Magnetic Resonance Imaging (MRI)-Targeted Biopsy in Patients with Prostate-Specific Antigen (PSA) Levels <20 ng/mL: A Single-Center Study in Northeastern China.

BACKGROUND We investigated the feasibility of applying magnetic resonance imaging (MRI)-targeted biopsy (TB) in patients with prostate-specific antigen (PSA) levels <20 ng/mL. MATERIAL AND METHODS We retrospectively analyzed 218 patients with PSA levels <20 ng/mL and suspicious lesions according to the Prostate Imaging Recording and Data System version 2.0 (PI-RADS v2). All 218 men underwent transperineal MRI-TB, followed by template-guided 12-core systematic biopsy (SB). Of the 218 patients undergoing TB, 100 received MRI-ultrasound-assisted software fusion biopsy (FB) and 118 received cognitive biopsy (CB). Clinically significant prostate cancer (csPCa) was defined as a Gleason score ≥3+4. RESULTS The overall TB positive rate was similar to that of SB (P=0.156), but with a higher diagnostic rate for csPCa (P=0.034). SB misdiagnosed csPCa in 11.47% of cases; TB misdiagnosed csPCa in 5.50% of cases. SB+TB detected more tumors with a Gleason score of 7 than did SB alone (43 vs 22). Detection rates of csPCa were similar for CB and FB (P=0.217). In total, 47 men had 2 MRI-determined suspicious areas. Of 265 suspicious areas, 143 (53.96%) had a PI-RADS v2 score of 3; 92 (34.71%) had a score of 4; and 30 (11.32%) had a score of 5. The positive detection rates for csPCa in patients with PI-RADS v2 scores of 3, 4, and 5, were 11.19%, 48.91%, and 80.00%, respectively. CONCLUSIONS TB increased the positive biopsy detection rate but missed some cases of csPCa. TB combined with SB may be the most suitable biopsy for patients with PSA <20 ng/mL.

A Mendelian randomization study on causal effects of leisure sedentary behavior on the risk of erectile dysfunction.

BACKGROUND: Erectile dysfunction has been associated with leisure sedentary behavior in several epidemiological and observational studies. However, the interpretation of these findings is difficult due to residual confounding or reverse causality. OBJECTIVES: To explore the causal association between leisure sedentary behavior and erectile dysfunction, and to explore the underlying mechanism using Mendelian randomization. MATERIALS AND METHODS: In the present study, publicly available large-scale genome-wide association studies of leisure sedentary behaviors (television watching, computer use, and driving), erectile dysfunction, sex hormones (total testosterone, bioactive testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, and sex hormone binding globulin), biomarkers of endothelial function (C reactive protein, E-selectin, and matrix metalloproteinase 7), and psychiatric symptoms (depression and anxiety) were used to perform two-sample Mendelian randomization analyses. The inverse variance weighting method was the main method used to estimate the association, and sensitivity analyses were also performed. RESULTS: A greater risk of erectile dysfunction was significantly associated with a higher genetic susceptibility to leisure computer usage (odds ratio = 3.57; 95% confidence interval = 1.78-7.16; p < 0.001). No evidence was obtained to suggest that watching television or driving for leisure increased the risk of erectile dysfunction. No association was found between computer use and depression, anxiety, C reactive protein, E-selectin, matrix metalloproteinase 7, or other sex hormones, with the exception of follicle-stimulating hormone levels (odds ratio = 0.29; 95% confidence interval = 0.12-0.69; p = 0.01). No indication of heterogeneity or pleiotropy was identified by sensitivity analysis. DISCUSSION: Extended computer usage for leisure raised the likelihood of developing erectile dysfunction, which may be associated to lower follicle-stimulating hormone levels; however, the role of endothelial dysfunction and psychological disorders in the development of erectile dysfunction should not be underestimated. Moderate physical activity may help to correct the dysfunction. CONCLUSION: The present study offered substantial evidence for a positive causal association between computer use and the risk of erectile dysfunction. However, a definitive causal association needs to be established by further research.

No association effect of genetic polymorphism was observed between polycystic ovary syndrome and cardiovascular diseases risk: a mendelian randomization study.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is one of the risk factors for cardiovascular diseases (CVDs). However, the possible association between PCOS and common CVDs remains inconclusive. The aim of this study was to explore the potential relationship between PCOS and CVDs using genetic polymorphisms. METHODS: We conducted two-sample Mendelian randomization (MR) analyses. In our study, 14 single nucleotide polymorphisms (SNPs) in Europeans and another 13 SNPs in Asians were applied as instrumental variables for PCOS. The largest published meta-genome-wide association studies of European ancestry and the BioBank Japan Project of Asian ancestry were used to collect the outcome data. MR analysis was performed using inverse variance weighting as the primary method. Several sensitivity analyses and instrumental variable strength evaluations were also performed to verify the reliability of results. RESULTS: Our analysis revealed that any potential causal association between genetically-predicted PCOS and the risk of CVDs do not exist. These CVDs include peripheral artery disease, atrial fibrillation, arrhythmia, cardiovascular diseases, heart failure, peripheral vascular disease, hypertension, ischemic stroke, myocardial infarction and venous thromboembolisms. Associations could not be found even after the SNPs linked to these possible confounders (body mass index, waist-to-hip ratio, and serum testosterone) were deleted. Sensitivity analysis demonstrated no presence of horizontal pleiotropy or heterogeneity. CONCLUSION: The present mendelian randomization study suggests that genetically-predicted PCOS may not be associated with the risk of CVDs.

Review of mendelian randomization studies on age at natural menopause.

Menopause marks the end of the reproductive phase of life. Based on epidemiological studies, abnormal age at natural menopause (ANM) is thought to contribute to a number of adverse outcomes, such as osteoporosis, cardiovascular disease, and cancer. However, the causality of these associations remains unclear. A powerful epidemiological method known as Mendelian randomization (MR) can be used to clarify the causality between ANM and other diseases or traits. The present review describes MR studies that included ANM as an exposure, outcome and mediator. The findings of MR analyses on ANM have revealed that higher body mass index, poor educational level, early age at menarche, early age at first live birth, early age at first sexual intercourse, and autoimmune thyroid disease appear to be involved in early ANM etiology. The etiology of late ANM appears to be influenced by higher free thyroxine 4 and methylene tetrahydrofolate reductase gene mutations. Furthermore, early ANM has been found to be causally associated with an increased risk of osteoporosis, fracture, type 2 diabetes mellitus, glycosylated hemoglobin, and the homeostasis model of insulin resistance level. In addition, late ANM has been found to be causally associated with an increased systolic blood pressure, higher risk of breast cancer, endometrial cancer, endometrioid ovarian carcinoma, lung cancer, longevity, airflow obstruction, and lower risk of Parkinson's disease. ANM is also a mediator for breast cancer caused by birth weight and childhood body size. However, due to the different instrumental variables used, some results of studies are inconsistent. Future studies with more valid genetic variants are needed for traits with discrepancies between MRs or between MR and other types of epidemiological studies.

Construction of the prognostic model in non-metastatic renal cancer patients with venous tumor thrombus.

Background: Venous system invasion is a prominent characteristic of local progression in renal cancer and treatment-naïve renal cancer patients with venous tumor thrombus (VTT) gained short natural course and poor prognosis. This study aimed to investigate the efficacy of the surgery and prognostic factors in non-metastatic renal cancer patients with VTT and to construct a nomogram prognostic model. Methods: Clinical data of 114 non-metastatic renal cancer patients with VTT who underwent surgical treatment from January 2011 to September 2022 were retrospectively analyzed. In order to find independent risk factors of prognosis, survival analysis was performed via univariate and multivariate Cox regression models and Kaplan-Meier method. Nomogram prognostic model was established to calculate patients' risk scores. Receiver operating characteristic curve and decision curve analysis were conducted to evaluate the efficacy of the prognostic model. Results: A total of 114 patients were included in this study and there were 48, 12, 25, 23, and 6 cases of grade 0-IV VTT. No perioperative death occurred. The 3-year probabilities of overall survival (OS) and 5-year probabilities of OS were 67% and 43.8%, respectively. Multivariate Cox regression analysis revealed that kidney tumor diameter, preoperative lactate dehydrogenase (LDH), and preoperative neutrophils were independent risk factors. Nomogram was constructed to predict prognosis in renal cancer patients with VTT based on above indicators and Mayo VTT grading. The area under the ROC curve of 1-, 2-, 3-, and 5-year OS of the patients were 0.82, 0.67, 0.57, and 0.55 respectively. Conclusions: Surgical treatment enables renal cancer patients with VTT to gain a better prognosis. Kidney tumor diameter, preoperative LDH, and preoperative neutrophils were independent risk factors. The nomogram perfects the Mayo grading, and provides a reliable reference for evaluation of prognosis of renal cancer patients with VTT.

Excavation of diagnostic biomarkers and construction of prognostic model for clear cell renal cell carcinoma based on urine proteomics.

Purpose: Clear cell renal cell carcinoma (ccRCC) is the most common pathology type in kidney cancer. However, the prognosis of advanced ccRCC is unsatisfactory. Thus, early diagnosis becomes one of the most important research priorities of ccRCC. However, currently available studies about ccRCC lack urine-related further studies. In this study, we applied proteomics to search urinary biomarkers to assist early diagnosis of ccRCC. In addition, we constructed a prognostic model to assist judge patients' prognosis. Materials and methods: Urine which was used to perform 4D label-free quantitative proteomics was collected from 12 ccRCC patients and 11 non-tumor patients with no urinary system diseases. The urine of 12 patients with ccRCC confirmed by pathological examination after surgery was collected before operatoin. Bioinformatics analysis was used to describe the urinary proteomics landscape of these patients with ccRCC. The top ten proteins with the highest expression content were selected as the basis for subsequent validation. Urine from 46 ccRCC patients and 45 control patients were collected to use for verification by enzyme linked immunosorbent assay (ELISA). In order to assess the prognostic value of urine proteomics, a prognostic model was constructed by COX regression analysis on the intersection of RNA-sequencing data in The Cancer Genome Atlas (TCGA) database and our urine proteomic data. Results: 133 proteins differentially expressed in the urinary samples were found and 85 proteins (Fold Change, FC>1.5) were identified up-regulated while 48 down-regulated (FC<0.5). Top 10 proteins including S100A14, PKHD1L1, FABP4, ITIH2, C3, C8G, C2, ATF6, ANGPTL6, F13B were performed ELISA to verify. The results showed that PKHD1L1, ANGPTL6, FABP4 and C3 were statistically significant (P<0.05). We performed multivariate logistic regression analysis and plotted a nomogram. Receiver operating characteristic (ROC) curve indicted that the diagnostic efficiency of combined indicators is satisfactory (Aare under curve, AUC=0.835). Furthermore, the prognostic value of the urine proteomics was explored through the intersection between urine proteomics and TCGA RNA-seq data. Thus, COX regression analysis showed that VSIG4, HLA-DRA, SERPINF1, and IGLV2-23 were statistically significant (P<0.05). Conclusion: Our study indicated that the application of urine proteomics to explore diagnostic biomarkers and to construct prognostic models of renal clear cell carcinoma is of certain clinical value. PKHD1L1, ANGPTL6, FABP4 and C3 can assist to diagnose ccRCC. The prognostic model constituted of VSIG4, HLA-DRA, SERPINF1, and IGLV2-23 can significantly predict the prognosis of ccRCC patients, but this still needs more clinical trials to verify.

Causal effects of hypertension on risk of erectile dysfunction: A two-sample Mendelian randomization study.

Background: Erection dysfunction has been associated with hypertension in several epidemiological and observational studies. But the causal association between hypertension and erectile dysfunction requires further investigation. Methods: A two-sample Mendelian randomization (MR) was conducted to analyze the causal effect of hypertension on risk of erection dysfunction. Large-scale publicly available genome-wide association study data were used to estimate the putative causality between hypertension and risk of erectile dysfunction. A total of 67 independent single nucleotide polymorphisms were selected as instrumental variables. Inverse-variant weighted, maximum likelihood, weighted median, penalized weighted median, and MR-PRESSO approaches were utilized in MR analyses. Heterogeneity test, horizontal pleiotropy test, and leave-one-out method were used to prove the stability of the results. Results: In total, all P values were less than 0.05, demonstrating a positive causal link between hypertension and risk of erectile dysfunction in multiple MR methods, such as inverse-variant weighted (random and fixed effect) (OR 3.8315, 95% CI 2.3004-6.3817, P = 0.0085), maximum likelihood (OR 3.8877, 95% CI 2.3224-6.5081, P = 0.0085), weighted median (OR 4.9720, 95% CI 2.3645-10.4550, P = 0.0309), penalized weighted median (OR 4.9760, 95% CI 2.3201-10.6721, P = 0.0355), and MR-PRESSO (OR 3.6185, 95% CI 2.2387-5.8488, P = 0.0092). Sensitivity analysis detected no evidence of heterogeneity, pleiotropy, or outlier single nucleotide polymorphisms. Conclusion: The study revealed a positive causal link between the presence of hypertension and the risk of erectile dysfunction. More attention should be paid during the management of hypertension with the purpose of preventing erectile dysfunction or improving erectile function.

Management of pregnant patients with pulmonary arterial hypertension.

Pregnant individuals with pulmonary arterial hypertension (PAH) have significantly high risks of maternal and perinatal mortality. Profound changes in plasma volume, cardiac output and systemic vascular resistance can all increase the strain being placed on the right ventricle, leading to heart failure and cardiovascular collapse. Given the complex network of opposing physiological changes, strict contraception and reduction of hemodynamic fluctuations during pregnancy are important methods of minimizing the risk of maternal mortality and improving the outcomes following pregnancy. In this review, we discuss the recent research progress into pre-conception management and the various therapeutic strategies for pregnant individuals with PAH.

[A comparative study of incidence and prevalence of Crohn's disease in mainland China in different periods].

OBJECTIVE: To collect data and analyze the current status and prevalence changes of Crohn's disease (CD) in mainland China in recent decades. METHODS: A computer-based literature search was previously performed by using 50-year (1950 to 2002) of records of CD from the Chinese Database of Biology and Medicine (CBM) (1979 to 2002) and a manual year-by-year search of the literature (1950 to 1978). Using similar method, descriptive epidemiological data from 2003 to 2007 were collected, analyzed and compared with previous research. RESULTS: Four hundred and seventeen relevant papers during 2003 and 2007 were collected and 62 papers were eligible for inclusion. Within 62 papers, a total of 2149 cases with CD from 2003 to 2007 have been reported nationwide, comprising 1288 male and 861 female patients, with a 1.50:1 male predominance, and indicating 1.41 time of increment as compared with our previous result (ie, 1526 cases from 1950 - 2002). There were no obvious changes in incidence age (younger and middle age were main components) and sex ratio (number of male was still larger than that of female). The extrapolated CD incidence and prevalence rates were 1.21/100 000 person·year and 2.29/100 000, respectively, which were higher than that of year 1950 - 2002, 0.28/100 000 person·year and 1.38/100 000, respectively. CONCLUSIONS: The incidence and prevalence rates of CD have been increasing rapidly, but these rates are still lower than those in Western world.

Predictive Performance of Serum ß-hCG MoM Levels for Preeclampsia Screening: A Meta-Analysis.

Objective: The aim of the present study was to investigate the predictive value of using the multiple of the median (MoM) of ß-human chorionic gonadotropin (ß-hCG) levels in patients with preeclampsia (PE) and healthy pregnant women. Methods: Electronic databases including PubMed, EBSCO, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), SinoMed, Wangfang and the Weipu Journal were searched up to May 31, 2020. Two reviewers independently selected the articles and extracted data on study characteristics, quality and results. A random-effects model was employed, and standardized mean difference and 95% confidence intervals were calculated. Twenty-one case-control studies were analyzed in the present meta-analysis, including a total of 2,266 cases and 25,872 healthy controls. Results: Women who were diagnosed with PE were found to have higher early second-trimester levels of serum ß-hCG MoM compared with healthy controls, although the levels in the first trimester were not significantly different. Ethnicity subgroup analysis demonstrated that the MoM of ß-hCG serum levels was significantly higher in PE patients in both Asian and Caucasian populations during the early second trimester. Conclusion: The MoM of ß-hCG serum levels was found to be a valuable clinical indicator for predicting PE in the early second trimester, but had little predictive value in the first trimester. However, further assessment of the predictive capacity of ß-hCG within larger, diverse populations is required.

Crohn's disease in mainland China: a systematic analysis of 50 years of research.

BACKGROUND: Crohn's disease appears to be increasing in frequency in many areas of the world. However, little information with regard to disease incidence, prevalence and temporal trends has been published in China. OBJECTIVE: The aim of this review is to better understand the occurrence of Crohn's disease in mainland China, and to give an overview of the current status of the disease. METHODS: We used a computer-based literature search using 50-years of records from the Chinese Database of Biology and Medicine (CBM, 1979-2002), combined with a manual year-by-year search of the literature from 1950 to 1979. Each article was double-reviewed, and all descriptive epidemiological data were recorded, pooled and statistically analyzed. RESULTS: In total, 1526 cases of Crohn's disease since 1950 have been reported by more than 50 hospitals from 22 provinces and cities in mainland China, comprising 884 male and 642 female patients, with a 1.38:1 male predominance. More than 70% of patients were aged 20 to 50 years old, with a mean age of 37.2 +/- 2.68 (ranging from 1 to 83) years. The extrapolated disease incidence and prevalence rates are 0.28/100,000 person years and 1.38/100,000 persons, respectively. CONCLUSIONS: The incidence and prevalence rates of Crohn's disease are still lower than those in Western and other Asian countries, but these rates have been increasing rapidly, and the disease is no longer uncommon. An underestimation may occur because the patients who were misdiagnosed or did not seek medical advice could not be included in the study. A future population-based survey is warranted.

[Lactobacillus casei microbiological assay of plasma and RBC concentrations of folic acid with 96-well microtiiter plates].

To investigate the plasma and RBC concentrations of folic acid in normal persons. Microbiological assay was used to determine the plasma and RBC folic acid in 59 normal persons by using of 96-well microtiter plasma. The results showed that the plasma and RBC folio acid concentration were (8.2 +/- 2.9) microgram/L and (337.5 +/- 91.0) microgram/L in male and female normal persons (aged 18 to 32) respectively. The coefficient Variations determined within assay and between assay were 2.2% and 4.7% respectively. This method may reduce reagent costs, shortened the assay time, increase the sensitivity and improve the reproducibility. It can be used for large scale survey.

Existence of myodural bridge in the trachemys scripta elegans: indication of its important physiological function / Existencia del puente miodural en trachemys scripta elegans: indicación de su importante función fisiológica

The myodural bridge (MDB) is confirmed that connecting the most of suboccipital muscles to the cervical dura mater through the posterior intervertebral spaces and widely exists in mammals and birds. In order to reveal whether the MDB is universally existing in amniota of vertebrates, we explored the existence and the morphological features of the MDB in the Trachemys scripta elegans. Twenty fresh red-eared slider specimens were observed by the gross anatomy dissection and histological analysis. In the results, three kind of muscles in the postoccipital region of the red-eared slider were found. The rectus capitis dorsum minor muscle originated from the posterior margin of the occiput (C0) and terminated at the spinous process of the atlas (C1). The transversospinales muscle was attached to the vertebral arch and the postzygapophysis of the atlas and extended to the spinous process of the axis (C2). The C2-C3 intertransversales muscle were extended from the postzygapophysis of C2 and the one of C3. The three muscles covered the dorsal interspaces among C0-C3, and meantime they were closely connected with dense connective tissues, which filled in these interspaces. Each of these thick dense connective tissue membranes sent off several short and strong fibrous bundles ventrally to merge with the cervical spinal dura mater. Furthermore the connective tissues connecting these muscles with cervical spinal dura mater directly were revealed under the microscopy and they consisted of parallel and intensive collagen fibers with orientation from dorsal to ventral. In conclusion, this study for the first time demonstrated the existence of the MDB in the testudines, in all of the dorsal atlantooccipital, atlantoaxial and C2-C3 intervertebral spaces. Based on our results and comparative anatomical evidences in recent year, it could be inferred that the MDB might be its highly conserved structure in the evolution of amniota.

Se confirma que el puente miodural (PMD) conecta la mayoría de los músculos suboccipitales con la duramadre cervical a través de los espacios intervertebrales posteriores y existe ampliamente en mamíferos y aves. Para revelar si el MDB existe universalmente en la amniota de vertebrados, exploramos la existencia y las características morfológicas del PMD en Trachemys scripta elegans. Veinte muestras se observaron mediante disección anatómica y análisis histológico. En los resultados, se encontraron tres tipos de músculos en la región occipital. El músculo recto capitis dorsum minor se originó en el margen posterior del occipital (C0) y terminó en el proceso espinoso del atlas (C1). El músculo transverso espinal se unió al arco vertebral y el proceso del atlas y se extendió al proceso espinoso del axis (C2). El músculo intertransversario C2-C3 se extendió entre los procesos transversos de C2 y el de C3. Los tres músculos cubrían los espacios intermedios dorsales entre C0-C3 y, mientras tanto, estaban estrechamente conectados con tejidos conectivos densos, que rellenaban estos espacios. Cada una de estas membranas densas de tejido conectivo envían varios haces fibrosos cortos y fuertes ventralmente para fusionarse con la duramadre espinal cervical. Además, los tejidos conectivos que conectan estos músculos con la duramadre cervical y espinal se revelaron directamente bajo microscopía y consistían en intensas fibras de colágeno, paralelas, con orientación desde dorsal a ventral. En conclusión, este estudio demostró por primera vez la existencia del PMD en los estudios de prueba, en todos los espacios dorsales atlantooccipital, atlantoaxial e intervertebral C2-C3. Sobre la base de nuestros resultados y las evidencias anatómicas comparativas de los últimos años, se podría inferir que el PMD podría ser una estructura altamente conservada en la evolución de la amniota.

Prevalence and incidence rates of Crohn's disease in mainland China: a meta-analysis of 55 years of research.

OBJECTIVES: To better understand the occurrence of Crohn's disease in mainland China and to give an updated overview of the current status of the disease. METHODS: We previously performed a computer-based literature search using 50 years of records from the Chinese Database of Biology and Medicine (1979 to 2002), combined with a manual year-by-year search of the literature from 1950 to 1978. Using a similar method, descriptive epidemiological data of the last 5 years (2003 to September 2007) were collected, pooled with our previous data and re-analyzed. RESULTS: In total, 3618 cases of Crohn's disease since 1950 have been reported from 29 provinces and cities in mainland China, comprising 2112 male and 1506 female patients, with a male predominance of 1.40:1. More than 75 percent of the patients were aged from 20 to 50 years old, with a mean age of 36.9 +/- 4.4 (1- 84) years. The extrapolated disease incidence and prevalence rates are 0.848/10(5) and 2.29/10(5) person/year, respectively. CONCLUSION: The incidence and prevalence rates of Crohn's disease have been increasing rapidly, and the disease is no longer uncommon in China, but these rates are still lower than those in developed countries and other Asian countries. An underestimation may occur because patients who were misdiagnosed or did not seek medical advice could not be included in the study. A future population-based survey is warranted.