Exploration of the influence of GOLGA8B on prostate cancer progression and the resistance of castration-resistant prostate cancer to cabazitaxel.

Castration-resistant prostate cancer (CRPC) represents the final stage of prostate cancer (PCa). Cabazitaxel, a taxane chemotherapy drug, is used in treating CRPC. However, patients with CRPC eventually develop resistance to cabazitaxel, and the underlying mechanism remains unclear. Here, we aimed to investigate potential genetic alterations that may play a role in CRPC resistance to cabazitaxel. Using microarray data from the GSE158494 dataset, we identified ten critical genes (CXCL8, ITGB8, CLIP4, MAP1B, WIPI1, MMP13, CXCL1, C1S, GOLGA8B, and CXCL6) associated with CRPC cell resistance to cabazitaxel. The potential function of these key genes in PCa progression was analyzed using different databases, including Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA). Our findings revealed altered expression of these genes in the development of PCa. Furthermore, CXCL1 and GOLGA8B were found to influence the disease-free survival (DFS) status of patients with PCa, with GOLGA8B affecting the overall prognosis in patients with PCa. Additionally, GOLGA8B expression was associated with the infiltration of various immune cells in PCa, and it was upregulated in clinical PCa and CRPC samples. Through CCK-8 assays, we established that GOLGA8B could influence the sensitivity of CRPC cells to cabazitaxel and docetaxel. In conclusion, we identified GOLGA8B as a crucial gene that influences PCa progression and contributes to CRPC resistance to cabazitaxel.

PRL-mediated STAT5B/ARRB2 pathway promotes the progression of prostate cancer through the activation of MAPK signaling.

Previous study showed that higher expression of prolactin (PRL) was found in CRPC samples compared with hormone-naive prostate cancer (HNPC) and benign prostatic hyperplasia (BPH) samples. We further investigate the function of PRL in prostate cancer (PCa) and explored its downstream effects. We found heterogeneous expression of the PRLR in clinical prostate samples. The VCaP and 22Rv1 cells exhibited PRLR expression. Among the downstream proteins, STAT5B was the dominant subtype in clinical samples and cell lines. Human recombinant PRL stimulation of PCa cells with PRLR expression resulted in increased phosphorylation of STAT5B(pSTAT5B) and progression of PCa in vitro and in vivo, and STAT5B knockdown can suppress the malignant behavior of PCa. To understand the mechanism further, we performed Bioinformatic analysis, ChIP qPCR, and luciferase reporter gene assay. The results revealed that ARRB2 was the transcription target gene of STAT5B, and higher expression of ARRB2 was related to higher aggression and poorer prognosis of PCa. Additionally, Gene set enrichment analysis indicated that higher expression of ARRB2 was significantly enriched in the MAPK signaling pathway. Immunohistochemistry (IHC) demonstrated elevated pSTAT5B, ARRB2, and pERK1/2 expression levels in CRPC tissues compared to HNPC and BPH. Mechanically, ARRB2 enhanced the activation of the MAPK pathway by binding to ERK1/2, thereby promoting the phosphorylation of ERK1/2 (pERK1/2). In conclusion, our study demonstrated that PRL stimulation can promote the progression of PCa through STAT5B/ARRB2 pathway and activation of MAPK signaling, which can be suppressed by intervention targeting STAT5B. Blockade of the STAT5B can be a potential therapeutic target for PCa.

Glycolysis related lncRNA SNHG3 / miR-139-5p / PKM2 axis promotes castration-resistant prostate cancer (CRPC) development and enzalutamide resistance.

Although androgen deprivation therapy (ADT) by the anti-androgen drug enzalutamide (Enz) may improve the survival level of patients with castration-resistant prostate cancer (CRPC), most patients may eventually fail due to the acquired resistance. The reprogramming of glucose metabolism is one type of the paramount hallmarks of cancers. PKM2 (Pyruvate kinase isozyme typeM2) is a speed-limiting enzyme in the glycolytic mechanism, and has high expression in a variety of cancers. Emerging evidence has unveiled that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have impact on tumor development and therapeutic efficacy by regulating PKM2 expression. Herein, we found that lncRNA SNHG3, a highly expressed lncRNA in CRPC via bioinformatics analysis, promoted the invasive ability and the Enz resistance of the PCa cells. KEGG pathway enrichment analysis indicated that glucose metabolic process was tightly correlated with lncRNA SNHG3 level, suggesting lncRNA SNHG3 may affect glucose metabolism. Indeed, glucose uptake and lactate content determinations confirmed that lncRNA SNHG3 promoted the process of glycolysis. Mechanistic dissection demonstrated that lncRNA SNHG3 facilitated the advance of CRPC by adjusting the expression of PKM2. Further explorations unraveled the role of lncRNA SNHG3 as a 'sponge' of miR-139-5p and released its binding with PKM2 mRNA, leading to PKM2 up-regulation. Together, Our studies suggest that lncRNA SNHG3 / miR-139-5p / PKM2 pathway promotes the development of CRPC via regulating glycolysis process and provides valuable insight into a novel therapeutic approach for the disordered disease.

CYP19A1 is downregulated by BRD4 and suppresses castration-resistant prostate cancer cell invasion and proliferation by decreasing AR expression.

Castration-resistant prostate cancer (CRPC) is the final stage of prostate cancer (PCa). As the main androgen in males, testosterone, and its androgen receptor (AR) play an important role in CRPC. The enzyme that catalyzes testosterone, aromatase, can be influenced by CYP19A1 activity - thus possibly affecting both AR expression and CRPC. However, the function of CYP19A1 in CRPC remains unclear. Using data derived from public databases and clinical samples, we analyzed the expression of CYP19A1 in PCa and CRPC specimens. The effect of CYP19A1 on cell invasion and proliferation was investigated in vitro and in vivo; while its function in metabolizing testosterone was detected in vitro. The effect of BRD4 on CYP19A1 and AR was investigated by qRT-PCR and western blot; whereas the effect of JQ1 on cells was assessed based on the IC50 value. We found that CYP19A1 was downregulated in CRPC samples and cells which correlated with a decrease in CRPC cell invasion and proliferation, and an increase in AR expression. Inversely, CYP19A1 affected CRPC cell invasion and proliferation by suppressing the expression of AR which may be attributed to the metabolism of testosterone by CYP19A1. Moreover, the BRD4 inhibitor JQ1 induced the CYP19A1 expression and suppressed the AR expression. Following BRD4 knockdown, CYP19A1 showed higher expression while AR expression was decreased. Our findings demonstrated that CYP19A1 could reduce CRPC cell invasion and proliferation by targeting AR, and this process could be regulated by BRD4. CYP19A1 may be a potential therapeutic target and enhance BRD4 inhibition in treating CRPC.

Identification of cuproptosis-related genes for predicting the development of prostate cancer.

Copper can be toxic at very high intracellular concentrations and can inhibit prostate cancer (PCa) progression. Recently, a study reported the mechanism of cuproptosis and the potentially associated genes. However, the function of these cuproptosis-related genes in PCa remains unknown. Based on the RNA sequence and clinical data from public databases, we analyzed the clinical value of cuproptosis-related genes in PCa. DLD, DLAT, PDHA1, and CDKN2A were expressed differently between normal and PCa tissues. The FDX1, LIAS, DLAT, GLS, and CDKN2A genes can affect PCa progression, while PDHA1 and CDKN2A influence the patients' disease-free survival (DFS) status. The expression of LIAS, LIPT1, DLAT, and PDHB did not alter upon the incidence of PCa in Chinese patients. A constructed regression model showed that FDX1, PDHA1, MTF1, and CDKN2A can be risk factors leading to PCa in both Western and Chinese patients with PCa. The lasso regression model reflected that these genes can affect the patients' DFS status. Additionally, the cuproptosis-related genes were associated with immune cell infiltration. We also verified the high expression of PDHA1 and CDKN2A, in clinical samples. In conclusion, we identified a novel cuproptosis-related gene signature for predicting the development of PCa.

Identification and validation of MSMB as a critical gene for prostate cancer development in obese people.

Prostate cancer (PCA) is one of the most common types of cancer and can seriously endanger the health of older men. Obesity is prevalent all around the world and triggered by lots of factors such as diet, environment and fat metabolism disorder can cause many neoplasms, including PCA. Evidence suggests that genetic changes increase the risk of PCA and obesity. However, the specific obesity-related genes leading to PCA are unknown. Obesity-related genes associated with PCA were identified and analyzed though three public electronic databases: Gene Expression Omnibus, The Cancer Genome Atlas, and Chinese Prostate Cancer Genome and Epigenome Atlas. The effect of obesity-related genes in PCA were analyzed using clinical data from different databases, while associations with immune cells were determined by TIMER web tool. The expression and function of obesity-related genes were verified using clinical samples from obese patients with PCA and PCA cells. We found that four genes, MSMB, BMP5, THBS4, and POPDC3, may lead to PCA occurrence in patients with obesity. In Gene Expression Omnibus database, MSMB and BMP5 were downregulated, while THBS4 and POPDC3 were upregulated. This trend was mainly preserved in the other electronic databases. We also discovered MSMB and THBS4 can affect PCA progression, and all these genes were risk factors for castration-resistant prostate cancer. Moreover, MSMB can impact disease-free survival status of patients with PCA. These obesity-related genes were also correlated with immune cells and immune cell infiltration in PCA. We further uncovered that MSMB was downregulated in clinical PCA and castration-resistant prostate cancer samples from patients with obesity and MSMB decreased PCA cells proliferation. These results indicate that MSMB is essential for PCA development in people with obesity and can be a biomarker for predicting PCA occurrence and progression in obese people.

Analysis of cardiovascular disease factors on SARS-CoV-2 infection severity.

Background: At present, COVID-19 is a global pandemic and is seriously harmful to humans. In this retrospective study, the aim was to investigate the interaction between CVD and COVID-19. Methods: A total of 180 patients diagnosed with COVID-19 in Yichang Central People's Hospital from 29 January to 17 March 2020 were initially included. The medical history, clinical manifestations at the time of admission, laboratory test results, hospitalization time and complications were recorded. According to the medical history, the patients were assigned to the nonsevere group with non-CVD (n = 90), the nonsevere group with CVD (n = 22), the severe group with non-CVD (n = 40) and the severe group with CVD (n = 28). Results: In the severe group, compared with non-CVD patients, CVD patients had a significantly higher incidence of fever (P < 0.05). However, compared with the nonsevere group, the severe group had significantly higher proportions of patients with hypertension, type 2 diabetes mellitus, CHD and HF (all P < 0.05). Among the patients with nonsevere COVID-19, the WBC count and the levels of IL-6, CRP, D-dimer, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the CVD patients than in the non-CVD patients (all P < 0.05). However, among the patients with severe COVID-19, only the level of NT-proBNP was significantly higher in CVD patients than in non-CVD patients (P < 0.05). In addition, the WBC count and the levels of IL-6, CRP, D-dimer, CKMB, ALT, AST, SCR, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the severe group than in the nonsevere group (all P < 0.05). However, among the patients with severe COVID-19, the incidences of acute myocardial injury, acute kidney injury, arrhythmia, and sudden death were significantly higher in the CVD group than in the non-CVD group (all P < 0.05). The same results were found in the comparison of the nonsevere group with the severe group. Among the patients with nonsevere COVID-19, those without CVD had a mean hospitalization duration of 25.25 (SD 7.61) days, while those with CVD had a mean hospitalization duration of 28.77 (SD 6.11) days; the difference was significant (P < 0.05). The same results were found in the comparison of the severe group. Conclusions: CVD affects the severity of COVID-19. COVID-19 also increases the risk of severe CVD.

Antecedentes: La infección por SARS-CoV-2 está provocando graves consecuencias en la humanidad. El objetivo de este estudio retrospectivo fue investigar el impacto de las enfermedades cardiovasculares (ECV) en la gravedad de dicha infección. Métodos: Entre el 29 de enero y el 17 de marzo de 2020, se diagnosticaron 180 pacientes con neumonía por SARS-CoV-2 en el Hospital Popular Central de Yichang. Se registraron los antecedentes, manifestaciones clínicas, resultados de laboratorio, tiempo de hospitalización y complicaciones. Los pacientes se dividieron en cuatro grupos: 1) infección no grave sin ECV (n = 90), 2) infección no grave con ECV (n = 22), 3) infección grave sin ECV (n = 40) y 4) infección grave con ECV (n = 28). Resultados: La prevalencia de fiebre en los pacientes con ECV fue significativamente mayor que en aquellos sin ECV (P < 0,05). Sin embargo, en comparación con los pacientes no graves, la proporción de pacientes con hipertensión, diabetes mellitus tipo 2, cardiopatía coronaria e insuficiencia cardíaca en los pacientes graves fue significativamente mayor (p< 0,05). Los niveles de recuento de leucocitos, IL-6, PCR, dímero D, NT-proBNP y glucemia en ayunas (GA) en pacientes con ECV fueron significativamente mayores que en los de pacientes sin ECV, aunque los niveles de Hb fueron significativamente menores que los de los pacientes sin ECV (p< 0,05). Sin embargo, los valores de NT-proBNP en pacientes con ECV fueron significativamente mayores que en los pacientes sin ECV (P< 0,05). Además, el recuento de leucocitos y los niveles de IL-6, PCR, dímero D, CK-MB, ALT, AST, creatinina, NT-proBNPy GA en el grupo de pacientes graves fueron significativamente mayores que en el grupo no grave, mientras que los valores de Hb fueron significativamente menores que en el grupo no grave (p< 0,05). La prevalencia de lesión miocárdica aguda, lesión renal aguda, arritmia y muerte súbita en el grupo con ECV fue significativamente mayor que en el grupo sin ECV (p< 0,05). Los mismos resultados se encontraron al comparar los pacientes no graves con aquellos con infección grave. Entre los pacientes no graves, la duración media de la estancia hospitalaria fue de 25,25 (DE: 7,61) días en los pacientes sin ECV, mientras que la duración media de la estancia hospitalaria fue de 28,77 (DE: 6,11) días en los pacientes con ECV (p< 0,05). Los mismos resultados se observaron al comparar los dos grupos con infección grave. Conclusiones: La infección por SARS-CoV-2 es de evolución más grave en los pacientes con ECV.

New progress in diagnosis and treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease. Although great progress has been made in its diagnosis and treatment in recent years, its mortality rate is still very significant. The pathophysiology and pathogenesis of PAH are complex and involve endothelial dysfunction, chronic inflammation, smooth muscle cell proliferation, pulmonary arteriole occlusion, antiapoptosis and pulmonary vascular remodeling. These factors will accelerate the progression of the disease, leading to poor prognosis. Therefore, accurate etiological diagnosis, treatment and prognosis judgment are particularly important. Here, we systematically review the pathophysiology, diagnosis, genetics, prognosis and treatment of PAH.

Analysis of cardiovascular disease factors on SARS-CoV-2 infection severity

Background:At present, COVID-19 is a global pandemic and is seriously harmful to humans. In this retrospective study, the aim was to investigate the interaction between CVD and COVID-19.Methods:A total of 180 patients diagnosed with COVID-19 in Yichang Central People's Hospital from 29 January to 17 March 2020 were initially included. The medical history, clinical manifestations at the time of admission, laboratory test results, hospitalization time and complications were recorded. According to the medical history, the patients were assigned to the nonsevere group with non-CVD (n=90), the nonsevere group with CVD (n=22), the severe group with non-CVD (n=40) and the severe group with CVD (n=28).Results:In the severe group, compared with non-CVD patients, CVD patients had a significantly higher incidence of fever (P<0.05). However, compared with the nonsevere group, the severe group had significantly higher proportions of patients with hypertension, type 2 diabetes mellitus, CHD and HF (all P<0.05). Among the patients with nonsevere COVID-19, the WBC count and the levels of IL-6, CRP, D-dimer, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the CVD patients than in the non-CVD patients (all P<0.05). However, among the patients with severe COVID-19, only the level of NT-proBNP was significantly higher in CVD patients than in non-CVD patients (P<0.05). In addition, the WBC count and the levels of IL-6, CRP, D-dimer, CKMB, ALT, AST, SCR, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the severe group than in the nonsevere group (all P<0.05). (AU)

Antecedentes:La infección por SARS-CoV-2 está provocando graves consecuencias en la humanidad. El objetivo de este estudio retrospectivo fue investigar el impacto de las enfermedades cardiovasculares (ECV) en la gravedad de dicha infección.Métodos:Entre el 29 de enero y el 17 de marzo de 2020, se diagnosticaron 180 pacientes con neumonía por SARS-CoV-2 en el Hospital Popular Central de Yichang. Se registraron los antecedentes, manifestaciones clínicas, resultados de laboratorio, tiempo de hospitalización y complicaciones. Los pacientes se dividieron en cuatro grupos: 1) infección no grave sin ECV (n=90), 2) infección no grave con ECV (n=22), 3) infección grave sin ECV (n=40) y 4) infección grave con ECV (n=28).Resultados:La prevalencia de fiebre en los pacientes con ECV fue significativamente mayor que en aquellos sin ECV (P<0,05). Sin embargo, en comparación con los pacientes no graves, la proporción de pacientes con hipertensión, diabetes mellitus tipo 2, cardiopatía coronaria e insuficiencia cardíaca en los pacientes graves fue significativamente mayor (p<0,05). Los niveles de recuento de leucocitos, IL-6, PCR, dímero D, NT-proBNP y glucemia en ayunas (GA) en pacientes con ECV fueron significativamente mayores que en los de pacientes sin ECV, aunque los niveles de Hb fueron significativamente menores que los de los pacientes sin ECV (p<0,05). Sin embargo, los valores de NT-proBNP en pacientes con ECV fueron significativamente mayores que en los pacientes sin ECV (P<0,05). (AU)

The critical role and molecular mechanisms of ferroptosis in antioxidant systems: a narrative review.

Background and Objective: Ferroptosis is a recently discovered form of cell death which differs from other forms of cell death in terms of morphology, biochemistry, and regulatory mechanisms. Ferroptosis is regulated by a complex system and the precise molecular mechanisms are still being elucidated. Over the past few years, extensive research has revealed that the essence of ferroptosis is iron-dependent accumulation of lipid hydroperoxides induced by oxidative stress, and the System Xc-glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway is the main ferroptosis prevention system. Meanwhile, other antioxidant systems have also been implicated in regulating ferroptosis, including the transsulfuration pathway, mevalonate pathway, ferroptosis inhibitory protein 1 (FSP1)-Coenzyme Q10 (CoQ10) pathway, dihydroorotate dehydrogenase (DHODH)-dihydroubiquione (CoQH2) pathway, and GTP cyclohydrolase-1 (GCH1)-tetrahydrobiopterin (BH4) pathway. This article reviews the molecular mechanisms of ferroptosis and its critical role in antioxidant systems, aiming to reveal that antioxidation is an important method of inhibiting ferroptosis and to provide a new direction for the treatment of ferroptosis-related diseases. Methods: We searched all original papers and reviews about the molecular mechanisms of ferroptosis in antioxidant systems using PubMed to November 2021. The search terms used included: 'ferroptosis', 'ferroptosis inducers', 'ferroptosis inhibitors', 'ferroptosis and GSH', 'ferroptosis and GPX4', 'ferroptosis and System Xc-', 'SLC7A11', 'P53', 'NRF2 and ferroptosis', 'iron metabolism', 'lipid peroxidation', 'antioxidant systems', 'transsulfuration pathway', 'mevalonate pathway', 'FSP1-CoQ10', 'DHODH-CoQH2', and 'GCH1-BH4'. Key Content and Findings: We first introduced the origin of ferroptosis and its common inhibitors and inducers. Next, we discussed the molecular mechanisms of ferroptosis and its role in antioxidant systems in existing studies. Finally, we briefly summarized the relationship between ferroptosis and diseases. It reveals that antioxidation is an important method of inhibiting ferroptosis. Conclusions: This review discusses the recent rapid progress in the understanding of the molecular mechanisms of ferroptosis and its role in several antioxidant systems.

An Early Warning of Atrial Fibrillation Based on Short-Time ECG Signals.

This study introduces a method to classify single-lead ECG signals by extracting features through traditional methods and deep neural network methods. At first step, the statistical type features of the ECG signals are exacted by traditional methods, including time domain features, frequency domain features, and medical domain features. And then, deep neural networks are used to extract the deeper features of the ECG signal. The database of ECG signals is from Cinc 17, which have 8528 samples of short-time ECG signal. The huge amount of data makes the classification and identification more accurate by atrial fibrillation, normal sinus rhythm, noise, and indiscernible. Compare the base model built by the classified data and the data collected by the ECG device of CareON to enable daily early screening and a remote alert function with WeChat app. This method can extend the prevention, detection, and diagnosis of heart disease to the family, company, and other out-of-hospital scenarios, thus enabling faster treatment of heart patients and saving medical resources.

CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine.

Background: Prostate cancer (PCa) is a common malignancy occurring in men. As both an endocrine and gonadal organ, prostate is closely correlated with androgen. So, androgen deprivation therapy (ADT) is effective for treating PCa. However, patients will develop castration-resistant prostate cancer (CRPC) stage after ADT. Many other treatments for CRPC exist, including chemotherapy. Vinblastine, a chemotherapeutic drug, is used to treat CRPC. However, patients will develop resistance to vinblastine. Genetic alterations have been speculated to play a critical role in CRPC resistance to vinblastine; however, its mechanism remains unclear. Methods: Various databases, such as Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA), were used to collect the RNA-sequence data of PCa and CRPC patients and vinblastine-resistant PCa cells. Using online tools, Metascape and TIMER, the pathways and immune infiltration associated with vinblastine resistance-related genes in PCa were analyzed. The function of these genes was verified in clinical samples and CRPC cells. Results: Using GSE81277 dataset, we collected the RNA-sequence data of vinblastine sensitive and resistant LNCaP cells and found nine genes (CDC20, LRRFIP1, CCNB1, GPSM2, AURKA, EBLN2, CCDC150, CENPA and TROAP) that correlated with vinblastine resistance. Furthermore, CCNB1, GPSM2 and AURKA were differently expressed between normal prostate and PCa tissues, even influencing PCa progression. The GSE35988 dataset revealed that CCNB1 and AURKA were upregulated in PCa and CRPC samples. Various genes were also found to affect the survival status of PCa patients based on TCGA. These genes were also related to immune cell infiltration. Finally, we verified the function of CCNB1 and AURKA and observed that they were upregulated in PCa and CRPC clinical samples and increased the sensitivity of CRPC cells to vinblastine. Conclusion: CCNB1 and AURKA are central to CRPC resistance to vinblastine and affect PCa progression.

Analysis of cardiovascular disease factors on SARS-CoV-2 infection severity.

BACKGROUND: At present, COVID-19 is a global pandemic and is seriously harmful to humans. In this retrospective study, the aim was to investigate the interaction between CVD and COVID-19. METHODS: A total of 180 patients diagnosed with COVID-19 in Yichang Central People's Hospital from 29 January to 17 March 2020 were initially included. The medical history, clinical manifestations at the time of admission, laboratory test results, hospitalization time and complications were recorded. According to the medical history, the patients were assigned to the nonsevere group with non-CVD (n=90), the nonsevere group with CVD (n=22), the severe group with non-CVD (n=40) and the severe group with CVD (n=28). RESULTS: In the severe group, compared with non-CVD patients, CVD patients had a significantly higher incidence of fever (P<0.05). However, compared with the nonsevere group, the severe group had significantly higher proportions of patients with hypertension, type 2 diabetes mellitus, CHD and HF (all P<0.05). Among the patients with nonsevere COVID-19, the WBC count and the levels of IL-6, CRP, D-dimer, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the CVD patients than in the non-CVD patients (all P<0.05). However, among the patients with severe COVID-19, only the level of NT-proBNP was significantly higher in CVD patients than in non-CVD patients (P<0.05). In addition, the WBC count and the levels of IL-6, CRP, D-dimer, CKMB, ALT, AST, SCR, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the severe group than in the nonsevere group (all P<0.05). However, among the patients with severe COVID-19, the incidences of acute myocardial injury, acute kidney injury, arrhythmia, and sudden death were significantly higher in the CVD group than in the non-CVD group (all P<0.05). The same results were found in the comparison of the nonsevere group with the severe group. Among the patients with nonsevere COVID-19, those without CVD had a mean hospitalization duration of 25.25 (SD 7.61) days, while those with CVD had a mean hospitalization duration of 28.77 (SD 6.11) days; the difference was significant (P<0.05). The same results were found in the comparison of the severe group. CONCLUSIONS: CVD affects the severity of COVID-19. COVID-19 also increases the risk of severe CVD.

Immune microenvironment infiltration landscape and immune-related subtypes in prostate cancer.

Background: The tumor microenvironment (TME) primarily comprises cancer cells, cancer-infiltrating immune cells, and stromal cells. The tumor cells alter the TME by secreting signaling molecules to induce immune tolerance. The immune cell infiltrating the TME influences the prognosis of patients with cancers. However, immune cell infiltration (ICI) in the TME of patients with prostate cancer (PC) has not yet been studied. Methods: In this study, we used Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and Estimation of Stromal and Immune cells in Malignant Tumors using Expression data (ESTIMATE) algorithms to identify three ICI clusters based on 1,099 genes associated with ICI in the TME. The patients were classified into three distinct ICI gene clusters based on overlapping differentially expressed genes in ICI clusters. Furthermore, the ICI scores were calculated using principal component analysis. Results: The results revealed that patients with high ICI scores had poor prognoses and reduced expression of immune-checkpoint genes and immune-related genes. Furthermore, the transforming growth factor-beta (TGF-ß) and WNT-ß signaling pathways were enriched in the high ICI score subgroup, which suggests that suppression of T cells could contribute to poor prognosis of patients with PC. A positive correlation was observed between the high-ICI-score subgroup and the high tumor mutation burden (TMB) value. Patients with low ICI scores could benefit from immunotherapy, indicating that the ICI score could be used to predict the efficacy of immunotherapeutic response. Conclusions: In summary, we provide a comprehensive overview of the landscape of ICI in PC, which could aid in designing the strategies for immunotherapy for patients with PC.

Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review.

Bipolar androgen therapy (BAT) is a new endocrinologic treatment for castration-resistant prostate cancer (CRPC) that can restore some patients' sensitivity to drugs such as abiraterone (Abi) and enzalutamide (Enz). We performed a meta-analysis using STATA16. Sensitivity analyses were performed by examining the effects of individual studies using different effect models and detecting any publication bias using the Harbord test. In a total of 108 unique records, ten studies were included in the final meta-analysis. Participants who underwent BAT achieved a PSA50 response rate of 27% (95%CI [0.22,0.31], I2=17.98%), ORR of 34% (95%CI [0.24,0.43], I2=0), and incidence of AEs (grade≥3) of 14% (95%CI [0.09,0.19], I2=0). Patients who completed BAT proceeded to AR-targeted therapy (Abi or Enz) and achieved a PSA50 response rate of 57% (95% CI [0.36,0.78], I2=0). Patients with prior Enz resistance had a stronger impact on the PSA50 of AR-target therapy rechallenge. The results of this meta-analysis indicate that BAT is a safe and effective treatment for patients who have progressed after Abi or Enz. BAT can trigger the resensitization of patients with CRPC to subsequent endocrine therapy and improve the overall survival of patients and their quality of life.

Identification of quantitative trait loci associated with upper temperature tolerance in turbot, Scophthalmus maximus.

Temperature tolerance is an important trait from both an economic and evolutionary perspective in fish. Because of difficulties with measurements, genome-wide selection using quantitative trait loci (QTLs) affecting Upper temperature tolerance may be an alternative for genetic improvement. Turbot Scophthalmus maximus (L.) is a cold-water marine fish with high economic value in Europe and Asia. The genetic bases of upper temperature tolerance (UTTs) traits have been rarely studied. In this study, we constructed a genetic linkage map of turbot using simple sequence repeats (SSRs) and single nucleotide polymorphism (SNP) markers. A total of 190 SSR and 8,123 SNP were assigned to 22 linkage groups (LGs) of a consensus map, which spanned 3,648.29 cM of the turbot genome, with an average interval of 0.44 cM. Moreover, we re-anchored genome sequences, allowing 93.8% physical sequences to be clustered into 22 turbot pseudo-chromosomes. A high synteny was observed between two assemblies from the literature. QTL mapping and validation analysis identified thirteen QLTs which are major effect QTLs, of these, 206 linked SNP loci, and two linked SSR loci were considered to have significant QTL effects. Association analysis for UTTs with 129 QTL markers was performed for different families, results showed that eight SNP loci were significantly correlated with UTT, which markers could be helpful in selecting thermal tolerant breeds of turbot. 1,363 gene sequences were genomically annotated, and 26 QTL markers were annotated. We believe these genes could be valuable candidates affecting high temperatures, providing valuable genomic resources for the study of genetic mechanisms regulating thermal stress. Similarly, they may be used in marker-assisted selection (MAS) programs to improve turbot performance.

Molecular characterization of ubiquitin-conjugating enzyme gene ube2h and siRNA-mediated regulation on targeting p53 in turbot, Scophthalmus maximus.

Ubiquitin-conjugating enzymes are key factors in the ubiquitin proteasome pathway (UPP), which play key roles in ubiquitination. These enzymes affect the efficiency of UPP during stress conditions. P53 has important control of cell cycle arrest and apoptosis in response to cellular stress; these modifications are critical for the stability and transcriptional activity of p53 as the protein activates downstream target genes that dictate the cellular response. However, few studies have investigated the effects of thermal stress in turbot (Scophthalmus maximus), specifically the UPP signaling pathway, and the crosstalk between the ube2h and p53. In this study, the rapid amplification of cDNA ends was used to obtain a full-length cDNA of the turbot UBE2H gene (Sm-ube2h) and perform bioinformatics analysis. Our results showed that the cDNA of the Sm-ube2h was 718 bp in length, encoding a 189 amino acid protein, with a theoretical isoelectric point of 4.77. It also contained a catalytic (UBCc) domain. Expression of Sm-ube2h in different tissues was detected and quantified by qPCR, which was highest in the spleen and lowest in the liver. We also investigated the Sm-ube2h expression profiles in the liver and heart after thermal stress, and changes in Sm-ube2h and p53 under thermal stress, upon RNA interference. Our data speculated that Sm-ube2h and p53 exhibited antagonistic effects under normal temperature conditions after ube2h interference, but displayed synergistic effects under thermal stress, suggesting the crosstalk between UPP and p53 signaling pathway. Our results improved our understanding of the underlying molecular mechanism of thermal tolerance in turbot.

Detection Method and System of the Human Body Characteristic Index Based on TCM.

As traditional Chinese medicine (TCM) has gained more and more recognition in the world, Chinese medicine has also played its important role. However, traditional Chinese medicine equipment is relatively deficient, with insufficient functions and low degree of digitalization. For example, existing auscultation equipment can obtain few human characteristic indicators, which is difficult to meet the needs of reference in traditional Chinese medicine diagnosis. Based on this, this paper designed a human body characteristic index detection system based on the principle of traditional Chinese medicine, which includes respiratory and heartbeat signal acquisition device, meridian and acupoint signal acquisition device, temperature signal acquisition device, pulse and blood pressure acquisition device, processing module, keyword module, and output module. The respiratory and heartbeat signal acquisition device is used to collect the respiratory and heartbeat signal of human body. Meridian acupoint signal acquisition device is used to collect human meridian acupoint radio signals. The temperature signal acquisition device is used to collect the infrared temperature light wave signal of human body. Pulse and blood pressure acquisition devices are used to collect pulse and blood pressure signals. The processing module is used to obtain one or more human body characteristic indicators according to one or more of the respiration and heartbeat signals, meridians and acupoints signals, temperature signals, pulse, and blood pressure, including Qi and blood characteristic indicators, viscera and six meridian characteristic indicators, and temperature characteristic indicators. The keyword corresponding module is used to obtain the corresponding keyword representing the physiological state information of human body according to the one or more human body characteristic indicators. The output module is used to output the human body characteristic index and the key words. It includes the key words of Qi and blood state information, the key words of viscera state information, the key words of Qi and blood state information, etc. The system can be used for serious disease screening, chronic disease management, and risk early warning.

Cellular FADD-like IL-1ß-converting enzyme-inhibitory protein attenuates myocardial ischemia/reperfusion injury via suppressing apoptosis and autophagy simultaneously.

BACKGROUND AND AIMS: Myocardial ischemia/reperfusion injury (MI/RI) is a result of coronary revascularization, and often increases cell apoptosis and autophagy. Downregulated cellular FADD-like-IL-1ß-converting enzyme-inhibitory protein (cFLIP) was associated with development of several myocardial diseases, whether overexpression of cFLIP can attenuate MI/RI remains unclear. This study aimed to determine the effects of cFLIP on apoptosis and autophagy in MI/RI. METHODS AND RESULTS: Ischemia/reperfusion (I/R) rat model and hypoxia/reoxygenation (H/R) cardiomyocytes model were established. Both I/R injury and H/R injury down-regulated expression of two cFLIP isoforms (cFLIPL and cFLIPS), and instigated apoptosis and autophagy simultaneously. Overexpression of cFLIPL and/or cFLIPS led to a significant increase in cardiomyocytes viability in vitro, and also reduced the myocardial infarct volume in vivo, these changes were associated with suppressed apoptosis and autophagy. Mechanistically, overexpression of cFLIP significantly downregulated pro-apoptotic molecules (Caspase-3, -8, -9), and pro-autophagic molecules (Beclin-1 and LC3-II). Moreover, cFLIP significantly suppressed activity of NF-κB pathway to upregulate the expression of Bcl-2, which is the molecular of interplay of apoptosis and autophagy. CONCLUSION: Overexpression of cFLIP significantly attenuated MI/RI both in vivo and vitro via suppression of apoptosis and lethal autophagy. cFLIP can suppress activity of NF-κB pathway, and further upregulated expression of Bcl-2.

Statistical Analysis of the Relationship between AETA Electromagnetic Anomalies and Local Earthquakes.

To verify the relationship between AETA (Acoustic and Electromagnetics to Artificial Intelligence (AI)) electromagnetic anomalies and local earthquakes, we have performed statistical studies on the electromagnetic data observed at AETA station. To ensure the accuracy of statistical results, 20 AETA stations with few data missing and abundant local earthquake events were selected as research objects. A modified PCA method was used to obtain the sequence representing the signal anomaly. Statistical results of superposed epoch analysis have indicated that 80% of AETA stations have significant relationship between electromagnetic anomalies and local earthquakes. These anomalies are more likely to appear before the earthquakes rather than after them. Further, we used Molchan's error diagram to evaluate the electromagnetic signal anomalies at stations with significant relationships. All area skill scores are greater than 0. The above results have indicated that AETA electromagnetic anomalies contain precursory information and have the potential to improve local earthquake forecasting.