Identification and validation of RB1 as an immune-related prognostic signature based on tumor mutation burdens in bladder cancer.

Bladder cancer (BCa) is one of the most common malignant tumors in the urinary system. Developing effective prognostic gene and exploring the immune cells that affect the prognosis of tumor are required. Full transcriptome data ( n = 433), clinical information ( n = 581) and mutation sequencing ( n = 412) were obtained from The Cancer Genome Atlas and independent mutation sequencing data of 101 samples were acquired from International Cancer Genome Consortium. Statistical processing was conducted using R packages. Gene biologically functional research was performed with gene set enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes database. Twenty-two types of immune cell infiltration were assessed and calculated in 398 samples of BCa. Furthermore, the expression of immune-related prognostic signature was verified. The relationship between prognostic gene and immune cells was explored preliminarily. Tumor mutation burdens of mutant-type groups were higher than wild-type groups of 19 genes, except for FGFR3 and CREBBP. Kaplan-Meier analysis showed that high frequency of retinoblastomal 1 (RB1) mutation led to poor prognosis of BCa patients and was an independent prognostic factor ( P = 0.004; HR = 1.776). Proportions and correlation of 22 types of immune cells in 433 samples were determined. We found that RB1 expression decreased in BCa validated through quantitative PCR and immunohistochemistry. In addition, regulatory T cells (Tregs) were detected as a negatively correlated type of immune cell to mutation of RB1, whereas fluorescence costaining showed that Foxp3 expression of Tregs infiltration was negatively related to the expression of RB1. Mutation of RB1 can be identified as an independent prognostic predictor of BCa, and it may suppress the infiltration of Tregs in BCa tissues, increasing the incidence of tumor immune escape.

Analysis of the Current Situation and Influencing Factors of Coping Styles in Ischemic Stroke Patients.

Objective: To explore the current situation and influencing factors of coping styles in ischemic stroke patients. Methods: 250 ischemic stroke patients admitted to our hospital from September 2019 to September 2021 were selected as the study subjects to obtain the general information of patients, and the corresponding indexes of patients were evaluated by the method of document investigation to analyze the current situation and influencing factors of coping styles in ischemic stroke patients. Results: Under stressful conditions, patients with no dependence on life-support level, without anxiety and depression, enjoying a high quality of life, and with high self-efficacy were more likely to adopt the positive coping styles (P < .05). Logistic regression analysis showed that infarction area, life-support level, and self-efficacy were independent risk factors for coping style in patients with ischemic stroke (all P < .05). Conclusion: Ischemic stroke patients tend to adopt negative coping styles. Infarction area, life-support level, and self-efficacy of ischemic stroke patients are found to be the main factors affecting their coping styles.

Severe varicella-zoster virus meningoencephalomyelitis coexisting with visceral disseminated varicella-zoster virus infection in a patient with lupus nephritis: A case report.

RATIONALE: Meningoencephalomyelitis and visceral dissemination infection are rare but life-threatening complications of either the primary infection or reactivation of varicella-zoster virus (VZV) in immunocompromised patients. To date, few studies have reported the co-existence of VZV meningoencephalomyelitis and the visceral dissemination of VZV infection. PATIENT CONCERNS: A 23-year-old male was diagnosed with lupus nephritis class III and was being treated with oral prednisone and tacrolimus. The patient exhibited herpes zoster 21-day after the initiation of therapy and experienced unbearable abdominal pain and generalized seizures 11 days after the onset of a zoster rash. Magnetic resonance imaging showed progressive lesions in the cerebrum, brainstem, and cerebellum, as well as meningeal thickening and thoracic myelitis. Computed tomography showed pulmonary interstitial infiltration, partial intestinal dilatation, and effusion. Metagenomic next-generation sequencing revealed 198,269 and 152,222 VZV-specific reads in the cerebrospinal fluid and bronchoalveolar lavage fluid, respectively. DIAGNOSES: Based on the clinical and genetic findings, this patient was finally diagnosed with VZV meningoencephalomyelitis and visceral disseminated VZV infection. INTERVENTIONS: The patient received intravenous acyclovir (0.5 g every 8 hours) combined with plasma exchange and intravenous immunoglobulin. Treatment against secondary bacterial and fungal infections, organ support therapy and rehabilitation training were given simultaneously. OUTCOME: The patient's peripheral muscle strength did not improve and repeated metagenomic next-generation sequencing showed the persistence of VZV-specific reads in the cerebrospinal fluid. The patient finally abandoned therapy due to financial constraints at the 1-month follow-up. LESSONS: Patients with autoimmune diseases receiving immunosuppressive therapy should be warned about the possibility of developing serious neurological infections and visceral disseminated VZV infections as side effects. Early diagnosis and the early initiation of intravenous acyclovir therapy are important for such cases.

Bioinformatics analysis of the potential regulatory mechanisms of renal fibrosis and the screening and identification of factors related to human renal fibrosis.

Background: This paper aimed to identify the key genes and potential mechanisms of renal fibrosis, and provide methods of evaluation and new ideas for the early diagnosis and treatment of renal fibrosis. Methods: The GSE102515 dataset was searched from the Gene Expression Omnibus (GEO) database was searched, the differential genes were screened out, and the down-regulated and up-regulated genes were identified. Enrichment analysis of differential genes in the development of renal fibrosis was carried out using the DAVID database, differential genes were analyzed using the STRING database, and Cytoscape software was used for visual processing. Results: Eighteen up-regulated genes and ten down-regulated genes were screened. Differential genes are mainly involved in the integrin-mediated signaling pathway and mitotic sister chromatid binding, etc. We found that the molecular functions (MFs) of the differential genes are phospholipid binding and regulatory region DNA binding, etc. Moreover, the cellular components (CCs) of the differential genes are mainly related to low-density lipoprotein (LDL) particles and nuclei. Screening revealed that ADM, ARRB1, AVPR2, CCR1, MTNR1A, PTH, and S1PR2 were core genes in the interaction network of renal fibrosis risk-related proteins. Conclusions: In this study, the differential genes in the occurrence of renal fibrosis were screened out via dataset analysis. It was found that ADM, ARRB1, AVPR2, CCR1, MTNR1A, PTH, and S1PR2 may be important participants in the development of renal fibrosis, which provides analytical support for the identification of valuable markers of renal fibrosis.

Application of extracorporeal therapies in critically ill COVID-19 patients.

The coronavirus disease 2019 (COVID-19) pandemic is a major public health event caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has spread widely all over the world. A high proportion of patients become severely or critically ill, and suffer high mortality due to respiratory failure and multiple organ dysfunction. Therefore, providing timely and effective treatment for critically ill patients is essential to reduce overall mortality. Convalescent plasma therapy and pharmacological treatments, such as aerosol inhalation of interferon-α (IFN-α), corticosteroids, and tocilizumab, have all been applied in clinical practice; however, their effects remain controversial. Recent studies have shown that extracorporeal therapies might have a potential role in treating critically ill COVID-19 patients. In this review, we examine the application of continuous renal replacement therapy (CRRT), therapeutic plasma exchange (TPE), hemoadsorption (HA), extracorporeal membrane oxygenation (ECMO), and extracorporeal carbon dioxide removal (ECCO2R) in critically ill COVID-19 patients to provide support for the further diagnosis and treatment of COVID-19.

Transient receptor potential ankyrin 1 mediates cisplatin-induced apoptosis in renal tubular cells via calcium-dependent signaling pathway.

BACKGROUND: Cisplatin has been a vital drug used for tumor treatment because of its excellent effect on numerous malignant solid cancers. Nonetheless, its nephrotoxicity is non-negligible in clinical practice. This study aims to provide a new understanding of the molecular mechanism of transient receptor potential ankyrin 1 (TRPA1) in cisplatin-induced renal apoptosis. METHODS: We evaluated the effect on apoptosis, TRPA1 expression, and intracellular calcium concentration of human kidney 2 (HK-2) cells induced by diamminedichloroplatinum (DDP). Additionally, we also assessed DDP-induced apoptosis, the expression of Bax, caspase3, cleaved-cas3, p53, Bcl-2 and intracellular calcium concentration combined with HC-030031 and/or pifithrin-α. The effect of FK506 on apoptosis of HK-2 cells induced by DDP and the expression of the nuclear factor of activated T cells (NFAT) protein treated with HC-030031, pifithrin-α, and/or FK506 were also explored. RESULTS: The results showed that apoptosis, TRPA1 expression, and intracellular calcium concentration of HK-2 cell induced by DDP were enhanced in a dose-dependent manner. HC-030031 and pifithrin-α relieved apoptosis, and intracellular calcium concentration and the expression of NFAT and phospho-NFAT (p-NFAT) were induced by DDP. HC-030031 combined with pifithrin-α further aggravated the above-mentioned tendency, including relieved apoptosis, intracellular calcium concentration, and NFAT and p-NFAT expression. HC-030031 and FK506 decelerated the apoptosis, and NFAT and p-NFAT expression of HK-2 cells was induced by DDP, while simultaneous treatment with HC-030031 and FK506 further decreased apoptosis and protein expression. However, the expression of Bcl-2 increased when HC-030031, pifithrin-α, or FK506 was used alone, and HC-030031 combined with pifithrin-α or FK506 further improved the expression of Bcl-2. CONCLUSIONS: TRPA1 mediates cisplatin-induced apoptosis in renal tubular cells via the calcineurin-nuclear factor of activated T-cells-p53 signaling pathway.

Clinical Study on Effect of Solution Focused Approach on the Complications, Pain, Sleep, and Quality of Life in Patients with Hepatocellular Carcinoma Undergoing TACE.

OBJECTIVE: The objective of this study is to explore the effect of solution focused approach (SFA) on the complications, pain, sleep, and quality of life in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization (TACE). METHODS: Total of 106 patients with hepatocellular carcinoma who underwent TACE in our hospital from July 2019 to June 2020 were selected. According to the admission time, they were divided into the control group (n = 53) and the observation group (n = 53). The control group implemented routine nursing intervention, and the observation group implemented SFA on the basis of the control group. The clinical data, complications, pain, sleep status, and quality of life scores were compared between the two groups. RESULTS: The total incidence of complications in the observation group (16.98%) was lower than that in the control group (33.96%) (P < 0.05). There was no significant difference in the score of pain perception between the two groups (P > 0.05). The scores of sleep status in the observation group were lower than those in the control group (P < 0.05). The quality of life scores in the observation group was higher than that in the control group (P < 0.05). CONCLUSION: SFA can effectively reduce the complications, relieve pain, improve sleep status, and improve the quality of life in patients with hepatocellular carcinoma undergoing TACE.

The relationship between prescription of ultrafiltration and intradialytic hypotension in Chinese hemodialysis patients.

BACKGROUND: Intradialytic hypotension (IDH) remains the most frequent severe side effect of hemodialysis (HD) and increases patient morbidity and mortality. Excessive ultrafiltration (UF) is considered the leading cause of IDH. This study developed a suitable prescription of UF to reduce the incidences of IDH episodes. METHODS: A retrospective study was performed to analyze 33,224 HD/hemodiafiltration (HDF) treatments in 312 patients. The prescription of UF were determined following the International Society of Peritoneal Dialysis (ISPD) guideline. The Pearson's method was used to study the correlation between relative variables. The receiver operating characteristic (ROC) curve was used to predict the value of the UF/weight ratio (UF/Wt) for IDH in all patients to establish a diagnostic cut-off point. Univariate and multivariate logistic regression analyses were applied to study the risk factors of IDH. RESULTS: Twelve thousand five hundred and fifty-eight sessions of IDH (38.7%) were identified, among which 1,224 (3.6%) were recorded with intervention against IDH. Both the systolic blood pressure (SBP) and mean arterial pressure (MAP) of the hemodialytic patients were positively correlated with the UF quantity and the UF/Wt, but negatively correlated with blood flow. The ROC curve showed that UF/Wt =0.04 was the cut-off point for IDH. Age [per 10-year increment, odds ratio (OR) =1.005, 95% confidence interval (CI): 1.004 to 1.007, P=0.000], diabetes mellitus (OR =1.209, 95% CI: 1.122 to 1.303, P=0.000), and UF/Wt >0.04 (OR =1.605, 95% CI: 1.532 to 1.682, P=0.000) were all independently associated with higher incidences of IDH. CONCLUSIONS: IDH commonly occurs during HD in Chinese patients. Unchangeable factors such as diabetes and age, and modifiable factors including UF were associated with IDH. A UF/Wt threshold more than 0.04 may be a potential alert for avoiding IDH, especially in the elderly and diabetic patients.

Application of self-care based on full-course individualized health education in patients with chronic heart failure and its influencing factors.

BACKGROUND: The treatment of heart failure not only needs to relieve the clinical symptoms and improve the quality of life for patients but also needs to select scientific and reasonable ways to prevent or delay the progression of the disease, thus reducing the mortality and hospitalization rate. Although the previous regimen can effectively relieve symptoms in the early stage of treatment, long-term use may cause adverse events, such as arrhythmia, and even increase mortality. Therefore, conventional treatment cannot meet the actual health needs of patients, and scientific nursing intervention is very necessary. AIM: To investigate the application of self-care based on full-course individualized health education (FCIHE) and its influencing factors in patients with chronic heart failure (CHF). METHODS: We enrolled CHF patients who were admitted to our center between September 2015 and June 2016 and divided them into an intervention group (n = 50) and control group (n = 50) using a random number table. Routine nursing care was applied to the control group, and FCIHE was offered to the intervention group. The self-care behavior, 6-min walking distance (6MWD), and 36-item short form health survey (SF-36) scores were compared between the two groups. The influencing factors of the self-care were also analyzed. RESULTS: The 6MWD was not significantly different between the two groups at admission (P > 0.05); however, at 3 and 6 mo after discharge, 6MWD was significantly increased, and it was significantly longer in the intervention group (P < 0.05). The scores for self-care behavior showed no significant difference at admission between the two groups (P > 0.05); however, at 3 and 6 mo after discharge, the total scores for self-care maintenance, management, confidence, and behavior of the intervention group were significantly higher than those of the control group (P < 0.05). There were no significant differences in the SF-36 scores at admission (P > 0.05); however, at 3 mo and 6 mo after discharge, the scores for all eight subscales, including physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social functioning, role-limitations due to emotional problems, and mental health, were significantly higher in the intervention group (P < 0.05). As shown by logistic regression analysis, the influencing factors of self-care mainly included age, cardiac function class, and education background (odds ratio > 1; all P < 0.05). CONCLUSION: FCIHE improved self-care behavior and cardiac function in CHF patients. Age, cardiac function, and education level affected the implementation of self-care among CHF patients.

The pro-apoptosis effect of sinomenine in renal carcinoma via inducing autophagy through inactivating PI3K/AKT/mTOR pathway.

Renal cell carcinoma (RCC) is a heterogeneous histological disease and the most common kidney cancer. The mortality rate of RCC remains high despite the improved treatment. Sinomenine is an isoquinoline extracted from Chinese medicinal plant Sinomenium acutum, famous for its ability to suppress several cancer cell types. Our research aimed to explore the anti-cancer potential of sinomenine in RCC. Results showed that sinomenine reduced the viability by reducing sphere-forming ability and enhancing pro-apoptosis effect in ACHN cells in a dose dependent manner. The expression levels of proliferation/apoptosis markers further validated the result. In addition, sinomenine significantly regulated the level of autophagy-related proteins with decreased expression of p62, and increased Beclin1 and LC3 II/LC3 I. Furthermore, phosphatidylinositol-3 kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR), the negatively regulated cell autophagy signaling pathway, was inhibited by sinomenine with decreased membrane translocation of AKT in ACHN cell lines. All in all, our study demonstrated that sinomenine promoted apoptosis in RCC via enhancing autophagy through PI3K/AKT/mTOR pathway.