Establishment and validation of serum lipid-based nomogram for predicting the risk of prostate cancer.

BACKGROUND: This study aimed to explore the value of combined serum lipids with clinical symptoms to diagnose prostate cancer (PCa), and to develop and validate a Nomogram and prediction model to better select patients at risk of PCa for prostate biopsy. METHODS: Retrospective analysis of 548 patients who underwent prostate biopsies as a result of high serum prostate-specific antigen (PSA) levels or irregular digital rectal examinations (DRE) was conducted. The enrolled patients were randomly assigned to the training groups (n = 384, 70%) and validation groups (n = 164, 30%). To identify independent variables for PCa, serum lipids (TC, TG, HDL, LDL, apoA-1, and apoB) were taken into account in the multivariable logistic regression analyses of the training group, and established predictive models. After that, we evaluated prediction models with clinical markers using decision curves and the area under the curve (AUC). Based on training group data, a Nomogram was developed to predict PCa. RESULTS: 210 (54.70%) of the patients in the training group were diagnosed with PCa. Multivariate regression analysis showed that total PSA, f/tPSA, PSA density (PSAD), TG, LDL, DRE, and TRUS were independent risk predictors of PCa. A prediction model utilizing a Nomogram was constructed with a cut-off value of 0.502. The training and validation groups achieved area under the curve (AUC) values of 0.846 and 0.814 respectively. According to the decision curve analysis (DCA), the prediction model yielded optimal overall net benefits in both the training and validation groups, which is better than the optimal net benefit of PSA alone. After comparing our developed prediction model with two domestic models and PCPT-RC, we found that our prediction model exhibited significantly superior predictive performance. Furthermore, in comparison with clinical indicators, our Nomogram's ability to predict prostate cancer showed good estimation, suggesting its potential as a reliable tool for prognostication. CONCLUSIONS: The prediction model and Nomogram, which utilize both blood lipid levels and clinical signs, demonstrated improved accuracy in predicting the risk of prostate cancer, and consequently can guide the selection of appropriate diagnostic strategies for each patient in a more personalized manner.

Continuous purification and culture of rat type 1 and type 2 alveolar epithelial cells by magnetic cell sorting.

PURPOSE: The incidence of acute lung injury (ALI) in severe trauma patients is 48% and the mortality rate following acute respiratory distress syndrome evolved from ALI is up to 68.5%. Alveolar epithelial type 1 cells (AEC1s) and type 2 cells (AEC2s) are the key cells in the repair of injured lungs as well as fetal lung development. Therefore, the purification and culture of AEC1s and AEC2s play an important role in the research of repair and regeneration of lung tissue. METHODS: Sprague-Dawley rats (3-4 weeks, 120-150 g) were purchased for experiment. Dispase and DNase I were jointly used to digest lung tissue to obtain a single-cell suspension of whole lung cells, and then magnetic bead cell sorting was performed to isolate T1α positive cells as AEC1s from the single-cell suspension by using polyclonal rabbit anti-T1a (a specific AEC1s membrane protein) antibodies combined with anti-rabbit IgG microbeads. Afterwards, alveolar epithelial cell membrane marker protein EpCAM was designed as a key label to sort AEC2s from the remaining T1α-neg cells by another positive immunomagnetic selection using monoclonal mouse anti-EpCAM antibodies and anti-mouse IgG microbeads. Cell purity was identified by immunofluorescence staining and flow cytometry. RESULTS: The purity of AEC1s and AEC2s was 88.3% ± 3.8% and 92.6% ± 2.7%, respectively. The cell growth was observed as follows: AEC1s stretched within the 12-16 h, but the cells proliferated slowly; while AEC2s began to stretch after 24 h and proliferated rapidly from the 2nd day and began to differentiate after 3 days. CONCLUSION: AEC1s and AEC2s sorted by this method have high purity and good viability. Therefore, our method provides a new approach for the isolation and culture of AEC1s and AEC2s as well as a new strategy for the research of lung repair and regeneration.

Citronellal ameliorates doxorubicin-induced hepatotoxicity via antioxidative stress, antiapoptosis, and proangiogenesis in rats.

Doxorubicin (DOX) is a very effective broad-spectrum anticancer drug, yet its clinical application is badly restricted due to its serious side effects. Citronellal (CT), a specialized metabolite of plants found in Cymbopogon spp., is proved to exhibit many beneficial properties. In the current study, we intended to investigate the effect of CT on DOX-induced hepatotoxicity in rats. Rats were treated with CT (200 mg/kg b.w./day orally), and given DOX (2.5 mg/kg b.w./week, intraperitoneally) to induce hepatotoxicity for six consecutive weeks. The results showed that CT administration could attenuate the DOX-induced pathological changes of liver tissues and ameliorated the inappropriate alteration of liver function biomarkers (serum glutamic aspartate aminotransferase, glutamic pyruvic transaminase, and albumin) in serum and oxidative stress parameters (malondialdehyde, superoxide dismutase, and reduced glutathione) in the liver. Moreover, CT mitigated the Bax/Bcl-2 ratio and caspase-3 expression to inhibit cell apoptosis. Further study indicated that CT therapy could enhance the protein levels of p-PI3K, p-Akt, and CD31 in the liver. These results demonstrate that CT can ameliorate DOX-induced hepatotoxicity in rats mediated by antioxidative stress, antiapoptosis, and proangiogenesis.

Value of lung ultrasound score for evaluation of blast lung injury in goats.

PURPOSE: To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury. METHODS: Twenty female healthy goats were randomly divided into three groups by different driving pressures: 4.0 MPa group (n = 4), 4.5 MPa group (n = 12) and 5.0 MPa group (n = 4). The severe blast lung injury model of goats was established using a BST-I bio-shock tube. Vital signs (respiration, heart rate and blood pressure), lung ultrasound score (LUS), PO2/FiO2 and extravascular lung water (EVLW) were measured before injury (0 h) and at 0.5 h, 3 h, 6 h, 9 h, 12 h after injury. Computed tomography scan was performed before injury (0 h) and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume. The correlation of LUS with PaO2/FiO2, EVLW, and lung injury ratio (lesion volume/total lung volume*100%) was analyzed. All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination. Statistical analysis was performed by the SPSS 22.0 software. The measurement data were expressed as mean ± standard deviation. The means of two samples were compared using independent-sample t-test. Pearson correlation analysis was conducted. RESULTS: (1) At 12 h after injury, the mortality of goats was 0, 41.67% and 100% in the 4.0 Mpa, 4.5 MPa and 5.0 MPa groups, respectively; the area of pulmonary hemorrhage was 20.00% ± 13.14% in the 4.0 Mpa group and 42.14% ± 15.33% in the 4.5 MPa group. A severe lung shock injury model was established under the driving pressure of 4.5 MPa. (2) The respiratory rate, heart rate, LUS and EVLW were significantly increased, while PaO2/FiO2 was significantly reduced immediately after injury, and then they gradually recovered and became stabilized at 3 h after injury. (3) LUS was positively correlated with EVLW (3 h: r = 0.597, 6 h: r = 0.698, 9 h: r = 0.729; p < 0.05) and lung injury ratio (12 h: r = 0.884, p < 0.05), negatively correlated with PaO2/FiO2 (3 h: r = -0.871, 6 h: r = -0.637, 9 h: r = -0.658; p < 0.05). CONCLUSION: We established a severe blast lung injury model of goats using the BST-I bio-shock tube under the driving pressure of 4.5 MPa and confirmed that ultrasound can be used for quick evaluation and dynamic monitoring of blast lung injury.

Decursin induces apoptosis in glioblastoma cells, but not in glial cells via a mitochondria-related caspase pathway.

Decursin is a major biological active component of Angelica gigas Nakai and is known to induce apoptosis of metastatic prostatic cancer cells. Recently, other reports have been commissioned to examine the anticancer activities of this plant. In this study, we evaluated the inhibitory activity and related mechanism of action of decursin against glioblastoma cell line. Decursin demonstrated cytotoxic effects on U87 and C6 glioma cells in a dose-dependent manner but not in primary glial cells. Additionally, decursin increased apoptotic bodies and phosphorylated JNK and p38 in U87 cells. Decursin also down-regulated Bcl-2 as well as cell cycle dependent proteins, CDK-4 and cyclin D1. Furthermore, decursin-induced apoptosis was dependent on the caspase activation in U87 cells. Taken together, our data provide the evidence that decursin induces apoptosis in glioblastoma cells, making it a potential candidate as a chemotherapeutic drug against brain tumor.

Endothelial-mesenchymal transition as a novel mechanism for generating myofibroblasts during wound healing and scarring.

BACKGROUND: The endothelial-mesenchymal transition (EndMT) is an important mechanism in tissue regeneration and the development of organ fibrosis. Whether EndMT occurs in wound healing and scarring remains unknown. MATERIALS AND METHODS: The isolated cells from the normal dermal tissue and the wound tissue of mouse with full-thickness skin wound, and human scar tissue sections were performed with CD31/factorVII and α-SMA immunohistochemical staining and H and E staining. The ratio of factor VII or CD31/α-SMA double-positive cells in factor VII-positive cells was assessed in the isolated cells and in scar tissues. RESULTS: In this study, we found that approximately 27-60% of ECs coexpressed VII factor and α-SMA in the isolated cells from the wound tissues of mice, which was significantly higher than that of normal dermal tissue cells. Accordingly, the number of CD31/α-SMA double-positive cells in mouse wound tissue sections was also significantly more than that in normal dermal tissue sections. In scar tissues, in addition to high-density microvessels, a large number of proliferative ECs in scar strama and CD31/α-SMA double-positive cells were also found. Approximately 46.82 to 84.11% of ECs and 68.77 to 95.25% of myofibroblasts coexpressed VII factor and α-SMA, and these two values in hypertrophic scars were significantly higher than those in keloids. CONCLUSION: These results confirmed that ECs might contribute to the emergence of myofibroblasts in the wound and scar tissue via the process of EndMT.

Age-Related Sex Disparities in Esophageal Cancer Survival: A Population-Based Study in the United States.

Background: The association between sex and the survival of patients with esophageal cancer (EC) remains controversial. We sought to systematically investigate sex-based disparities in EC survival using the Surveillance, Epidemiology, and End Results (SEER) registry data from the United States. Methods: Patients with EC diagnosed from 2004 to 2015 registered in the SEER database were selected. The association between sex and cancer-specific survival (CSS) was evaluated using survival analysis. The Inverse Probability Weighting (IPW) approach was applied to reduce the observed bias between males and females. Subgroup analyses were used to investigate the robustness of the sex-based disparity and to explore potential interaction effects with other variables. Results: Overall, 29,312 eligible EC patients were analyzed, of whom 5,781 were females, and 23,531 were males. Females had higher crude CSS compared to males (10-year CSS: 24.5 vs. 21.3%; P < 0.001). Similar results were obtained after adjusting for selection bias using the IPW approach and multivariate regression. Subgroup analyses confirmed the relative robustness of sex as a prognostic factor. However, significant interactions were observed between sex and other variables, such as age, race, tumor grade, histology, and treatment modality. In particular, there was no survival advantage for premenopausal females compared to their male counterparts, but the association between sex and EC survival was prominent in 46-55-year-old patients. Conclusions: Female EC patients had better long-term survival than males. The association between sex and EC survival vary according to age, race, tumor grade, histology, and treatment modality. Sex-based disparity in EC-specific survival was age-related in the United States population.

[Pollution Characterization and Comprehensive Water Quality Assessment of Rain-source River: A Case Study of the Longgang River in Shenzhen].

Rain-source urban rivers are an important part of the urban ecosystem. Due to the small water environment capacity and the rapid development of the regional economy and society, they are vulnerable to serious pollution. The goal of this study was to identify the main pollution characteristics of river water quality and to carry out a scientific comprehensive water quality assessment. Water samples from 12 sampling locations of the Longgang River in Shenzhen, a typical rain-source urban river, were collected from January to December in 2018. According to the Environmental Quality Standard for Surface Water (GB 3838-2002), 22 water quality indicators were analyzed, and the water quality of Longgang River was comprehensively evaluated using the single-factor assessment method, comprehensive pollution index method, and principal component analysis method. The results of the single-factor assessment method showed that water quality of all sampling sites of the Longgang River met the Class V of the Environmental Quality Standard for Surface Water (GB 3838-2002), and the Tiaojiao Shui and Longxi River met the Class Ⅳ and Class Ⅲ of the Environmental Quality Standard for Surface Water (GB 3838-2002), respectively. The results of the comprehensive pollution index method showed that the water quality of 12 sampling sites was clean or relatively clean. Both the results of the comprehensive pollution index and principal component comprehensive score showed that the water quality of Longxi River, Nanyue River, and Tianjiao Shui were the best among all sampling sites. There is still room for improvement in the Wutongshan River, Dakang River, Ailian River, Dingshan River, and Huangsha River, and significant consideration should be given to parameters such as nutrients (TN, TP, and NH4+-N), organic matter (COD and BOD5), fecal coliform, and anionic surfactants. The three methods were a combination of qualitative and quantitative evaluation. The results of each method were not identical. Thus, it is very necessary to explore the comprehensive water quality assessment using various methods for making scientific and reasonable water pollution control strategies.

Identifying stage-associated hub genes in bladder cancer via weighted gene co-expression network and robust rank aggregation analyses.

BACKGROUND: Bladder cancer (BC) is among the most frequent cancers globally. Although substantial efforts have been put to understand its pathogenesis, its underlying molecular mechanisms have not been fully elucidated. METHODS: The robust rank aggregation approach was adopted to integrate 4 eligible bladder urothelial carcinoma microarray datasets from the Gene Expression Omnibus. Differentially expressed gene sets were identified between tumor samples and equivalent healthy samples. We constructed gene co-expression networks using weighted gene co-expression network to explore the alleged relationship between BC clinical characteristics and gene sets, as well as to identify hub genes. We also incorporated the weighted gene co-expression network and robust rank aggregation to screen differentially expressed genes. RESULTS: CDH11, COL6A3, EDNRA, and SERPINF1 were selected from the key module and validated. Based on the results, significant downregulation of the hub genes occurred during the early stages of BC. Moreover, receiver operating characteristics curves and Kaplan-Meier plots showed that the genes exhibited favorable diagnostic and prognostic value for BC. Based on gene set enrichment analysis for single hub gene, all the genes were closely linked to BC cell proliferation. CONCLUSIONS: These results offer unique insight into the pathogenesis of BC and recognize CDH11, COL6A3, EDNRA, and SERPINF1 as potential biomarkers with diagnostic and prognostic roles in BC.

Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options.

Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.