Factors influencing DVT formation in sepsis.

INTRODUCTION: Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. METHODS: In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. MAIN RESULTS: In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value < 0.001). In terms of comorbidities, septic patients with hypertension and atrial fibrillation were prone to DVT (p value 0.045 and 0.048). Inflammatory cytokines, such as procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, had no significant correlation with DVT in patients with sepsis (p value 0.364, 0.882, 0.912, 0.789, 0.245, and 0.780). Levels of serum albumin correlated with DVT in patients with sepsis (p value 0.003). The SOFA total score had no relationship with DVT formation (p value 0.254). Coagulation and respiration function were negatively correlated with DVT (p value 0.018). Liver function was positively correlated with DVT (p value 0.020). Patients in the DVT group had longer duration of mechanical ventilation and longer intensive care unit (ICU) stays (p value < 0.001 and 0.006). There was no significant difference in survival in septic patients with and without DVT (p value 0.868). CONCLUSIONS: The SOFA total score had no relationship with DVT formation. The function of each organ had different effects on DVT formation. Better coagulation and respiration function, easier DVT formation. Poorer liver function, easier DVT formation. DVT was associated with longer duration of mechanical ventilation and longer ICU stays.

Effect of ICU quality control indicators on VAP incidence rate and mortality: a retrospective study of 1267 hospitals in China.

PURPOSE: To investigate the effects of ICU quality control indicators on the VAP incidence rate and mortality in China throughout 2019. METHODS: This was a retrospective study. A total of 1267 ICUs from 30 provinces in mainland China were included. Data were collected using the National Clinical Improvement System Data that report ICU information. Ten related quality control indicators were analyzed, including 5 structural factors (patient-to-bed ratio, physician-to-bed ratio, nurse-to-bed ratio, patient-to-physician ratio, and patient-to-nurse ratio), 3 process factors (unplanned endotracheal extubation rate, reintubation rate within 48 h, and microbiology detection rate before antibiotic use), and 2 outcome factors (VAP incidence rate and mortality). The information on the most common infectious pathogens and the most commonly used antibiotics in ICU was also collected. The Poisson regression model was used to identify the impact of factors on the incidence rate and mortality of VAP. RESULTS: The incidence rate of VAP in these hospitals in 2019 was 5.03 (2.38, 10.25) per 1000 ventilator days, and the mortality of VAP was 11.11 (0.32, 26.00) %. The most common causative pathogen was Acinetobacter baumannii (in 39.98% of hospitals), followed by Klebsiella pneumoniae (38.26%), Pseudomonas aeruginosa, and Escherichia coli. In 26.90% of hospitals, third-generation cephalosporin was the most used antibiotic, followed by carbapenem (24.22%), penicillin and beta-lactamase inhibitor combination (20.09%), cephalosporin with beta-lactamase inhibitor (17.93%). All the structural factors were significantly associated with VAP incidence rate, but not with the mortality, although the trend was inconsistent. Process factors including unplanned endotracheal extubation rate, reintubation rate in 48 h, and microbiology detection rate before antibiotic use were associated with higher VAP mortality, while unplanned endotracheal extubation rate and reintubation rate in 48 h were associated with higher VAP mortality. Furthermore, K. pneumoniae as the most common pathogen was associated with higher VAP mortality, and carbapenems as the most used antibiotics were associated with lower VAP mortality. CONCLUSION: This study highlights the association between the ICU quality control (QC) factors and VAP incidence rate and mortality. The process factors rather than the structural factors need to be further improved for the QC of VAP in the ICU.

[Medication versus health education for patients with type â ¢ prostatitis-like symptoms: A prospective randomized control study].

OBJECTIVE: To investigate the necessity of medication for patients with type Ⅲ prostatitis-like symptoms for less than 3 months. METHODS: We enrolled in this study 171 outpatients with type Ⅲ prostatitis-like symptoms for less than 3 months in our hospital from November 2016 to October 2017, and randomly divided them into groups A (n = 57), B (n = 57) and C (n = 57). The patients of group A received tamsulosin, levofloxacin and health education, those of group B tamsulosin and health education, and those of group C health education only. Three months later, we evaluated the therapeutic effects according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores of the patients, 4-point reduction in the total score indicating effectiveness. RESULTS: After 3 months of treatment, the total NIH-CPSI scores of the patients in groups A, B and C were decreased by (9.0 ± 2.9), (8.2 ± 3.4) and (8.6 ± 3.2) points respectively, all indicating effectiveness, the pain scores (4.2 ± 1.8), (4.0 ± 1.9) and (4.2 ± 1.6) points, the urinary symptom scores decreased by decreased by (2.4 ± 1.2), (2.4 ± 1.4) and (2.2 ± 1.2) points, and quality of life scores decreased by (2.4 ± 1.4), (1.9 ± 1.4) and (2.2 ± 1.3) points, none with statistically significant difference among the three groups (P > 0.05). CONCLUSIONS: Health education is proved to have a therapeutic effect on type Ⅲ prostatitis-like symptoms similar to that of alpha receptor blockers.

Heat shock factor 1 (HSF1) controls chemoresistance and autophagy through transcriptional regulation of autophagy-related protein 7 (ATG7).

Heat shock factor 1 (HSF1), a master regulator of heat shock responses, plays an important role in tumorigenesis. In this study we demonstrated that HSF1 is required for chemotherapeutic agent-induced cytoprotective autophagy through transcriptional up-regulation of autophagy-related gene ATG7. Interestingly, this is independent of the HSF1 heat shock response function. Treatment of cancer cells with the FDA-approved chemotherapeutic agent carboplatin induced autophagy and growth inhibition, which were significantly increased upon knockdown of HSF1. Mechanistic studies revealed that HSF1 regulates autophagy by directly binding to ATG7 promoter and transcriptionally up-regulating its expression. Significantly, breast cancer patient sample study revealed that a higher ATG7 expression level is associated with poor patient survival. This novel finding was further confirmed by analysis of two independent patient databases, demonstrating a prognostic value of ATG7. Furthermore, a strong positive correlation was observed between levels of HSF1 and ATG7 in triple-negative breast cancer patient samples, thus validating our in vitro findings. This is the first study identifying a critical role for HSF1 in controlling cytoprotective autophagy through regulation of ATG7, which is distinct from the HSF1 function in the heat shock response. This is also the first study demonstrating a prognostic value of ATG7 in breast cancer patients. These findings strongly argue that combining chemotherapeutic agents with autophagy inhibition by repressing HSF1/ATG7 axis represents a promising strategy for future cancer treatment.

Activation of nuclear factor κB pathway and downstream targets survivin and livin by SHARPIN contributes to the progression and metastasis of prostate cancer.

BACKGROUND: Nuclear factor κB (NFκB) signaling is strongly associated with tumor progression, and studies have shown that SHANK-associated RH domain interacting protein (SHARPIN) is crucial for NFκB pathway activation. However, the expression and functions of SHARPIN in prostate cancer (PCa) have not yet been defined. METHODS: The expression of SHARPIN in PCa cell lines and tissues was evaluated with western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. After SHARPIN was silenced in the PCa cell lines, western blots were used to confirm that SHARPIN physically associated with components of the NFκB pathway and the downstream targets (survivin and livin). The functions of SHARPIN in cell proliferation, migration, and invasion in vitro were measured with 5-(3-carboxymethoxyphenyl)-2-(4,5-dimenthylthiazoly)-3-(4-sulfophenyl)tetrazolium, inner salt (MTS), Transwell, and invasion assays, respectively. Flow cytometry was employed to evaluate cell apoptosis. Furthermore, tumorigenesis in vivo was examined with tumorigenicity assays. RESULTS: SHARPIN expression was upregulated in PCa cell lines and tissues. The knockdown of SHARPIN or incubation with Bay 11-7082 (an NFκB inhibitor) led to dramatically decreased levels of phosphorylated IκBα and phosphorylated p65 in comparison with the control group. Downregulation of survivin and livin due to SHARPIN inhibition was attributable to transcriptional repression (P < .05). Decreases in cell viability, migration, invasion, and survival with a higher sensitivity to docetaxel in vitro and with repressed tumorigenesis in vivo were observed upon SHARPIN silencing, and this was consistent with the results from inhibition of the NFκB pathway and its downstream targets. CONCLUSION: The current study demonstrates that overexpression of SHARPIN promotes activation of the NFκB pathway and downstream targets survivin and livin, which potentially contributes to PCa development.

Identification and preliminary analysis of hub genes associated with bladder cancer progression by comprehensive bioinformatics analysis.

Bladder cancer (BC) is a crisis to human health. It is necessary to understand the molecular mechanisms of the development and progression of BC to determine treatment options. Publicly available expression data were obtained from TCGA and GEO databases to spot differentially expressed genes (DEGs) between cancer and normal bladder tissues. Weighted co-expression networks were constructed, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Associations in hub genes, immune infiltration, and immune therapy were evaluated separately. Protein-protein interaction (PPI) networks for the genes identified in the normal and tumor groups were launched. 3461 DEGs in the TCGA dataset and 1069 DEGs in the GSE dataset were identified, including 87 overlapping genes between cancer and normal bladder groups. Hub genes in the tumor group were mainly enriched for cell proliferation, while hub genes in the normal group were related to the synthesis and secretion of neurotransmitters. Based on survival analysis, CDH19, RELN, PLP1, and TRIB3 were considerably associated with prognosis (P < 0.05). CDH19, RELN, PLP1, and TRIB3 may play important roles in the development of BC and are potential biomarkers in therapy and prognosis.

SOFA in sepsis: with or without GCS.

PURPOSE: Sepsis is a global public health burden. The sequential organ failure assessment (SOFA) is the most commonly used scoring system for diagnosing sepsis and assessing severity. Due to the widespread use of endotracheal intubation and sedative medications in sepsis, the accuracy of the Glasgow Coma Score (GCS) is the lowest in SOFA. We designed this multicenter, cross-sectional study to investigate the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis. METHODS: First, 3048 patients with sepsis admitted to Peking Union Medical College Hospital (PUMCH) were enrolled in this survey. The data were collected from June 8, 2013 to October 12, 2022. Second, 18,108 patients with sepsis in the eICU database were enrolled. Third, 2397 septic patients with respiratory system ≥ 3 points in SOFA in the eICU database were included. We investigated the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis in various ICUs of PUMCH, and then we validated the results in the eICU database. MAIN RESULTS: In data of ICUs in PUMCH, the predictive efficiency of SOFA without GCS (AUROC [95% CI], 24 h, 0.724 [0.688, 0.760], 48 h, 0.734 [0.699, 0.769], 72 h, 0.748 [0.713, 0.783], 168 h, 0.781 [0.747, 0.815]) was higher than that of SOFA with GCS (AUROC [95% CI], 24 h, 0.708 [0.672, 0.744], 48 h, 0.721 [0.685, 0.757], 72 h, 0.735 [0.700, 0.757], 168 h, 0.770 [0.736, 0.804]) on ICU mortality in patients with sepsis, and the difference was statistically significant (P value, 24 h, 0.001, 48 h, 0.003, 72 h, 0.004, 168 h, 0.005). In septic patients with respiratory system ≥ 3 points in SOFA in the eICU database, although the difference was not statistically significant (P value, 24 h, 0.148, 48 h, 0.178, 72 h, 0.132, 168 h, 0.790), SOFA without GCS (AUROC [95% CI], 24 h, 0.601 [0.576, 0.626], 48 h, 0.625 [0.601, 0.649], 72 h, 0.639 [0.615, 0.663], 168 h, 0.653 [0.629, 0.677]) had a higher predictive efficiency on ICU mortality than SOFA with GCS (AUROC [95% CI], 24 h, 0.591 [0.566, 0.616], 48 h, 0.616 [0.592, 0.640], 72 h, 0.628 [0.604, 0.652], 168 h, 0.651 [0.627, 0.675]). CONCLUSIONS: In severe sepsis, it is realistic and feasible to discontinue the routine GCS for SOFA in patients with a respiratory system ≥ 3 points, and even better predict ICU mortality.

Prostate specific membrane antigen (PSMA): a novel modulator of p38 for proliferation, migration, and survival in prostate cancer cells.

BACKGROUND: Regulated activation of p38 is crucial for cell proliferation, survival, and metabolism. Our previous studies had showed that prostate specific membrane antigen (PSMA) can facilitate the proliferation, migration, survival of the LNCaP prostate cancer cell line, but the mechanisms are poorly defined. METHODS: Our LNCaP cells had been stably transfected with lentivirus-mediated shRNA for PSMA silencing in previous study. We first testify the efficacy of PSMA knockdown in our LNCaP cell line. Then using this PSMA (-) LNCaP cell line, we compared the expression of PSMA and P-p38 by Western blotting among groups. Furthermore, we also performed immunofluorescence to confirm the change of P-p38 in cells. Then, cell viability and migration were measured by cell counting kit-8 reagent and Transwell analysis respectively. Flow cytometry was employed to evaluate cell survival. RESULTS: After silencing the expression of PSMA, the level of the phospho-p38 (P-p38) decreased approximate 40% compared with the blank and NC groups (P < 0.05). When the cells were incubated with SB203582 (p38 inhibitor), the P-p38 in three groups was at low level and no difference among groups (P > 0.05). Then the results of immunofluorescence further proved the relationship between PSMA and P-p38. Decrease of cell viability, migration, and survival was observed upon PSMA silencing. SB203580, a specific inhibitor of p38 MAPK pathway, also reduced proliferation, migration, and survival of LNCaP cells. CONCLUSION: These data suggests PSMA may stimulate prostate cancer cells proliferation, migration and survival through p38 MAPK pathway, revealing a novel mechanism for PSMA playing positive role on LNCaP cells.

A BIGRU-Based Stacked Attention Network for Biomedical Named Entity Recognition with Chinese EMRs.

Biomedical named entity recognition (BNER) is an effective method to structure the medical text data. It is an important basic task for building the medical application services such as the medical knowledge graphs and the intelligent auxiliary diagnosis systems. Existing medical named entity recognition methods generally leverage the word embedding model to construct text representation, and then integrate multiple semantic understanding models to enhance the semantic understanding ability of the model to achieve high-performance entity recognition. However, in the medical field, there are many professional terms that rarely appear in the general field, which cannot be represented well by the general domain word embedding model. Second, existing approaches typically only focus on the extraction of global semantic features, which generate a loss of local semantic features between characters. Moreover, as the word embedding dimension becomes much higher, the standard single-layer structure fails to fully and deeply extract the global semantic features. We put forward the BIGRU-based Stacked Attention Network (BSAN) model for biomedical named entity recognition. Firstly, we use the large-scale real-world medical electronic medical record (EMR) data to fine-tune BERT to build the proprietary embedding representations of the medical terms. Second, we use the Convolutional Neural Network model to extract semantic features. Finally, a stacked BIGRU is constructed using a multi-layer structure and a novel stacking method. It not only enables comprehensive and in-depth extraction of global semantic features, but also requires less time. Experimentally validated on the real-world datasets in Chinese EMRs, the proposed BSAN model achieves 90.9% performance on F1-values, which is stronger than the BNER performance of other state-of-the-art models.

RNA Sequencing (RNA-Seq) Analysis Reveals Liver Lipid Metabolism Divergent Adaptive Response to Low- and High-Salinity Stress in Spotted Scat (Scatophagus argus).

Spotted scat (Scatophagus argus) can tolerate a wide range of salinity fluctuations. It is a good model for studying environmental salinity adaptation. Lipid metabolism plays an important role in salinity adaptation in fish. To elucidate the mechanism of lipid metabolism in the osmoregulation, the liver transcriptome was analyzed after 22 d culture with a salinity of 5 ppt (Low-salinity group: LS), 25 ppt (Control group: Ctrl), and 35 ppt (High-salinity group: HS) water by using RNA sequencing (RNA-seq) in spotted scat. RNA-seq analysis showed that 1276 and 2768 differentially expressed genes (DEGs) were identified in the LS vs. Ctrl and HS vs. Ctrl, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the pathways of steroid hormone biosynthesis, steroid biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, and lipid metabolism were significantly enriched in the LS vs. Ctrl. The genes of steroid biosynthesis (sqle, dhcr7, and cyp51a1), steroid hormone biosynthesis (ugt2a1, ugt2a2, ugt2b20, and ugt2b31), and glycerophospholipid metabolism (cept1, pla2g4a, and ptdss2) were significantly down-regulated in the LS vs. Ctrl. The pathways related to lipid metabolisms, such as fatty acid metabolism, fatty acid biosynthesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, adipocytokine signaling pathway, fatty acid degradation, and unsaturated fatty acid biosynthesis, were significantly enriched in the HS vs. Ctrl. The genes of unsaturated fatty acid biosynthesis (scd1, hacd3, fads2, pecr, and elovl1) and adipocytokine signaling pathway (g6pc1, socs1, socs3, adipor2, pck1, and pparα) were significantly up-regulated in the HS vs. Ctrl. These results suggest that the difference in liver lipid metabolism is important to adapt to low- and high-salinity stress in spotted scat, which clarifies the molecular regulatory mechanisms of salinity adaptation in euryhaline fish.

Multidimensional dynamic prediction model for hospitalized patients with the omicron variant in China.

Purpose: To establish dynamic prediction models by machine learning using daily multidimensional data for coronavirus disease 2019 (COVID-19) patients. Methods: Hospitalized COVID-19 patients at Peking Union Medical College Hospital from Nov 2nd, 2022, to Jan 13th, 2023, were enrolled in this study. The outcome was defined as deterioration or recovery of the patient's condition. Demographics, comorbidities, laboratory test results, vital signs, and treatments were used to train the model. To predict the following days, a separate XGBoost model was trained and validated. The Shapley additive explanations method was used to analyze feature importance. Results: A total of 995 patients were enrolled, generating 7228 and 3170 observations for each prediction model. In the deterioration prediction model, the minimum area under the receiver operating characteristic curve (AUROC) for the following 7 days was 0.786 (95% CI 0.721-0.851), while the AUROC on the next day was 0.872 (0.831-0.913). In the recovery prediction model, the minimum AUROC for the following 3 days was 0.675 (0.583-0.767), while the AUROC on the next day was 0.823 (0.770-0.876). The top 5 features for deterioration prediction on the 7th day were disease course, length of hospital stay, hypertension, and diastolic blood pressure. Those for recovery prediction on the 3rd day were age, D-dimer levels, disease course, creatinine levels and corticosteroid therapy. Conclusion: The models could accurately predict the dynamics of Omicron patients' conditions using daily multidimensional variables, revealing important features including comorbidities (e.g., hyperlipidemia), age, disease course, vital signs, D-dimer levels, corticosteroid therapy and oxygen therapy.

Association between ICU quality and in-hospital mortality of V-V ECMO-supported patients-the ECMO quality improvement action (EQIA) study: a national cohort study in China from 2017 to 2019.

This cohort study was performed to explore the influence of intensive care unit (ICU) quality on in-hospital mortality of veno-venous (V-V) extracorporeal membrane oxygenation (ECMO)-supported patients in China. The study involved all V-V ECMO-supported patients in 318 of 1700 tertiary hospitals from 2017 to 2019, using data from the National Clinical Improvement System and China National Critical Care Quality Control Center. ICU quality was assessed by quality control indicators and capacity parameters. Among the 2563 V-V ECMO-supported patients in 318 hospitals, a significant correlation was found between ECMO-related complications and prognosis. The reintubation rate within 48 hours after extubation and the total ICU mortality rate were independent risk factors for higher in-hospital mortality of V-V ECMO-supported patients (cutoff: 1.5% and 7.0%; 95% confidence interval: 1.05-1.48 and 1.04-1.45; odds ratios: 1.25 and 1.23; P = 0.012 and P = 0.015, respectively). Meanwhile, the V-V ECMO center volume was a protective factor (cutoff of ≥ 50 cases within the 3-year study period; 95% confidence interval: 0.57-0.83, odds ratio: 0.69, P = 0.0001). The subgroup analysis of 864 patients in 11 high-volume centers further strengthened these findings. Thus, ICU quality may play an important role in improving the prognosis of V-V ECMO-supported patients.

Invasive mammary carcinoma with neuroendocrine differentiation: histological features and diagnostic challenges.

AIMS: The aim of this study was to review the histomorphological features of primary neuroendocrine carcinomas (NEC) of the breast, in order to identify features useful in recognition of this entity for appropriate classification. METHODS AND RESULTS: 2003 World Health Organization (WHO) classification of tumors of the breast and female genital organs defined NEC of the breast as a subtype of invasive mammary carcinoma in which >50% of the tumor cells express neuroendocrine markers. Seventy-four cases that fulfilled the WHO diagnostic criteria for NEC of the breast, excluding small cell carcinoma and low-grade solid papillary carcinoma with a predominant in-situ component, were identified between 1984 and 2008 from MD Anderson Cancer Center, and were included in the study. NECs of the breast had variable histomorphological features. The most common histologic patterns were papillary (80%) and nested (64%). Mixed growth patterns were common (59%), including admixed ductal component. The tumor cells could be polygonal, round, plasmacytoid, spindled, or with signet ring cell features. The cytoplasm could be granular, eosinophilic, clear, or finely vacuolated. These tumors frequently mimicked invasive or in situ ductal carcinoma, or invasive lobular carcinoma. CONCLUSIONS: NEC of the breast is underrecognized. Careful attention to cytologic and architectural features can help to identify cases that require further immunophenotypic confirmation for correct tumor classification.

Targeted Methylation of the LncRNA NEAT1 Suppresses Malignancy of Renal Cell Carcinoma.

Long-chain non-coding RNA (LncRNA) has been found to play an important role in the regulation of the occurrence and progression of renal cell carcinoma (RCC). In this study, we demonstrated that LncRNA NEAT1 expression and m6A methylation level was decreased in RCC tissues. Further, the downregulated expression level of LncRNA NEAT1 was associated with poor prognosis for RCC patients. Then we used CRIPSR/dCas13b-METTL3 to methylate LncRNA NEAT1 in RCC cells. The results showed that the expression level of LncRNA NEAT1 was upregulated after methylated by dCas13b-METTL3 in RCC cells. And the proliferation and migration ability of RCC cells was decreased after methylated LncRNA NEAT1. Finally, we examined the effect of LncRNA NEAT1 hypermethylation on the transcriptome. We found differentially expressed genes in RCC cells were associated with "cGMP-PKG signaling pathway", "Cell adhesion molecules" and "Pathways in cancer". In conclusion, CRISPR/Cas13b-METTL3 targeting LncRNA NEAT1 m6A methylation activates LncRNA NEAT1 expression and provides a new target for treatment of RCC.

Multimolecular complex of Par-4 and E2F1 binding to Smac promoter contributes to glutamate-induced apoptosis in human- bone mesenchymal stem cells.

Neural cells undergo glutamate-induced apoptosis in ischaemic brain tissue, in which prostate apoptosis response-4 gene (Par-4) is involved. Human-bone mesenchymal stem cells can be utilized as an effective therapy for ischemic brain injury. In this study, we found that glutamate could induce apoptosis in human-bone mesenchymal stem cells, accompanied by increased expression of Par-4 gene and Smac release from mitochondria. Repressing Par-4 expression attenuated the glutamate-induced apoptosis. Both Par-4 protein and E2F1 protein could bind to E2F1-binding BS3 site on Smac promoter and participated in the formation of a proteins-DNA complex. Moreover, in the complex, E2F1, not Par-4, was found to be directly bound to the Smac promoter, suggesting that Par-4 exerted indirectly its transcriptional control on the Smac gene though interacting with E2F1. Expression of full-length Par-4 in human-bone mesenchymal cells resulted in increased activity of the Smac promoter. In addition, the indirect transcripional regulation of Par-4 on Smac depended on its COOH terminus-mediated interaction between Par-4 and E2F1. We conclude that the formation of proteins-DNA complex, containing Par-4 protein, E2F1 protein and the Smac promoter, contributes to the pro-apoptotic effect on glutamate-treated human-bone mesenchymal stem cells.

[Inhibition and significance of pigment epithelium-derived factor in the development and metastasis of prostate cancer].

OBJECTIVE: To study the inhibition and significance of pigment epithelium-derived factor (PEDF) in the development and metastasis of prostate cancer. METHODS: The expression of PEDF was examined in the normal prostate tissue, benign prostatic hyperplasia, prostate cancer tissue and prostate cancer cell lines, PC-3 and Lncap by immunohistochemical SP method and Western blot. In combination with clinical data, statistical analysis was performed to evaluate the relation of the expression level of PEDF in prostate cancer and the relationship between different histological grades of prostate cancer. RESULTS: In normal prostate tissue and benign prostate tissue, the expression of PEDF were elevated and it was far higher than the prostate cancer and prostate cancer cell line. The expression of PEDF and the pathological grade of prostate cancer were related to the differentiated carcinoma of prostate tissue, and the expression level of PEDF in poorly differentiated carcinoma below the highly differentiated carcinoma of prostate cancer. In metastatic prostate cancer, the expression of PEDF was lower than that of prostate cancer without metastasis (12% vs 43.1%). CONCLUSION: The expression of PEDF and the incidence of prostate cancer have a negative correlation. The lower grade of prostate cancer cells, the less the tissue expression of PEDF and the higher tendency of invasion and metastasis.

CRISPR-Cas13-Mediated Knockdown of lncRNA-GACAT3 Inhibited Cell Proliferation and Motility, and Induced Apoptosis by Increasing p21, Bax, and E-Cadherin Expression in Bladder Cancer.

The current study is to investigate the expression pattern and biological function of long non-coding RNA Focally gastric cancer-associated transcript3 (GACAT3) in bladder cancer. Real-time quantitative qPCR was used to detect the expression level of GACAT-3 in tumor tissues and paired normal tissues. Human bladder cancer T24 and 5637 cell lines were transiently transfected with specific CRISPR-Cas13 or negative control CRISPR-Cas13. Cell migration, proliferation, and apoptosis were measured by using wound healing assay CCK-8 assay and Caspase-3 ELISA assay, respectively. The expression changes of p21, Bax, and E-cadherin after knockdown of GACAT3 were detected by using Western blot. The results demonstrated that GACAT3 was up-regulated in bladder cancer tissues than that in the paired normal tissues. Inhibition of cell proliferation, increased apoptosis, and decreased motility were observed in T24 and 5637 cell lines transfected by CRISPR-Cas13 targeting GACAT3. Downregulation of GACAT3 increased p21, Bax, and E-cadherin expression and silencing these genes could eliminate the phenotypic changes induced by knockdown of GACAT3. A ceRNA mechanism for GACAT3 was also revealed. By using CRISPR-Cas13 biotechnology, we suggested that GACAT3 may be a novel target for diagnosis and treatment of bladder cancer.

CREB and Sp1 regulate the human CD2AP gene promoter activity in renal tubular epithelial cells.

The human CD2-associated protein (CD2AP) is involved in several molecular signaling pathways and is an important factor responsible for nephrotic syndrome. Here we report the identification of the transcription start point and promoter region of the human CD2AP gene in renal tubular epithelial cells. With luciferase assays and deletion analysis, we found that the region between -558 and -1bp ahead of the transcription start point is indispensable for the promoter activity of the human CD2AP gene. A CREB site and two Sp1 sites were essential for maintaining the basal transcriptional activity of the human CD2AP promoter. Overexpression of phosphorylated CREB and Sp1 transactivated the human CD2AP promoter, whereas small interfering RNA-mediated blockage of CREB and Sp1 genes expressions inhibited markedly its activity. These findings provide the first analysis of the human CD2AP gene promoter and demonstrate that not only CREB but also Sp1 plays a critical role in regulating basal CD2AP promoter activity in renal tubular epithelial cells.

Overexpression of CRNDE promotes the progression of bladder cancer.

Accumulating evidences indicate that long non-coding RNAs (lncRNAs) are indispensable in cancer initiation and progression. Dysregulation of functional lncRNAs can promote the development of cancers. Previous research have revealed that augmented expression of CRNDE caused poor prognosis of cancer patients and facilitate the tumor progress in various cancers. Nevertheless, the underlying roles of CRNDE in bladder cancer progression are not entirely clear. To further identify the effects CRNDE in bladder cancer progression, we performed the gain and loss of function assay. In this work, we have presented evidence that CRNDE was significantly increased in bladder cancer, and overexpressed expression of CRNDE was positively related with advanced TNM stage of bladder cancer patients. In addition, in vitro experiments showed that CRNDE strengthened cell migration/proliferation and inhibited cell apoptosis in bladder cancer. To sum up, our results exhibited new understand into the role of lncRNA CRNDE in the development of bladder cancer.