Application of intelligent nursing system based on big data in maintenance hemodialysis patients.

Maintenance hemodialysis (MHD) is one of the most important renal replacement therapies for patients with end-stage renal disease. However, long-term and frequent treatment not only damages the physiological functions of patients but also leads to serious economic burdens and mental stress. This can easily cause a series of psychological disorders in patients, resulting in severe rejection and fear of MHD. To reduce patient resistance and improve the quality of life of MHD, this article built an intelligent nursing system based on big data and then used the constructed intelligent nursing system to research MHD. Through experiments, it has been found that compared to self-efficacy intervention, intelligent nursing systems can control the concurrent rate of MHD patients below 14 %, and self-efficacy intervention methods can control the concurrent rate of MHD patients above 13 %. Moreover, using intelligent nursing systems can improve the ability of MHD patients to self-care. At the same time, before the use of intelligent nursing systems, the nursing satisfaction of MHD patients also varied greatly, with the overall satisfaction rate after use being 70 % higher than before. Using intelligent nursing systems can improve the satisfaction of MHD patients with nursing outcomes.

Hnrnpk protects against osteoarthritis through targeting WWC1 mRNA and inhibiting Hippo signaling pathway.

Osteoarthritis (OA) is an age-related or post-traumatic degenerative whole joint disease characterized by the rupture of articular cartilage homeostasis, the regulatory mechanisms of which remain elusive. This study identifies the essential role of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in maintaining articular cartilage homeostasis. Hnrnpk expression is markedly downregulated in human and mice OA cartilage. The deletion of Hnrnpk effectively accelerates the development of post-traumatic and age-dependent OA in mice. Mechanistically, the KH1 and KH2 domain of Hnrnpk bind and degrade the mRNA of WWC1. Hnrnpk deletion increases WWC1 expression, which in turn leads to the activation of Hippo signaling and ultimately aggravates OA. In particular, intra-articular injection of LPA and adeno-associated virus serotype 5 expressing WWC1 RNA interference ameliorates cartilage degeneration induced by Hnrnpk deletion, and intra-articular injection of adeno-associated virus serotype 5 expressing Hnrnpk protects against OA. Collectively, this study reveals the critical roles of Hnrnpk in inhibiting OA development through WWC1-dependent downregulation of Hippo signaling in chondrocytes and defines a potential target for the prevention and treatment of OA.

Tumor-secreted IFI35 promotes proliferation and cytotoxic activity of CD8+ T cells through PI3K/AKT/mTOR signaling pathway in colorectal cancer.

BACKGROUND: A large proportion of the patients with cancer do not respond to immunotherapies. Recent studies suggested an important role for tumor-infiltrating cytotoxic T lymphocytes (CTL) in enhancing response to immunotherapy. Here, we aim to identify gene that induce proliferative and cytotoxic states of CD8+ T cells, and to investigate its effect on CAR-T cells against colorectal cancer. METHODS: Correlation between the expression of IFI35 with the activation and cytotoxicity of CD8+ T cells was assessed with TCGA and proteomic databases. Then we constructed murine colon cancer cells over-expressing IFI35 and tested their effect on anti-tumor immunity in both immunodeficient and immunocompetent mouse models. Flow cytometry and immunohistochemistry were performed to assess the immune microenvironment. Western blot analysis was used to identify the potential down-stream signaling pathway regulated by IFI35. We further investigated the efficacy of the rhIFI35 protein in combination with immunotherapeutic treatment. RESULTS: The transcriptional and proteomic analysis of the activation and cytotoxicity of CD8+ T cells in human cancer samples demonstrated that IFI35 expression is correlated with increased CD8+ T cell infiltration and predicted a better outcome in colorectal cancer. The number and cytotoxicity of CD8+ T cells were significantly increased in IFI35-overexpressing tumors. Mechanistically, we identified that the IFNγ-STAT1-IRF7 axis stimulated IFI35 expression, and that IFI35-mediated regulation of CD8+ T cell proliferation and cytotoxicity was dependent on PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, IFI35 protein enhanced the efficacy of CAR-T cells against colorectal cancer cells. CONCLUSION: Our findings identify IFI35 as a new biomarker that can enhance the proliferation and function of CD8+ T cells, as well as increase the efficacy of CAR-T cells against colorectal cancer cells.

The Effect of Face-Voice Gender Consistency on Impression Evaluation.

Face and voice are important information cues of interpersonal interaction. Most previous studies have investigated the cross-modal perception of face and voice from the perspective of cognitive psychology, but few empirical studies have focused on the effect of gender consistency of face and voice on the impression evaluation of the target from the perspective of social cognition. Based on the two-stage model of stereotype activation and the stereotype content model, this research examined the effects of face-voice gender consistency on impression evaluation (gender categorization and warmth competence evaluation) by using a cross-modal priming paradigm (Study 1, 20 males and 23 females, Mage = 21.00, SDage = 2.59), a sequential presentation task (Study 2a, 57 males and 70 females, Mage = 18.54, SDage = 1.54; Study 2b, 52 males and 51 females, Mage = 18.54, SDage = 1.36), and a simultaneous presentation task (Study 3, 51 males and 55 females, Mage = 23.58, SDage = 3.20), respectively. The results showed that: (1) there was a face-voice gender consistency preference in gender categorization, and the response of face-voice consistent condition was faster than that of inconsistent condition; (2) compared with the face-voice gender-inconsistent individuals, the participants showed a higher and more stable evaluation of the warmth and competence of the gender-consistent individuals, indicating the effect of matching preference of the face-voice gender consistency on the impression evaluation; (3) people paid more attention to the gender information of faces in the impression evaluation, and the female face could improve people's evaluation on the target's warmth and competence; (4) males were more intolerant of face-voice gender inconsistency when presented sequentially; the "voice needs to match face" effect was stronger for females when presented simultaneously. These findings, on the one hand, enrich and expand previous theories and research on cross-modal processing of face and voice from the perspective of social cognitive impression evaluation; on the other hand, these findings have important practical implications for impression management and decision-making in social interaction.

Discovery of an autophagy inducer J3 to lower mutant huntingtin and alleviate Huntington's disease-related phenotype.

Huntington's disease (HD) is a neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein encoded from extra tracts of CAG repeats in exon 1 of the HTT gene. mHTT proteins are neurotoxic to render the death of neurons and a series of disease-associated phenotypes. The mHTT is degraded through autophagy pathway and ubiquitin-proteasome system (UPS). This study identified a small molecule, J3, as an autophagy inducer by high-content screening. The results revealed that J3 could inhibit mTOR, thus promoting autophagic flux and long-lived protein degradation. Further, J3 selectively lowered the soluble and insoluble mHTT but not wild type HTT levels in cell models. The HdhQ140 mice showed reduced HD-associated activity and loss of motor functions. However, administration of J3 showed increased activity and a slight improvement in the motor function in the open-field test, balance beam test, and rotarod tests. Furthermore, in vivo studies revealed that J3 decreased T-HTT and misfolded protein levels in the striatum and increased the levels of the medium spiny neuron marker DARPP-32. In addition, J3 showed good permeability across the brain-blood barrier efficiently, suggesting that J3 was a promising candidate for the treatment of HD.

Clinical study of centrality index in predicting the postoperative pathological nuclear grade of clear cell renal cell carcinoma.

OBJECTIVE: This study aimed to investigate whether the centrality index score (C index) can be used to predict the histological nuclear grade of clear cell renal cell carcinoma (ccRCC) and guide the clinical treatment of this disease. METHODS: This study included 194 patients with ccRCC who underwent renal surgery at our center between 2016 and 2020 and had complete computed tomography or computed tomography angiography (CT/CTA) data and C index. The relationship between the pathological grade of renal masses and the C index was evaluated. RESULTS: In univariate analysis, the gender, body mass index (BMI), tumor size, or height from the center of the renal hilum to the maximum diameter of the tumor along the 90° vertical axis (in cm) is y. The horizontal distance from the reference point of the central axis of the renal hilum to the tumor center is x. The distance from the center of the kidney to the center of the tumor is c and the C index was significantly correlated with postoperative tumor grade (p < 0.05). Multivariate analysis showed that tumor size and C index were independent prognostic factors for the preoperative prediction of the pathological grade factor of ccRCC. The receiver operating characteristic curves of the multi-parameter regression model [0.9471, 95% confidence interval (95% CI) 0.9138-0.9803], C index (0.9324, 95% CI 0.8899-0.9748), and tumor size (0.9307, 95% CI 0.8951-0.9663) were compared. CONCLUSION: Tumor size and C index were independent prognostic factors for high-grade pathology, and large tumors and small C index were associated with high-grade pathology. Therefore, the C index can help urologists make treatment decisions.

TSG-6 promotes Cancer Cell aggressiveness in a CD44-Dependent Manner and Reprograms Normal Fibroblasts to create a Pro-metastatic Microenvironment in Colorectal Cancer.

Tumor necrosis factor α stimulated gene 6 (TSG-6), a 30-KD secretory protein, plays an essential role in modulating inflammatory responses and extracellular matrix remodeling. However, little is known regarding the role of TSG-6 in human cancers. Here, we investigated the mechanism of action and the role of TSG-6 in colorectal cancer (CRC) metastasis. We found that TSG-6 was highly expressed in tumor tissues and was associated with poor prognosis and metastasis in CRC. Mechanistically, TSG-6 overexpression in CRC cells resulted in ERK activation and epithelial-mesenchymal transition by means of stabilizing CD44 and facilitating the CD44-EGFR complex formation on the cell membrane. Consequently, this resulted in the promotion of tumor migration and invasion both in vitro and in vivo. Notably, our data showed that CRC cells secreted TSG-6 could trigger a paracrine activation of JAK2-STAT3 signaling and reprogram normal fibroblasts into cancer-associated fibroblasts, which exhibited upregulation of pro-metastatic cytokines (CCL5 and MMP3) and higher movement ability. In animal models, the co-injection of cancer cells and TSG6-reprogrammed fibroblasts led to a significant increase in tumor metastasis. Our findings indicated that TSG-6 overexpression in CRC cells could promote cancer metastasis in both an autocrine and paracrine manner. Therefore, targeting TSG-6 might be a potential therapeutic strategy for the treatment of metastatic CRC.

Robot-Assisted versus Laparoscopic Partial Nephrectomy for Giant Sporadic Renal Angiomyolipomas of ≥7 cm: A Propensity Score-Matched Analysis.

BACKGROUND: To compare the perioperative and functional outcomes between robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for giant sporadic renal angiomyolipomas (AMLs) of ≥7 cm. MATERIALS AND METHODS: Patients with sporadic renal AMLs of ≥7 cm who underwent RAPN or LPN in the First Affiliated Hospital of Nanchang University between 2015 and 2020 were retrospectively analyzed. Propensity score matching (1 : 1) was performed to adjust for potential baseline confounders. Perioperative and functional outcomes of the RAPN and LPN groups were collected and compared. RESULT: After propensity score matching, no statistically significant differences in baseline characteristics were found between the groups (41 vs. 41). Within the matched cohort, the warm ischemia time (WIT) in the RAPN group was significantly shorter than that in the LPN group (21 vs. 27 min, p < 0.001). In addition, the RAPN group was associated with improved postoperative renal function (72.8 vs. 69.8 mL/min/1.73 m2, p=0.045). WIT and preoperative renal function are independent predictors of renal function at 6 months postoperatively, and renal score and operation method are independent predictors of WIT. CONCLUSION: RAPN and LPN are safe and feasible minimally invasive treatments for sporadic giant renal AMLs, but RAPN is associated with shorter WIT and better postoperative renal functional preservation. WIT and preoperative renal function are independent predictors of renal function at 6 months postoperatively, while the RENAL score and surgical method are independent risk factors to WIT. For giant and complex renal AMLs, RAPN is the first choice when condition permits.

Vesicle transporter GOLT1B mediates the cell membrane localization of DVL2 and PD-L2 and promotes colorectal cancer metastasis.

BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed and second leading cause of cancer death worldwide. Hallmark proteins processing is usually dysregulated in cancers. Finding key regulatory molecules is of great importance for CRC metastasis intervention. GOLT1B is a vesicle transport protein which is involved in cytosolic proteins trafficking. However, its role in cancer has never been addressed. METHODS: CRC cell lines and subcutaneous xenograft animal model were utilized to investigate the biological function of GOLT1B. Patients samples were used to validate the correlation between GOLT1B and clinical outcome. In vivo targeted delivery of GOLT1B-siRNA was investigated in PDX (Patient derived tumor xenograft) model. RESULTS: We found that GOLT1B was highly expressed in CRC, and was an independent prognostic marker of overall survival (OS) and progression free survival (PFS). GOLT1B could promote CRC metastasis in vitro and in vivo. GOLT1B overexpression could increase DVL2 level and enhance its plasma membrane translocation, which subsequently activated downstream Wnt/ß-catenin pathway and increase the nuclear ß-catenin level, hence induce epithelial-mesenchymal transition (EMT). In addition, GOLT1B could also interact with PD-L2 and increase its membrane level. Co-culture of GOLT1B-overexpresed CRC cells with Jurkat cells significantly induced T cells apoptosis, which might further promote cancer cell the migration and invasion. Further, targeted delivery of GOLT1B siRNA could significantly inhibit tumor progression in GOLT1B highly expressed PDX model. CONCLUSION: Taken together, our findings suggest that the vesicle transporter GOLT1B could promote CRC metastasis not only by assisting DVL2 translocation and activating Wnt/ß-catenin pathway, but also facilitating PD-L2 membrane localization to induce immune suppression. Targeted inhibition of GOLT1B could be a potential therapeutic strategy for CRC treatment.

Novel Combination Therapies for the Treatment of Bladder Cancer.

Bladder cancer is the ninth most frequently diagnosed cancer world-wide and ranks 13th in cancer-related deaths. Two tremendous breakthroughs in bladder cancer therapy over the last decades are the approval of immune checkpoint inhibitors(ICIs)and the fibroblast growth factor receptor tyrosine kinase inhibitor (FGFR-TKI) erdafitinib for treating this deadly disease. Despite the beneficial effects of these approaches, the low response rate and the potential resistance of the cancer are major concerns. Hence, novel combination therapies to overcome these limitations have been investigated. In this context, combining immunotherapy with targeted drugs is an appealing therapeutic option to improve response and reduce the emergence of resistance in the management of bladder cancer. In this review, the rationale of using different therapeutic combinations is discussed according to the mechanistic differences, emphasizing the efficacy and safety based on evidence collected from preclinical and clinical studies. Finally, we highlight the limitations of these combinations and provide suggestions for further efforts in this challenging field.

Dual Inhibition of Pirarubicin-Induced AKT and ERK Activations by Phenformin Sensitively Suppresses Bladder Cancer Growth.

Activations of Akt or ERK pathway induced by clinical drugs promote therapeutic failure due to decrease of drug response, and no available strategies have been developed to solve these problems. In this study, we found that pirarubicin (THP), one important chemotherapeutic drug for treating bladder cancer intravesically, dramatically elevated phosphorylations of both Akt and Erk1/2 in addition to inducing DNA damage. MK2206 or AZD6244, representative Akt and Erk1/2 inhibitors, respectively, profoundly sensitized bladder cancer cells to THP treatment. Interestingly, we found that inhibition of a single arm of either Akt or Erk1/2 pathway would induce the increase of another arm, indicating the existence of the crosstalk between these two pathways. Thus, simultaneous suppression of both signals may be needed for increasing the sensitivity of THP. On the other hand, we revealed that phenformin efficiently inhibited both Akt and Erk1/2 phosphorylation in a dose-dependent manner. Furthermore, we demonstrated that phenformin, mimicking dual inhibitors, plays dramatically synergistic action with THP both in vitro and in vivo. Our findings suggest that combination therapy of THP with dual inhibitors may constitute a successful strategy for improving chemotherapy response.