Self-Rectifying All-Optical Modulated Optoelectronic Multistates Memristor Crossbar Array for Neuromorphic Computing.

Researching optoelectronic memristors capable of integrating sensory and processing functions is essential for advancing the development of efficient neuromorphic vision. Here, we experimentally demonstrated an all-optical controlled and self-rectifying optoelectronic memristor (OEM) crossbar array with the function of multilevel storage under light stimuli. The NiO/TiO2 device exhibits an ultrahigh (>104) rectifying ratio (RR) thus overcoming the presence of sneak current. The reversible conductance modulation without electric signal involvement provides a novel way to realize ultrafast information processing. The proposed OEM array realized synaptic functions observed in the human brain, including long-term potentiation (LTP), long-term depression (LTD), paired-pulse facilitation (PPF), the transition from short-term memory (STM) to long-term memory (LTM), and learning experience behaviors successfully. The authors present a novel OEM crossbar that possesses complete light-modulation capabilities, potentially advancing the future development of efficient neuromorphic vision.

Novel Three-Dimensional Artificial Neural Network Based on an Eight-Layer Vertical Memristor with an Ultrahigh Rectify Ratio (>107) and an Ultrahigh Nonlinearity (>105) for Neuromorphic Computing.

In recent years, memristors have successfully demonstrated their significant potential in artificial neural networks (ANNs) and neuromorphic computing. Nonetheless, ANNs constructed by crossbar arrays suffer from cross-talk issues and low integration densities. Here, we propose an eight-layer three-dimensional (3D) vertical crossbar memristor with an ultrahigh rectify ratio (RR > 107) and an ultrahigh nonlinearity (>105) to overcome these limitations, which enables it to reach a >1 Tb array size without reading failure. Furthermore, the proposed 3D RRAM shows advanced endurance (>1010 cycles), retention (>104 s), and uniformity. In addition, several synaptic functions observed in the human brain were mimicked. On the basis of the advanced performance, we constructed a novel 3D ANN, whose learning efficiency and recognition accuracy were enhanced significantly compared with those of conventional single-layer ANNs. These findings hold promise for the development of highly efficient, precise, integrated, and stable VLSI neuromorphic computing systems.

The Doping Effect on the Intrinsic Ferroelectricity in Hafnium Oxide-Based Nano-Ferroelectric Devices.

Hafnium oxide (HfO2)-based ferroelectric tunnel junctions (FTJs) have been extensively evaluated for high-speed and low-power memory applications. Herein, we investigated the influence of Al content in HfAlO thin films on the ferroelectric characteristics of HfAlO-based FTJs. Among HfAlO devices with different Hf/Al ratios (20:1, 34:1, and 50:1), the HfAlO device with Hf/Al ratio of 34:1 exhibited the highest remanent polarization and excellent memory characteristics and, thereby, the best ferroelectricity among the investigated devices. Furthermore, first-principal analyses verified that HfAlO thin films with Hf/Al ratio of 34:1 promoted the formation of the orthorhombic phase against the paraelectric phase as well as alumina impurities and, thus, enhanced the ferroelectricity of the device, providing theoretical support for supporting experimental results. The findings of this study provide insights for developing HfAlO-based FTJs for next-generation in-memory computing applications.

Insights into Permanent Encodings of Macroscopic Spike Patterns by Magnetic-Field-Directed Evaporative Self-Assembly from Ferrofluids.

Field-directed assembly has the potential to make large hierarchically ordered structures from nanoscale objects. Shear forces and optical, electric, and magnetic fields have been used for this purpose. Ferrofluids consist of magnetic nanoparticles hosted in mobile liquids. Though they exhibit rich structures and lattice patterns in response to an applied magnetic field, the patterns collapse when the field is removed. Recently, we adapted evaporation-induced self-assembly to obtain permanent encodings of the complex field response of magnetite nanoparticles in alkane media. The encodings are characterized by order that culminates in macrostructures comprising kinetically trapped spike patterns. The present work examines a number of variables that control pattern formation associated with this encoding. Control variables include applied magnetic field strength, magnetic field gradient, nanoparticle concentration, solvent evaporation conditions, and alkane solvent chain length. The pattern formation process is captured in six stages of evolution until the solvent host has evaporated and the pattern is permanently fixed. The macropatterns consist of hexagonal arrays that coexist with different pentagonal and heptagonal defects. The Voronoi entropy is calculated for different patterns that arise due to changes in the control parameters. Insight into order in the lattice patterns is achieved by extracting measurables like peak-to-peak spike wavelength, spike population, spike height, and base diameter from the patterns. The pattern measurables depend nonlinearly on the magnetic field gradient, solvent evaporation rate, and solvent chain length. Nanoparticle concentration does not impact the measurables significantly. Nonetheless, the results agree qualitatively with a linear expression for the critical magnetization and wavelength that explicitly contains the field gradient and surface tension.

Integrated In-Sensor Computing Optoelectronic Device for Environment-Adaptable Artificial Retina Perception Application.

With the development and application of artificial intelligence, there is an appeal to the exploitation of various sensors and memories. As the most important perception of human beings, vision occupies more than 80% of all the received information. Inspired by biological eyes, an artificial retina based on 2D Janus MoSSe was fabricated, which could simulate functions of visual perception with electronic/ion and optical comodulation. Furthermore, inspired by human brain, sensing, memory, and neuromorphic computing functions were integrated on one device for multifunctional intelligent electronics, which was beneficial for scalability and high efficiency. Through the formation of faradic electric double layer (EDL) at the metal-oxide/electrolyte interfaces could realize synaptic weight changes. On the basis of the optoelectronic performances, light adaptation of biological eyes, preprocessing, and recognition of handwritten digits were implemented successfully. This work may provide a strategy for the future integrated sensing-memory-processing device for optoelectronic artificial retina perception application.

Establishment of a five-enzalutamide-resistance-related-gene-based classifier for recurrence-free survival predicting of prostate cancer.

To identify prostate cancer (PCa) patients with a high risk of recurrence is critical before delivering adjuvant treatment. We developed a classifier based on the Enzalutamide treatment resistance-related genes to assist the currently available staging system in predicting the recurrence-free survival (RFS) prognosis of PCa patients. We overlapped the DEGs from two datasets to obtain a more convincing Enzalutamide-resistance-related-gene (ERRG) cluster. The five-ERRG-based classifier obtained good predictive values in both the training and validation cohorts. The classifier precisely predicted RFS of patients in four cohorts, independent of patient age, pathological tumour stage, Gleason score and PSA levels. The classifier and the clinicopathological factors were combined to construct a nomogram, which had an increased predictive accuracy than that of each variable alone. Besides, we also compared the differences between high- and low-risk subgroups and found their differences were enriched in cancer progression-related pathways. The five-ERRG-based classifier is a practical and reliable predictor, which adds value to the existing staging system for predicting the RFS prognosis of PCa after radical prostatectomy, enabling physicians to make more informed treatment decisions concerning adjuvant therapy.

Identification of novel susceptibility factors related to CP/CPPS-like symptoms: Evidence from a multicenter case-control study.

BACKGROUND: We aimed to systematically identify novel susceptible factors related to the occurrence and development of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)-like symptoms that were not limited to lifestyles or dietary habits in Chinese population. METHODS: We recruited participants from three centers (Shanghai [northeast], Hefei [east], and Lanzhou [northwest]) from August 2020 to June 2021. Demographics, lifestyles, dietary habits, past medical history, and national institutes of health-chronic prostatitis symptom index (NIH-CPSI) were collected from the individuals via optimized questionnaires. Logistic regression analysis and multivariate adjustment models were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to assess the association between these variables and CP/CPPS-like symptoms. RESULTS: A total of 1851 participants were enrolled in this study (764 cases and 1087 controls). Age distributions differed between groups (median, range: 32, 18-74 vs. 29, 18-70, p < 0.001). After adjustment, physicochemical occupational hazards were identified significantly related to CP/CPPS-like symptom occurrence and development (ORoccurrence : 1.389, 95% CI: 1.031-1.870, p < 0.001; ORdevelopment : 2.222, 95% CI: 1.464-3.372, p < 0.001); besides, greater than or equal to four ejaculations per week significantly increased the likelihood of CP/CPPS-like symptoms compared with one ejaculation per week (ORoccurrence : 3.051, 95% CI: 1.598-5.827, p = 0.001). For these patients, who were easily felt gastrointestinal discomfort caused by spicy food intake, they had a higher incidence to affect with CP/CPPS-like symptoms (ORoccurrence : 2.258, 95% CI: 1.858-2.745, p < 0.001). In addition, history of drug allergy and genitourinary infections were identified as independent susceptible factors for the occurrence of CP/CPPS-like symptoms (ORoccurrence : 1.689, 95% CI: 1.007-2.834, p = 0.047; ORoccurrence : 3.442, 95% CI: 2.202-5.382, p < 0.001, respectively), while the history of rheumatic immune diseases was found tightly associated with the development of CP/CPPS-like symptoms (ORdevelopment : 2.002, 95% CI: 1.008-4.058, p = 0.048). CONCLUSION: Infection/inflammatory/immune-related disorders, novel dietary habits, and lifestyles associated with the susceptibility of CP/CPPS-like symptoms' occurrence and development are identified. Altering these irregular conditions serves as potential strategies for the treatment of patients with CP/CPPS-like symptoms.

MOVICS: an R package for multi-omics integration and visualization in cancer subtyping.

SUMMARY: Stratification of cancer patients into distinct molecular subgroups based on multi-omics data is an important issue in the context of precision medicine. Here, we present MOVICS, an R package for multi-omics integration and visualization in cancer subtyping. MOVICS provides a unified interface for 10 state-of-the-art multi-omics integrative clustering algorithms, and incorporates the most commonly used downstream analyses in cancer subtyping researches, including characterization and comparison of identified subtypes from multiple perspectives, and verification of subtypes in external cohort using two model-free approaches for multiclass prediction. MOVICS also creates feature rich customizable visualizations with minimal effort. By analysing two published breast cancer cohort, we signifies that MOVICS can serve a wide range of users and assist cancer therapy by moving away from the 'one-size-fits-all' approach to patient care. AVAILABILITY AND IMPLEMENTATION: MOVICS package and online tutorial are freely available at https://github.com/xlucpu/MOVICS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Ten-Eleven Translocation 1 Promotes Malignant Progression of Cholangiocarcinoma With Wild-Type Isocitrate Dehydrogenase 1.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a highly lethal disease without effective therapeutic approaches. The whole-genome sequencing data indicate that about 20% of patients with CCA have isocitrate dehydrogenase 1 (IDH1) mutations, which have been suggested to target 2-oxoglutarate (OG)-dependent dioxygenases in promoting CCA carcinogenesis. However, the clinical study indicates that patients with CCA and mutant IDH1 have better prognosis than those with wild-type IDH1, further complicating the roles of 2-OG-dependent enzymes. APPROACH AND RESULTS: This study aimed to clarify if ten-eleven translocation 1 (TET1), which is one of the 2-OG-dependent enzymes functioning in regulating 5-hydroxymethylcytosine (5hmC) formation, is involved in CCA progression. By analyzing The Cancer Genome Atlas (TCGA) data set, TET1 mRNA was found to be substantially up-regulated in patients with CCA when compared with noncancerous bile ducts. Additionally, TET1 protein expression was significantly elevated in human CCA tumors. CCA cells were challenged with α-ketoglutarate (α-KG) and dimethyl-α-KG (DM-α-KG), which are cosubstrates for TET1 dioxygenase. The treatments with α-KG and DM-α-KG promoted 5hmC formation and malignancy of CCA cells. Molecular and pharmacological approaches were used to inhibit TET1 activity, and these treatments substantially suppressed 5hmC and CCA carcinogenesis. Mechanistically, it was found that knockdown of TET1 may suppress CCA progression by targeting cell growth and apoptosis through epigenetic regulation. Consistently, targeting TET1 significantly inhibited CCA malignant progression in a liver orthotopic xenograft model by targeting cell growth and apoptosis. CONCLUSIONS: Our data suggest that expression of TET1 is highly associated with CCA carcinogenesis. It will be important to evaluate TET1 expression in CCA tumors before application of the IDH1 mutation inhibitor because the inhibitor suppresses 2-hydroxyglutarate expression, which may result in activation of TET, potentially leading to CCA malignancy.

Establishment and Validation of Coagulation Factor-Based Nomogram for Predicting the Recurrence-Free Survival of Prostate Cancer.

INTRODUCTION: We aimed to establish and validate a coagulation feature-based nomogram to predict recurrence-free survival in prostate cancer patients. METHODS: The study included 168 prostate cancer patients who had received radical prostatectomy between 2012 and 2018. Kaplan-Meier plot and log-rank analysis were used to screen recurrence-free survival-related features. The nomogram was established by combining the significant coagulation features with clinicopathological characteristics by using Cox regression analysis. The accuracy and clinical significance of the nomogram model were assessed by the receiver operating characteristic curve, Kaplan-Meier plot, and calibration plot. We explored the correlation between coagulation pathway activity and patient prognosis in public datasets by using gene set variation analysis (GSVA). RESULTS: The results suggested that patients classified by the nomogram into the high-risk subgroup showed unfavorable prognoses compared with those in the low-risk subgroup in both the training (log-rank p < 0.0001) and validation (log-rank p = 0.0004) cohorts. The nomogram model exhibited high discriminative accuracy in the training cohort (1-year area under the curve [AUC] of 0.74 and 3-year AUC of 0.69), which was confirmed in the internal validation cohort (C-index = 0.651). The calibration plots confirmed good concordance for the prediction of recurrence-free survival at 1 and 3 years. Subgroup analyses confirmed the utility of this model in different clinicopathological subgroups. Finally, GSVA suggested that patients with higher coagulation pathway scores mostly had unfavorable prognoses compared to those with lower scores, a result consistent with the findings above. CONCLUSIONS: We developed a practical nomogram model for predicting recurrence-free survival in prostate cancer patients. This model may offer clinicians prognostic assessments and facilitate personalized treatment.

Dietary habits and lifestyle related to the effectiveness of low-intensity extracorporeal shock wave therapy for chronic prostatitis/chronic pelvic pain syndrome-like symptoms: Initial results.

To identify factors that could influence the treatment outcomes of low-intensity extracorporeal shock wave therapy (Li-ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)-like symptoms and establish a predictive model based on these factors to precisely screen individuals who might be more suitable for Li-ESWT. This study enrolled 84 patients with CP/CPPS-like symptoms who received Li-ESWT. Patients were divided into an effective group and an ineffective group based on the reduction of their National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). A nomogram was established based on logistic regression analyses. Then, receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) were used to evaluate the nomogram. Univariate and multivariate logistic regression analysis showed that a higher NIH-CPSI score, a habit of holding urine, alcohol consumption, and urination soon after intercourse were independent predictors of Li-ESWT efficacy (p < 0.05). The nomogram constructed based on these four indicators and the added age effectively predicted the probability of Li-ESWT effectiveness for CP/CPPS-like symptoms (0.809 [95% CI: 0.717-0.901]; Hosmer-Lemeshow: p = 0.936). This study established a predictive model for the efficacy of Li-ESWT in treating CP/CPPS-like symptoms patients and help improve the management of CP/CPPS-like symptoms.

Efficacy and safety evaluation of low-intensity extracorporeal shock wave therapy on prostatitis-like symptoms: An open-label, single-arm trial.

The present work aims to evaluate the clinical efficacy and safety of low-intensity extracorporeal shock wave therapy (Li-ESWT) on patients with prostatitis-like symptoms (PLS). Patients with PLS were recruited and received four-week Li-ESWT (once per week), which was conducted at a frequency of 3 Hz with a preferred energy flow density of 0.25 mJ/mm2 . The scores of the National Institute of Health Chronic Prostatitis Symptoms Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and Visual Analogue Scale (VAS) were recorded to assess the remission of disease in the 0, 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks. A decrease of the NIH-CPSI score ≥6 was regarded as the effectiveness standard of Li-ESWT. Among 91 enrolled patients, the scores of all validated questionnaires presented significant improvements in the 4th week (p < .05) compared with that in baseline, except for IIEF-5. The treatment effective rates in the 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks were 28.57%, 38.46%, 47.25%, 51.65%, 57.30%, 68.18% and 69.44%, respectively. No pronounced undesirable side effect has occurred. Li-ESWT is effective and safe in treating PLS. The efficacy can be maintained within three months.

[Omics molecular subtyping, prognostic prediction and individualized treatment of prostate cancer: Advances in studies].

Prostate cancer (PCa) is a most common malignancy in males. It has a greater heterogeneity than other cancers, which poses a real challenge to the clinical diagnosis, classification and prognostic monitoring. At present, high-, medium- and low-risk PCa patients are classified mainly by Gleason scores and the PSA level, which, however, fail to reveal the diverse molecular heterogeneity and precisely distinguish the molecular subtypes of PCa. With the development of high-throughput sequencing, more and more studies on the molecular classification of the malignancy have paved the theoretical ground for the early diagnosis, efficacy prediction and individualized treatment of PCa. This study reviews the molecular classification, prognosis prediction and individualized treatment of PCa to date, hoping to contribute to the development of the precise treatment of PCa.

[Establishment of a prostate cancer prognostic risk model based on the TCGA database and inflammation-related genes].

OBJECTIVE: To investigate the effect of inflammation-related genes on the prognosis of prostate cancer (PCa). METHODS: We downloaded PCa-related clinical data and mRNA sequencing data from the database Cancer Genome Atlas (TCGA) and inflammation-related pathway gene sets from MsigDB. Using univariate regression and LASSO regression analyses, we screened inflammation-related genes for the construction of a prognostic risk model and evaluated the performance of the model in predicting the prognosis of PCa by Kaplan-Meier and ROC analyses. Based on the nomogram, we calculated the risk scores of the patients, divided them into a high-risk and a low-risk group based on the median values of their risk scores, identified differentially expressed genes for enrichment analysis and verified the expression level of SPHK1 in the PCa tissue microarrays by immunohistochemical staining. RESULTS: Totally 19 inflammation-related genes were identified from 172 candidate genes for the construction of the prognostic risk model, including the risk genes CD14, PIK3R5, GABBR1, RELA, IRF7, SCARF1, MSR1, SPHK1, OSM and STAB1, and the protective genes AQP9, LPAR1, ATP2C1, NDP, CXCL6, P2RY2, DCBLD2, PCDH7, and IFNAR1. Kaplan-Meier analysis showed that the patients with high risk scores had a significantly lower recurrence-free survival and a worse prognosis than those with low risk scores. Differentially expressed genes were involved mainly in the activation of inflammatory response pathways. Immunohistochemical results indicated that the expression of SPHK1 was significantly higher in the tumorous than in the normal tissue and increased with the Gleason score. There was a correlation between the SPHK1 expression and envelope invasion. CONCLUSION: The prognostic risk model of inflammation-related genes constructed based on the TCGA database can effectively predict the prognosis of PCa.

Multiomics data reveals the influences of myasthenia gravis on thymoma and its precision treatment.

Thymoma is a rare characterized by a unique association with autoimmune diseases, especially myasthenia gravis (MG). However, little is known about the molecular characteristics of MG-associated thymoma individuals. We aim to examine the influences of MG on thymoma by analyzing multiomics data. A total of 105 samples with thymoma was analyzed from TCGA and these samples were divided into subgroups with MG (MGT) or without MG (MGF) according to clinical information. We then characterized the differential gene expression, pathway activity, somatic mutation frequency, and likelihood of responding to chemotherapies and immunotherapies of the two identified subgroups. MGT subgroup was characterized by elevated inflammatory responses and metabolically related pathways, whereas the MGF subgroup was predicted to be more sensitive to chemotherapy and presented with mesenchymal characteristics. More copy number amplifications and deletions were observed in MGT, whereas GTF2I mutations occur at significantly higher frequencies in MGF. Two molecular subtypes were further identified within MGF samples by unsupervised clustering where one subtype was enriched in TGF-ß and WNT pathways with higher sensitivity to relevant targeted drugs but hardly respond to immunotherapy. For another subtype, a higher recurrence rate of thymoma and more likelihood of responding to immunotherapy were observed. Our findings presented a comprehensive molecular characterization of thymoma patients given the status of MG, and provided potential strategies to help individualized management and treatment.

4-Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy for chronic prostatitis.

BACKGROUND: Hyaluronan (HA), an extracellular matrix component, accumulates in most chronic inflammatory tissues. Here, we studied the impact of HA on the pathogenesis of chronic prostatitis. MATERIALS AND METHODS: First, we sorted demographic characteristics and peripheral blood serum samples from patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to assess the relationship between the levels of HA in peripheral blood serum and the severity of inflammation in patients. Second, we induced an experimental autoimmune prostatitis (EAP) mouse model and treated the mice with 4-methylumbelliferone (4-MU) (200 mg/kg/day). After the mice were sacrificed, RNA from Th1 cells of the mouse spleens was extracted for RNA sequencing. We used weighted gene co-expression network analysis (WGCNA) to identify co-expressed gene modules and hub-gene related to the pathogenesis of EAP. The expression of critical genes associated with the identified pathway was confirmed by using western blot analysis. RESULTS: HA was significantly more highly expressed in CP/CPPS patients than in healthy volunteers and positively correlated with the severity of pain, urination symptoms, and quality of life. Besides, the protein expression of HA was significantly higher in prostate tissues derived from EAP models than in those derived from controls. 4-MU, an oral inhibitor of HA synthesis, relieved immunocyte infiltration to the prostate and significantly reduced the proportion of Th1 cells. Based on the WGCNA, we identified 18 co-expression modules and identified that the Grey60 and brown modules were positively associated with the EAP and negatively associated with the Control and 4-MU-treated groups. Pathway enrichment analyses and western blot assays proved that HA potentially activated the cell cycle pathway, increasing the proportion of Th1 cells promoting chronic prostatitis pathogenesis, while these processes were reversed by 4-MU treatment. CONCLUSIONS: Our results suggest that HA is elevated in patients with CP/CPPS compared with healthy controls and that targeting HA through 4-MU suppresses the activity of the cell cycle-related pathway, potentially by decreasing the proportion of Th1 cells and relieving chronic prostatitis. Our findings might inspire the clinical treatment of chronic prostatitis.

Activated autophagy restored the impaired frequency and function of regulatory T cells in chronic prostatitis.

BACKGROUND: Chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS) is a disease with an unclear pathogenesis. Recent studies have reported that regulatory T (Treg) cells might be involved in the development of CP/CPPS. In this study we aimed to examine the functional role of Treg cells and explore the possible regulatory mechanism of Treg cells in CP/CPPS. METHODS: An experimental autoimmune prostatitis (EAP) mouse model was constructed; the numbers and functions of Treg cells in the EAP and control groups were tested. Then, cell differentiation experiments were conducted to evaluate the regulatory effect of autophagy on Treg cell differentiation. Furthermore, autologous CD4+ CD25- cells and CD4+ CD25+ cells from the two groups were magnetically sorted and cocultured to observe differences in cellular inhibitory functions. Finally, in an in vivo experiment, rapamycin was intraperitoneally injected into EAP mice for 4 weeks to observe the therapeutic effects. RESULTS: We found that the number and function of Treg cells in the EAP group were diminished compared to those in the control group. Meanwhile, the tolerance of pain in EAP mice had also decreased. Moreover, after using the autophagy activator rapamycin, the expression of the inflammatory cytokines interleukin-1ß was decreased and the pain symptoms were alleviated. A mechanistic study found that autophagy activation promoted the differentiation of Treg and increased the suppressive functions of Treg cells, along with the elevated expression of GATA-3 and cytotoxic T lymphocyte antigen 4 (CTLA-4). Furthermore, in vivo administration of the autophagy activator rapamycin had similar effects on recovering the frequency and function of Treg cells as well as the expression of GATA-3 and CTLA-4. CONCLUSION: The impaired frequency and function of Treg cells may contribute to the progression of CP/CPPS, and autophagy is a protective mechanism that promotes the differentiation of Treg cells and restores the suppressive functions of Treg cells. Autophagy may be a novel therapeutic option for patients with CP/CPPS.

Immunological alterations in patients with chronic prostatitis/chronic pelvic pain syndrome and experimental autoimmune prostatitis model: A systematic review and meta-analysis.

BACKGROUND: As one of the most common conditions in urological outpatients, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) puzzles many individuals because of its unclear etiology and lack of effective treatment. Recently, immunological alterations underpinning CP/CPPS have been extensively investigated. METHODS: The PubMed, Web of Science, Cochrane library, and EMBASE databases were used to search original articles on immune mediators in patients with CP/CPPS and in experimental autoimmune prostatitis (EAP) models through April 10, 2020. Standardized mean differences (SMD) were calculated to summarize the differences in immune mediator levels between groups. Funnel plot, Begg's funnel plot, Egger's regression test, and the sensitivity analysis were applied to determine and visualize the stability of our findings. RESULTS: A total of 34 original studies were included in the meta-analysis, including 24 studies on patients with CP/CPPS and 10 studies on EAP models. We found that TNF-α, IL-1ß, IL-6, and IL-8 were the four immune mediators that elevated in most of the samples derived from patients with CP/CPPS and the EAP models. The adjusted publication bias analysis indicated that publication bias was not existed, and the sensitivity analyses showed that the results were stable. CONCLUSIONS: Immune responses play significant roles during the pathogenesis of CP/CPPS by promoting intraprostatic inflammation. Our findings provide potential diagnostic and therapeutic targets for CP/CPPS patients.

Integrative analysis the characterization of peroxiredoxins in pan-cancer.

BACKGROUND: Peroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth. In addition, previous studies report that PRDXs play critical roles in the occurrence and development of carcinomas. However, few studies have conducted systematic analysis of PRDXs in cancers. Therefore, the present study sought to explore the molecular characteristics and potential clinical significance of PRDX family members in pan cancer and further validate the function of PRDX6 in bladder urothelial carcinoma (BLCA). METHODS: A comprehensive analysis of PRDXs in 33 types of cancer was performed based on the TCGA database. This involved an analysis of mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, both the gain and loss of function strategies were used to assess the importance and mechanism of PRDX6 in the cell cycle of BLCA. RESULT: Analysis showed abnormal expression of PRDX1-6 in several types of cancer compared to normal tissues. Univariate Cox proportional hazard regression analysis showed that expression levels of PRDX1, PRDX4 and PRDX6 were mostly associated with poor survival of OS, DSS and PFI, and PRDX2 and PRDX3 with favorable survival. In addition, the expression of PRDX genes were positively correlated with CNV and negatively with methylation. Moreover, analysis based on PharmacoDB dataset showed that the augmented levels of PRDX1, PRDX3 and PRDX6 were significantly correlated with EGFR/VEGFR inhibitor drugs. Furthermore, knocking down of PRDX6 inhibited growth of cancer cells through the JAK2-STAT3 in bladder cell lines. CONCLUSIONS: PRDXs are potential biomarkers and therapeutic targets for several carcinomas, especially for BLCA. In addition, PRDX6 could regulate proliferation of cancer cell via JAK2-STAT3 pathway and involve into the process of cell cycle in BLCA.

Neo-adjuvant radiation therapy provides a survival advantage in T3-T4 nodal positive gastric and gastroesophageal junction adenocarcinoma: a SEER database analysis.

BACKGROUND: Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs. METHODS: We retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (T1-2N-, T1-2N+, T3-4N-, and T3-4N+). RESULTS: Overall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in T3-4N+ subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66-0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P <  0.001), but not in diffuse type (P = 0.11) for T3-4N+ patients. In the multivariate competing risk model, NRT still showed survival advantage only in T3-4 N+ patients (subdistribution HR: 0.77; 95% CI: 0.64-0.93; P = 0.006), but not in other subgroups. CONCLUSIONS: NRT might benefit resectable gastric and GEJ cancer patients of T3-4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.