Incremental predictive value of platelet parameters for preeclampsia: results from a large prospective cohort study.

BACKGROUND: Platelet parameters during pregnancy were associated with the risk of preeclampsia (PE), but the predictive value of these parameters for PE remained unclear. Our aim was to clarify the individual and incremental predictive value of platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) for PE. METHODS: This study was based on the Born in Guangzhou Cohort Study in China. Data on platelet parameters were extracted from medical records of routine prenatal examinations. Receiver operating characteristic (ROC) curve was performed to analyze the predictive ability of platelet parameters for PE. Maternal characteristic factors proposed by NICE and ACOG were used to develop the base model. Detection rate (DR), integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI) were calculated compared with the base model to assess the incremental predictive value of platelet parameters. RESULTS: A total of 30,401 pregnancies were included in this study, of which 376 (1.24%) were diagnosed with PE. Higher levels of PC and PCT were observed at 12-19 gestational weeks in women who developed PE later. However, no platelet parameters before 20 weeks of gestation reliably distinguished between PE complicated pregnancy and non-PE complicated pregnancy, with all values of the areas under the ROC curves (AUC) below 0.70. The addition of platelet parameters at 16-19 gestational weeks to the base model increased the DR for preterm PE from 22.9 to 31.4% at a fixed false positive rate of 5%, improved the AUC from 0.775 to 0.849 (p = 0.015), and yielded a NRI of 0.793 (p < 0.001), and an IDI of 0.0069 (p = 0.035). Less but significant improvement in prediction performance was also observed for term PE and total PE when all the four platelet parameters were added to the base model. CONCLUSIONS: Although no single platelet parameter at the early stage of pregnancy identified PE with high accuracy, the addition of platelet parameters to known independent risk factors could improve the prediction of PE.

QTc intervals are not prolonged in former ELBW infants at pre-adolescent age.

BACKGROUND: Whether preterm birth is associated with cardiac conduction or repolarization abnormalities in later life is still poorly explored, with conflicting data on QTc prolongation in former extreme low birth weight (ELBW, <1000 g) infants. METHODS: Twelve lead electrocardiograms (ECG) at rest, collected in the PREMATurity as predictor of children's Cardiovascular-renal Health (PREMATCH) study in former ELBW cases and term controls during pre-adolescence (8-14 years) were analyzed on corrected QT time (QTc, Bazett) and QT dispersion (QTd). ECG findings were compared between groups (Mann-Whitney), and associations with clinical and biochemical findings were explored (Spearman). In ELBW cases, associations between QTc and perinatal characteristics (at birth, neonatal stay) were explored (Mann-Whitney, Spearman). RESULTS: QTc and QTd were similar between 93 ELBW cases and 87 controls [409 (range 360-465) versus 409 (337-460); 40 (0-100) versus 39 (0-110)] ms. Age, height, weight, or body mass index were not associated with the QTc interval, while female sex (median difference 11.4 ms) and lower potassium (r = -0.26) were associated with longer QTc interval. We could not observe any significant association between QTc interval and perinatal characteristics. CONCLUSIONS: There were no differences in QTc or QTd between ELBW and term controls in ECGs at rest in pre-adolescents. IMPACT: This study aimed to assess the differences in QTc and QTd intervals between extreme low birth weight infants (ELBW) and term controls in electrocardiographic measurements at rest during pre-adolescence. This analysis confirmed the absence of significant differences in QTc or QTd findings between ELBW cases and term controls, while female sex and lower potassium were associated with a prolonged QTc interval. These data suggest that QTc screening strategies-including for pharmacovigilance-should not differentiate between former ELBW cases and term controls. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02147457.

Combined effects of air pollutants on gestational diabetes mellitus: A prospective cohort study.

Exposures to multiple air pollutants during pregnancy have been associated with the risk of gestational diabetes mellitus (GDM). However, their combined effects are unclear. We aimed to evaluate the combined associations of five air pollutants from pre-pregnancy to the 2nd trimester with GDM. This study included 20,113 participants from the Born in Guangzhou Cohort Study (BIGCS). The inverse distance-weighted models were used to estimate individual air pollutant exposure, namely ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), particulate matter less than 10 µm in diameter (PM10), and less than 2.5 µm in diameter (PM2.5). We estimated stage-specific associations of air pollutants with GDM using generalized estimating equation, and departures from additive joint effects were assessed using the relative excess risk (RERI) and the joint relative risk (JRR). Of the 20,113 participants, 3440 women (17.1%) were diagnosed with GDM. In the adjusted model, increased concentrations of O3 and SO2 3-6 months before pregnancy were associated with GDM occurrence, as well as O3 and PM10 in the 1st trimester, the adjusted relative risk (95% confident intervals) [RRs (95%CI)] ranged from 1.05 (1.00, 1.09) to 1.21 (1.04, 1.40). The largest JRR for GDM was the combination of SO2, NO2, and PM10 in the 1st trimester (JRR = 1.32, 95% CI: 1.10, 1.59). The JRR for O3 and SO2 was less than their additive joint effects [RERI = -0.25 (-0.47, -0.04), P for interaction = 0.048]. Associations of air pollutants with GDM differed somewhat by pre-pregnancy BMI and season. This study added new evidence to the current understanding of the combined effects of multiple air pollutants on GDM. Public health strategies were needed to reduce the adverse effects of air pollution exposure on pregnant women.

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial: rational and protocol.

BACKGROUND: Hypertension and diabetes cause chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD) as forerunners of disability and death. Home blood pressure telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling prevention. METHODS: UPRIGHT-HTM (Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform [NCT04299529]) is an investigator-initiated 5-year clinical trial with patient-centred design, which will randomise 1148 patients to be recruited in Europe, sub-Saharan Africa and South America. During the whole study, HTM data will be collected and freely accessible for patients and caregivers. The UPP, measured at enrolment only, will be communicated early during follow-up to 50% of patients and their caregivers (intervention), but only at trial closure in 50% (control). The hypothesis is that early knowledge of the UPP risk profile will lead to more rigorous risk factor management and result in benefit. Eligible patients, aged 55-75 years old, are asymptomatic, but have ≥5 CKD- or DVD-related risk factors, preferably including hypertension, type-2 diabetes, or both. The primary endpoint is a composite of new-onset intermediate and hard cardiovascular and renal outcomes. Demonstrating that combining UPP with HTM is feasible in a multicultural context and defining the molecular signatures of early CKD and DVD are secondary endpoints. EXPECTED OUTCOMES: The expected outcome is that application of UPP on top of HTM will be superior to HTM alone in the prevention of CKD and DVD and associated complications and that UPP allows shifting emphasis from treating to preventing disease, thereby empowering patients.

Enhanced Superdense Coding over Correlated Amplitude Damping Channel.

Quantum channels with correlated effects are realistic scenarios for the study of noisy quantum communication when the channels are consecutively used. In this paper, superdense coding is reexamined under a correlated amplitude damping (CAD) channel. Two techniques named as weak measurement and environment-assisted measurement are utilized to enhance the capacity of superdense coding. The results show that both of them enable us to battle against the CAD decoherence and improve the capacity with a certain probability. Remarkably, the scheme of environment-assisted measurement always outperforms the scheme of weak measurement in both improving the capacity and successful probability. These notable superiorities could be attributed to the fact that environment-assisted measurement can extract additional information from the environment and thus it performs much better.

[A Study on the Risk Factors for Early Postpartum Urinary Incontinence in Chengdu].

OBJECTIVE: To investigate the incidence of early postpartum urinary incontinence in parturients from Chengdu, and to find out the high-risk factors for reference for clinical diagnosis and treatment. METHODS: A total of 9 918 parturient women who gave delivery at the West China Second University Hospital of Sichuan University from January 2014 to January 2018 were enrolled and reviewed 6 weeks after delivery. The prevalence of urinary incontinence at 6 weeks postpartum was investigated by questionnaire. χ2 test and multivariate logistic regression analysis were used to analyze the risk factors affecting the prevalence. RESULTS: 9 550 parturient women were actually investigated. The prevalence of urinary incontinence was 15.53% (1 483/9 550) at 6 weeks postpartum in Chengdu, among which stress urinary incontinence was the most common (73.03%, 1 083/1 483). Univariate analysis showed that age, pelvic surgery history, prenatal body mass index (BMI), urinary incontinence during pregnancy, neonatal body mass, the number of parturition, delivery mode, lateral perineal incision, perineal laceration and prolonged second stage of labor were all correlated with the occurrence of urinary incontinence at 6 weeks postpartum (P < 0.05). Multivariate logistic regression analysis showed that cesarean section can reduce the risk of urinary incontinence compared with vaginal delivery 〔odds ratio (OR)=0.373, P < 0.001〕. Age≥35 yr. (OR=1.803, P=0.001), pelvic surgery history (OR=1.260, P=0.003), BMI≥28 kg/m2 during pregnancy (OR=1.694, P=0.025), urinary incontinence during pregnancy (OR=2.605, P < 0.001), neonatal body mass ≥4 kg (OR=2.307, P=0.040), multipara (OR=1.284, P=0.023) and perineal laceration (OR=1.372, P=0.035) were independent risk factors for urinary incontinence at 6 weeks postpartum. CONCLUSIONS: Urinary incontinence at 6 weeks postpartum is not rare in Chengdu, and stress urinary incontinence is more frequent. Eutocia, elderly parturient, multipara, pelvic surgery history, prenatal obesity, urinary incontinence during pregnancy, large neonatal body mass and perineal laceration are the main risk factors for urinary incontinence at 6 weeks postpartum.

[Analysis on mechanisms and medication rules of herbal prescriptions for nonalcoholic fatty liver disease based on methods of data mining and biological information].

To explore the medication rules of herbal prescriptions for nonalcoholic fatty liver disease,and analyze the possible drug targets and interactions,in order to explore the mechanisms of the herbs. Randomized controlled trials of herbal prescriptions for treating nonalcoholic fatty liver disease were collected from CNKI,Wan Fang,VIP,Sino Med and PubMed databases. The properties,flavors and meridian tropism of herbs were analyzed by using systematic cluster analysis method with SPSS 19. 0 software. Subsequently,the association rules of herbs were analyzed by using Clementine 12. 0 software. Finally,the interactions between targets and relevant signaling pathways were analyzed by Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) and Kyoto Encyclopedia of Genes and Genomes(KEGG). In the 88 prescriptions screened out,the commonly used herbs were Salvia miltiorrhiza,Bupleurum chinense,Alisma orientale,and Crataegus pinnatifida,and the potential signaling pathways were PPAR signaling pathway and calcium signaling pathway. The results showed that the main effects of herbal prescriptions were to improve blood flow/clear blood stasis,clear heatiness/dampness,promote digestion and strengthen spleen. And its mechanism of action may be achieved through the regulation of PPAR signaling pathway and calcium signaling pathway.

Probiotics for vulvovaginal candidiasis in non-pregnant women.

BACKGROUND: Vulvovaginal candidiasis (VVC) is estimated to be the second most common form of infection after bacterial vaginosis. The ability of probiotics in maintaining and recovering the normal vaginal microbiota, and their potential ability to resist Candidas give rise to the concept of using probiotics for the treatment of VVC. OBJECTIVES: To assess the effectiveness and safety of probiotics for the treatment of vulvovaginal candidiasis in non-pregnant women. SEARCH METHODS: We searched the following databases to October 2017: Sexually Transmitted Infections Cochrane Review Group's Specialized Register, CENTRAL, MEDLINE, Embase and eight other databases. We searched in following international resources: World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, Web of Science and OpenGrey. We checked specialty journals, reference lists of published articles and conference proceedings. We collected information from pharmaceutical companies and experts in the field. SELECTION CRITERIA: Randomized controlled trials (RCT) using probiotics, alone or as adjuvants to conventional antifungal drugs, to treat VVC in non-pregnant women. Trials recruiting women with recurrent VVC, coinfection with other vulvovaginal infections, diabetes mellitus, immunosuppressive disorders or taking immunosuppressant medication were ineligible for inclusion. Probiotics were included if they were made from single or multiple species and in any preparation type/dosage/route of administration. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and quality and extracted data. We resolved any disagreements through consensus. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: Ten RCTs (1656 participants) met our inclusion criteria, and pharmaceutical industry funded none of these trials. All trials used probiotics as adjuvant therapy to antifungal drugs. Probiotics increased the rate of short-term clinical cure (risk ratio (RR) 1.14, 95% confidence interval (CI) 1.05 to 1.24, 695 participants, 5 studies, low quality evidence) and mycological cure (RR 1.06, 95% CI 1.02 to 1.10, 969 participants, 7 studies, low quality evidence) and decreased relapse rate at one month (RR 0.34, 95% CI 0.17 to 0.68, 388 participants, 3 studies, very low quality evidence). However, this effect did not translate into a higher frequency of long-term clinical cure (one month after treatment: RR 1.07, 95% CI 0.86 to 1.33, 172 participants, 1 study, very low quality evidence; three months after treatment: RR 1.30, 95% CI 1.00 to 1.70, 172 participants, one study, very low quality evidence) or mycological cure (one month after treatment: RR 1.26, 95% CI 0.93 to 1.71, 627 participants, 3 studies, very low quality evidence; three months after treatment: RR 1.16, 95% CI 1.00 to 1.35, 172 participants, one study, very low quality evidence). Probiotics use did not increase the frequency of serious (RR 0.80, 95% CI 0.22 to 2.94; 440 participants, 2 studies, low quality evidence). We found no eligible RCTs for outcomes as time to first relapse, need for additional treatment at the end of therapy, patient satisfaction and cost effectiveness. AUTHORS' CONCLUSIONS: Low and very low quality evidence shows that, compared with conventional treatment, the use of probiotics as an adjuvant therapy could increases the rate of short-term clinical and mycological cure and decrease the relapse rate at one month but this did not translate into a higher frequency of long-term clinical or mycological cure. Probiotics use does not seem to increase the frequency of serious or non-serious adverse events. There is a need for well-designed RCTs with standardized methodologies, longer follow-up and larger sample size.

[Effects of Cellular Density on the Induction of Suspension Globe of Ovarian Cancer Stem Cells].

OBJECTIVE: To determine the effect of cellular density on the separation and identification of cancer stem cells from human ovarian clear cell carcinoma cell line ES-2 and adenocarcinoma cell line A2780. METHODS: ES-2 and A2780 cells were cultured with human recombinant epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) and bovine serum albumin and insulin in serum free medium. The cancer stem cells were obtained through serial passages. Changes in cell morphology,expressions of surface marker CD133 and CD44,and soft AGAR clone forming in the stem cells were examined under different cell density,either in serum-supplemented medium (SSM group) or in serum free medium (SFM group). RESULTS: Under the density of 2×104 mL-1,ES-2 cells survived in SFM,but did not form stem cells. When the density increased to 5×104 mL-1 or 1×105 mL-1,ES-2 cells survived in SFM,proliferated and formed stem cells. Compared with adherent cells,the suspension globe of stem cells expressed high levels of CD133 and CD44 ( P<0.05),with proliferation and clone forming ability after serial passages. The stem cell balls under the density of 5×104 mL-1 had stronger ability of tumor formation. A2780 cells formed suspension globe under the density of 1×104 mL-1 and 3×104 mL-1,but larger and more transparent balls were observed under the density of 3×104 mL-1 density. No suspension globe was formed under the density of 5×104 mL-1. More CD133+/CD44+cells were detected by flow cytometry under the density of 3×104 mL-1,compared with that under the density of 1×104 mL-1 ( P<0.05). Tumor stem cells grew faster under the density of 3×104 mL-1. CONCLUSION: The optimal density for identifying stem cells from human ovarian cancer is 5×104 mL-1 for ES-2 and 3×104 mL-1 for A2780,respectively.

Does local ambient temperature impact children's blood pressure? A Chinese National Survey.

BACKGROUND: Several studies demonstrated a short-term association between ambient temperature and blood pressure. However, few studies have assessed the long-term effect of ambient temperature on children's blood pressure. The present study aimed to investigate the association between long-term exposure to local ambient temperature and children's blood pressure in China. METHODS: We analyzed the systolic (SBP) and diastolic blood pressure (DBP) data of 71,763 children from 2010 Chinese National Survey on Students' Construction and Health (CHNSCH), and local annual average ambient temperature, relative humidity, air pollutants data from China Meteorological Administration and Ministry of Environment Protection of China. We used generalized additive model (GAM) with non-linear function to examine the effects of ambient temperature on children's blood pressure. RESULTS: The results showed that decrease of ambient temperature was negatively associated with increase of both SBP and DBP in Chinese children while adjusting for individual characteristics, socioeconomic conditions, air pollutants and relative humidity. The largest alteration of SBP related to the temperature difference was observed from 20.4 to 9.6 °C, with 9.0 mmHg (95 % CI: 8.4, 9.5) increase in SBP, while the largest alteration of DBP was observed from 21.7 to 10.2 °C, with 6.1 mmHg (95 % CI: 5.6, 6.6) increase in DBP. However, when temperature below 9.6 and 10.2 °C, SBP and DBP started to decrease, which might be caused by the use of heating system in the extreme cold areas. CONCLUSIONS: Public health policy should be improved for protecting children's cardiovascular health from adverse effects of low temperature. Development of heating system in moderate cold area might be a good solution.

[Study on the relations among the screen-based sedentary behaviors, family factors and body mass index of children].

OBJECTIVE: To explore the relations among screen-based sedentary behaviors (SSB), family factors and body mass index (BMI) of children, and to study how family factors have effect on BMI through influencing SSB. METHODS: A total of 1,846 students aged 7-11 years from 12 primary schools in one district of Beijing were included. Their body weight and height were measured to calculate the BMI. The time of SSB and family factors were investigated by using questionnaires. The time of SSB was the total time of watching TV and videos, playing computer games and iPad each day during the past 7 days recalled by children. The family factors included the parents' education, occupation, the parents'time of SSB, whether the parents told their child the harm of SSB, the parents'time limit for the children's SSB. The parents'education and occupation were used for calculating the family socioeconomic score. RESULTS: The median time of SSB for children was 1 hour/day, and the interquartile range was 1 hour/day. The BMI of the children with the parents' time limit for the children's SSB less than 120 min/day were smaller than the children with the parents'time limit not less than 120 min/day, in both the boys (1.63 kg/m2, P<0.001) and the girls (0.85 kg/m2, P=0.004). The family socioeconomic score, the parents'SSB time, whether the parents told their children the harm of SSB were not related to the children's BMI . The mediation effects of SSB time for children on the association between the parents'time limit for the children's SSB and BMI were -0.222 kg/m2 (95%CI:-0.432, -0.095) for boys and -0.187 kg/m2 (95%CI: -0.507, -0.049) for girls, which accounted for 13.67% of the total effects for boys and 22.11% for girls. CONCLUSION: The parents' time limit for the children's SSB has effect on their BMI through influencing their SSB time. Parents' supervision on the behaviors of children produces larger benefit for BMI than health education conveyed by parents. Therefore, parents' participation in supervising the behaviors of children are indispensable for preventing and controlling childhood obesity.

How to enhance the applicability of a risk prediction model for term small-for-gestational-age neonates in clinical settings?

OBJECTIVE: To construct a simple term small-for-gestational-age (SGA) neonate prediction model that is clinically practical. METHODS: This analysis was based on the Born in Guangzhou Cohort Study (BIGCS). Mothers who had a singleton pregnancy, delivered a term neonate, and had an ultrasonography within 30 + 0 to 32 + 6 weeks of gestation were included. Term SGA was defined with customized population percentiles. Prediction models were constructed with backward selection logistic regression in a four-step approach, where model 1 contained fetal biometrics only, models 2 and 3 included maternal features and a time factor (weeks between ultrasonography and delivery), respectively; and model 4 contained all features mentioned. The prediction performance of individual models was evaluated based on area under the curve (AUC) and a calibration test was performed. RESULTS: The prevalence of SGA in the study population of 21 346 women was 11.5%. With a complete-case analysis approach, data of 19 954 women were used for model construction and validation. The AUC of the four models were 0.781, 0.793, 0.823, and 0.834, respectively, and all were well-calibrated. Model 3 consisted of fetal biometrics and corrected for time to delivery was chosen as the final model to build risk prediction graphs for clinical use. CONCLUSION: A prediction model derived from fetal biometrics in early third trimester is satisfactory to predict SGA.

Maintenance chemotherapy for ovarian cancer.

BACKGROUND: Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum-based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. OBJECTIVES: To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). SEARCH METHODS: In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, The Cochrane Central Register of Controlled Trails (CENTRAL, The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For this update, the searches were extended to October 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression-free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention-to-treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. MAIN RESULTS: We included eight trials (1644 women). When all chemotherapy regimens were combined, meta-analysis indicated no significant difference in three-, five- and 10-year OS or PFS. For five-year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10) and for the five-year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10-year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three- and five-year OS rates have no significant difference between the two groups. AUTHORS' CONCLUSIONS: There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required.

The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. AIM OF THE STUDY: The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. METHODS: To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. RESULTS: Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. CONCLUSION: According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

Two-Year Responses of Renal Function to First Occupational Lead Exposure.

Introduction: Whether in advanced countries lead exposure still contributes to renal impairment is debated, because blood lead (BL) level is declining toward preindustrial levels and because longitudinal studies correlating renal function and BL changes over time are scarce. Methods: The Study for Promotion of Health in Recycling Lead (SPHERL) evaluated the 2-year renal function responses in 251 workers (mean age, 29.7 years) transiting from environmental to occupational exposure. Main study end point was the estimated glomerular filtration rate (eGFR) derived from serum creatinine (eGFRcrt), cystatin C (eGFRcys), or both (eGFRcc). BL level was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dl). Results: In the follow-up, mean baseline BL level of 4.13 µg/dl increased 3.30-fold. In fully adjusted mixed models, additionally accounting for the within-participant clustering of the 1- and 2-year follow-up data, a 3-fold BL level increment was not significantly correlated with changes in eGFR with estimates amounting to -0.86 (95% CI: -2.39 to 0.67), -1.58 (-3.34 to 0.18), and -1.32 (-2.66 to 0.03) ml/min per 1.73 m2 for eGFRcrt, eGFRcys, or eGFRcc, respectively. Baseline BL level and the cumulative lead burden did not materially modify these estimates, but baseline eGFR was a major determinant of eGFR changes showing regression to the mean during follow-up. Responses of serum osmolarity, urinary gravity, or the urinary albumin-to-creatinine ratio (ACR) were also unrelated to the BL level increment. The age-related decreases in eGFRcrt, eGFRcys, and eGFRcc were -1.41, -0.96, and -1.10 ml/min per 1.73 m2, respectively. Conclusion: In the current study, the 2-year changes in renal function were unrelated to the increase in BL level. However, given the CIs around the point estimates of the changes in eGFRcc and eGFRcys, a larger study with longer follow-up is being planned.

Open-Angle Glaucomatous Optic Neuropathy Is Related to Dips Rather Than Increases in the Mean Arterial Pressure Over 24-H.

BACKGROUND: Mean arterial pressure (MAP) drives ocular perfusion. Excessive 24-h MAP variability relates to glaucoma, however, whether this is due to dips or increases in the blood pressure (BP) is undocumented. We investigated the association of open-angle glaucoma (OAG) in relation to the 5 largest MAP dips/increases over 24-h, henceforth called dips/blips. METHODS: In the Maracaibo Aging Study (MAS), 93 participants aged ≥40 y (women, 87.1%; mean age, 61.9 y) underwent baseline ophthalmological and 24-h ambulatory BP monitoring assessments. OAG was the presence of optic nerve damage and visual field defects. Statistical methods included logistic regression and the generalized R2 statistic. For replication, 48 OAG cases at the Leuven Glaucoma Clinic were matched with 48 controls recruited from Flemish population. RESULTS: In the MAS, 26 participants had OAG. OAG compared to non-OAG participants experienced longer and deeper dips (116.5 vs. 102.7 minutes; to 60.3 vs. 66.6 mm Hg; -21.0 vs. -18.0 mm Hg absolute or 0.79 vs. 0.81 relative dip compared to the preceding reading). The adjusted odds ratios associated with dip measures ranged from 2.25 (95% confidence interval [CI], 1.31-4.85; P = 0.009) to 3.39 (95% CI, 1.36-8.46; P = 0.008). On top of covariables and 24-MAP level/variability, the dip measures increased the model performance (P ≤ 0.025). Blips did not associate with OAG. The case-control study replicated the MAS observations. CONCLUSIONS: Dips rather than increases in the 24-h MAP level were associated with increased risk for OAG. An ophthalmological examination combined with 24-h BP monitoring might be precautious steps required in normotensive and hypertensive patients at risk of OAG.

The International Database of Central Arterial Properties for Risk Stratification: Research Objectives and Baseline Characteristics of Participants.

OBJECTIVE: To address to what extent central hemodynamic measurements, improve risk stratification, and determine outcome-based diagnostic thresholds, we constructed the International Database of Central Arterial Properties for Risk Stratification (IDCARS), allowing a participant-level meta-analysis. The purpose of this article was to describe the characteristics of IDCARS participants and to highlight research perspectives. METHODS: Longitudinal or cross-sectional cohort studies with central blood pressure measured with the SphygmoCor devices and software were included. RESULTS: The database included 10,930 subjects (54.8% women; median age 46.0 years) from 13 studies in Europe, Africa, Asia, and South America. The prevalence of office hypertension was 4,446 (40.1%), of which 2,713 (61.0%) were treated, and of diabetes mellitus was 629 (5.8%). The peripheral and central systolic/diastolic blood pressure averaged 129.5/78.7 mm Hg and 118.2/79.7 mm Hg, respectively. Mean aortic pulse wave velocity was 7.3 m per seconds. Among 6,871 participants enrolled in 9 longitudinal studies, the median follow-up was 4.2 years (5th-95th percentile interval, 1.3-12.2 years). During 38,957 person-years of follow-up, 339 participants experienced a composite cardiovascular event and 212 died, 67 of cardiovascular disease. CONCLUSIONS: IDCARS will provide a unique opportunity to investigate hypotheses on central hemodynamic measurements that could not reliably be studied in individual studies. The results of these analyses might inform guidelines and be of help to clinicians involved in the management of patients with suspected or established hypertension.

Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations.

BACKGROUND: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes. METHOD: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models. RESULTS: The 11 848 participants from 13 cohorts (age 53 ±â€Š16 years, 50% men) were followed for up for 13.7 ±â€Š6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated ( r  = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range. CONCLUSION: This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age.

Identification of maternal continuous glucose monitoring metrics related to newborn birth weight in pregnant women with gestational diabetes.

PURPOSE: To identify the specific glucose metrics derived from maternal continuous glucose monitoring (CGM) data, which were associated with a higher percentile of offspring birth weight. METHODS: In this cohort study, we recruited singleton pregnant women with GDM who underwent CGM for 5-14 days at a mean of 28.8 gestational weeks between Jan 2017 and Nov 2018. Commonly used single summary glucose metrics of glucose exposure (including mean 24-h, daytime, and nighttime glucose level) and variability (including J-index and mean amplitude of glycaemic excursions) were derived from CGM data. A novel comprehensive glucose metric-hours per-day spent in a severe variability glucose mode (HSSV)-was identified using the spectral clustering method, which reflects both glucose level and variability. Multiple linear regression models were used to estimate the associations of sex- and gestational age-adjusted birth weight percentile with CGM parameters. RESULTS: Ninety-seven women comprising 127,279 glucose measurements were included. Each 1-SD increase in maternal nighttime mean glucose level and HSSV was associated with 6.0 (95% CI 0.4, 11.5) and 6.3 (95% CI 0.4, 12.2) percentage points increase in birth weight percentile, respectively. No associations were found between other glucose metrics and birth weight percentile. CONCLUSION: Nighttime mean glucose level has a comparable effect size to HSSV in association with fetal growth, suggesting that endogenous hyperglycemia might drive the association between maternal hyperglycemia and birth weight. Further studies need to examine the effect of lowering nighttime glucose level and/or HSSV on preventing fetal overgrowth in GDM women.

Two-Year Responses of Heart Rate and Heart Rate Variability to First Occupational Lead Exposure.

[Figure: see text].