analysis (HR=2.622; 95% CI, 1.68-4.129). Comparatively, the expression of Ki-67, p53, and nm23 was not associated with OS. Conclusion:In this study, we discovered that PABPC1 is a prognostic biomarker and a therapeutic target for ESCC, particularly early-stage ESCC.

Rationale: While cell-cell interaction plays a critical role in physiology and disease, a comprehensive understanding of its dynamics in vascular homeostasis and diseases is yet absent. Methods: Here, by use of single-cell RNA-sequencing and multi-color staining, we delineate the cellular composition and spatial characterization of human aorta with or without aortic dissection (AD). Results: Scrutinization of cell subtype alterations revealed significantly changed fibroblast (FB)-smooth muscle cell (SMC) interactions in AD. Of these cellular interactions, LOX high fibroblast (fibroblast subtype 2, FB2) in diseased state exerted the most pronounced effects on pathological deterioration of SMCs in AD. In addition, pharmacologically targeting the BMP (bone morphogenetic protein) signaling pathway effectively suppressed FB2 state transition and reduced AD incidence in mice. Finally, COL5A1 (collagen type V alpha 1 chain), one of the secreted proteins released from FB2, was significantly higher in the plasma of AD patients than in control patients, suggesting its potential use as a biomarker for AD diagnosis. Conclusions: Our work not only identified a pivotal role of a specific FB subtype in AD progression, but also shed light on cell interaction dynamics in vascular diseases.

Donor SUMO4 rs237025 genetic variant was associated with higher Tac C/D ratios in the early period after LT, which might be related to the down-regulation of CYP3A5 enzyme through the NF-kB signalling pathway.

Background. Hypertension, as the most common comorbidity for patients with coronavirus disease 19 (COVID-19), has resulted in cases with more severe symptoms and higher mortality. The risk factors associated with COVID-19 in patients with hypertension are unknown. Methods. All the available and confirmed patients with COVID-19 from February 3 to March 10, 2020, were enrolled from Huoshenshan Hospital, Wuhan, China. The demographic characteristics, clinical manifestations, laboratory data, radiological assessments, and treatments on admission were extracted and compared. Univariate and multivariate logistic regression methods were used to explore risk factors associated with COVID-19 in patients with hypertension and the severity of the cohort. Results. A total of 430 available patients with COVID-19 were enrolled in the study, including 151 eligible patients with COVID-19 and hypertension. After PSM analysis, 141 patients without hypertension and 141 cases with hypertension were well matched. Compared with cases without hypertension, patients with hypertension were more severe (28.4% vs. 12.1%, p = 0.001 ). In multivariate analysis, we found that neutrophil count (OR: 1.471; p = 0.001 ), coronary heart disease (OR: 5.281; p = 0.011 ), and the level of K+ (OR: 0.273; p < 0.001 ) were associated with patients with hypertension. In addition, the percentage of pulmonary infection volume was larger in cases with hypertension (4.55 vs. 5.8, p = 0.017 ) and was a high risk factor for severe COVID-19 in patients with hypertension (OR: 1.084; p < 0.001 ). Conclusion. On admission, coronary heart disease, neutrophil count, and the level of K+ were associated with COVID-19 patients with hypertension. The percentage of the pulmonary infection volume was significantly larger in COVID-19 patients with hypertension and was a risk factor for COVID-19 severity of the cohort.

Objective To characterize the clinical features of a female with P450 oxidoreductase (POR) deficiency and to investigate the underlying mechanisms of POR inactivation. Methods The proband was a 35-year-old woman with primary infertility and menstrual irregularity. The reproductive endocrine profile was evaluated. DNA sequencing was conducted for the identification of POR gene mutation. RT-PCR was performed to confirm the impact of the mutation on POR mRNA. A molecular model was built for the structural analysis of mutant POR protein. ResultsThe evaluation of reproductive endocrine profile revealed elevation of serum follicle-stimulating hormone (11.48 mIU/ ml), progesterone (11.00 ng/ml), 17α-hydroxyprogesterone (24.24 nmol/l), dehydroepiandrosterone (6300 nmol/l), and androstenedione (3.89 nmol/l) and decreased estradiol (36.02 pg/ml). Sequencing of the POR gene showed the female was a compound heterozygote of the paternal P399_E401 deletion and a novel maternal IVS14-1G>C mutation. Functional analysis revealed IVS14-1G>C mutation caused alternative splicing of POR mRNA, with the loss of 12 nucleotides in exon 15 (c.1898_1909delGTCTACGTCCAG). Also, the resulting mutant POR protein had a V603_Q606 deletion, which inactivated the nucleotide-binding domain of NADPH in POR protein (K602_Q606). Conclusion The mutation IVS14-1G>C of the POR gene could cause alternative splicing of POR mRNA and dysfunction of the resulting POR protein. Under proper IVF strategy with glucocorticoid therapy and endometrial preparation, females with mild POR deficiency still have the opportunity to have a live birth.Keywords Cytochrome P450 oxidoreductase deficiency . Live birth . In vitro fertilization . Alternative splicing . Compound heterozygote Précis Clinical and genetic analysis of POR deficiency in a female.

Background Polycystic ovary syndrome (PCOS) is the most common type of endocrine disorder, affecting 5–11% of women of reproductive age worldwide. microRNAs (miRNAs) stably exist in circulating blood encapsulated in extracellular vesicles such as exosomes; therefore, serum miRNAs have the potential to serve as novel PCOS biomarkers. Methods To identify miRNA biomarkers that are associated with PCOS, we performed a comprehensive sequence-based characterization of the PCOS serum miRNA landscape. The serum exosomes were successfully isolated and characterized in a variety of ways. Next, sequence-based analysis was performed on serum exosomes to screen the differentially expressed miRNAs in women with and without PCOS. Results The sequence data revealed that the levels of 54 miRNAs significantly differed between PCOS patients and normal controls. The levels of these miRNAs were detected by RT-qPCR. The results show that hsa-miR-1299, hsa-miR-6818-5p hsa-miR-192-5p, and hsa-miR-145-5p are significantly differentially expressed in PCOS patients serum exosomes and identify these microRNAs as potential biomarkers for PCOS. Furthermore, Gene Ontology (GO) analyses and KEGG pathway analyses of the miRNA targets further allowed to explore the potential implication of the miRNAs in PCOS. Conclusion Our findings suggest that serum exosomal miRNAs serve important roles in PCOS and may be used as novel molecular biomarkers for clinical diagnosis.