Annual space weather fluctuations and telomere length dynamics in a longitudinal cohort of older men: the Normative Aging Study.

BACKGROUND: Space weather has been associated with increased risk of cardiovascular diseases in space and flight crew. However, limited research has focused on the ground population, particularly among the elderly who are vulnerable to aging-related diseases. OBJECTIVE: We evaluated the association between space weather alterations and biological aging using leukocyte telomere length as a biomarker in healthy elderly men. METHODS: We used data from the Normative Aging Study, a longitudinal cohort of healthy elderly men in Massachusetts, USA. Leukocyte telomere length and health information were measured at in-person examinations approximately every three years, contributing to a total of 1,850 visits from 791 participants. Regional space weather information was collected daily, including cosmic ray-induced ionization, neutrons, sunspot number, interplanetary magnetic field, and Kp-index as our exposure of interest. We used mixed-effects models with a random intercept per individual to evaluate the associations between annual averages of space weather indicators and relative telomere length while accounting for participant demographics, environmental parameters, and secular trends. RESULTS: The mean age at baseline was 72.36 years. A one-year increment in age is associated with a 1.21% reduction in leukocyte telomere length. In the fully adjusted model accounting for individual and environmental factors, an interquartile range (IQR) increase of annual cosmic ray induced ionization (110.0 ion pairs cm-3 sec-1) was associated with a 17.64% (95%CI: -27.73%, -7.55%) decrease in leukocyte telomere length, equivalent to 15-years age increment. Solar and geomagnetic activities were associated with increased leukocyte telomere length, but the association became absent after adjusting for cosmic ray indicators. IMPACT: Galactic cosmic rays may accelerate the aging process in populations on the Earth, despite the protection by the Earth's atmosphere and magnetic field. This research enhances our understanding of how changes in space weather can impact health, highlights potential risks from space to Earth's inhabitants, and helps inform health strategies for vulnerable populations.

Beneficial effects of silibinin on serum lipids, bile acids, and gut microbiota in methionine-choline-deficient diet-induced mice.

Background and purpose: Silibinin (SIL) is a flavonoid lignin isolated from the fruit and seeds of silybum marianum that exhibits good therapeutic potential for NASH. However, the effects of SIL on serum lipids, bile acids (BAs), and gut microbiota (GM) in NASH mice remain unknown. The present work aimed to explore the beneficial effects of SIL supplementation on serum lipids, bile acids, and gut microbiota in MCD mice. Experimental approach: After male C57BL/6 mice were fed with a methionine-choline deficient (MCD) diet and simultaneously gavaged with SIL (20 mg/kg. d) for 8 weeks, the pathological changes of liver tissue were observed by oil red O, haematoxylin-eosin, and Masson tricolor staining; the levels of serum AST and ALT, and liver TG and MDA were detected by assay kits; metabonomics and 16S rDNA sequencing were used to analyze the composition of serum lipids and BAs and the abundance of GM; and the mRNA expression levels of hepatic genes related to BAs homeostasis were detected by RT-qPCR. Results: The results indicated that SIL treatment decreased the levels of 26 lipids (including four arachidonic acids, seven FFAs, 12 acyl carnitines, and three GPs) and two BAs (23-DCA, GLCA), while Dubosiella increased the levels of 10 lipids (including TxB3, PG16:0_18:1, Cer t18:0/24:0 and 7 TGs), five BAs (ß-MCA, α-MCA, UDCA, 3-oxo-DCA and HCA), and two GMs (Verrucomicrobiota and Akkermansiaceae) of MCD mice, but had no significant effect on the mRNA expression of CYP7A1, CYP27A1, Bsep, Mrp2, Ntcp, or Oatp1b2. Therefore, influencing GM composition and then regulating the levels of serum lipids and BAs through enterohepatic axis should be an important mechanism of SIL-induced alleviative effect on MCD mice. More importantly, we found that SIL had a good coordination in regulating the abundance of GM and the contents of serum lipids and BAs in MCD mice, that is, when the abundance of probiotics was up-regulated, the content of beneficial unsaturated fatty acids in serum was up-regulated, while the serum levels of harmful lipids and BAs were down-regulated. Conclusion: The alleviating effect of SIL on NASH may be closely related to the correction of intestinal bacteria disorder, serum bile acid, and lipid metabolic disturbance in mice.

Honokiol affects the composition of gut microbiota and the metabolism of lipid and bile acid in methionine-choline deficiency diet-induced NASH mice.

Honokiol (HNK), one of the main active components of Magnolia officinalis, has a positive effect on non-alcoholic steatohepatitis (NASH). However, the effects of HNK on the composition of serum lipids and bile acids (BAs) and gut microbiota (GM) of NASH mice are still unknown.C57BL/6 mice were fed with methionine-choline deficiency (MCD) diet and gavaged with HNK (20 mg/kg/d) for 8 weeks, then the serum lipids and BAs were detected by LC-MS, the composition of ileum microflora and the mRNA expression of hepatic BAs homeostasis related genes were analyzed by 16S rDNA sequencing and RT-qPCR, respectively. HNK treatment decreased the degree of hepatic lipid drops, inflammatory cell infiltration and fibrosis. Meantime, the serum levels of 34 lipids and 4 BAs in MCD mice were significantly altered by HNK treatment, as well as the increased abundance of Ruminococcaceae, Caulobacteraceae and Brevundimonas, and the decreased abundance of Firmicutes and Dubosiella. Besides, HNK treatment increased the hepatic mRNA expression of Oatp1b2 in MCD mice. The ameliorating effect of HNK on NASH may be partly related to its correction on the disorders of GM, serum lipids and BAs of MCD mice.

Wood smoke exposure affects lung aging, quality of life, and all-cause mortality in New Mexican smokers.

BACKGROUND: The role of wood smoke (WS) exposure in the etiology of chronic obstructive pulmonary disease (COPD), lung cancer (LC), and mortality remains elusive in adults from countries with low ambient levels of combustion-emitted particulate matter. This study aims to delineate the impact of WS exposure on lung health and mortality in adults age 40 and older who ever smoked. METHODS: We assessed health impact of self-reported "ever WS exposure for over a year" in the Lovelace Smokers Cohort using both objective measures (i.e., lung function decline, LC incidence, and deaths) and two health related quality-of-life questionnaires (i.e., lung disease-specific St. George's Respiratory Questionnaire [SGRQ] and the generic 36-item short-form health survey). RESULTS: Compared to subjects without WS exposure, subjects with WS exposure had a more rapid decline of FEV1 (- 4.3 ml/s, P = 0.025) and FEV1/FVC ratio (- 0.093%, P = 0.015), but not of FVC (- 2.4 ml, P = 0.30). Age modified the impacts of WS exposure on lung function decline. WS exposure impaired all health domains with the increase in SGRQ scores exceeding the minimal clinically important difference. WS exposure increased hazard for incidence of LC and death of all-cause, cardiopulmonary diseases, and cancers by > 50% and shortened the lifespan by 3.5 year. We found no evidence for differential misclassification or confounding from socioeconomic status for the health effects of WS exposure. CONCLUSIONS: We identified epidemiological evidence supporting WS exposure as an independent etiological factor for the development of COPD through accelerating lung function decline in an obstructive pattern. Time-to-event analyses of LC incidence and cancer-specific mortality provide human evidence supporting the carcinogenicity of WS exposure.

Early natural menopause is associated with poor lung health and increased mortality among female smokers.

BACKGROUND: Early natural menopause has been regarded as a biomarker of reproductive and somatic aging. Cigarette smoking is the most harmful factor for lung health and also an established risk factor for early menopause. Understanding the effect of early menopause on health outcomes in middle-aged and older female smokers is important to develop preventive strategies. OBJECTIVE: This study aimed to examine the associations of early menopause with multiple lung health and aging biomarkers, lung cancer risk, and all-cause and cause-specific mortality in postmenopausal women who were moderate or heavy smokers. STUDY DESIGN: This study was conducted on postmenopausal women with natural (n=1038) or surgical (n=628) menopause from the Pittsburgh Lung Screening Study. The Pittsburgh Lung Screening Study is a community-based research cohort of current and former smokers, screened with low-dose computed tomography and followed up for lung cancer. Early menopause was defined as occurring before 45 years of age. The analyses were stratified by menopause types because of the different biological and medical causes of natural and surgical menopause. Statistical methods included linear model, generalized linear model, linear mixed-effects model, and time-to-event analysis. RESULTS: The average age of the 1666 female smokers was 59.4±6.7 years, with 1519 (91.2%) of the population as non-Hispanic Whites and 1064 (63.9%) of the population as current smokers at baseline. Overall, 646 (39%) women reported early menopause, including 198 (19.1%) women with natural menopause and 448 (71.3%) women with surgical menopause (P<.001). Demographic variables did not differ between early and nonearly menopause groups, regardless of menopause type. Significant associations were identified between early natural menopause and higher risk of wheezing (odds ratio, 1.65; P<.01), chronic bronchitis (odds ratio, 1.73; P<.01), and radiographic emphysema (odds ratio, 1.70; P<.001) and lower baseline lung spirometry in an obstructive pattern (-104.8 mL/s for forced expiratory volume in the first second with P<.01, -78.6 mL for forced vital capacity with P=.04, and -2.1% for forced expiratory volume in the first second-to-forced vital capacity ratio with P=.01). In addition, early natural menopause was associated with a more rapid decline of forced expiratory volume in the first second-to-forced vital capacity ratio (-0.16% per year; P=.01) and incident airway obstruction (odds ratio, 2.02; P=.04). Furthermore, women early natural menopause had a 40% increased risk of death (P=.023), which was mainly driven by respiratory diseases (hazard ratio, 2.32; P<.001). Mediation analyses further identified that more than 33.3% of the magnitude of the associations between early natural menopause and all-cause and respiratory mortality were explained by baseline forced expiratory volume in the first second. Additional analyses in women with natural menopause identified that the associations between continuous smoking and subsequent lung cancer risk and cancer mortality were moderated by early menopause status, and females with early natural menopause who continued smoking had the worst outcomes (hazard ratio, >4.6; P<.001). This study did not find associations reported above in female smokers with surgical menopause. CONCLUSION: Early natural menopause was found to be a risk factor for malignant and nonmalignant lung diseases and mortality in middle-aged and older female smokers. These findings have strong public health relevance as preventive strategies, including smoking cessation and chest computed tomography screening, should target this population (ie, female smokers with early natural menopause) to improve their postmenopausal health and well-being.

Spirometry at diagnosis and overall survival in non-small cell lung cancer patients.

Pulmonary function can predict all-cause mortality, and chronic obstructive pulmonary disease (COPD) is associated with worse overall survival (OS) in non-small cell lung cancer (NSCLC) patients. Though pre-operative lung function is predictive of in-hospital mortality following lung cancer surgery, its predictive utility for long-term survival is unclear. The prognostic role of commonly used spirometry tests in survival of lung cancer also remains uncertain. This study evaluates the role of spirometry at lung cancer diagnosis in predicting OS of NSCLC patients. This was a retrospective study using data from the Boston Lung Cancer Study on newly diagnosed NSCLC patients with spirometry tests performed before cancer therapy (n = 2805). Spirometric test values, after being categorized using quartiles, were analyzed for association with OS using univariate and risk-adjusted multiple regression models. Further, we analyzed OS by the status of COPD determined by spirometry, and, among those with COPD, by its stage defined by the Global Initiative for Chronic Obstructive Lung Disease criteria. Both univariate and multiple regression models demonstrated that lower quartiles of actual and percent predicted forced expiratory volume in 1 second and forced vital capacity at lung cancer diagnosis were significantly associated with worse OS. Spirometry-determined COPD, and more advanced stage of COPD at lung cancer diagnosis were associated with worse lung cancer OS. The findings provide evidence that a good pulmonary function at diagnosis may help improve OS in NSCLC patients.

Identification and Validation of a Prognostic Signature for Prostate Cancer Based on Ferroptosis-Related Genes.

Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, ferroptosis related genes (FRGs) in prostate cancer (PCa) are not been well studied. In this study, we collected the mRNA expression profiles and clinical information of PCa patients from TCGA and MSKCC databases. The univariate, LASSO, and multivariate Cox regression analyses were performed to construct a prognostic signature. Seven FRGs, AKR1C3, ALOXE3, ATP5MC3, CARS1, MT1G, PTGS2, and TFRC, were included to establish a risk model, which was validated in the MSKCC dataset. The results showed that the high-risk group was apparently correlated with copy number alteration load, tumor burden mutation, immune cell infiltration, mRNAsi, immunotherapy, and bicalutamide response. Moreover, we found that TFRC overexpression induced the proliferation and invasion of PCa cell lines in vitro. These results demonstrate that this risk model can accurately predict prognosis, suggesting that FRGs are promising prognostic biomarkers and potential drug targets in PCa patients.

RETRACTED: Liposomal valinomycin mediated cellular K+ leak promoting apoptosis of liver cancer cells.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the corresponding author. It has been found that Fig 2B contains manipulated components, and Fig 5A partially overlaps with Fig 6 of a published paper authored by Mirza Muhammad Faran Ashraf Baig, et, al., The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors, J. Pharm. Anal. 11 (2021) 174-182, https://doi.org/10.1016/j.jpha.2020.10.003. The corresponding author indicated that they cannot guarantee the integrity of the images in the manuscript, as well as the conclusions of the paper. As a result, the Editor-in-Chief has decided to retract the paper. The corresponding author deeply regrets the circumstances and apologizes to the scientific community for not having detected this prior to publication.

Characteristics and risk differences of different tumor size on localized prostate cancer: A retrospective cohort study in the SEER database.

OBJECTIVE: We aimed to evaluate the role of tumor size in predicting tumor risk for localized prostate cancer (PCa) patients undergoing radical prostatectomy (RP). METHODS: Twenty-five thousand, one hundred twenty-seven men with PCa receiving RP from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier plots and multivariable Cox regression analyses were used to illustrate overall survival (OS) according to the tumor size. The tumor size was confirmed by postoperative pathology after RP. RESULTS: Among overall localized PCa, 84.6% were high-risk PCa, 9.2% were intermediate-risk PCa, and 6.2% were low-risk PCa. Multivariate analyses demonstrated that tumor size ≥21 mm was an independent risk predict factor of low-risk PCa (odds ratio [OR]: 11.940; 95% CI, 9.404-15.161; p < 0.001) and intermediate-risk PCa (OR: 1.887; 95% CI, 1.586-2.245; p < 0.001). Tumor sizes ≤5 mm significantly correlated with high-risk PCa (p < 0.001). Tumor size ≤5 mm had the worst OS in overall localized PCa and high-risk PCa (p < 0.001). CONCLUSIONS: In localized PCa, tumor sizes ≥21 mm may help predict low or intermediate-risk PCa, while tumor sizes ≤5 mm might help predict high-risk PCa. In clinical practice, we should be on high alert for patients with tumors size ≤5 mm due to its poor prognosis after RP.

Honokiol Alleviates Methionine-Choline Deficient Diet-Induced Hepatic Steatosis and Oxidative Stress in C57BL/6 Mice by Regulating CFLAR-JNK Pathway.

BACKGROUND: Honokiol (HNK) has been reported to possess various beneficial effects in the context of metabolic disorders, including fatty liver, insulin resistance, and oxidative stress which are closely related to nonalcoholic steatohepatitis (NASH), however with no particular reference to CFLAR or JNK. METHODS: C57BL/6 mice were fed methionine-choline-deficient (MCD) diet and administered simultaneously with HNK (10 and 20 mg/kg once a day, ig) for 6 weeks, and NCTC1469 cells were pretreated, respectively, by oleic acid (OA, 0.5 mmol/L) plus palmitic acid (PA, 0.25 mmol/L) for 24 h, and adenovirus-down Cflar for 24 h, then exposed to HNK (10 and 20 µmol/L) for 24 h. Commercial kits, H&E, MT, ORO staining, RT-qPCR, and Western blotting were used to detect the biomarkers, hepatic histological changes, and the expression of key genes involved in NASH. RESULTS: The in vivo results showed that HNK suppressed the phosphorylation of JNK (pJNK) by activating CFLAR; enhanced the mRNA expression of lipid metabolism-related genes Acox, Cpt1α, Fabp5, Gpat, Mttp, Pparα, and Scd-1; and decreased the levels of hepatic TG, TC, and MDA, as well as the levels of serum ALT and AST. Additionally, HNK enhanced the protein expression of oxidative stress-related key regulatory gene NRF2 and the activities of antioxidases HO-1, CAT, and GSH-Px and decreased the protein levels of prooxidases CYP4A and CYP2E1. The in vivo effects of HNK on the expression of CLFAR, pJNK, and NRF2 were proved by the in vitro experiments. Moreover, HNK promoted the phosphorylation of IRS1 (pIRS1) in both tested cells and increased the uptake of fluorescent glucose 2-NBDG in OA- and PA-pretreated cells. CONCLUSIONS: HNK ameliorated NASH mainly by activating the CFLAR-JNK pathway, which not only alleviated fat deposition by promoting the efflux and ß-oxidation of fatty acids in the liver but also attenuated hepatic oxidative damage and insulin resistance by upregulating the expression of NRF2 and pIRS1.

Erratum: Silencing miR-454 suppresses cell proliferation, migration and invasion via directly targeting MECP2 in renal cell carcinoma.

[This corrects the article on p. 4277 in vol. 12, PMID: 32913504.].

Incidental para-ureteral aggressive angiomyxoma: a rare case report and literature review.

BACKGROUND: Aggressive angiomyxoma (AA) is a rare tumor that typically occurs in the pelvis and perineum, most commonly in women of reproductive age. However, no para-ureteral AA has been reported according to the literature. Case presentation We herein describe the first case of para-ureteral AA. A 62-year-old male presented to our institute in March 2017 with a para-ureteral mass that was 15 mm in diameter incidentally. No symptom was observed and laboratory analysis was unremarkable. Magnetic resonance and computed tomography imaging showed a non-enhancing mass abutting the left ureter without causing obstruction. Laparoscopic resection of the mass was performed without injury to the ureter. Pathologic and immunohistochemical results were consistent with AA. Till now, no recurrence was noticed. CONCLUSIONS: We reported a rare case of para-ureteral AA, along with a literature review. Early diagnosis, proper surgical plan and long-term close follow-up is recommended for its high risk of recurrence and malignant potential.

Silencing miR-454 suppresses cell proliferation, migration and invasion via directly targeting MECP2 in renal cell carcinoma.

Renal cell cancer (RCC) is one of the most common malignant tumors of the urinary system. MicroRNA-454 (miR-454) has been reported to play an important role in various cancer progressions, such as hepatocellular carcinoma, breast cancer and glioblastoma. Nevertheless, its effect on RCC still remains unknown. We aimed to investigate the biological function and underlying mechanisms of miR-454 in RCC. The expressions of miR-454 and MECP2 in RCC tissues were assessed using data from TCGA database and our own clinical samples. Functional experiments Cell Counting Kit-8 (CCK-8), colony formation, wound healing and Transwell assays were applied to detect the effects of miR-454 and MECP2 in RCC. The interaction between miR-454 and MECP2 was assessed by western blot and luciferase reporter assays. MiR-454 was upregulated in RCC tissues and cell lines compared with matched adjacent normal tissues and the normal kidney tubular epithelial cell line HK-2. MiR-454 inhibition and methyl-CpG binding protein 2 (MECP2) overexpression could both decrease the proliferative, migrative and invasive abilities of RCC cells. Higher expression of miR-454 predicted a poor overall survival (OS) (HR: 1.8; P < 0.05), while MECP2 level was positively related with RCC OS (HR: 0.55; P < 0.05) and disease-free survival (HR: 0.56; P < 0.05). Mechanistically, we showed that miR-454 could directly target the downstream gene MECP2. Our findings indicated that miR-454 accelerates RCC progression via suppressing MECP2 expression, which may provide a novel potential target of RCC treatment in the future.

Perioperative Chemotherapy on Survival in Patients With Upper Urinary Tract Urothelial Carcinoma Undergoing Nephroureterectomy: A Population-Based Study.

Objectives: To estimate the stage-specific impact of perioperative chemotherapy on survival for upper urinary tract urothelial carcinoma (UTUC) patients treated with nephroureterectomy (NU). Methods: Overall, 7,278 UTUC patients treated with NU from 2004 to 2015 were identified within the SEER database. Kaplan-Meier plots were used to elucidate overall survival (OS) and cancer-specific survival (CSS) rates. Multivariable Cox regression analyses were used to test the impact of chemotherapy on survival rates, after stratifying according to pathological stage. Results: Chemotherapy was performed in 17.3% of patients and in 5.7, 11.5, 25.4, and 51.3% of patients with, respectively, pT1, pT2, pT3, and pT4 disease (P < 0.001). In multivariable analyses, perioperative chemotherapy was associated with a lower OS in pT2 patients and a lower CSS in pT1 disease (both P < 0.05), while predisposed to a higher OS in pT3 and pT4 patients (both P < 0.01). Moreover, perioperative chemotherapy was prone to a higher OS or CSS in pN+ disease compared to no chemotherapy (both P < 0.01). Conclusion: Perioperative chemotherapy was more frequently performed in locally advanced UTUC patients. The beneficial effect of chemotherapy on OS was evident in pT3/pT4 and pN+ patients. In addition, a clear CSS benefit was observed in patients who received chemotherapy for pN+ UTUC, while perioperative chemotherapy may reduce CSS for pT1 and OS for pT2 patients following NU.

Changes in Bone Metabolism After Sleeve Gastrectomy Versus Gastric Bypass: a Meta-Analysis.

BACKGROUND: Gastric bypass (GB) and sleeve gastrectomy (SG) are two common types of bariatric surgery that carry many potential complications. Among these complications, bone metabolism-related diseases have attracted substantial attention; however, no meta-analysis of them has been performed to date. METHODS: We searched PubMed, Web of Science, The Cochrane Library, and Embase to identify relevant studies published before January 2019. The following indicators were evaluated: serum parathyroid hormone (PTH), calcium, phosphorus and 25-hydroxyvitamin D levels, body mass index (BMI), and bone mineral density (BMD). RESULTS: Thirteen studies met our inclusion criteria. Overall results showed that patients undergoing GB had lower levels of 25-hydroxyvitamin D (MD = - 1.85, 95% CI (- 3.32, - 0.39) P = 0.01) and calcium (MD = - 0.15, 95% CI (- 0.24, - 0.07) P = 0.0006) as well as higher levels of PTH (MD = 3.58, 95% CI (0.61, 7.09) P = 0.02) and phosphorus (MD = 0.22, 95% CI (0.10, 0.35) P = 0.0005). The results of BMI and BMD were comparable in each group. CONCLUSION: Our meta-analysis suggested that obese patients undergoing GB had lower levels of serum calcium and 25-hydroxyvitamin D as well as higher levels of serum phosphorus and PTH. To prevent postoperative bone metabolism-related diseases, appropriate postoperative interventions should be undertaken for particular surgical procedures.

Impact of peri-prostatic fat measurements using MRI on the prediction of prostate cancer with transrectal ultrasound-guided biopsy.

OBJECTIVES: To estimate the impact of peri-prostatic fat (PPF) measurements using preoperative magnetic resonance imaging on the prediction of prostate cancer (PCa) with transrectal ultrasound-guided biopsy. PATIENTS AND METHODS: We performed a retrospective 2-center study on 660 consecutive patients receiving transrectal ultrasound-guided biopsy-biopsy from June 2016 to October 2018. Pathologic and immunohistochemical characteristics were collected. PPF measurements including PPF area (PPFA) and PPFA to prostate area (PA) ratio (PPFA/PA) were assessed by preoperative staging magnetic resonance imaging. Clinical variables were correlated with Gleason score by using Spearman (ρ) correlation coefficients. Multivariable analysis was performed to identify independent predictors of PCa. The diagnostic performance was estimated using ROC curves. RESULTS: The Gleason score was significantly correlated with age (ρ = 0.114, P = 0.035), prostate-specific antigen (PSA) (ρ = 0.482, P < 0.001), PIRADS scoring (ρ = 0.403, P < 0.001) and PPFA/PA (ρ = 0.238, P < 0.001). Multivariate analysis revealed that PPFA/PA, age, digital rectal examination, family history of PCa, PSA, and PIRADS scoring were independently predictive of PCa. The ROC AUC to detect PCa or clinically significant PCa (CS-PCa; Gleason Score 3 + 4 or greater) improved with the addition of PPFA/PA (PCa: 0.93 vs. 0.89; CS-PCa: 0.92 vs. 0.90). CONCLUSION: PPFA/PA is an independent predictor for PCa along with age, digital rectal examination, family history of PCa, PSA, and PIRADS scoring. PPF measurements especially PPFA/PA may help detect PCa or CS-PCa, thus helping improve PCa risk stratification and screening to avoid unnecessary biopsies.

Effect of lymph node dissection on stage-specific survival in patients with upper urinary tract urothelial carcinoma treated with nephroureterectomy.

BACKGROUND: We aimed to estimate the stage-specific impact of lymph node dissection (LND) on survival for upper urinary tract urothelial carcinoma (UTUC) patients treated with nephroureterectomy (NU). METHODS: Overall, 7278 UTUC patients undergoing NU within the SEER database from 2004 to 2015 were identified. Kaplan-Meier plots illustrated overall survival (OS) and cancer-specific survival (CSS) rates according to LND status. Multivariable Cox regression analyses assessed the effect of LND on OS and CSS rates stratified by pathological tumor stage. RESULTS: LND was performed in 26.9% of patients, and in 18.6, 23.3, 31.2 and 45.9% for pT1, pT2, pT3 and pT4 patients, respectively (P <  0.001). In multivariable Cox regression analyses, LND was associated with a higher OS or CSS in UTUC patients with pT3 and pT4 disease (all P <  0.05), but failed to achieve independent predictor status in patients with pT1 and pT2 disease (all P > 0.05). LND with 1 to 3 regional lymph nodes removed was prone to a higher OS or CSS only in pT4 compared to no LND (both P <  0.01). LND with 4 or more regional lymph nodes removed predisposed to a higher OS or CSS in pT3 or pT4 (all P <  0.05). CONCLUSIONS: The beneficial effect of LND especially LND with 4 or more regional lymph nodes removed on survival was evident in pT3/4 patients. LND can be considered for pT3 and pT4, for pT1/2 remains to be seen, both of which will be verified by further prospective studies.

The items in the Chinese version of the Montreal cognitive assessment basic discriminate among different severities of Alzheimer's disease.

BACKGROUND: To determine whether items of the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC) could discriminate among cognitively normal controls (NC), and those with mild cognitive impairment (MCI), mild Alzheimer's disease (AD), and moderate-severe (AD), as well as their sensitivity and specificity. METHODS: MCI (n = 456), mild AD (n = 502) and moderate-severe AD (n = 102) patients were recruited from the memory clinic, Huashan Hospital, Shanghai, China. NC (n = 329) were recruited from health checkup outpatients. Five MoCA-BC item scores were collected in interviews. RESULTS: The MoCA-BC orientation test had high sensitivity and specificity for discrimination among MCI, mild AD and moderate-severe AD. The delayed recall memory test had high sensitivity and specificity for MCI screening. The verbal fluency test was efficient for detecting MCI and differentiating AD severity. CONCLUSIONS: Various items of the MoCA-BC can identify MCI patients early and identify the severity of dementia.

A right eye amaurosis patient with congenital absence of the internal carotid artery: A care compliant case report.

RATIONALE: Absence or hypoplasia of the internal carotid artery (ICA) are rare developmental anomalies. Usually, patients with ICA agenesis are asymptomatic due to collateral circulation, but they may present with seizures, headache, or transient ischemic attack. We report a patient with right ICA absence in whom "paroxysmal right eye amaurosis" was the main symptom. PATIENT CONCERNS: A 76-year-old male patient suffered from "paroxysmal right eye amaurosis for 3 years". Three years prior, the patient had suffered sudden one-minute right eye amaurosis without any obvious cause. The attack reoccurred 1-2 times/year until one week before admission when he experienced two sudden right eye amaurosis. DIAGNOSIS: Congenital absence of the right ICA was diagnosed. In this patient with congenital absence of the right ICA, the ipsilateral anterior cerebral artery (ACA) was compensated by the anterior communicating artery (ACOM), and the ipsilateral middle cerebral artery (MCA) emerged from the carotid siphon of the contralateral ICA. INTERVENTIONS: The patient was given antiplatelet treatment consisting of aspirin and atorvastatin after admission and instructed to maintain the treatment after discharge. OUTCOMES: No symptom onset was observed during follow-up. LESSONS: Here, we report the patient's clinical manifestations and imaging findings and analyze the cause of the condition to provide a clinical reference for the study of congenital absence of the ICA.

Silibinin ameliorates hepatic lipid accumulation and oxidative stress in mice with non-alcoholic steatohepatitis by regulating CFLAR-JNK pathway.

Non-alcoholic steatohepatitis (NASH) is a chronic metabolic syndrome and the CFLAR-JNK pathway can reverse the process of NASH. Although silibinin is used for the treatment of NASH in clinical, its effect on CFLAR-JNK pathway in NASH remains unclear. This study aimed to investigate the effect of silibinin on CFLAR-JNK pathway in NASH models both in vivo and in vitro. The in vivo study was performed using male C57BL/6 mice fed with methionine- choline-deficient diet and simultaneously treated with silibinin for 6 weeks. The in vitro study was performed by using mouse NCTC-1469 cells which were respectively pretreated with oleic acid plus palmitic acid, and adenovirus-down Cflar for 24 h, then treated with silibinin for 24 h. After the drug treatment, the key indicators involved in CFLAR-JNK pathway including hepatic injury, lipid metabolism and oxidative stress were determined. Silibinin significantly activated CFLAR and inhibited the phosphorylation of JNK, up-regulated the mRNA expression of Pparα, Fabp5, Cpt1α, Acox, Scd-1, Gpat and Mttp, reduced the activities of serum ALT and AST and the contents of hepatic TG, TC and MDA, increased the expression of NRF2 and the activities of CAT, GSH-Px and HO-1, and decreased the activities and expression of CYP2E1 and CYP4A in vivo. These effects were confirmed by the in vitro experiments. Silibinin prevented NASH by regulating CFLAR-JNK pathway, and thereby on one hand promoting the ß-oxidation and efflux of fatty acids in liver to relieve lipid accumulation, and on the other hand inducing antioxidase activity (CAT, GSH-Px and HO-1) and inhibiting pro-oxidase activity (CYP2E1 and CYP4A) to relieve oxidative stress.