Age effect on the shared etiology of glycemic traits and serum lipids: evidence from a Chinese twin study.

PURPOSE: Diabetes and dyslipidemia are among the most common chronic diseases with increasing global disease burdens, and they frequently occur together. The study aimed to investigate differences in the heritability of glycemic traits and serum lipid indicators and differences in overlapping genetic and environmental influences between them across age groups. METHODS: This study included 1189 twin pairs from the Chinese National Twin Registry and divided them into three groups: aged ≤ 40, 41-50, and > 50 years old. Univariate and bivariate structural equation models (SEMs) were conducted on glycemic indicators and serum lipid indicators, including blood glucose (GLU), glycated hemoglobin A1c (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), in the total sample and three age groups. RESULTS: All phenotypes showed moderate to high heritability (0.37-0.64). The heritability of HbA1c demonstrated a downward trend with age (HbA1c: 0.50-0.79), while others remained relatively stable (GLU: 0.55-0.62, TC: 0.58-0.66, TG: 0.50-0.63, LDL-C: 0.24-0.58, HDL-C: 0.31-0.57). The bivariate SEMs demonstrated that GLU and HbA1c were correlated with each serum lipid indicator (0.10-0.17), except HDL-C. Except for HbA1c and LDL-C, as well as HbA1c and HDL-C, differences in genetic correlations underlying glycemic traits and serum lipids between age groups were observed, with the youngest group showing a significantly higher genetic correlation than the oldest group. CONCLUSION: Across the whole adulthood, genetic influences were consistently important for GLU, TC, TG, LDL-C and HDL-C, and age may affect the shared genetic influences between glycemic traits and serum lipids. Further studies are needed to elucidate the role of age in the interactions of genes related to glycemic traits and serum lipids.

Uric acid is negatively associated with cognition in the first- episode of schizophrenia.

BACKGROUND: We explored the relationship between levels of serum uric acid (UA) and cognitive impairment in people with schizophrenia to order to better protect and improve cognitive function in such patients. METHODS: A uricase method evaluated serum UA levels in 82 individuals with first-episode schizophrenia and in 39 healthy controls. The Brief Psychiatric Rating Scale (BPRS) and the event-related potential P300 were used to assess the patient's psychiatric symptoms and cognitive functioning. The link between serum UA levels, BPRS scores, and P300 was investigated. RESULTS: Prior to treatment, serum UA levels and latency N3 in the study group were significantly higher than in the control group, whereas the amplitude P3 was considerably lower. After therapy, the study group's BPRS scores, serum UA levels, latency N3, and amplitude P3 were lower than before treatment. According to correlation analysis, serum UA levels in the pre-treatment study group significantly positively correlated with BPRS score and latency N3 but not amplitude P3. After therapy, serum UA levels were no longer substantially related to the BPRS score or amplitude P3 but strongly and positively correlated with latency N3. CONCLUSIONS: First-episode schizophrenia patients have higher serum UA levels than the general population which partly reflects poor cognitive performance. Improving patients' cognitive function may be facilitated by lowering serum UA levels.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Characterization and profiling of the microRNA in small extracellular vesicles isolated from goat milk samples collected during the first week postpartum.

Colostrum contains nutrients, immunoglobulins, and various bioactive compounds such as microRNA (miRNA). Less is known about the temporal changes in miRNA profiles in ruminant milk samples during the first week postpartum. In this study, we characterized and compared the profiles of miRNA in the small extracellular vesicles (sEV) isolated from colostrum (CM, collected immediately after parturition, n = 8) and transition milk (TM, collected 7 d postpartum, n = 8) from eight 1-yr-old Guanzhong dairy goats with a milk yield of approximately 500 kg/year. A total of 192 unique sEV-associated miRNA (transcripts per million >1 at least 4 samples in either CM or TM) were identified in all samples. There were 29 miRNA uniquely identified in the TM samples while no miRNA was uniquely identified in the CM samples. The abundance of the top 10 miRNA accounted for 82.4% ± 4.0% (± SD) of the total abundance, with let-7 families (e.g., let-7a/b/c-5p) being predominant in all samples. The top 10 miRNA were predicted to target 1,008 unique genes that may regulate pathways such as focal adhesion, TGF-ß signaling, and axon guidance. The expression patterns of EV miRNA were similar between the 2 sample groups, although the abundance of let-7c-5p and miR-30a-3p was higher, whereas that of let-7i-5p and miR-103-3p was lower in CM than in TM. In conclusion, the core miRNAome identified in the samples from CM and TM may play an important role in cell proliferation, bone homeostasis, and neuronal network formation in newborn goat kids. The lack of differential miRNA expression between the CM and TM samples may be due to a relatively short sampling interval in which diet composition, intake and health status of ewes, and environment were relatively stable.

The generation of genuine quadripartite Einstein-Podolsky-Rosen steering in an optical superlattice.

Einstein-Podolsky-Rosen (EPR) steering is a quantum effect based on quantum entanglement and it is the key resource for building quantum networks because of its useful properties. Based on the criterion for genuine multipartite EPR steering, the genuine quadripartite EPR steering is confirmed and it can be generated by a spontaneous parametric down-conversion cascaded process with two sum-frequency generations in an optical superlattice. This occurs either below the oscillation threshold and without oscillation threshold. The influence of the parameters of cascaded nonlinear process on the quadripartite EPR steering among signal, idler, and two sum-frequency beams are also discussed. Choosing appropriate nonlinear parameters can achieve good quadripartite quantum steering. This scheme of the generation of genuine quadripartite EPR steering has potential applications in quantum communication and computing.

Potential functions and causal associations of VPS29 in hepatocellular carcinoma: a bioinformatic and Mendelian randomization study.

OBJECTIVE: Vacuolar protein sorting-associated protein 29 (VPS29) plays a certain role in cancer, but its biological significance in hepatocellular carcinoma (HCC) has not been studied. We utilized bioinformatics and Mendelian randomization (MR) analysis to explore the potential function of the VPS29 gene in HCC, as well as the causal relationship between VPS29 protein and HCC. MATERIALS AND METHODS: We downloaded the raw data from TCGA, GEO, and IEU OpenGWAS databases. We used R software for data processing and analysis to explore the relationship between the VPS29 gene and the expression, prognosis, clinical features, methylation, immune microenvironment, tumor mutation burden, and drug sensitivity in HCC patients. Additionally, a two-sample Mendelian randomization analysis was conducted to investigate the causal relationship between the VPS29 protein and HCC. RESULTS: VPS29 was found to be overexpressed in various types of cancer, including HCC, and its elevated expression often predicts poor prognosis in HCC patients. Univariate and multivariate Cox analysis demonstrated that VPS29 was an independent prognostic factor in HCC patients. The ROC curve indicated that VPS29 has a high diagnostic value in HCC. There were differential expressions of VPS29 in various clinical feature subgroups. The expression of VPS29 was negatively correlated with methylation levels, and multiple methylation sites were identified in the promoter region, including cg20877181, cg03867797, cg10025392, cg21605021, which were associated with poorer overall survival (OS) at low methylation levels. VPS29 was associated with immune cell infiltration disorders, including CD8+ T cells, Eosinophils, Neutrophils, Tcm, NK CD56bright cells, TFH, Th2 cells, Th17 cells, etc. Drug sensitivity analysis showed that VPS29 could be indicative of treatment response to 10 common antineoplastic drugs in different expression subgroups. Inverse variance weighted (IVW) analysis revealed a significant increase in HCC risk associated with VPS29 [odds ratio (OR): 1.440; 95% confidence interval (CI): 1.195-1.736], and sensitivity analysis showed no heterogeneity or pleiotropy. CONCLUSIONS: VPS29 is a risk factor for the occurrence and progression of HCC and may serve as a molecular biomarker for the diagnosis and prognosis of HCC.

[UhpTE350Q mutation along with the presence of fosA6/5 genes in the genome probably contributes to inherent fosfomycin resistance of Klebsiella pneumoniae].

OBJECTIVE: To investigate the molecular mechanism underlying inherent fosfomycin resistance of Klebsiella pneumoniae (K. pneumoniae). METHODS: The draft genomic sequences of 14 clinical hypervirulent/hypermucoviscous K. pneumoniae (HvKP/ HmKP) isolates were obtained using the next-generation sequencing technology. The genomic sequences were analyzed using the Resistance Gene Identifier (RGI) software for predicting the resistome based on homology and SNP models in the Comprehensive Antibiotic Resistance Database (CARD) and for identification of the presence of phosphomycin resistancerelated genes uhpt and fosA and their mutations in the bacterial genomes. The results were verified by analyzing a total of 521 full-length genomic sequences of K. pneumonia strains obtained from GenBank. RESULTS: All the 14 clinical isolates of HvKP/ HmKP carried hexose phosphate transporter (UhpT) gene mutation, in which the glutamic acid was mutated to glutamine at 350aa (UhpTE350Q mutation); the presence of fosA6 gene was detected in 12 (85.71%) of the isolates and fosA5 gene was detected in the other 2 (14.29%) isolates. Analysis of the genomic sequences of 521 K. pneumonia strains from GenBank showed that 508 (97.50%) strains carried UhpTE350Q mutation, 439 (84.26%) strains harbored fosA6, and 80 (15.36%) strains harbored fosA5; 507 (97.31%) strains were found to have both UhpTE350Q mutation and fosA6/5 genes in the genome. Only 12 (2.30%) strains carried fosA6/5 genes without UhpTE350Q mutation; 1 (0.19%) strain had only UhpTE350Q mutation without fosA6/5 genes, and another strain contained neither UhpTE350Q mutation nor fosA6/5 genes. CONCLUSION: UhpTE350Q mutation with the presence of fosA6/5 genes are ubiquitous in K. pneumonia genomes, indicating a possible intrinsic mechanism of fosfomycin resistance in the bacterium to limit the use of fosfomycin against infections caused by K. pneumoniae, especially the multi-resistant HvKP/HmKP strains.

[Safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant chemotherapy combined with immunotherapy].

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.

[Efficacy of plasma exchange in severe crescentic IgA nephropathy: A multicentered, cohort study].

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m2), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m2) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m2)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION: The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.

[Chronic kidney disease in community: Current state for screening and management].

OBJECTIVE: To understand the current state and problem of screening and management of chronic kidney disease (CKD) in the community, and to explore the improving strategies. METHODS: We established a community-CKD integrated data science platform based on medical information from 79 community health centers, in Xicheng District, Beijing. Patients who referred to 79 community health centers from 21 June 2015 to 20 November 2021 were retrospectively included in this study using the CKD data platform. The monitoring of the indicator of kidney injury, risk factor control, medicine use and device configuration in community were assessed in the study. RESULTS: In the study, 70.6% of the population were identified with high risk of CKD in the total 374 498 individuals who referred to the community health centers. Hypertension (62.3%), coronary heart disease (43.3%) and diabetes (30.4%) were the most common risk factors in high-risk CKD population. Only 17.2% of the patients with high risk of CKD were screened for kidney injury including at least one serum creatine (Scr) or albuminuria test, among which 10 992 (24.2%) individuals were defined as CKD. 22.7% (11 338/49 908) of the total patients with kidney screening in community were defined as CKD, of whom, 42.6% and 46.1% were identified by estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m2) and abnormalities of urinary proteins, respectively. The overall CKD detection rate in the community was 5.2% (19 299/374 498), and the miss-diagnosis rate of CKD was 38.1%. Of the 79 community health centers, 13 (16.5%) were equipped with ACR testing device, and eGFR was reported directly in 66 (83.5%) centers. Altogether 60.3% and 99.7% of the community CKD patients achieved glucose control and blood pressure control, respectively, and 59.3% of the CKD patients who had proteinuria was treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. CONCLUSION: High-risk CKD population account for a substantial proportion of patients who refer to the community. Early screening, prevention and management of CKD in the community are of great importance to improve the prognosis and decrease the burden of CKD. It's essential to establish a screening and monitoring system, strengthen standardized management and clinician training for improving the ability of CKD management in the community.

Waveguide scattering antennas made by direct laser writing in bulk glass for spectrometry applications in the short-wave IR.

A buried straight waveguide perturbed periodically by six antennas composed of submicronic cylinder voids is entirely fabricated using ultrafast laser photoinscription. The light scattered from each antenna is oriented vertically and is detected by a short-wave IR camera bonded to the surface of the glass with no relay optics. The response of each antenna is analyzed using a wavelength tunable laser source and compared to simulated responses verifying the behavior of the antenna. These results show the good potential of the direct laser writing technique to realize monolithic embedded detectors by combining complex optical functions within a 3D design. A wavelength meter application with a spectral resolution of 150 pm is proposed to demonstrate this combination.

Structural connections between the noradrenergic and cholinergic system shape the dynamics of functional brain networks.

Complex cognitive abilities are thought to arise from the ability of the brain to adaptively reconfigure its internal network structure as a function of task demands. Recent work has suggested that this inherent flexibility may in part be conferred by the widespread projections of the ascending arousal systems. While the different components of the ascending arousal system are often studied in isolation, there are anatomical connections between neuromodulatory hubs that we hypothesise are crucial for mediating key features of adaptive network dynamics, such as the balance between integration and segregation. To test this hypothesis, we estimated the strength of structural connectivity between key hubs of the noradrenergic and cholinergic arousal systems (the locus coeruleus [LC] and nucleus basalis of Meynert [nbM], respectively). We then asked whether the strength of structural LC and nbM inter-connectivity was related to individual differences in the emergent, dynamical signatures of functional integration measured from resting state fMRI data, such as network and attractor topography. We observed a significant positive relationship between the strength of white-matter connections between the LC and nbM and the extent of network-level integration following BOLD signal peaks in LC relative to nbM activity. In addition, individuals with denser white-matter streamlines interconnecting neuromodulatory hubs also demonstrated a heightened ability to shift to novel brain states. These results suggest that individuals with stronger structural connectivity between the noradrenergic and cholinergic systems have a greater capacity to mediate the flexible network dynamics required to support complex, adaptive behaviour. Furthermore, our results highlight the underlying static features of the neuromodulatory hubs can impose some constraints on the dynamic features of the brain.

The cross-sectional study of depressive symptoms and associated factors among adolescents by backpropagation neural network.

OBJECTIVES: This study aimed to investigate the association between depressive symptoms and diet- and lifestyle-related behaviors among adolescents. STUDY DESIGN: Cross-sectional study. METHODS: Our study used stratified random cluster sampling method to recruit 6,251 adolescents aged 11-19 years as samples for research and analysis. The Center for Epidemiological Studies Depression Scale was used to assess depressive symptoms. Chi-squared test, t test, and logistic regression were used to explore the diet and lifestyle factors of depressive symptoms. Backpropagation (BP) neural network model was used to investigate the ranking of diet and lifestyle behaviors factors of depressive symptoms. RESULTS: The prevalence of depressive symptoms among adolescents was 32.1%. Multivariable logistic regression was used to determine 10 important variables of depressive symptoms. After ranking the importance by BP neural network, the top three important variables were found, which were sleep duration (100%), screen time (49.1%), and breakfast (23.6%). CONCLUSION: Sleep duration, screen time, and breakfast were associated factors with the most significant impacts on depressive symptoms.

Incidence and risk factors of female urinary incontinence: a 4-year longitudinal study among 24 985 adult women in China.

OBJECTIVE: To estimate the incidence of urinary incontinence (UI), including its subtypes stress UI (SUI), urgency UI (UUI) and mixed UI (MUI), and to examine risk factors for de novo SUI and UUI in Chinese women. DESIGN: Nationwide longitudinal study. SETTING: Six geographic regions of China. PARTICIPANTS: Women aged ≥20 years old were included using a multistage, stratified, cluster sampling method. METHODS: This study was conducted between May 2014 and March 2016, with follow up in 2018. Data on demographics, medical history, lifestyle and physiological and anthropometric information were collected. MAIN OUTCOME MEASUREMENTS: Incidence, rate ratio (RR). RESULTS: Analyses included 24 985 women (mean age 41.9 years).The follow-up response rate was 55.5%, median follow-up time was 3.7 years. The standardised incidences of UI, SUI, UUI and MUI were 21.2, 13.1, 3.0 and 5.1 per 1000 person-years, respectively. Risk factors for de novo SUI included delivery pattern (vaginal spontaneous delivery RR 2.12, 95% CI 1.62-2.78 and instrumental delivery RR 3.30, 95% CI 1.99-5.45), high body mass index (BMI) (overweight RR 1.52, 95% CI 1.33-1.74 and obesity RR 1.67, 95% CI 1.32-2.11), cigarette smoking (RR 1.54, 95% CI 1.12-2.12), chronic cough (RR 1.44, 95% CI 1.17-1.76), diabetes (RR 1.33, 95% CI 1.10-1.60) and older age (50-59 years RR 1.49, 95% CI 1.16-1.90 and 60-69 years RR 1.61, 95% CI 1.22-2.13).The risk factors significantly associated with de novo UUI were age (RR increased from 1.21, 95% CI 0.74-1.99, at 30-39 years to 6.3, 95% CI 3.85-10.30, at >70 years) and diabetes (RR 1.48, 95% CI 1.05-2.09). CONCLUSIONS: The incidence of female UI is 21.2 per 1000 person-years in China. Delivery (vaginal spontaneous delivery, instrumental delivery), high BMI, cigarette smoking, chronic cough, diabetes and older age were risk factors. TWEETABLE ABSTRACT: The incidence of female urinary incontinence was 21.2 per 1000 person-years in China. Delivery, BMI, diabetes and old age are risk factors.

Thiophene and diaminobenzo- (1,2,5-thiadiazol)- based DAD-type near-infrared fluorescent probe for nitric oxide: A theoretical research.

A near-infrared fluorescent probe (LS-NO) for the real-time detection of nitric oxide (NO) in inflammatory bowel disease (IBD) was developed recently. The probe used oligoglycol morpholine-functionalized thiophene as strong electron donors and diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor and NO trapping group. It could detect exogenous and endogenous NO in the lysosomes of living cells with high sensitivity and specificity. To further understand the fluorescent mechanism and character of the probes LS-NO and LS-TZ (after the reaction of the probe LS-NO with NO), the electron transfer in the excitation and emitting process within the model molecules DAD-NO and DAD-TZ was analyzed in detail under the density functional theory. The calculation results indicated the transformation from diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor to triazolo-benzo-(1,2,5-thiadiazole) as a strong electron acceptor made LS-NO an effective "off-on" near-infrared NO fluorescent probe.

Ivy Sign in Moyamoya Disease: A Comparative Study of the FLAIR Vascular Hyperintensity Sign Against Contrast-Enhanced MRI.

BACKGROUND AND PURPOSE: The ability of the ivy sign on contrast-enhanced T1-weighted MR imaging (CEMR) to reflect cerebral perfusion and postoperative revascularization in Moyamoya disease remains largely unknown. We aimed to compare the capabilities of CEMR and FLAIR. MATERIALS AND METHODS: CEMR, FLAIR, arterial spin-labeling, and DSA were performed in 44 patients with Moyamoya disease. The ivy sign was scored separately on CEMR and FLAIR using the Alberta Stroke Program Early CT Score. The status of leptomeningeal collaterals was scored on DSA. The postoperative Matsushima grade was evaluated at least 3 months after surgical revascularization. RESULTS: Scoring of the ivy sign on CEMR showed excellent interrater reliability, and FLAIR vascular hyperintensity showed moderate interrater reliability. Correlation analyses revealed that DSA scores were more consistent with the CEMR-based ivy sign score (r = 0.25, P = .03) than with FLAIR vascular hyperintensity (r = 0.05, P = .65). The CEMR-based ivy sign score was significantly correlated with CBF in late-Suzuki stage Moyamoya disease (t = -2.64, P = .02). The CEMR-based ivy sign score at baseline was significantly correlated with the postoperative Matsushima grade (r = 0.48, P = .03). CONCLUSIONS: In this study, CEMR outperformed FLAIR in capturing the ivy sign in Moyamoya disease. In addition, the CEMR-based ivy sign score provided adequate information on hemodynamic status and postoperative neovascularization. The current study suggested that CEMR could be considered as an alternative to FLAIR in future studies investigating leptomeningeal collaterals in Moyamoya disease.

Effects of replacing soybean meal with pumpkin seed cake and dried distillers grains with solubles on milk performance and antioxidant functions in dairy cows.

Pumpkin seed cake (PSC), a byproduct of pumpkin seed oil processing, is used in ruminant feed as a beneficial protein source. Experiments were conducted to evaluate PSC as a substitute for soybean meal in the diets of lactating cows based on performance, rumen fermentation, antioxidant function and nitrogen partitioning. Six multiparous lactating cows were used in a replicated 3 × 3 Latin square experiment with 27-day periods. The cows were randomly divided into three treatment groups: group (1) was fed a diet containing no PSC (0PSC), and groups (2) and (3) were fed diets in which soybean meal was replaced with PSC and dried distillers grains with solubles (DDGS) at levels of 50% (50PSC) and 100% (100PSC), respectively. The diets were isonitrogenous and contained identical roughage but different proportions of PSC and DDGS. Replacement of soybean meal with PSC and DDGS did not influence rumen degradation, milk performance, rumen fermentation, DM intake or apparent total tract digestibility, and nitrogen partitioning between milk, feces and urine did not differ in the animals fed the three diets. However, compared with a diet containing no PSC, the total antioxidant capacity (P < 0.05) and antioxidant enzymes (total superoxide dismutase, glutathione peroxidase and catalase) activities (P < 0.05) were increased in the animals that received the 50PSC and 100PSC diets. In contrast, addition of PSC significantly reduced concentrations of aspartate transaminase (P < 0.05), alkaline phosphatase (P < 0.05) and malondialdehyde (P < 0.05) in the plasma. These results demonstrate that PSC can be completely substituted for soybean meal in the diet of dairy cows without any negative impact on milk performance, rumen fermentation or apparent digestibility and that this dietary change improves antioxidant functions and blood parameters in dairy cows, indicating that PSC has the potential for use as a feed source for dairy cows.

Cinnamic Acid Increased the Incidence of Fusarium Wilt by Increasing the Pathogenicity of Fusarium oxysporum and Reducing the Physiological and Biochemical Resistance of Faba Bean, Which Was Alleviated by Intercropping With Wheat.

BACKGROUND: Continuous cropping has resulted in the accumulation of self-toxic substances in faba beans which has restricted their global production. Intercropping is widely used to alleviate these problems. AIMS: To explore the role of cinnamic acid stress in faba bean physiology and disease resistance, and the potential mitigating effects of intercropping the faba bean with wheat. METHODS: Faba bean seedlings were grown with or without wheat in both field and hydroponic conditions in the presence of different cinnamic acid concentrations and Fusarium oxysporum (FOF), the occurrence of. Fusarium-mediated wilt and oxidative stress, as well as plant growth indices and the anti-pathogen defense system were analyzed. RESULTS: Cinnamic acid significantly increased Fusarium pathogenicity, inhibited the activity of defense enzymes and reduced the ability of plants to resist pathogens, indicating the importance of cinnamic acid in the promotion of Fusarium wilt resulting in reduced seedling growth. Intercropping with wheat improved plant resistance by alleviating cinnamic acid-induced stress, which promoted crop growth and decreased the incidence and disease index of Fusarium wilt. CONCLUSION: Cinnamic acid promotes Fusarium wilt by stimulating pathogen enzyme production and destroying the defense capability of faba bean roots. Intercropping reduces Fusarium wilt by alleviating the damage caused by cinnamic acid to the defense system of the faba bean root system.

Circ-ABCB10 acts as an oncogene in glioma cells via regulation of the miR-620/FABP5 axis.

OBJECTIVE: This study aims to investigate the biological function of circular RNA ABCB10 (circ-ABCB10) in regulating the progression of glioma and to study the possible underlying mechanisms. PATIENTS AND METHODS: The expression levels of circ-ABCB10, miR-620 and FABP5 mRNA in glioma tissues, normal surrounding tissues and glioma cell lines were measured by Real-time PCR (RT-PCR). Circ-ABCB10 was silenced by siRNA in glioma cell lines (U87, T98G). The proliferation, migration and invasion of glioma cells were measured by MTT, wound healing and transwell assays, respectively. The relationship between circ-ABCB10, miR-620 and FABP5 was tested by Dual-Luciferase assay. The expression of proteins was measured by Western blot. The cell cycle distribution and apoptosis were measured by flow cytometry. RESULTS: The expression levels of circ-ABCB10 and FABP5 in glioma tissues and cells were significantly higher than those in their normal counterparts. Moreover, the expression of miR-620 was lower in glioma tissues. Silencing of circ-ABCB10 in glioma cells significantly inhibited the proliferation, migration and invasion of glioma cells. Moreover, downregulation of circ-ABCB10 induced cell cycle arrest and apoptosis in glioma cells. Furthermore, inhibition of miR-620 showed the opposite effects to silencing circ-ABCB10 on glioma cells. Dual-Luciferase reporter assays demonstrated that circ-ABCB10 could bind to miR-620 and that FABP5 was a direct target of miR-620. Western blot results showed that circ-ABCB10 could stabilize the expression of FABP5, while miR-620 decreased the expression of FABP5. Furthermore, overexpression of FABP5 abrogated the silencing effects of circ-ABCB10 in glioma cells. CONCLUSIONS: These data suggest that circ-ABCB10 affects glioma progression by regulating the miR-620/FABP5 axis, and circ-ABCB10 might be used as a potential target for the treatment of glioma.

High long non-coding LIFR-AS1 expression correlates with poor survival in gastric carcinoma.

OBJECTIVE: Abundant evidence has demonstrated that long non-coding RNAs (lncRNAs) play key roles in the development of human neoplasms. A novel cancer-related lncRNA, leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1), has been reported to be under-expressed in breast cancer and associated with poor prognosis, but its significance in gastric cancer (GC) remains to be determined. Therefore, we assessed the prognostic and diagnostic value of LIFR-AS1 in GC. PATIENTS AND METHODS: Quantitative RT-PCR assay was used to detect the expression levels of LIFR-AS1 in GC tissues and adjacent normal tissues. The correlation between LIFR-AS1 expression and clinicopathological features was analyzed by Pearson's χ2-test. The disease-free survival and overall survival rates of GC patients were calculated by the Kaplan-Meier method. Cox regression analysis was used to assess factors related to survival. RESULTS: In this study, levels of LIFR-AS1 were significantly higher in GC tumor samples relative to adjacent normal tissue samples. A ROC analysis suggested LIFR-AS1 expression could be reliably used to differentiate between normal and GC tumor tissue. In addition, elevated LIFR-AS1 expression was positively correlated with more advanced and aggressive GC features, such as larger tumor size, lymphatic metastasis, and more advanced TNM stage. Survival analyses revealed that elevated LIFR-AS1 expression was correlated with worse overall survival and disease-free survival. Multivariate analysis further confirmed the relevance of LIFR-AS1 as an independent predictor of GC patient outcomes. CONCLUSIONS: In summary, these results indicate that the lncRNA LIFR-AS1 is a promising prognostic indicator in GC patients.