Associations Between Polymorphisms in Genes Related to Oxidative Stress and DNA Repair, Interactions With Serum Antioxidants, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

Study of polymorphisms in genes related to the generation and removal of oxidative stress and repair of oxidative DNA damage will lead to new insights into the genetic basis of prostate cancer. In the Prostate Cancer Prevention Trial (PCPT), a double-blind, randomized controlled trial testing finasteride versus placebo for prostate cancer prevention, we intend to investigate the role of oxidative stress/DNA repair mechanisms in prostate cancer etiology and whether these polymorphisms modify prostate cancer risk by interacting with antioxidant status in both placebo and finasteride arms. We evaluated associations of selected candidate polymorphisms in genes in these pathways, and interactions with pre-diagnostic serum antioxidants, and the risk of prostate cancer among 1,598 cases and 1,706 frequency-matched controls enrolled in the PCPT. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted logistic regression models. While there were no statistically significant associations observed in the placebo arm, several SNPs were associated with prostate cancer in the finasteride arm. Specifically, APEX1-rs1760944 was associated with increased risk of total prostate cancer (per minor allele: p-trend=0.04). OGG1-rs1052133 was positively (CG/GG vs. CC: OR=1.32, 95% CI: 1.01-1.73) and NOS3-rs1799983 was inversely (per minor allele: p-trend=0.04) associated with risk of low-grade prostate cancer. LIG3-rs1052536 and XRCC1-rs25489 were suggestively associated with reduced risk of high-grade prostate cancer (per minor allele: both p-trend=0.04). In the placebo arm, significant associations were observed among men with higher serum lycopene for APEX1-rs1760944 and NQO1-rs1800566, or higher serum β-cryptoxanthin for ERCC4-rs1800067. In the finasteride arm, stronger associations were observed among men with lower serum lycopene for NOS3-rs1799983, higher serum α-carotene, β-carotene, and β-cryptoxanthin for LIG3-rs1052536, or lower serum retinol for SOD2-rs1799725. These results suggest that germline variations in oxidative stress and DNA repair pathways may contribute to prostate carcinogenesis and that these associations may differ by intraprostatic sex steroid hormone status and be further modified by antioxidant status. Findings provide insights into the complex role of gene, gene-antioxidant and -finasteride interactions in prostate cancer etiology, and thus may lead to the development of preventative strategies.

Incidence and risk factors associated with preoperative deep venous thrombosis in the young and middle-aged patients after hip fracture

Objective This study aims to investigate the incidence, occurrence timing and locations of preoperative DVT and identify the associated factors in this group. Methods A retrospective analysis of collected data in young and middle-aged (18–59 years) patients who presented with hip fracture between October 2015 and December 2018 was conducted. Before operation, patients were routinely examined for DVT by Duplex ultrasonography (DUS). Electronic medical records were retrieved to collect the data, involving demographics, comorbidities, injury and laboratory biomarkers after admission. Multivariate logistic regression analysis was performed to identify factors that were independently associated with DVT. Results Eight hundred and fifty-seven patients were included, and 51 (6.0%) were diagnosed with preoperative DVT, with 2.5% for proximal DVT. The average age of patients with DVT is 48.7 ± 9.4 year, while that of patients without DVT is 45.0 ± 10.9 year. The mean time from injury to diagnosis of DVT was 6.8 ± 5.5 days, 43.1% cases occurring at day 2–4 after injury. Among 51 patients with DVT, 97 thrombi were found. Most patients had thrombi at injured extremity (72.5%), 19.6% at uninjured and 7.8% at bilateral extremities. There are significantly difference between patients with DVT and patients without DVT in term of prevalence of total protein (41.2% vs 24.4%, P = 0.008), albumin (54.9% vs 25.6%, P = 0.001), low lactate dehydrogenase (51.0% vs 30.3%, P = 0.002), lower serum sodium concentration (60.8% vs 29.9%, P = 0.001), lower RBC count (68.6% vs 37.0%, P = 0.001), lower HGB (51.0% vs 35.1%, P = 0.022), higher HCT (86.3% vs 35.1%, P = 0.022) and higher platelet count (37.3% vs 11.3%, P = 0.001). The multivariate analyses showed increasing age in year (OR 1.04, 95% CI; P = 0.020), delay to DUS (OR, 1.26; P = 0.001), abnormal LDH (OR, 1.45; P = 0.026), lower serum sodium concentration (OR, 2.56; P = 0.007), and higher HCT level (OR, 4.11; P = 0.003) were independently associated with DVT. Conclusion These findings could be beneficial in informed preventive of DVT and optimized management of hip fracture in specific group of young and mid-aged patients.

Preeclampsia at delivery is associated with lower serum vitamin D and higher antiangiogenic factors: a case control study

Background Preeclampsia is characterized by decreased trophoblastic angiogenesis leading to abnormal invasion of spiral arteries, shallow implantation and resulting in compromised placentation with poor uteroplacental perfusion. Vitamin D plays an important role in pregnancy influencing implantation, angiogenesis and placental development. The objective of this study was to determine whether there is an association between serum vitamin D levels, and anti-angiogenic factors at the time of delivery and the occurrence of preeclampsia. Methods This nested case control study analyzed frozen serum samples at the time of delivery and related clinical data from women with singleton liveborn pregnancies who had participated in studies of the NICHD Stillbirth Collaborative Research Network. Women with a recorded finding of preeclampsia and who had received magnesium sulfate treatment prior to delivery were considered index cases (N = 56). Women without a finding of preeclampsia were controls (N = 341). Results Women with preeclampsia had 14.5% lower serum vitamin D levels than women in the control group (16.5 ng/ml vs. 19 ng/ml, p = 0.014) with 64.5% higher sFlt-1 levels (11,600 pg/ml vs. 7050 pg/ml, p < 0.001) and greater than 2 times higher endoglin levels (18.6 ng/ml vs. 8.7 ng/ml, < 0.001). After controlling for gestational age at delivery and maternal BMI, vitamin D levels were 0.88 times lower (P = 0.051), while endoglin levels were 2.5 times higher and sFlt-1 levels were 2.1 times higher than in control pregnancies (P < 0.001). Conclusions Women with preeclampsia at time of delivery have higher maternal antiangiogenetic factors and may have lower maternal serum vitamin D levels. These findings may lead to a better understanding of the underlying etiology of preeclampsia as well as possible modifiable treatment options which could include assuring adequate levels of maternal serum vitamin D prior to pregnancy.

Admission Lower Serum Phosphate Ion Levels Predict Acute Hydrocephalus of Aneurysmal Subarachnoid Hemorrhage

Introduction: The relationship between serum phosphate ion (sPi) and the occurrence of acute hydrocephalus (aHCP) in aneurysmal subarachnoid hemorrhage (aSAH) remains largely unknown and controversial. The primary aim of this study was to investigate the association between sPi on admission and aHCP following aSAH.Methods: The study included 635 patients over the age of 19 years diagnosed with aSAH in our institution from September 2012 to June 2018. Data on clinical characteristics, laboratory parameters, treatments, and outcomes were collected and analyzed. The association between lower sPi levels and aHCP was assessed in univariate and multivariate analyses. Propensity-score matching (PSM) analysis was performed to reduce significant differences in baseline characteristics between the aHCP group and non-HCP group.Results: The overall incidence of aHCP following aSAH was 19.37% (123/512). Lower sPi levels were detected in patients with aHCP compared with those without [0.86 (0.67–1.06) vs. 1.04 (0.84–1.21) mmol/L] in the univariate analysis. In the multivariate analysis, lower sPi level, high modified Fisher (mFisher) grade, and high Hunt-Hess grade were associated with aHCP [odds ratios (OR) 1.729, 95% confidence interval (CI) 1.139–2.623, p = 0.01; mFisher OR 0.097,95% CI 0.055–0.172, p &lt; 0.001; Hunt-Hess, OR 0.555, 95% CI 0.320–0.961, P = 0.036]. After PSM, the matched aHCP group had a significantly lower sPi level than the matched non-aHCP group [0.86 (0.67–1.06) vs. 0.94 (0.76–1.12) mmol/L, p = 0.044]. The area under the curve (AUC) of the sPi level and the logistic regression model based on these predictors (sPi, Hunt-Hess grade, and mFisher grade) was 0.667 and 0.840 (sensitivity of 88.6% and specificity of 68.4%) for predicting aHCP, respectively.Conclusions: Lower sPi levels predict the occurrence of aHCP, and the model constructed by sPi levels, Hunt-Hess grade, and mFisher grade markedly enhances the prediction of aHCP after aSAH.

Triiodothyronine (T3), inflammation and mortality risk in patients with acute myocardial infarction

Objectives: To study the relationship between serum free T3 (FT3), C-reactive protein (CRP), and all-cause mortality in patients with acute myocardial infarction (AMI). Design: Prospective multicentre longitudinal cohort study. Methods: Between December 2014 and December 2016, thyroid function and CRP were analysed in AMI (both ST- and non-ST-elevation) patients from the ThyrAMI-1 study. The relationship of FT3 and CRP at baseline with all-cause mortality up to June 2020 was assessed. Mediation analysis was performed to evaluate if CRP mediated the relationship between FT3 and mortality. Results: In 1919 AMI patients [29.2% women, mean (SD) age 64.2 (12.1) years and 48.7% STEMI] followed over a median (inter-quartile range) period of 51 (46 to 58) months, there were 277 (14.4%) deaths. Overall, lower serum FT3 and higher CRP levels were associated with higher risk of mortality. When divided into tertiles based on levels of FT3 and CRP, the group with the lowest FT3 and highest CRP levels had 2.5-fold increase in mortality risk [adjusted hazard ratio (95% confidence interval) of 2.48 (1.82 to 3.16)] compared to the group with the highest FT3 and lowest CRP values. CRP mediated 9.8% (95% confidence interval 6.1 to 15.0%) of the relationship between FT3 and mortality. Conclusions: In AMI patients, lower serum FT3 levels on admission are associated with a higher mortality risk, which is partly mediated by inflammation. Adequately designed trials to explore potential benefits of T3 in AMI patients are required.

Effect of Dexmedetomidine Administation on Analgesic, Respiration and Inflammatory Responses in Patients Undergoing Percutaneous Endoscopic Lumbar Discectomy: A Prospective Observational Study

BackgroundLocal anesthesia has been recommended for percutaneous endoscopic lumbar discectomy (PELD) in recent years; however, the efficacy, including oxidative stress, inflammatory reactions and ventilation effects, when intravenous dexmedetomidine (DEX) is administered during PELD has not been thoroughly described.MethodsSixty patients undergoing PELD were randomly allocated to either an intravenous DEX sedation group (Group A) or a normal saline group (Group B). Respiratory data, including minute ventilation (MV), tidal volume (TV), and respiratory rate (RR), were recorded using a respiratory volume monitor (RVM), and pulse oxygen saturation (SpO2) was measured by pulse oximetry. The visual analog score (VAS) and the plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were also recorded to evaluate oxidative stress and inflammatory reactions.ResultsThere were no significant differences in RR, MV, TV and SpO2 between the two groups at any time point (p>0.05). Group B exhibited lower serum levels of GSH-PX (p<0.0001) and higher serum levels of MDA (p<0.0001) than Group A at the end of surgery. Twenty-four hours after surgery, Group B exhibited higher serum levels of IL-6 (p=0.0033), TNF-α(p=0.0002), and MDA (p<0.0001) and lower serum levels of GSH-PX (p<0.0001) than Group A. In addition, Group B exhibited lower VAS (p<0.0001) than Group A.ConclusionsDEX administration using an RVM not only provides convenient analgesia and ventilation but also alleviates oxidative stress and inflammatory reactions in patients undergoing PELD .Trial registration ChiCTR2100044715(http://www.chictr.org.cn/index.aspx)

Assessing the Effects of Vitamin D on Neural Network Function in Patients With Parkinson’s Disease by Measuring the Fraction Amplitude of Low-Frequency Fluctuation

Background: Recently, many studies have shown that low vitamin D (VD) levels may be related to an increased risk of Parkinson’s disease (PD), but the underlying mechanisms remain unclear.Objective: To explore the relationship between PD and VD levels, as well as to analyze the effects of VD on spontaneous brain activity and explore the possible mechanism of its involvement in PD risk.Methods: In a cross-sectional study, we quantified the difference in VD levels between 330 PD patients and 209 healthy controls (HC) to explore the correlation between VD and PD risk. We also acquired resting-state Functional Magnetic Resonance Imaging (rs-fMRI) data from 46 PD patients and 21 HC. The PD patients were divided into three groups according to 25(OH)D levels: PD patients with VD deficiency (PD + VDD), PD patients with VD insufficiency (PD + VDI), and PD patients with normal VD (PD + NVD). The effect of VD status on spontaneous neuronal activity in the whole brain was analyzed by measuring the fraction amplitude of low-frequency fluctuation (fALFF).Results: Compared with HC, the PD patients had lower serum 25(OH)D levels (23.60 ± 7.27 vs. 25.60 ± 5.78, P &lt; 0.001). The 25(OH)D level may have a potential dose-dependent effect on the risk of PD (Ptrend = 0.007). A high risk of PD was associated with VD deficiency [25(OH)D &lt; 20 ng/mL, OR = 2.319], and the lowest quartile of 25(OH)D concentration was associated with a high risk of PD (OR = 1.941). In the rs-fMRI study, PD + VDD patients had wider brain regions with altered fALFF than other PD groups when compared with the corresponding HC groups. Both PD + VDD and PD + VDI showed higher fALFF in the cuneus, left precuneus, calcarine cortex and right lingual, as well as lower fALFF in the left middle temporal gyrus. PD + VDD patients also showed higher fALFF in the left superior, middle and inferior frontal gyri, as well as the left precentral gyrus than HC. Among PD patients, there was only a statistically significant difference in fALFF between the PD + VDD and PD + NVD groups. Compared with the PD + NVD group, PD + VDD patients exhibited higher fALFF in the left precentral and left postcentral gyrus, as well as the left inferior parietal lobule.Conclusion: These results demonstrate that PD patients had lower serum VD levels than HC, and VD may have a potential dose-dependent effect on PD risk. Lower serum VD levels can affect the spontaneous neuronal activity of default-mode network (DMN) and visual pathway neurons in PD patients, providing a possible mechanism for its effect on PD risk.

Machine Retrograde Perfusion of Deceased Donor Kidneys: A Prospective Study

Objective: To maximize the utilization of potential kidneys, improving perfusion and preservation techniques is necessary.Methods: We investigated the safety and efficacy of retrograde machine perfusion of kidneys from deceased donors. A total of 30 kidneys were included and all the grafts were preserved in the Kidney Transporter machines. A total of 15 kidneys that received retrograde perfusion (RP) were selected as the RP group (n = 15) and their counterparts received standard antegrade perfusion (AP) as the control group (n = 15).Results: All the recipients were followed up for 6 months. Renal resistance in the RP group remained stable during the perfusion. There was no primary nonfunction. No difference in the incidence of delayed graft function was found in both groups (3 in RP vs. 2 in AP, p = 0.62). The RP group had lower serum creatinine (RP vs. AP, 102.20 vs. 138.67, p = 0.05) and blood urea nitrogen (RP vs. AP, 6.44 vs. 8.71, p = 0.05) than that in the AP group at 6 months. Both the groups had comparable estimated glomerular filtration rate and cystatin C within 6 months.Conclusion: This novel technique may be an effective and safe alternative for kidney preservation.