A nomogram to predict cryptococcal meningitis in patients with pulmonary cryptococcosis.

Background: The most serious manifestation of pulmonary cryptococcosis is complicated with cryptococcal meningitis, while its clinical manifestations lack specificity with delayed diagnosis and high mortality. The early prediction of this complication can assist doctors to carry out clinical interventions in time, thus improving the cure rate. This study aimed to construct a nomogram to predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis through a scoring system. Methods: The clinical data of 525 patients with pulmonary cryptococcosis were retrospectively analyzed, including 317 cases (60.38 %) with cryptococcal meningitis and 208 cases (39.62 %) without cryptococcal meningitis. The risk factors of cryptococcal meningitis were screened by univariate analysis, LASSO regression analysis and multivariate logistic regression analysis. Then the risk factors were incorporated into the nomogram scoring system to establish a prediction model. The model was validated by receiver operating characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve. Results: Fourteen risk factors for cryptococcal meningitis in patients with pulmonary cryptococcosis were screened out by statistical method, including 6 clinical manifestations (fever, headache, nausea, psychiatric symptoms, tuberculosis, hematologic malignancy) and 8 clinical indicators (neutrophils, lymphocytes, glutamic oxaloacetic transaminase, T cells, helper T cells, killer T cells, NK cells and B cells). The AUC value was 0.978 (CI 96.2 %∼98.9 %), indicating the nomogram was well verified. Conclusion: The nomogram scoring system constructed in this study can accurately predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis, which may provide a reference for clinical diagnosis and treatment of patients with cryptococcal meningitis.

Testing region selection and prognostic analysis of MLH1 promoter methylation in colorectal cancer in China.

Background: MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC). The study aims to identify specific methylation regions in the MLH1 promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with MLH1 methylation. Methods: A total of 580 CRC cases were included. The DNA mismatch repair (MMR) protein expression was assessed by using immunohistochemistry (IHC). The methylation status of the Regions A, B, C, D, and E in the MLH1 promoter was tested by using bisulfite sequencing PCR. The specificities of the five regions were calculated. Associations between MLH1 methylation and clinicopathologic characteristics were evaluated. Kaplan-Meier analyses for overall survival (OS) were carried out. Results: In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%. In the MLH1-deficient CRCs, the frequencies of MLH1 methylation and BRAFV600E mutation were 52.6% and 14.6%, respectively; BRAFV600E mutation occurred in 27.7% of patients with MLH1-methylated CRC. In the MMR-deficient patients, compared with MLH1 unmethylation, MLH1 methylation was more common in patients who were aged ≥50 years, female, had no family history of LS-related tumors, and had tumors located at the right colon. In the MMR-deficient patients, the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (P = 0.047). Conclusions: Regions D and E in the MLH1 promoter are recommended for determining the MLH1 methylation status in screening for LS in MLH1-deficient CRC. In MMR-deficient patients, the MLH1-methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.

Research progress on the role of p53 in pulmonary arterial hypertension.

PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by increased pulmonary vascular resistance and pulmonary arterial pressure. At present, the definitive pathology of PAH has not been elucidated and its effective treatment remains lacking. Despite PAHs having multiple pathogeneses, the cancer-like characteristics of cells have been considered the main reason for PAH progression. RECENT FINDINGS: p53 protein, an important tumor suppressor, regulates a multitude of gene expressions to maintain normal cellular functions and suppress the progression of malignant tumors. Recently, p53 has been found to exert multiple biological effects on cardiovascular diseases. Since PAH shares similar metabolic features with cancer cells, the regulatory roles of p53 in PAH are mainly the induction of cell cycle, inhibition of cell proliferation, and promotion of apoptosis. SUMMARY: This paper summarized the advanced findings on the molecular mechanisms and regulatory functions of p53 in PAH, aiming to reveal the potential therapeutic targets for PAH.

M2 macrophage-derived paracrine factor TNFSF13 affects the fibrogenic alterations in endothelial cells and cardiac fibroblasts by mediating the NF-κB and Akt pathway.

Heart failure remains a global threaten to public health, cardiac fibrosis being a crucial event during the development and progression of heart failure. Reportedly, M2 macrophages might affect endothelial cell (ECs) and fibroblast proliferation and functions through paracrine signaling, participating in myocardial fibrosis. In this study, differentially expressed paracrine factors between M0/1 and M2 macrophages were analyzed and the expression of TNFSF13 was most significant in M2 macrophages. Culture medium (CM) of M2 (M2 CM) coculture to ECs and cardiac fibroblasts (CFbs) significantly promoted the cell proliferation of ECs and CFbs, respectively, and elevated α-smooth muscle actin (α-SMA), collagen I, and vimentin levels within both cell lines; moreover, M2 CM-induced changes in ECs and CFbs were partially abolished by TNFSF13 knockdown in M2 macrophages. Lastly, the NF-κB and Akt signaling pathways were proved to participate in TNFSF13-mediated M2 CM effects on ECs and CFbs. In conclusion, TNFSF13, a paracrine factor upregulated in M2 macrophages, could mediate the promotive effects of M2 CM on EC and CFb proliferation and fibrogenic alterations.

Prognosis and immunotherapy efficacy in dMMR&MSS colorectal cancer patients and an MSI status predicting model.

The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI-PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI-PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI-PCR in 1622 CRC patients (ZS6Y-1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI-predicting nomogram. We propose a new nomogram-based assay to find patients with dMMR&MSS, in which the MSI-PCR assay only detects dMMR patients with MSS predictive results. We applied the new strategy to a random cohort of 248 CRC patients (ZS6Y-2 cohort). The consistency of MMR IHC and MSI-PCR in the ZS6Y-1 cohort was 95.7% (1553/1622). Both pMMR&MSS and dMMR&MSS groups experienced significantly shorter overall survival (OS) than those in dMMR by IHC and MSI-H by MSI-PCR (dMMR&MSI-H) group (hazard ratio [HR] = 2.429, 95% confidence interval [CI]: 1.89-3.116, p < .01; HR = 21.96, 95% CI: 7.24-66.61, p < .01). The dMMR&MSS group experienced shorter OS than the pMMR&MSS group, but the difference did not reach significance (log rank test, p = .0686). In the immunotherapy group, the progression-free survival of dMMR&MSS patients was significantly shorter than that of dMMR&MSI-H patients (HR = 13.83, 95% CI: 1.508-126.8, p < .05). The ZS6Y-MSI-Pre nomogram (C-index = 0.816, 95% CI: 0.792-0.841, already online) found 66% (2/3) dMMR&MSS patients in the ZS6Y-2 cohort. There are significant differences in OS and immunotherapy effect between dMMR&MSI-H and dMMR&MSS patients. Our prediction model provides an economical way to screen dMMR&MSS patients.

LncRNA HCG11 enhances the chemosensitivity of non-small cell lung cancer cells to Gemcitabine via miR-17-5p/p21 axis.

BACKGROUND: This study investigated the inhibitory effects of lncRNA HLA Complex Group 11 (HCG11) on non-small cell lung cancer (NSCLC) and the molecular mechanisms. RESEARCH DESIGN AND METHODS: Bioinformatics analysis was conducted to determine the downstream targeted gene miR-17-5p/p21 and predict their binding sites. qRT-PCR and Western blot were used to detect expression levels, and dual luciferase and RIP assays were adopted to verify binding relationship. RESULTS: The lncRNA HCG11/miR-17-5p/p21 axis was found to regulate drug resistance, proliferation, apoptosis, and cell cycle of A549 and A549-Gemcitabine (GEM) cells. HCG11 acted as a ceRNA binding to miR-17-5p, which repressed p21 expression in turn. In vivo experiments demonstrated that HCG11 hindered tumor growth. Therefore, lncRNA HCG11, by targeting the miR-17-5p/p21 axis, suppressed GEM resistance and malignant progression of NSCLC cells. CONCLUSIONS: This study provides a reference for investigating the potential value of lncRNA HCG11 in the diagnosis of NSCLC and finding potential targets against clinical chemotherapeutic resistance in NSCLC.

Head-to-head comparative study: evaluating three panels for MSI-PCR testing in patients with colorectal and gastric cancer.

AIMS: Due to the lack of large clinical cohorts in the Chinese populations with colorectal cancer (CRC) and gastric cancer (GC), there is no consensus among the preferred panel for microsatellite instability (MSI)-PCR testing. This study aims to evaluate a more appropriate panel. METHODS: We tested the MSI status of 2572 patients with CRC and GC using the NCI panel and 2 mononucleotide panels (5 and 6 mononucleotide panels). Immunohistochemistry (IHC) was employed to perform mismatch repair protein testing in 1976 samples. RESULTS: We collected 2572 patients with CRC and GC. The National Cancer Institute (NCI) panel failed to detect 13 cases. Of the 2559 cases that received results from all three panels, 2544 showed consistent results. In the remaining 15 cases, 9 showed discrepancies between MSI-H and MSI-L, and 6 showed discrepancies between MSI-L and microsatellite stability (MSS). The misdiagnosis rate of MSI-L was significantly lower in two mononucleotide panels than in the NCI panel (12.5% vs 87.5%, p=0.010) in CRC. In patients with GC, only the NCI panel detected three MSI-L cases, while the results of the two mononucleotide panels were one MSI-H and two MSS. Based on their IHC results, the MSI-L misdiagnosis rate of the NCI panel was 33.3%. Furthermore, compared with two mononucleotide panels, the NCI panel had a much lower rate of all loci instability in CRC (90.8% and 90.3% vs 25.2%) and GC (89.5% and 89.5% vs 12.0%). CONCLUSION: In Chinese patients with CRC and GC, the five and six mononucleotide panels have advantages for detecting MSI over the NCI panel.

LACC1: A critical involvement in macrophage immunometabolism.

Laccase domain-containing 1 (LACC1) protein is an enzyme highly expressed in inflammatory macrophages, and studies have shown that it has a key role in diseases such as inflammatory bowel disease, arthritis, and microbial infections. Therefore, in this review, we focus on LACC1-mediated catalysis. In detail, LACC1 converts l-CITrulline (l-CIT) to l-ORNithine (l-ORN) and isocyanic acid in mice and humans and acts as a bridge between proinflammatory nitric oxide synthase (NOS2) and polyamine immunometabolism, thus exerting anti-inflammatory and antibacterial effects. Considering the actions of LACC1, targeting LACC1 may be a potent therapeutic avenue for inflammation-related diseases and microbial infection diseases.

A review of the roles of constituent minerals and residual bitumen in the solid-liquid separation of oil sands tailings.

The efficient dewatering of fluid fine tailings (FFT) generated from warm-water extraction of Canadian oil sands is a major challenge that has limited the timely reclamation of the tailings. It is generally recognized that both chemical amendments and physical/mechanical solid-liquid separation treatments are required to speed up FFT dewatering. Significant efforts have been made to enhance the rate of solid-liquid separation of FFT in the past several decades. The fact that these efforts have met with limited successes calls for a better fundamental understanding of the solid-liquid separation process. In this work, we reviewed and critically analyzed the factors that contribute to the difficult dewatering of FFT, including the role of constituent minerals and residual bitumen. In particular, the effects of mineralogical composition, mineral particle size, and the role of residual bitumen on settling rate, hydraulic conductivity, and filtration rate are reviewed and discussed. This review also points out directions to accelerate the dewatering of FFT, such as reducing the effective volume fraction of swelling clays and releasing bitumen coating from clay surfaces, that may significantly increase the filtration rate of oil sands tailings.

Trityl Quinodimethane Derivatives as Unimolecular Triple-Function Extracellular EPR Probes for Redox, pH, and Oxygen.

Electron paramagnetic resonance (EPR) spectroscopy and imaging coupled with the use of suitable probes is a promising tool for assessment of the tumor microenvironment (TME). Measurement of multiple TME parameters by EPR is very desirable but challenging. Herein, we designed and synthesized a class of negative-charged trityl quinodimethane MTPs as unimolecular triple-function extracellular probes for redox, pH, and oxygen (O2) levels. Using the deuterated analogue, dMTP5, which has an optimal pKa as well as high sensitivity to bioreduction and O2, we reasonably evaluated pH effects on efflux of reducing agents from HepG2 cells and cellular O2 consumption.

Overexpression the BnLACS9 could increase the chlorophyll and oil content in Brassica napus.

BACKGROUND: Chlorophyll is a very important pigment involved in photosynthesis, while plant acyl-CoA biosynthesis is derived from plastid-localized fatty acids (FAs). Until now, the regulation of the acyl-CoA pathway for chlorophyll biosynthesis is still unknown. RESULTS: Here, we identified a long-chain acyl-CoA synthetase (LACS) gene BnLACS9 from Brassica napus. BnLACS9 complemented a LACS-deficient yeast strain YB525, which indicated that BnLACS9 has the LACS function. BnLACS9 was localized in the chloroplast envelope membrane, while mainly expressed in young leaves and flowers. Overexpression of BnLACS9 in Nicotiana benthamiana resulted in an increase in total CoA and MGDG content. In B. napus with overexpression of BnLACS9, the number of chloroplast grana lamellae and the chlorophyll content, as well as the MGDG and DGDG contents, increased compared to wild type. The net photosynthetic rate, dry weight of the entire plant and oil content of seeds increased significantly, accompanied by an increase in chlorophyll content. Transcriptome analysis revealed that overexpression of BnLACS9 improved the pathway of acyl-CoA biosynthesis and further improved the enzymes in the glycolipid synthesis pathway, while acyl-CoA was the substrate for glycolipid synthesis. The increased glycolipids, especially MGDG and DGDG, accelerated the formation of the chloroplast grana lamellae, which increased the number of chloroplast thylakoid grana lamella and further lead to increased chlorophyll content. CONCLUSIONS: In the present study, we demonstrated that BnLACS9 played a crucial role in glycolipids and chlorophyll biosynthesis in B. napus. The results also provide a new direction and theoretical basis for the improvement of the agronomic traits of plants.

Inhibitory effects and molecular mechanisms of ginsenoside Rg1 on the senescence of hematopoietic stem cells.

Hematopoietic stem cells (HSCs) produce all blood cell lineages and maintain life-long hematopoiesis. However, the self-renewal ability and differentiation capacity of HSCs reduces with age. The senescence of HSCs can lead to the imbalance of hematopoietic homeostasis and immune disorder and induce a variety of age-related diseases. Recent studies have shown that therapeutic interventions targeting the senescence of HSCs may prevent disease progression. Ginsenoside Rg1 (Rg1), extracted from roots or stems of ginseng, has beneficial antiaging activities. It has been reported that Rg1 can inhibit the senescence of HSCs. Here, we reviewed recent advances of Rg1 in inhibiting the senescence of HSCs and discussed related molecular mechanisms. Bioinformatics and network databases have been widely applied to drug discoveries. Here, we predicted potential antiaging targets of Rg1 explored by bioinformatic methods, which may help discover new targets of Rg1 and provide novel strategies for delaying the aging process of HSCs.

TRIM66 Promotes Malignant Progression of Non-Small-Cell Lung Cancer Cells via Targeting MMP9.

Lung cancer has a higher incidence and mortality rate than other cancers, and over 80% of lung cancer cases were classified as non-small-cell lung cancer (NSCLC). TRIM66 is one of the crucial members of TRIM, which has a deep connection with the behavior of various malignant tumors. But it remains uncertain regarding its exact function and underlying mechanism in NSCLC. In our study, qRT-PCR and Western blot were employed to validate that TRIM66 was overexpressed in NSCLC. The migration, invasion, and epithelial-mesenchymal transformation (EMT) progression of NSCLC cells were determined by Western blotting and Transwell experiments after knocking down TRIM66, and it was found that knockdown TRIM66 inhibited the migration, invasion, and EMT processes of NSCLC cells. Next, the binding relationship between TRIM66 and MMP9 was verified by Co-IP assay. After determining the interaction between them, rescue assays showed that overexpression of MMP9 was capable to promote the migration, invasion, and EMT of NSCLC cells. However, the transfection of si-TRIM66 could reverse this facilitating effectiveness. To sum up, we concluded that by targeting MMP9, TRIM66 could exert a cancer-promoting role in the progression of NSCLC cells.

Influence Factors and Predictive Models for the Outcome of Patients with Ischemic Stroke after Intravenous Thrombolysis: A Multicenter Retrospective Cohort Study.

Objective: Intravenous thrombolysis (IVT) is currently the main effective treatment for patients with ischemic stroke. This study aimed to analyze the factors affecting the early neurological recovery and prognosis of thrombolytic therapy after surgery and to construct predictive models. Materials and Methods: A total of 849 patients with ischemic stroke who received IVT treatment at six centers from June 2017 to March 2021 were included. Patients were divided into the training cohort and the validation cohort. Based on the independent factors that influence the early recovery of neurological function and the prognosis, the respective predictive nomograms were established. The predictive accuracy and discrimination ability of the nomograms were evaluated by ROC and calibration curve, while the decision curve and clinical impact curve were adopted to evaluate the clinical applicability of the nomograms. Results: The nomogram constructed based on the factors affecting the prognosis in 3 months had ideal accuracy as the AUC (95% CI) was 0.901 (0.874~0.927) in the training cohort and 0.877 (0.826~0.929) in the validation cohort. The accuracy of the nomogram is required to be improved, since the AUC (95% CI) of the training cohort and the validation cohort was 0.641 (0.597~0.685) and 0.627 (0.559~0.696), respectively. Conclusions: Based on this ideal and practical prediction model, we can early identify and actively intervene in patients with ischemic stroke after IVT to improve their prognosis. Nevertheless, the accuracy of predicting nomograms for the recovery of early neurological function after IVT still needs improvement.

White tea alleviates non-alcoholic fatty liver disease by regulating energy expenditure and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease, which lacks effective treatments. Abnormal lipid metabolism and inflammation are the most prominent pathological manifestations of NAFLD. Recently, it has been reported that white tea extract (WTE) can regulate lipid metabolism in human adipocytes and liver cancer cells in vitro. However, its beneficial effects on NAFLD and the underlying mechanisms remain largely unknown. Here, we showed that WTE alleviated obesity, lipid accumulation, hepatic steatosis, and liver injury in a mouse model of NAFLD. Mechanistically, we demonstrated that WTE exerted the anti-NAFLD effect by decreasing the expression of genes involved in lipid transport and synthesis processes while activating genes associated with energy expenditure. In addition, a comparison of the transcriptional responses of WTE with that of green tea extract (GTE) revealed that WTE can not only regulate lipid metabolism and stress response like GTE but also regulate antioxidant and inflammatory pathways more effectively. Taken together, our findings demonstrate that WTE inhibits the progression of NAFLD in a mouse model and indicate that WTE can be a potential dietary intervention for NAFLD.

Optimization of Early Antimicrobial Strategies for Lung Transplant Recipients Based on Metagenomic Next-Generation Sequencing.

The management of perioperative antibiotic options after lung transplantation varies widely around the world, but there is a common trend to limit antibiotic use duration. Metagenomic next-generation sequencing (mNGS) has become a hot spot in clinical pathogen detection due to its precise, rapid, and wide detection spectrum of pathogens. Thus, we defined a new antibiotic regimen adjustment strategy in the very early stage (within 7 days) after lung transplantation mainly depending on mNGS reports combined with clinical conditions to reduce the use of antibiotics. To verify the clinical effect of the strategy, we carried out this research. Thirty patients who underwent lung transplantation were finally included, whose information including etiology, antibiotic adjustment, and the effect of our strategy was recorded. Lung transplant recipients in this study were prescribed with initial antibiotic regimen immediately after surgery; their antibiotic regimens were adjusted according to the strategy. According to our study, the entire effectiveness of the strategy was 90.0% (27/30). Besides, a total of 86 samples containing donor lung tissue, recipient lung tissue, and bronchoalveolar lavage fluid (BALF) were obtained in this study; they were all sent to mNGS test, while BALF was also sent to pathogen culture. Their results showed that the positive rate of BALF samples was higher (86.67%) than that of donor's lung tissue (20.0%) or recipient's lung tissue (13.33%) by mNGS test, indicating BALF samples are more valuable than other clinical samples from early postoperative period to guide the early adjustment of antibiotics after lung transplantation. It is effective for mNGS combined with traditional methods and clinical situations to optimize antibiotic regimens in lung transplantation recipients within 7 days after surgery.

MALAT1 enhances gemcitabine resistance in non-small cell lung cancer cells by directly affecting miR-27a-5p/PBOV1 axis.

OBJECTIVE: MALAT1 has been implicated in tumor progression. But the mechanism and role underlying MALAT1 in non-small cell lung cancer (NSCLC) cell resistance to gemcitabine (GEM) remain rarely understood. METHODS: Through bioinformatics analysis, we predicted MALAT1/miR-27a-5p/PBOV1 regulatory axis and constructed GEM resistant A549/GEM cell line, and A549 was the parent cell line. qRT-PCR was utilized to assess MALAT1, miR-27a-5p and PBOV1 expression in A549 and A549/GEM cells. MTT method and colony formation assay were utilized to measure cell viability and cell proliferation. Flow cytometry was conducted to assess cell cycle and cell apoptosis. Wound healing and Transwell assays were conducted to measure cell migratory and invasive potentials. Dual-luciferase reporter gene assay and RNA immunoprecipitation were utilized to identify the targeted relationship between MALAT1 and miR-27a-5p, and the former assay was also utilized to determine the targeted relationship between miR-27a-5p and PBOV1. The impacts of MALAT1/miR-27a-5p/PBOV1 on tumor growth and GEM resistance of NSCLC cells in vivo were validated by using the tumor xenograft model. RESULTS: MALAT1 was observed to be highly expressed in tissues and cells of GEM resistant patients. Forced level of MALAT1 could markedly enhance A549 cell resistance to GEM, but this impact could be weakened by silencing MALAT1. MALAT1 downregulated miR-27a-5p level. PBOV1 was the target of miR-27a-5p and could significantly enhance GEM resistance of NSCLC cell. MALAT1 facilitated tumor growth in vivo via targeting miR-27a-5p/PBOV1 and enhanced resistance of NSCLC cells to GEM. CONCLUSION: MALAT1/miR-27a-5p/PBOV1 axis was implicated in NSCLC cell resistance to GEM. We deepened our understanding about how MALAT1 enhanced NSCLC cell resistance to GEM and provided development of therapeutic strategy for NSCLC with a possible target.

Functional Characterization of the Cystine-Rich-Receptor-like Kinases (CRKs) and Their Expression Response to Sclerotinia sclerotiorum and Abiotic Stresses in Brassica napus.

Cysteine-rich receptor-like kinases (CRKs) are transmembrane proteins that bind to the calcium ion to regulate stress-signaling and plant development-related pathways, as indicated by several pieces of evidence. However, the CRK gene family hasn't been inadequately examined in Brassica napus. In our study, 27 members of the CRK gene family were identified in Brassica napus, which are categorized into three phylogenetic groups and display synteny relationship to the Arabidopsis thaliana orthologs. All the CRK genes contain highly conserved N-terminal PKINASE domain; however, the distribution of motifs and gene structure were variable conserved. The functional divergence analysis between BnaCRK groups indicates a shift in evolutionary rate after duplication events, demonstrating that BnaCRKs might direct a specific function. RNA-Seq datasets and quantitative real-time PCR (qRT-PCR) exhibit the complex expression profile of the BnaCRKs in plant tissues under multiple stresses. Nevertheless, BnaA06CRK6-1 and BnaA08CRK8 from group B were perceived to play a predominant role in the Brassica napus stress signaling pathway in response to drought, salinity, and Sclerotinia sclerotiorum infection. Insights gained from this study improve our knowledge about the Brassica napus CRK gene family and provide a basis for enhancing the quality of rapeseed.

The Function of BDNF and Its Receptor in the Male Genitourinary System and Its Potential Clinical Application.

Background: Brain-derived neurotrophic factor (BDNF), as a member of the nerve growth factor family, has been mentioned more and more frequently in recent literature reports. Among them, content about the male genitourinary system is also increasing. Objective and Rationale: BDNF plays an important role in the male genitourinary system. At the same time, the literature in this field is constantly increasing. Therefore, we systematically summarized the literature in order to more intuitively show the function of BDNF and its receptor in the male genitourinary system and its potential clinical application. Search Methods: An electronic search of, e.g., PubMed, scholar.google and Scopus, for articles relating to BDNF and its receptor in the male genitourinary system. Outcomes: In the male genitourinary system, BDNF and its receptors TrkB and p75 participate in a series of normal physiological activities, such as the maturation and morphogenesis of testes and epididymis and maintenance of isolated sperm motility. Similarly, an imbalance of the circulating concentration of BDNF also mediates the pathophysiological process of many diseases, such as prostate cancer, benign prostatic hyperplasia, male infertility, diabetes erectile dysfunction, penile sclerosis, and bladder fibrosis. As a consequence, we conclude that BDNF and its receptor are key regulatory proteins in the male genitourinary system, which can be used as potential therapeutic targets and markers for disease diagnosis.

The Spectrum, Tendency and Predictive Value of PIK3CA Mutation in Chinese Colorectal Cancer Patients.

BACKGROUND: PIK3CA is a high-frequency mutation gene in colorectal cancer, while its prognostic value remains unclear. This study evaluated the mutation tendency, spectrum, prognosis power and predictive power in cetuximab treatment of PIK3CA in Chinese CRC cohort. METHODS: The PIK3CA exon 9 and 20 status of 5763 CRC patients was detected with Sanger sequencing and a high-resolution melting test. Clinicopathological characteristics of 5733 patients were analyzed. Kaplan-Meier method and nomogram were used to evaluate the overall survival curve and disease recurrence, respectively. RESULTS: Fifty-eight types of mutations in 13.4% (771/5733) of the patients were detected. From 2014 to 2018, the mutation rate of PIK3CA increased from 11.0% to 13.5%. At stage IV, exon 20 mutated patients suffered shorter overall survival time than wild-type patients (multivariate COX regression analysis, HR = 2.72, 95% CIs = 1.47-5.09; p-value = 0.012). At stage III, PIK3CA mutated patients were more likely to relapse (multivariate Logistic regression analysis, exon 9: OR = 2.54, 95% CI = 1.34-4.73, p = 0.003; exon 20: OR = 3.89, 95% CI = 1.66-9.10, p = 0.002). The concordance index of the nomogram for predicting the recurrence risk of stage III patients was 0.685. After cetuximab treatment, the median PFS of PIK3CA exon 9 wild-type patients (n = 9) and mutant patients (n = 5) did not reach a significant difference (3.6 months vs. 2.3 months, Log-rank test, p-value = 0.513). CONCLUSIONS: We found that PIK3CA mutation was an adverse predictive marker for the overall survival of stage IV patients and recurrence of stage III patients, respectively. Further more, we suggested that PIK3CA exon 9 mutations are not negative predictors of cetuximab treatment in KRAS, NRAS, and BRAF wild-type mCRC patients.