Associations of systemic inflammatory regulators with CKD and kidney function: evidence from the bidirectional mendelian randomization study.

BACKGROUND: Previous observational studies have reported that systemic inflammatory regulators are related to the development of chronic kidney disease (CKD); however, whether these associations are causal remains unclear. The current study aimed to investigate the potential causal relationships between systemic inflammatory regulators and CKD and kidney function. METHOD: We performed bidirectional two-sample Mendelian randomization (MR) analyses to infer the underlying causal associations between 41 systemic inflammatory regulators and CKD and kidney function. The inverse-variance weighting (IVW) test was used as the primary analysis method. In addition, sensitivity analyses were executed via the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and the weighted median test. RESULTS: The findings revealed 12 suggestive associations between 11 genetically predicted systemic inflammatory regulators and CKD or kidney function in the forward analyses, including 4 for CKD, 3 for blood urea nitrogen (BUN), 4 for eGFRcrea and 1 for eGFRcys. In the other direction, we identified 6 significant causal associations, including CKD with granulocyte-colony stimulating factor (GCSF) (IVW ß = 0.145; 95% CI, 0.042 to 0.248; P = 0.006), CKD with stem cell factor (SCF) (IVW ß = 0.228; 95% CI, 0.133 to 0.323; P = 2.40 × 10- 6), eGFRcrea with SCF (IVW ß =-2.90; 95% CI, -3.934 to -1.867; P = 3.76 × 10- 8), eGFRcys with GCSF (IVW ß =-1.382; 95% CI, -2.404 to -0.361; P = 0.008), eGFRcys with interferon gamma (IFNg) (IVW ß =-1.339; 95% CI, -2.313 to -0.366; P = 0.007) and eGFRcys with vascular endothelial growth factor (VEGF) (IVW ß =-1.709; 95% CI, -2.720 to -0.699; P = 9.13 × 10- 4). CONCLUSIONS: Our findings support causal links between systemic inflammatory regulators and CKD or kidney function both in the forward and reverse MR analyses.

Comparison of two techniques for the management of 2-3 cm lower pole renal calculi in obese patients.

OBJECTIVE: To compare the outcomes of mini percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) for the management of 2-3 cm lower pole renal calculi (LPC) in obese patients. PATIENTS AND METHODS: 120 obese patients with 2-3 cm LPC were randomly divided into mPNL group and RIRS group. Demography, clinical characteristics, perioperative complications, and stone free rate (SFR) were recorded. Stone-free status means no stone on computed tomography 3 months after surgery, or residual fragments were less than 3 mm. RESULTS: Baseline characteristics were similar between the two groups. The mean stone burden was 585.39 ± 131.06 mm2 in the mPNL group and 548.64 ± 123.55 mm2 in the RIRS group (P = 0.125). The SFR of mPNL group was significantly better than that of RIRS group (86.2% vs 61.4%, P = 0.002). Besides, the overall complication rate was 22.4% in the mPNL group and 7% in the RIRS group (P = 0.02). Patients performed with mPNL required longer length of hospital stay than those with RIRS (P = 0.001). There were no significant differences in operative time and stone composition between the two groups. CONCLUSION: In our study, both mPNL and RIRS are safe and effective techniques for the treatment of 2-3 cm LPC in obese patients. Compared to RIRS, mPNL has better SFR at the expense of the higher incidence of complications and prolonged length of hospital stay.

Colchicine for Secondary Prevention of Coronary Artery Disease: A Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Colchicine has become prominent as an anti-inflammatory therapy for secondary cardiovascular prevention in patients with coronary artery disease (CAD). This meta-analysis was performed to evaluate the efficacy and safety of colchicine in patients with CAD. METHODS: Randomised controlled trials (RCTs) that compare major adverse cardiovascular events (MACEs) between patients with CAD randomised to colchicine versus placebo (or no colchicine) were included. Random effect risk ratios (RRs) were calculated for clinical outcomes. RESULTS: A total of 12,071 patients in seven RCTs were included in the meta-analysis. Compared with placebo or no colchicine, colchicine was associated with a significantly lower incidence of MACEs (RR 0.64, 95% CI 0.51-0.80, p<0.01). The reduction in MACEs in the colchicine group was driven by statistically significant reductions in the incidence of myocardial ischaemia (RR 0.74, 95% CI 0.58-0.95, p=0.02), coronary revascularisation (RR 0.61, 95% CI 0.42-0.89, p=0.01), and stroke (RR 0.48, 95% CI 0.28-0.83, p=0.01). However, there was no statistically significant difference for cardiovascular death (RR 0.82, 95% CI 0.55-1.22, p=0.33). All-cause and non-cardiovascular mortality, gastrointestinal events, infection, and cancer were not significantly different between the colchicine and control groups. CONCLUSIONS: Colchicine is a reasonably efficacious and safe drug that could be successfully utilised for the secondary prevention of CAD.

Comparison of contrast-enhanced ultrasound versus conventional ultrasound-guided percutaneous nephrolithotomy in patients with nondilated collecting system: a randomized controlled trial.

OBJECTIVE: To compare the safety, effectiveness, and feasibility of contrast-enhanced ultrasound (CEUS) versus conventional ultrasound-guided percutaneous nephrolithotomy (PCNL) in patients with nondilated collecting system. METHODS: Between July 2018 and July 2020, 160 kidney stone patients with nondilated collecting system planned for PCNL were randomly assigned into two groups, CEUS with retrograde ureteral contrast injection and conventional ultrasound with retrograde ureteral normal saline injection. Patient's demographics, the success rate of puncture, success rate of a single-needle puncture, number of punctures, puncture time, perioperative outcomes, stone-free rate, and incidence of complications were compared. RESULTS: The success rate of a single-needle puncture for CEUS-guided PCNL was higher than that in the conventional ultrasound group (88.5% vs. 73.7%, p = 0.02). Patients performed with CEUS-guided PCNL required less needle passes (p = 0.02), shorter needle puncture time (p = 0.031), and shorter channel establishment time (p = 0.04) than those guided with conventional ultrasound. The postoperative hemoglobin decrease in the CEUS-guided PCNL group was less than that of the control group (p = 0.02). There was no significant difference in operating time, length of hospital stays, kidney function change, and complications between the two groups (p > 0.05). The 1-month stone-free rate was 94.9% in the CEUS group and 90.8% in the control group (p > 0.05). CONCLUSIONS: Compared with conventional ultrasound, CEUS-guided PCNL may facilitate ultrasound-guided PCNL for patients without hydronephrosis, and benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800016981 KEY POINTS: • Compared with conventional ultrasound, CEUS-guided PCNL is a safe and efficacious procedure for kidney stone patients with nondilated collecting system. • Compared with conventional ultrasound, CEUS-guided PCNL benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. • CEUS-guided PCNL associated with the more accurate needle puncture and acceptable complications.

Clinically significant drug-drug interaction between tacrolimus and fluconazole in stable renal transplant recipient and literature review.

WHAT IS KNOWN AND OBJECTIVE: Clinical use of fluconazole against fungal infections in renal transplant patients is complicated by the potentially marked and unpredictable drug-drug interactions (DDIs). We report a case of tacrolimus-fluconazole DDI in a stable renal transplant recipient and describe the mechanism, magnitude and duration of this DDI through a literature review. CASE SUMMARY: A 38-year-old woman experienced a 9.1-fold increase in dose-normalized tacrolimus trough level (trough concentration/weight-normalized daily dose) and an 87% decrease in weight-normalized daily dose (daily dose/body weight) in the treatment of documented Candida albicans oesophagitis by fluconazole. After discontinuation of fluconazole for 161 day, a 26% reduction in weight-normalized daily dose was required to maintain therapeutic exposure. WHAT IS NEW AND CONCLUSION: Oral fluconazole has a more significant impact on its drug interactions with tacrolimus than intravenous fluconazole. Gene screening for CYP3A5 6986 A>G and ABCB1 3435 C>T in organ transplant recipients may help in preventing DDI and facilitating tacrolimus dose adjustment.

Complete versus culprit-only revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease: a meta-analysis of randomized trials.

BACKGROUND: The best strategy for the treatment of the non-infarct artery in patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) undergoing primary percutaneous coronary intervention (PCI) is not yet defined. METHODS: We searched the literature for randomized controlled trials (RCTs) that compared complete revascularization (CR) with infarct-related coronary artery (IRA) only revascularization in hemodynamically stable patients with STEMI. Random effect risk ratios (RRs) were calculated for clinical outcomes. RESULTS: Nine RCTs with 2989 patients were included. No significant difference in all-cause mortality emerged between CR and IRA-only groups (relative risk [RR] = 0.74; 95% confidence interval [CI]: 0.52 to 1.04; p = 0.08). Compared with IRA-only, CR was associated with significantly lower rates of major adverse cardiac events (MACE) (RR = 0.53; 95% CI: 0.41 to 0.68; p < 0.001), cardiac death (RR = 0.48; 95% CI: 0.29 to 0.79; p = 0.004) and repeat revascularization (RR = 0.38; 95% CI: 0.30 to 0.47; p < 0.001). In subgroups analysis, immediate complete revascularization (ICR) reduced the risk of all-cause mortality (RR = 0.62; 95% CI: 0.39 to 0.97; p = 0.04), whereas staged complete revascularization (SCR) did not show any significant benefit in all-cause mortality (RR = 0.92; 95% CI: 0.46 to 1.86; p = 0.82). Stroke, contrast-induced nephropathy and major bleeding were not different between CR and IRA-only. CONCLUSIONS: For patients with STEMI and multivessel disease undergoing primary PCI, complete revascularization did not decrease the risk of all-cause mortality in current evidence from randomized trials. When feasible, immediate complete revascularization might be considered in patients with STEMI and multivessel disease.

Comparison of retroperitoneal laparoscopic versus open adrenalectomy for large pheochromocytoma: a single-center retrospective study.

BACKGROUND: It remains unclear whether retroperitoneal laparoscopic adrenalectomy (RLA) is safe and effective for the treatment of large pheochromocytoma (PHEO). This retrospective study aimed to identify the advantages and disadvantages of RLA compared to open adrenalectomy (OA). METHODS: This study included 147 patients who underwent RLA (n = 101) or OA (n = 46) for PHEO larger than 5 cm. Groups were balanced by propensity score matching (PSM) into 46 pairs. Perioperative variables and long-term follow-up results were compared between the two groups. RESULTS: After PSM, patients in the RLA group had a shorter operative time (218 vs. 245 min, P = 0.040), quicker bowel recovery (2 vs. 3 days, P = 0.046), and a shorter hospital stay (8 vs. 9 days, P = 0.010) compared to the OA group. The results of multiple linear regression analyses showed that the operative method (OA vs. RLA) had an influence on the above three postoperative variables (ß = 31.84, P = 0.046; ß = 0.76, P = 0.044; and ß = 1.25, P = 0.025, respectively). There was no significant difference in the proportion of patients with improved blood pressure (82.61% vs. 69.57%, P = 0.143) between the two groups. CONCLUSIONS: Both RLA and OA provide similar perioperative and long-term outcomes for the surgical management of large PHEO. RLA is an efficacious and safe surgical method for patients with PHEO larger than 5 cm in diameter.

Early Change in Global Longitudinal Strain is an Independent Predictor of Left Ventricular Adverse Remodelling in Patients With Right Ventricular Apical Pacing.

BACKGROUND: Right ventricular apical (RVA) pacing is related to adverse left ventricular (LV) remodelling. This study assessed changes in global longitudinal strain (GLS) after permanent RVA pacing, and investigated whether GLS at one month can predict later LV ejection fraction (LVEF) decline. METHODS: The study enrolled 68 patients with normal LVEF (≥50%) who underwent dual chamber pacemaker implantation for third-degree atrioventricular block. Global strains and LVEF were assessed using three-dimensional (3D) speckle tracking strain echocardiography (STE). RESULTS: At one month, GLS was significantly lower in those patients who developed pacing-induced LV dysfunction (PIVD), which was defined as a reduction in LVEF ≥5 percentage points at 12 months, than those who did not (-14.9±1.8 vs -16.1±1.7, p=0.014), although GLS was similar at baseline. In patients who developed PIVD, only GLS was significantly reduced at one month compared to baseline (-14.9±1.8 vs -16.6±1.2, p=0.022) whereas LVEF was not. Global longitudinal strain at one month was the only independent predictor for PIVD at 12 months on multivariate analysis (OR, 1.623; 95% CI, 0.986-2.210; p=0.009). Receiver operating characteristic (ROC) analysis showed that GLS at one month had a high predictive accuracy for the development of PIVD at 12 months, with an area under curve (AUC) of 0.88, 94% sensitivity, and 70% specificity. CONCLUSIONS: Global longitudinal strain at one month after pacemaker implantation had high predictive accuracy for identifying subsequent development of PIVD. Global longitudinal strain may be an invaluable parameter to predict LV adverse remodelling following permanent RVA pacing.

Changes in mineral elements and starch quality of grains during the improvement of japonica rice cultivars.

BACKGROUND: The improvement of rice cultivars plays an important role in yield increase. However, little is known about the changes in starch quality and mineral elements during the improvement of rice cultivars. This study was conducted to investigate the changes in starch quality and mineral elements in japonica rice cultivars. RESULTS: Twelve typical rice cultivars, applied in the production in Jiangsu province during the last 60 years, were grown in the paddy fields. These cultivars were classified into six types according to their application times, plant types and genotypes. The nitrogen (N), phosphorus (P) and, and potassium (K) were mainly distributed in endosperm, bran and bran, respectively. Secondary and micromineral nutrients were distributed throughout grains. With the improvement of cultivars, total N contents gradually decreased, while total P, K and magnesium contents increased in grains. Total copper and zinc contents in type 80'S in grains were highest. The improvement of cultivars enhanced palatability (better gelatinisation enthalpy and amylose content), taste (better protein content) and protein quality (better protein components and essential amino acids). Correlation analysis indicated the close relationship between mineral elements and starch quality. CONCLUSION: The mineral elements and starch quality of grains during the improvement of japonica rice cultivars are improved. © 2017 Society of Chemical Industry.

Genetic and pharmacological inhibition of Rheb1-mTORC1 signaling exerts cardioprotection against adverse cardiac remodeling in mice.

A previous study indicated that Rheb1 is required for mammalian target of TOR complex 1 (mTORC1) signaling in the brain. However, the function of Rheb1 in the heart is still elusive. In the present study, we deleted Rheb1 specifically in cardiomyocytes and found that reduced Rheb1 levels conferred cardioprotection against pathologic remodeling in myocardial infarction (MI) and pressure overload (transverse aortic constriction) mouse models. Cardiomyocyte apoptosis was reduced and mTORC1 activity was suppressed in cardiomyocyte Rheb1-deletion mice, suggesting that Rheb1 regulates mTORC1 activation in myocardium. Furthermore, we demonstrated that astragaloside IV (As-IV) could inhibit mTORC1, and As-IV treatment displayed similar protection against MI and transverse aortic constriction as Rheb1 genetic inhibition. This study indicates that Rheb1 is essential for mTORC1 activation in cardiomyocytes and suggests that targeting Rheb1-mTORC1 signaling, such as by As-IV treatment, may be an effective therapeutic method for treating patients with adverse cardiac remodeling after MI and hypertrophy.

Self-adhesive, freeze-tolerant, and strong hydrogel electrolyte containing xanthan gum enables the high-performance of zinc-ion hybrid supercapacitors.

Hydrogel electrolyte is an ideal candidate material for flexible energy storage devices due to its excellent softness and conductivity properties. However, challenges such as the inherent mechanical weakness, the susceptibility to be frozen in low-temperature environments, and the insufficiency of hydrogel-electrode contact persist. Herein, a "Multi in One" strategy is employed to effectively conquer these difficulties by endowing hydrogels with high strength, freeze-resistance, and self-adhesive ability. Multiple hydrogen bond networks and ion crosslinking networks are constructed within the hydrogel electrolyte (PVA/PAAc/XG) containing polyvinyl alcohol (PVA), acrylic acid (AAc), and xanthan gum (XG), promoting the enhanced mechanical property, and the adhesion to electrode materials is also improved through abundant active groups. The introduction of zinc ions provides the material with superior frost resistance while also promoting electrical conductivity. Leveraging its multifunction of superior mechanical strength, anti-freeze property, and self-adhesive characteristic, the PVA/PAAc/XG hydrogel electrolyte is employed to fabricate zinc ion hybrid supercapacitors (ZHS). Remarkably, ZHS exhibits outstanding electrochemical performance and cycle stability. A remarkable capacity retention rate of 83.86 % after 10,000 charge-discharge cycles can be achieved at high current densities, even when the operational temperature decreases to -60 °C, showing great potential in the field of flexible energy storage devices.

Compared analysis of LncRNA expression profiling in pdk1 gene knockout mice at two time points.

BACKGROUND/AIMS: Previous studies have indicated that long non-coding RNAs (lncRNA) are related to the occurrence and development of many human diseases, such as cancer and the HELLP and the brachydactyly syndromes. However, studies of LncRNA in heart failure have not yet been reported. Here, we investigated cardiac lncRNA expression profiles in the myocardial-specific knockout pdk1 gene (KO) mouse model of heart failure. METHODS: Cardiac samples were obtained from PDK1 KO and WT mice on postnatal (P) day 8 (P8) and day 40 (P40), and lncRNA expression profiles were analyzed by sequencing and screening using the Arraystar mouse lncRNA microarray. Quantitative real-time PCR analysis of these lncRNAs confirmed the identity of some genes. RESULTS: Comparisons of the KO and control groups showed fold changes of >1.5 in the expression levels of 2,024 lncRNAs at P8, while fold changes of >2 in the expression levels of 4,095 lncRNAs were detected at P40. Nineteen lncRNAs were validated by RT-PCR. Bioinformatic and pathway analyses indicated that mkk7, a sense overlap lncRNA, may be involved in the pathological processes of heart failure through the MAPK signaling pathway. CONCLUSION: These data reveal differentially expressed lncRNA in mice with a myocardial-specific deletion of the pdk1 gene, which may provide new insights into the mechanism of heart failure in PDK1 knockout mice.

α-Lipoic acid ameliorates mitochondrial impairment and reverses apoptosis in FABP3-overexpressing embryonic cancer cells.

Fatty acid-binding protein 3 (FABP3) is a low molecular weight protein with distinct tissue distribution, which may play an important role in fatty acid transport, cell growth, cellular signaling, and gene transcription. We have previously shown FABP3 was more highly expressed in myocardium with ventricular septal defects than in normal myocardium and furthermore, that overexpression of FABP3 causes mitochondrial dysfunction and induces apoptosis in the P19 mouse teratocarcinoma cell line (P19), which is a suitable model for the investigation of cardiac differentiation at the molecular and functional levels. α-Lipoic acid (α-LA), a natural dithiol compound with antioxidant properties, has been reported to protect mitochondrial function in cells. In this study, we established an FABP3-overexpressing P19 cell line for the investigation of the impact of α-LA on mitochondrial impairment and apoptosis in these cells. Mitochondrial morphology was evaluated by transmission electron microscopy, while the effects of α-LA on reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), intracellular ATP content and the amount of mitochondrial DNA were analyzed by flow cytometry, a commercially available assay and quantitative real-time PCR, respectively. The results revealed that α-LA ameliorated mitochondrial deformation and decreased intracellular ROS production. Furthermore, the MMP, intracellular ATP synthesis and the amount of mitochondrial DNA were also increased. Most significantly, α-LA was shown to reverse apoptosis. Collectively, our results indicate that abnormalities in FABP3 expression contribute to mitochondrial dysfunction and apoptosis, and that α-LA represents a suitable candidate for development as a treatment for apoptosis-related congenital cardiac malformations.

Knockdown of FABP3 impairs cardiac development in Zebrafish through the retinoic acid signaling pathway.

Fatty acid-binding protein 3 (FABP3) is a member of the intracellular lipid-binding protein family, and is primarily expressed in cardiac muscle tissue. Previously, we found that FABP3 is highly expressed in patients with ventricular-septal defects and is often used as a plasma biomarker in idiopathic dilated cardiomyopathy, and may play a significant role in the development of these defects in humans. In the present study, we aimed to investigate the role of FABP3 in the embryonic development of the zebrafish heart, and specifically how morpholino (MO) mediated knockdown of FABP3 would affect heart development in this species. Our results revealed that knockdown of FABP3 caused significant impairment of cardiac development observed, including developmental delay, pericardial edema, a linear heart tube phenotype, incomplete cardiac loop formation, abnormal positioning of the ventricles and atria, downregulated expression of cardiac-specific markers and decreased heart rate. Mechanistically, our data showed that the retinoic acid (RA) catabolizing enzyme Cyp26a1 was upregulated in FABP3-MO zebrafish, as indicated by in situ hybridization and real-time PCR. On the other hand, the expression level of the RA synthesizing enzyme Raldh2 did not significantly change in FABP3-MO injected zebrafish. Collectively, our results indicated that FABP3 knockdown had significant effects on cardiac development, and that dysregulated RA signaling was one of the mechanisms underlying this effect. As a result, these studies identify FABP3 as a candidate gene underlying the etiology of congenital heart defects.

Cardiac ablation of Rheb1 induces impaired heart growth, endoplasmic reticulum-associated apoptosis and heart failure in infant mice.

Ras homologue enriched in brain 1 (Rheb1) plays an important role in a variety of cellular processes. In this study, we investigate the role of Rheb1 in the post-natal heart. We found that deletion of the gene responsible for production of Rheb1 from cardiomyocytes of post-natal mice resulted in malignant arrhythmias, heart failure, and premature death of these mice. In addition, heart growth impairment, aberrant metabolism relative gene expression, and increased cardiomyocyte apoptosis were observed in Rheb1-knockout mice prior to the development of heart failure and arrhythmias. Also, protein kinase B (PKB/Akt) signaling was enhanced in Rheb1-knockout mice, and removal of phosphatase and tensin homolog (Pten) significantly prolonged the survival of Rheb1-knockouts. Furthermore, signaling via the mammalian target of rapamycin complex 1 (mTORC1) was abolished and C/EBP homologous protein (CHOP) and phosphorylation levels of c-Jun N-terminal kinase (JNK) were increased in Rheb1 mutant mice. In conclusion, this study demonstrates that Rheb1 is important for maintaining cardiac function in post-natal mice via regulation of mTORC1 activity and stress on the endoplasmic reticulum. Moreover, activation of Akt signaling helps to improve the survival of mice with advanced heart failure. Thus, this study provides direct evidence that Rheb1 performs multiple important functions in the heart of the post-natal mouse. Enhancing Akt activity improves the survival of infant mice with advanced heart failure.

Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study.

BACKGROUND: Previous observational studies have reported that lifestyle factors, metabolic factors and socioeconomic status are associated with the development of female pelvic organ prolapse (POP); however, whether these associations are causal remains unclear. The current study aimed to assess the causal effect of lifestyle factors, metabolic factors and socioeconomic status on POP risk. METHODS: We conducted a two-sample Mendelian randomization (MR) study based on summary-level data from the largest available genome-wide association studies (GWAS) to evaluate whether lifestyle factors, metabolic factors and socioeconomic status are causally related to POP. We used single nucleotide polymorphisms that are strongly associated with exposure at the genome-wide significance level (P < 5 × 10-8) as instrumental variables from genome-wide association studies. The method of random-effect inverse-variance weighting (IVW) was used as the primary analysis method, supplemented with the weighted median, MR-Egger and the MR pleiotropy residual sum and outlier applied to verify the MR assumptions. Two-step MR was conducted to investigate potential intermediate factors that are on the causal pathway from exposure to POP. RESULTS: There were associations with POP for genetically predicted waist-to-hip ratio (WHR) (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01-1.03 per SD-increase, P < 0.001), WHR adjusted for body mass index (WHRadjBMI) (OR 1.017, 95% CI 1.01-1.025 per SD-increase, P < 0.001) and education attainment (OR 0.986, 95% CI 0.98-0.991 per SD-increase) in the meta-analysis. Additionally, genetically predicted coffee consumption (OR per 50% increase 0.67, 95% CI 0.47-0.96, P = 0.03), vigorous physical activity (OR 0.83, 95% CI 0.69-0.98, P = 0.043) and high-density lipoprotein cholesterol (HDL-C) (OR 0.91, 95% CI 0.84-0.98 per SD-increase, P = 0.049) were inversely associated with POP in the FinnGen Consortium. The mediation analysis showed that the indirect effects of education attainment on POP were partly mediated by WHR and WHRadjBMI, with a mediated proportion of 27% and 13% in the UK Biobank study, respectively. CONCLUSIONS: Our study provides MR evidence of a robust causal association of WHR, WHRadjBMI and education attainment with POP.

Improved maximum likelihood method for P-S-N curve fitting method with small number specimens and application in T-welded joint.

In fatigue data analysis, fitting accurate P-S-N curve is problematic if only a small number of specimen is available, especially to evaluate the relationship between the stress level and the standard deviation. This paper proposes a sample information reconstruction method that can effectively solve this problem. Based on this method and the life equivalent principle, a new maximum likelihood method (which is abbreviated to improved maximum likelihood method) is proposed for P-S-N curve fitting. T-joint specimens of Q450NQR1 steel were fabricated and tested, then the P-S-N curves was fitted by the improved maximum likelihood method, least square method, maximum likelihood method, standard BS7608 and standard IIW. Finally, P-S-N curves by three methods and two standards are compared and analyzed. The results show that the relevant parameters of the P-S-N curve with 99.9% survival probability fitted by the improved maximum likelihood method are similar to those in the two standards, and it is indicated that the improved maximum likelihood method is a better way for P-S-N curve fitting with the small number of fatigue test specimens.

Serum osmolality was non-linearly associated with the risk of all-cause and cardiovascular mortality in patients with diabetes.

AIMS: This study aimed to evaluate the relationship between both low and high osmolarity and the risk of all-cause and cause-specific mortality in diabetic population. METHODS: All participants were included from the National Health and Nutrition Examination Survey 1999-2014. Baseline serum osmolality was determined from laboratory tests and cause of death from national death records. HRs and 95% CIs for all-cause mortality and cardiovascular mortality in diabetes were estimated using Cox proportional regression analysis. The non-linear relationship was explored using restricted cubic splines regression. RESULTS: Among 7622 individuals with diabetes, 1983 (12.4%) died during a total of 3.26 thousand person-years of follow-up. Compared with the reference category (281-284 mmol/kg), the multivariable-adjusted HRs and 95% CIs for all-cause mortality were 1.27 (1.16-1.40; p<0.001) in the lowest osmolality category (<201 mmol/kg) and 1.18 (1.09-1.28; p<0.001) in the highest osmolality category (>312 mmol/kg). Restricted cubic splines results showed that serum levels of osmolality had a U-shaped association with the risk of all-cause mortality, and L-shaped relationship with the risk of cardiovascular death. CONCLUSIONS: Both low osmolality and high osmolality were predictive of increased all-cause mortality in patients with diabetes, supporting a U-shaped relationship. Also, a lower serum osmolality increased the risk of cardiovascular mortality.

Silencing of FABP3 promotes apoptosis and induces mitochondrion impairment in embryonic carcinoma cells.

Fatty acid binding protein 3 (FABP3) (also known as H-FABP) is a member of the intracellular lipid-binding protein family, and is mainly expressed in cardiac muscle tissue. The in vivo function of FABP3 is proposed to be in fatty acid metabolism, trafficking, and cell signaling. Our previous study found that FABP3 is highly regulated in patients with ventricular septal defect (VSD), and may play a significant role in the development of human VSD. In the present study, we aimed to investigate the impact of FABP3 knockdown by RNA interference (RNAi) on apoptosis and mitochondrial function of embryonic carcinoma (P19) cells. The results revealed that downregulated FABP3 expression promoted apoptosis, and resulted in mitochondrial deformation, increased mitochondrial membrane potential (MMP), and decreased intracellular ATP synthesis. In addition, the knockdown of FABP3 also led to excess intracellular ROS production. However, there was no obvious influence on the amount of mitochondrial DNA. Collectively, our results indicated that FABP3 knockdown promoted apoptosis and caused mitochondrial dysfunction in P19 cells, which might be responsible for the development of human VSD.

The complete chloroplast genome sequence of Zanthoxylum undulatifolium Hemsl. (Rutaceae).

Zanthoxylum undulatifolium is an excellent economic tree species with important medical value. This study reports the first complete chloroplast genome sequence of Z. undulatifolium. Its whole chloroplast genome is 158,400 bp in length, including a large single-copy (LSC) region of 85,898 bp, a small single-copy (SSC) region of 17,610 bp, and two inverted repeat (IR) regions of 27,446 bp. The chloroplast genome contains a total of 132 genes, comprising 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The overall GC content of the chloroplast genome is 38.46%, with the corresponding values in the LSC, SSC, and IR regions are 36.87%, 33.51%, and 42.55%, respectively. Phylogenetic analysis revealed the sister relationship between Z. undulatifolium and Z. bungeanum.