Dualistic insulator states in 1T-TaS2 crystals.

While the monolayer sheet is well-established as a Mott-insulator with a finite energy gap, the insulating nature of bulk 1T-TaS2 crystals remains ambiguous due to their varying dimensionalities and alterable interlayer coupling. In this study, we present a unique approach to unlock the intertwined two-dimensional Mott-insulator and three-dimensional band-insulator states in bulk 1T-TaS2 crystals by structuring a laddering stack along the out-of-plane direction. Through modulating the interlayer coupling, the insulating nature can be switched between band-insulator and Mott-insulator mechanisms. Our findings demonstrate the duality of insulating nature in 1T-TaS2 crystals. By manipulating the translational degree of freedom in layered crystals, our discovery presents a promising strategy for exploring fascinating physics, independent of their dimensionality, thereby offering a "three-dimensional" control for the era of slidetronics.

Analysis of inpatient cost burden and influencing factors of seniors' patients with mental illness in Dalian, China.

BACKGROUND: As China's aging population continues to grow, the prevalence of mental illness among the seniors has been steadily increasing. The aim of this study is to reveal the changing trends and characteristics of economic burden among seniors patients with long-term hospitalization for mental illness, and to analyze the influencing factors. METHODS: The data for this study were gathered from seniors' patients with mental illness who were hospitalized and aged 60 years or older. The patients were admitted to four specialized and general hospitals located in Dalian city between January 2018 and December 2020. The types of diseases include affective mental disorders (mood disorders), Schizophrenia, schizotypal, and delusional disorders, Organic (including symptomatic) mental disorders, Neurotic, stress-related and somatoform disorders, Mental retardation, Mental and behavioral disorders due to substance use. (Identify the main diagnosis at discharge using ICD-10 coding). This study analyzed the basic characteristics and disease-related information of seniors patients with long-term psychiatric disorders who were hospitalized, and explored the factors influencing hospitalization costs among patients with different illnesses. RESULTS: Among the 3871 study subjects, the average length of hospital stay was 127.51 days. The average hospitalization expenses per case were 33,656.07 yuan. Seniors' patients with mental illness who receives treatment in specialized hospitals have higher hospitalization costs. Long-term hospitalization increases the total hospitalization costs. Age has an impact on hospitalization costs for patients with organic mental disorders. Patients with affective disorders (mood disorders) and neurotic, stress-related, and somatoform disorders who are covered by urban employee medical insurance have higher hospitalization costs.Patients with severe psychiatric disorders who have a 31-day readmission plan, as well as senior patients with somatoform disorders comorbid with other illnesses, incur higher hospitalization costs. CONCLUSIONS: We should take corresponding measures to reduce the number of readmissions for patients with severe mental illnesses. The impact of treatment methods and differences in healthcare institutions on total hospitalization costs deserves further research. It is necessary to strengthen the prevention and diagnosis of comorbid physical illnesses in patients with mental disorders. The burden of mental illnesses in the seniors is significant, and medical insurance policies should be inclined towards providing support.

P2X7 Receptor-Induced Bone Cancer Pain by Regulating Microglial Activity via NLRP3/IL-1beta Signaling.

BACKGROUND: Bone cancer pain (BCP) is the most severe and intractable type of cancer pain. Emerging evidence has demonstrated that activated microglia in the spinal cord could release a series of neurotoxic substances to stimulate neurons and form neuronal sensitization. The P2X7 receptor (P2X7R) is a nonselective ATP-gated ion channel predominantly present in microglia in the spinal cord as the key modulator of microglial activity. However, the specific effect and underlying molecular mechanism of P2X7R in BCP have not yet been elucidated. OBJECTIVES: This study aimed at investigating whether P2X7R-induced BCP by regulating microglial activity through NLRP3/IL-1beta signaling involvement in BCP. STUDY DESIGN: Controlled animal study. METHODS: A BCP animal model was established by injecting Walker-256 breast cancer cells into the tibia of female rats. Fifty percent paw withdrawal thresholds (50% PWTs), number of spontaneous flinches (NSF), and limb use scores were used to evaluate behavior in rats. P2X7R inhibitor brilliant blue G (BBG) was used to assess the role of P2X7R in BCP-induced NLRP3 inflammasome activation. Western blot, RT-PCR, and immunofluorescence were used for quantitative comparison. In vitro, BV2 cells were treated with lipopolysaccharide (LPS) and BzATP, in the presence or absence of P2X7 siRNA, with nigericin (an agonist of the NLRP3 inflammasome) to further study the mechanism of P2X7R regulate NLRP3/IL-1beta signaling. RESULTS: The inhibition of spinal P2X7R with BBG could effectively inhibit BCP due to suppressing the expression of NF-kappaB p-p65, NLRP3 inflammasome formation, and downstream pain factors IL-1beta. Furthermore, P2X7 siRNA could reduce microglial activity, the nuclear translocation of NF-kappaB, and the synthesis of NLRP3 and IL-1beta in BV2 cells. In addition, nigericin partially reversed the ameliorating effect of P2X7 siRNA on BV2 cells induced by LPS and BzATP. LIMITATIONS: BBG could relieve BCP but not improve the destruction of bone, which may be related to the specificity of inoculated cells. Further mechanisms should be investigated. CONCLUSION: These findings suggest that targeting the microglial P2X7R activated NLRP3/IL-1beta signaling pathway could serve as a potential strategy for BCP treatment.

P2X7 receptor induces microglia polarization to the M1 phenotype in cancer-induced bone pain rat models.

BACKGROUND: The transition from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype presents a novel therapeutic strategy for chronic pain. OBJECTIVE: We investigated the role of microglia polarization in cancer-induced bone pain (CIBP), as well as the role of the P2X7 receptor in modulating M1 to M2 polarization. METHODS: Walker-256 breast cancer cells were administered into tibias of female rats to induce bone cancer-associated cancer. RESULTS: During bone cancer development, the P2X7 receptor and M1 microglia markers were upregulated. In contrast, inhibition of the P2X7 receptor by BBG, a blood-brain barrier-permeable P2X7R-specific antagonist, alleviated the pain and promoted microglia polarization toward the M2 phenotype, while suppressing the M1 phenotype in vivo and in vitro. CONCLUSION: P2X7 receptor-mediated spinal microglia polarization is involved in alleviation of CIBP. Therefore, P2X7R is a potential option for CIBP treatment.

Identification of immunization-related new prognostic biomarkers for papillary renal cell carcinoma by integrated bioinformatics analysis.

BACKGROUND: Despite papillary renal cell carcinoma (pRCC) being the second most common type of kidney cancer, the underlying molecular mechanism remains unclear. Targeted therapies in the past have not been successful because of the lack of a clear understanding of the molecular mechanism. Hence, exploring the underlying mechanisms and seeking novel biomarkers for pursuing a precise prognostic biomarker and appropriate therapies are critical. MATERIAL AND METHODS: In our research, the differentially expressed genes (DEGs) were screened from the TCGA and GEO databases, and a total of 149 upregulated and 285 downregulated genes were sorted. This was followed by construction of functional enrichment and protein-protein interaction (PPI) network, and then the top 15 DEGs were selected for further analysis. The P4HB gene was chosen as our target gene by repetitively validating multiple datasets, and higher levels of P4HB expression predicted lower overall survival (OS) in patients with pRCC. RESULTS: We found that P4HB not only connects with immune cell infiltration and co-expression with PD-1, PD-L2, and CTLA-4, but also has a strong connection with the newly discovered hot gene, TOX. CONCLUSION: We speculate that P4HB is a novel gene involved in the progression of pRCC through immunomodulation.

Statin use and the overall survival of renal cell carcinoma: A meta-analysis.

PURPOSE: Statins are commonly prescribed drugs that reduce cholesterol levels and the risk of cardiovascular and cerebrovascular events. Clinical studies have shown that statins also possess cancer-preventive properties. Two studies have reported that statins also possess cancer-preventive properties; however, whether statins improve the prognosis of patients with renal cell carcinoma is still unclear. In this study, we used meta-analysis to evaluate the association between statin use and overall survival risk in patients with renal cell carcinoma. METHODS: Published studies on statin-treated renal cell carcinoma were retrieved from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure and Wanfang databases from inception to July 2019. The relevant data were extracted and a meta-analysis was performed using Cochrane Review Manager (RevMan 5.3) software. RESULTS: Data from five studies, which reported on 5,299 patients, were analysed. The application of statins showed no effects on the overall survival of patients with renal cell carcinoma compared with the control group (OR = 1.07, 95% CI:0.77 to 1.49, P = 0.68). CONCLUSIONS: The findings of this meta-analysis suggest that statin application does not affect the overall survival of patients with renal cell carcinoma.

TYROBP is a potential prognostic biomarker of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) exhibits high recurrence and metastasis rates. Although target therapy has significantly improved the prognosis of some patients with ccRCC, the median survival rate remains poor. Thus, there remains a need for the identification of novel potential targets for diagnosis and therapy. Here, we screened differentially expressed genes between ccRCC and normal tissues through analyzing The Cancer Genome Atlas database. We identified 55 up-regulated and 67 down-regulated genes associated with poor prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these genes were associated with glycometabolic process, complement and coagulation cascades. In addition, the eight down-regulated genes (HRG, FABP1, ALDOB, PCK1, HAO2, CASR, PLG, and HMGCS2) and two up-regulated genes (SERPINE1 and TYROBP) were filtered out. Finally, TYROBP was selected through repeated verification of various databases. High expression of TYROBP is associated with low survival rate in ccRCC, is closely related to immune cell infiltration and is coexpressed with Programmed cell death protein-1(PD-1) and Cytotoxic T lymphocyte-associated antigen-4(CTLA-4). In conclusion, TYROBP may have potential for diagnosis and treatment of ccRCC.

Whole-Course Application of Dexmedetomidine Combined with Ketorolac in Nonnarcotic Postoperative Analgesia for Patients with Lung Cancer Undergoing Thoracoscopic Surgery: A Randomized Control Trial.

BACKGROUND: Opioid-based postoperative analgesia provides adequate analgesia with much adverse effects and immunosuppression. Dexmedetomidine and ketorolac have properties of opioid-sparing, antiinflammation, and immune protection. OBJECTIVES: To investigate the efficacy and safety of whole-course application of dexmedetomidine combined with ketorolac in nonnarcotic postoperative analgesia and its effect on inflammatory response and immune function in thoracoscopic surgery of lung cancer. STUDY DESIGN: Double-blind, randomized control trial. SETTING: The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. METHODS: Sixty patients scheduled for thoracoscopic surgery were enrolled and randomly divided into 2 groups to receive a combination of intraoperative usage of dexmedetomidine and postoperative patient-controlled intravenous analgesia of dexmedetomidine 0.1 µg/kg/h and ketorolac 3 mg/kg (DEX group) or only postoperative patient-controlled intravenous analgesia of sufentanil 1.5 µg/kg and ketorolac 3 mg/kg (SUF group) for 48 hours. Vital signs, postoperative Visual Analog Scale (VAS) score, Ramsay sedation score, patient-controlled analgesia pressing times, consumption of sufentanil and rescue drug, and complications were compared between the 2 groups. The levels of inflammatory factors and immune function were also compared. RESULTS: A significant reduction in median blood pressures and heart rates within 48 hours after surgery and perioperative consumption of sufentanil were observed in the DEX group compared with the SUF group (P < 0.05). No statistically significant difference was found in VAS scores, patient-controlled analgesia pressing times, and rescue drug consumption between the 2 groups (P > 0.05). The incidence of nausea was significantly lower in the DEX group compared with the SUF group (P < 0.05). A significant decrease of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and increased CD4+ and CD4+/CD8+ were observed in the DEX group compared with the SUF group at 24 and 48 hours after surgery (P < 0.05). There was no difference in the levels of CD8+ and natural killer cells between the 2 groups (P > 0.05). LIMITATIONS: This study was limited by its sample size. CONCLUSIONS: Whole-course application of dexmedetomidine combined with ketorolac in nonnarcotic postoperative analgesia provided adequate and safe postoperative analgesia, reduced sufentanil consumption, analgesia-related complications, alleviated inflammatory response, and immunosuppression compared with sufentanil-based analgesia in thoracoscopic surgery. KEY WORDS: Dexmedetomidine, ketorolac, sufentanil, thoracoscopic surgery, postoperative analgesic, patient-controlled analgesia, inflammatory response, immune function.

Which Combination Treatment Is Better for Spinal Metastasis: Percutaneous Vertebroplasty With Radiofrequency Ablation, 125I Seed, Zoledronic Acid, or Radiotherapy?

BACKGROUND: Percutaneous vertebroplasty (PVP) can not only alleviate pain but also restore mechanical stability with injection of bone cement, whereas it exhibits a poor effect on antitumor activity. But through combinations with other therapies, it may be possible to achieve the maximum effect in clinical treatment. Thus, this study is designed to assess the clinical efficacy of PVP separately combined with 4 ways for spinal metastasis (SM) treatment. STUDY QUESTION: Which combination treatment is better for spinal metastasis, percutaneous vertebroplasty with radiofrequency ablation, I seed, zoledronic acid or radiotherapy? STUDY DESIGN: A total of 169 patients with SM were retrospectively recruited and randomly assigned to 4 groups to receive 4 different ways separately: 49 patients (group A) received PVP plus I seed, 51 (group B) received PVP plus radiofrequency ablation (RFA), 38 (group C) underwent PVP plus zoledronic acid (ZA), and 31 (group D) underwent PVP plus radiotherapy (RT). MEASURES AND OUTCOMES: All of them underwent routine examinations before operation. Visual analog scale (VAS), World Health Organization (WHO) Pain Relief, and ODI were applied to evaluate pain relief and motor function. RESULTS: PVP plus RT achieved the best efficacy in relieving pains, with the highest WHO Pain Relief (P < 0.05). The PVP plus RFA exhibited lowest ODI, suggesting the best outcome after treatment (P < 0.05). The PVP plus I showed the lowest VAS score, but it was the worst to improve the routine exercise ability and relieve pains from patients. The PVP plus ZA presented higher VAS and ODI (P < 0.05). CONCLUSIONS: PVP combined with I seed exhibited the best clinical efficacy in terms of VAS, PVP combined with RT was the best choice in terms of WHO Pain Relief, and PVP combined with RFA showed the best effect in terms of ODI for the treatment of SM.