Parvovirus B19 DNA and antibodies in Chinese plasma donors, plasma pools and plasma derivatives.

Background: Human parvovirus B19 (B19V) is a common contaminant found in plasma pools and plasma derivatives. Previous studies were mainly focused on limited aspects, further assessment of prevalence of B19V DNA and antibodies in plasma donors, the contamination of B19V in pooled plasma and plasma derivatives should be performed in China. Study Design and Methods: Individual plasma donors' samples from four provinces and pooled plasma from four Chinese blood product manufacturers were collected and screened using B19V DNA diagnostic kits between October 2018 and May 2020. The positive samples were investigated for the seroprevalence of B19V antibodies and subjected to sequence analysis and alignment for phylogenetic studies. Moreover, 11 plasma donors who were B19V DNA-positive at their first testing were also followed during the later donation period. Additionally, 400 plasma pools and 20 batches of plasma derivatives produced by pooled plasma with a viral load of B19V DNA exceeding 104IU/mL were also collected and tested for B19V DNA and antibodies. Objectives: To comprehensively and systematically determine the frequency and viral load of B19V DNA in plasma donors, pooled plasma, and plasma derivatives from four Chinese blood product manufacturers. Results: A total of 17,187 plasma donors were analyzed and 44 (0.26%) specimens were found positive for B19V DNA. The quantitative DNA levels ranged from 1.01 × 101 to 5.09 × 1012 IU/mL. Forty-four DNA-positive specimens were also investigated for the seroprevalence of B19V antibodies, 75.0% and 2.3% of which were seropositive for B19V IgG and IgM antibodies, respectively. The phylogenic analyses showed that the prevalent genotypes in the four provinces' plasma donors belonged to B19V Genotype 1. Eleven individual plasma donors who were B19V DNA-positive at the first donation were then followed for a period, and in general, the DNA levels of B19V gradually decreased. Moreover, 64.8% (259/400) of the pooled plasma was contaminated by B19V, with concentrations of 1.05 × 100-3.36 × 109IU/mL. Approximately 72.6% of the DNA-positive plasma pools were only moderately contaminated (<104 IU/mL), while 27.4% contained >104 IU/mL. Twenty batches of plasma derivatives produced by pooled plasma with a viral load of B19V DNA exceeding 104IU/mL were also tested. B19V was detected in 5/5 PCC samples and 5/5 factor VIII samples but was not found in the intravenous immune globulin and albumin samples. Conclusion: The contamination of B19V in pooled plasma and plasma-derived clotting factor concentrates is serious. Whether B19V nucleic acid testing (NAT) screening of plasma and plasma derivatives is launched in China, blood product manufacturers should spontaneously perform B19V NAT screening in plasma donors and mini-pool plasma. These measures can ensure that samples with high titer B19V DNA are discarded in order to prevent and control this transfusion transmitted virus.

Development and validation of a predictive model for penile cancer based on the surveillance, epidemiology, and end results database and multi-center cases.

PURPOSE: Penile cancer (PC) is a great impact on the quality of life and psychological status of patients. This study aimed to construct nomograms using data from the Surveillance, Epidemiology, and End Results (SEER) database to predict overall survival (OS) and cancer-specific survival (CSS) in patients with penile cancer (PC). METHODS: Patients were divided into a training cohort (n = 634) and a validation cohort (n = 272) in a 7:3 ratio. Independent risk factors influencing the prognosis of PC were screened using univariate and multivariate Cox analyses, and models for predicting PC were developed. Data from 203 patients with PC in four tertiary hospitals in Gansu Province from 2012 to 2021 were externally validated. RESULTS: Univariate analysis and multivariate analysis showed revealed that the OS-related factors were age, grade, T stage, N stage, M stage and tumor size (p < 0.05); the CSS-related factors were age, mode of surgery, T stage, N stage, M stage and tumor size (p < 0.05). The C-indices of the OS and CSS nomograms in the training cohort were 0.743 [95% confidence interval (CI) (0.714-0.772)] and 0.797 (0.762-0.832), respectively. The C-indices of the OS and CSS nomograms in the internal validation cohort were 0.735 (0.686-0.784) and 0.755 (0.688-0.822), respectively, and those in the external validation cohort were 0.801 (0.746-0.856) and 0.863 (0.812-0.914), respectively. Receiver operating characteristic (ROC) curves, calibration curves, and survival curves all demonstrated good predictive performance of the nomograms. CONCLUSION: The nomograms for PC were developed using the SEER database. The accuracy and clinical usefulness of the model were validated through a combination of internal and external validations.

Association between multiple sclerosis and cancer risk: An extensive review/meta and Mendelian randomization analyses.

BACKGROUND: Observational investigations examining cancer risk among multiple sclerosis (MS) patients have produced contradictory findings. Herein, we performed an extensive review and meta-analysis to evaluate the correlation and causation between MS and cancer incidence. METHODS: We systematically screened for published articles examining cancer incidences among MS patients within the Cochrane Library, PubMed, and Embase databases. Next, we employed STATA v.16.0 for data analysis. Following meta-analysis, we performed a two-sample Mendelian randomization (MR) analysis to uncover the underlying mechanism behind the MS-mediated regulation of certain cancers. RESULTS: Overall, we selected 18 articles encompassing 14 individual cancers incidences and a total of 368,952 patients for meta-analysis. Based on our analysis, there was reduced pancreatic (ES = 0.68; 95% CI: 0.49-0.93; I 2 = 0%) and ovarian cancer (ES = 0.65; 95% CI: 0.53-0.80; I 2 = 86.7%) co-occurrences among MS patients. Meanwhile, the incidences of breast (ES = 1.10; 95% CI: 1.01-1.21; I 2 = 60.9%) and brain cancers (ES = 1.94; 95% CI: 1.12-3.37; I 2 = 56.1%) were elevated among the same population. However, MR analysis revealed the opposite relation between MS and breast cancer risk (OR = 0.94392; 95% CI: 0.91011-0.97900, P = 0.002). Moreover, it revealed strong incidence of lung cancer (OR = 1.0004; 95% CI: 1.0001-1.0083, P = 0.001) among MS patients, as evidenced by the inverse variance weighting estimator. Lastly, MR found that other forms of cancers were not significantly related to MS. CONCLUSIONS: Using meta-analysis, we demonstrated that MS patients exhibited enhanced pancreatic and ovarian cancer risk, and diminished breast and brain cancer risk. However, using MR analysis, we discovered an inverse relation between MS and breast cancer risk, and additionally saw an uptick in lung cancer co-occurrence among MS patients.

Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy.

AIMS: Emerging evidence has related inflammation-based biomarkers to numerous carcinomas, including bladder carcinoma (BC). However, the role of inflammatory biomarkers in the prognosis of BC remains inconclusive. This study aimed to compare preoperative plasma fibrinogen (PF) and other inflammatory biomarkers such as the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), C-reactive protein (CRP) level, and serum albumin level to predict the prognosis of patients with BC. METHODS: This article focused on a retrospective analysis of 175 patients with newly diagnosed BC who were admitted to our hospital from March 2005 to March 2016. Of these BC patients, 136 had undergone radical cystectomy (RC). RESULTS: According to multivariate analysis, high PF level was an independent predictor of overall survival (OS) in 136 BC patients receiving RC (HR = 3.759; P = 0.011), but not for all 175 BC patients. Combining the NLR and PF values showed higher predictive accuracy for OS than NLR or PF alone (P < 0.05). Additionally, for 136 BC patients who had undergone RC, a close relationship was found between high PF levels (≥3.39 g/L) and lymph node metastasis (P = 0.011) and clinical T stage (P = 0.015). Furthermore, PF was a superior prognostic factor compared with the LMR, PLR, CRP, and albumin values in 136 BC patients who had undergone RC (P < 0.001). CONCLUSIONS: The preoperative PF level may be a prognostic biomarker; and when combined with the NLR, it can improve the predictive ability of the survival of BC patients, particularly of BC patients who underwent RC.

Dibutyltin Dichloride Retards Leydig Cell Developmental Regeneration in Adult Rat Testis.

Dibutyltin dichloride (DBTCl), widely used as plastic stabilizer, can cause comprehensive toxicity. The present study aims to investigate the effects of DBTCl on rat Leydig cell developmental regeneration and characterize the related mechanism. Adult male Sprague Dawley rats were randomly divided into four groups and gavaged with saline (control) or 5, 10, or 20 mg/kg/day of DBTCl consecutively for 10 days. At the end of the DBTCl treatment, all rats received a single intraperitoneal injection (i.p.,) of 75 mg/kg ethane dimethane sulfonate (EDS) to eliminate all the adult Leydig cells and to induce Leydig cell developmental regeneration. Leydig cell developmental regeneration was evaluated by measuring the levels of serum testosterone, luteinizing hormone, and follicle-stimulating hormone on days 7, 35, and 56 post-EDS. Leydig cell gene and protein expression levels, as well as cell morphology and cell counts were also carried out on day 56 post-EDS. The present study found that DBTCl significantly reduced serum testosterone levels on days 35 and 56 post-EDS, but increased serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels on day 56 at ≥ 5 mg/kg/day. The mRNA and protein levels of Leydig (Lhcgr, Scarb1, Star, Cyp11a1, Hsd17b3, and Hsd11b1) and Sertoli cells (Fshr, Amh, and Sox9) were significantly downregulated in the DBTCl-treated testes compared to the control. Immunohistochemical staining showed that DBTCl-treatment caused fewer regenerated Leydig cells and impaired Sertoli cell development and function in the testis on day 56 post-EDS. In conclusion, the present study demonstrates that DBTCl retards rat Leydig cell developmental regeneration by downregulating steroidogenesis-related enzymes at the gene and protein levels, inhibiting Leydig cell proliferation and impairing Sertoli cell function and development.

Screening and identification of specific markers for bladder transitional cell carcinoma from urine urothelial cells with suppressive subtractive hybridization and cDNA microarray.

OBJECTIVE: The objective of this study was to screen and identify differentially expressed genes in invasive bladder transitional cell carcinoma (BTCC). METHODS: Voided urine samples were collected from consecutive patients with BTCC and patients under surveillance for bladder cancer recurrence; voided urine samples from patients with non-malignant diseases served as control. We identified the differentially expressed genes by comparing urine samples of bladder carcinoma to that of the control group with suppressive subtractive hybridization (SSH) and cDNA microarray. The differentially expressed genes were verified by quantitative real-time polymerase chain reaction (QPCR). RESULTS: From the 762 white colonies, a total of 449 positive clones were obtained in which 112 were found to be upregulated in BTCC. Sequencing and homology analysis were performed for these 112 clonies. The detection rates of some known genes (including IGF-1, human telomerase reverse transcriptase [hTERT], bladder cancer specific nuclear matrix protein 4 [BLCA-4] and homeobox A13 [HOXA13]) for BTCC at the Ta, T1 and >T1 stages were 48%, 90% and 100%, respectively, with a specificity of 85%. The test specificity was 80% for the 30 control patients with urinary tract infections. The combination of BLCA-4 and HOXA13 could distinguish between low- and high-grade tumours, with specificity and sensitivity of 80%. CONCLUSION: We successfully constructed a reliable SSH library of BTCC and found that combination detection insulin-like growth factor 1 (IGF-1), hTERT, BLCA-4 and HOXA13 genes could help to evaluate BTCC at different stages.