AIM: To explore the different effect and mechanism of arsenic sulfide on telemorase activity and hTERT-mRNA expression in CML cell lines-KS62 and APL cell lines-NB4. METHODS: Telomerase activity was determined by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA). The expression of hTERT-mRNA was analyzed by semi-quantitative RT-PCR. Flow cytometry was used to analyze the cell cycle and apoptosis. RESULTS: 0.15-0.6 mg/L arsenic sulfide (72 h)can induce apoptosis and inhibit telomerase activity and hTERT-mRNA expression in NB4 cell. The concentration of arsenic sulfide with the same effect on K562 cell was 0.3-3 mg/U 0.3 mg/L arsenic sulfide (72 h) can cause the proportion of the NB4 cell in G2/M phase increased, but for K562 cell, The concentration of arsenic sulfide was 1.5 mg/L. CONCLUSION: Telomerase system may be one.of the pathway for arsenic sulfide inducing apoptosis of NB4 and K562 cell; G2/M phrase arrest may have correlation with decrease of telomerase activity; The sensitivity of NB4 and K562 call for arsenic sulfide is different, the mechanism of it need to study more.

Objective To investigate the expression of Toll-like receptor (TLR) in bone marrow mononuclear cells (BMMCs) of patients with multiple myeloma (MM) and its significance.Methods Totally 30 patients with MM were selected as observation group,and 10 patients with proliferative anemia were selected as control group.Patients in the observation group were treated with bortezomib combined with dexamethasone chemotherapy.The expression level of TLR in BMMCs was detected by real-time fluorescence quantitative method in both groups.The relationship between TLR and the clinical stages of MM was analyzed.Results The relative expression levels of TLR-4 and TLR-9 in BMMCs in the observation group were significantly higher than those in the control group (P ＜ 0.05).The expression levels of TLR-4 and TLR-9 in patients with different stages of MM showed significant differences (P ＜ 0.05).TLR-4 was positively correlated with M protein and β2-MG (r =0.673,0.466,P =0.023,0.041),and TLR-9 was also positively correlated with M protein and β2-MG (r =0.547,0.424,P =0.031,0.048).After treatment,the relative expression levels of TLR-4 and TLR-9 in BMMCs in patients with MM decreased significantly (P ＜ 0.05).Conclusion The expression levels of TLR-4 and TLR-9 are obviously higher in patients with MM,which is related to the clinical stage,M protein and β2-MG.

Objective To investigate the expression of Toll-like receptor (TLR) in bone marrow mononuclear cells (BMMCs) of patients with multiple myeloma (MM) and its significance.Methods Totally 30 patients with MM were selected as observation group,and 10 patients with proliferative anemia were selected as control group.Patients in the observation group were treated with bortezomib combined with dexamethasone chemotherapy.The expression level of TLR in BMMCs was detected by real-time fluorescence quantitative method in both groups.The relationship between TLR and the clinical stages of MM was analyzed.Results The relative expression levels of TLR-4 and TLR-9 in BMMCs in the observation group were significantly higher than those in the control group (P ＜ 0.05).The expression levels of TLR-4 and TLR-9 in patients with different stages of MM showed significant differences (P ＜ 0.05).TLR-4 was positively correlated with M protein and β2-MG (r =0.673,0.466,P =0.023,0.041),and TLR-9 was also positively correlated with M protein and β2-MG (r =0.547,0.424,P =0.031,0.048).After treatment,the relative expression levels of TLR-4 and TLR-9 in BMMCs in patients with MM decreased significantly (P ＜ 0.05).Conclusion The expression levels of TLR-4 and TLR-9 are obviously higher in patients with MM,which is related to the clinical stage,M protein and β2-MG.

PURPOSE: Tripartite-motif-containing protein 56 (TRIM56) has been found to exhibit a broad antiviral activity, depending upon E3 ligase activity. Here, we attempted to evaluate the function of TRIM56 in multiple myeloma (MM) and its underlying molecular basis. MATERIALS AND METHODS: TRIM56 expression at the mRNA and protein level was measured by qRT PCR and western blot analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry analysis was performed to investigate the effect of TRIM56 on MM cell proliferation and apoptosis. The concentrations of interferon (IFN)-β, interleukin (IL)-6, and tumor necrosis factor-α in MM cell culture supernatants were detected with respective commercial ELISA kits. Western blot was employed to determine the effect of TRIM56 on toll-like receptor 3 (TLR3)/toll-IL-1 receptor (TIR) domain-containing adaptor inducing IFN-β (TRIF) signaling pathway. RESULTS: TRIM56 expression was prominently decreased in MM cells. Poly (dA:dT)-induced TRIM56 overexpression in U266 cells suppressed proliferation, induced apoptosis, and enhanced inflammatory cytokine production, while TRIM56 knockdown improved growth, diminished apoptosis, and inhibited inflammatory cytokine secretion in RPMI8226 cells. Moreover, TRIM56 knockdown blocked TLR3 signaling pathway. Furthermore, poly (I:C), a TLR3 agonist, markedly abolished TRIM56 depletion-induced increase of proliferation, decrease of apoptosis, and reduction of inflammatory factor in MM cells. CONCLUSION: TRIM56 may act as a tumor suppressor in MM through activation of TLR3/TRIF signaling pathway, contributing to a better understanding of the molecular mechanism of TRIM56 involvement in MM pathogenesis and providing a promising therapy strategy for patients with MM.
Adaptor Proteins, Vesicular Transport/metabolism ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cytokines/secretion ; Disease Progression ; Down-Regulation/drug effects ; Gene Knockdown Techniques ; Humans ; Multiple Myeloma/metabolism ; Multiple Myeloma/pathology ; Poly I-C/pharmacology ; Signal Transduction/drug effects ; Toll-Like Receptor 3/metabolism ; Tripartite Motif Proteins/deficiency ; Tripartite Motif Proteins/metabolism ; Ubiquitin-Protein Ligases/deficiency ; Ubiquitin-Protein Ligases/metabolism

Objective? To explore the clinical effects of evidence-based psychological intervention on nursing care for middle-aged patients with ischemic stroke. Methods? Totally 120 patients aged 45-59 years who were hospitalized in the Department of Neurology, Cangzhou People's Hospital between February and July were selected, and stratified into intervention (n=60) and control (n=60) groups. Patients in the control group received conventional nursing care, while patients in the intervention group received psychological intervention based on conventional nursing care. Self-Depression Scale (SDS) was used to assess the status of patients in the two groups. Results? After 4 weeks, the SDS score of the intervention group was (52.37±4.38), whereas the SDS score of the control group was (58.81±3.44). The SDS score was lower in the intervention group than in the control group, and there was statistically significant difference between the two groups (P＜ 0.01). Conclusions? The evidence-based psychological intervention model helps to ameliorate the depression in middle-aged patients with ischemic stroke, which is worthy applying and promoting in clinical practice.

Objective:To investigate the prognosis after salvage radiotherapy with or without hormone therapy for prostate cancer.Methods:From May 2014 to December 2020, 248 patients undergoing salvage radiotherapy due to prostate-specific antigen (PSA)persistence or biochemical progression after radical prostatectomy at Sun Yat-sen University Cancer Center (n=157) and West China Hospital, Sichuan University (n=91) were analyzed. Median age was 66 (45-78) years old. Median PSA was 23.50 (0.18-845.00) ng/ml. The number of PSA persistence and biochemical progression were 143 (59%) and 105 (42%). The number of pT 2, pT 3a, pT 3b, pT 4, and unknown T stage was 99, 49, 78, 15 and 7 cases.The number of N 0, N 1 and unknown N stage was 153, 44 and 51 cases. 165 cases had positive surgical margin. Gleason score of 6, 7, 8, >8 score and unknown was in 12, 104, 34, 90 and 8 patients. Early and late salvage radiotherapy was performed in 117 and 131 patients, and 70 patients (28%) were CRPC. Hormone therapy was used combined with radiotherapy in 182 patients (73%). PSA decline after radiotherapy was compared with Chi-squre test. Kaplan-Meier method and log-rank test were used to compare progression free-survival (PFS)after radiotherapy. Univariate and multivariate analyses of PFS were performed using Cox proportional hazards model. Early salvage radiotherapy was defined as PSA≤0.5 ng/ml before radiotherapy, and late salvage radiotherapy was defined as PSA>0.5ng/ml. Results:PSA response (PSA decline ≥50%) rate was 94% (233/248), and 82% (203/248) patients had PSA decline ≥ 90%. Twelve (5%) patients had rising PSA after completing radiotherapy, but only 4 (2%) had real progression. The median PFS was 69 months (95% CI 68-70), and 3-year and 5-year PFS rate were 80% and 67%. PFS of PSA persistence and biochemical progression were similar ( HR =0.71, 95% CI 0.37-1.37, P=0.311). Compared with late salvage radiotherapy, early salvage radiotherapy had better PFS [69 (95% CI 68-70) vs. 59 (95% CI 44-74) months, P<0.001]. Compared with hormone sensitive, castration-resistant was associated with worse PFS (5-year PFS rate 74% vs. 51%, P<0.001). In multivariate analysis, Gleason score>8, castration-resistant and late salvage radiotherapy were unfavorable prognostic factors. Conclusions:In patients receiving salvage radiotherapy with or without hormone therapy for PSA persistence and biochemical progression after radical prostatectomy, high PSA level before radiotherapy and castration resistant is associated with poor prognosis.