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PURPOSE Bladder urothelial carcinoma (BLCA), the most common urinary tract malignancy, has a high recurrence rate and poor survival at late stages. Necroptosis, a form of programmed cell death, is involved in cancer development and progression, but its function in BLCA prognosis remains unclear. This study sought to investigate the role of necroptosis in the development and prognosis of BLCA. METHODS Clinical information and RNA expression matrix data were obtained from the databases. Survival analysis was performed to obtain survival- and necroptosis-related genes and identify any that overlapped. Consensus clustering analysis was used to create different subgroups by combining the overlapping gene expression matrix and clinical information. The tumor immune microenvironment and immune status of the different subgroups were determined using ESTIMATE, MCPcounter, and ssGSEA analysis. We performed differential analysis on the gene expression matrix of molecular subpopulations to find and screen out differentially expressed genes (DEGs). GO, KEGG, GSVA, and GSEA analyses were used to elucidate the underlying mechanisms of the DEGs. Lasso Cox regression analysis was used to build a prognostic risk model and perform a pan-cancer analysis of the screened genes. The results were used to define potential roles for these genes in other cancers and assess the efficacy of the risk model. RESULTS Cluster analysis identified two subgroups, C1 and C2, with significantly different survival rates. ESTIMATE, MCPcounter, and ssGSEA analyses showed that high immune scores, tumor purity, and immune status were associated with poorer prognoses. GO and KEGG functional enrichment analyses indicated that DEGs were mainly focused on tumor proliferation, invasion, and immunity and GSEA analysis suggested that necroptosis may affect Toll-like receptor signaling pathways, MAPK cascade regulation of leukocyte trafficking, and cytokine-cytokine receptor interaction pathways. Lasso Cox regression analysis was used to model the prognostic risk while screening for representative necroptosis-associated genes, ANXA1, ATAD3A, and TRPC6, with high potential for survival prediction in BLCA patients. The pan-cancer analysis indicated that the three representative genes were also differentially expressed in other cancer types. CONCLUSION Expression of necroptosis-related genes such as ANXA1, ATAD3A, and TRPC6 correlate with the immune microenvironment of BLCA patients and have the potential for use in disease prognostics.

The precise control of cardiomyocyte viability is imperative to combat myocardial ischemia-reperfusion injury (I/R), in which apoptosis and pyroptosis putatively contribute to the process. Recent researches indicated that GSDMD is involved in I/R as an executive protein of pyroptosis. However, its effect on other forms of cell death is unclear. We identified that GSDMD and GSDMD-N levels were significantly upregulated in the I/R myocardium of mice. Knockout of GSDMD conferred the resistance of the hearts to reperfusion injury in the acute phase of I/R but aggravated reperfusion injury in the chronic phase of I/R. Mechanistically, GSDMD deficiency induced the activation of PARylation and the consumption of NAD+ and ATP, leading to cardiomyocyte apoptosis. Moreover, PJ34, a putative PARP-1 inhibitor, reduced the myocardial injury caused by GSDMD deficiency. Our results reveal a novel action modality of GSDMD in the regulation of cardiomyocyte death; inhibition of GSDMD activates PARylation, suggesting the multidirectional role of GSDMD in I/R and providing a new theory for clinical treatment.

Objective: To investigate the genetic characteristics and transcriptional regulation of the SCN5A gene of Brugada syndrome (BrS) patients in China.Methods: Using PubMed, Medline, China National Knowledge Internet (CNKI), and Wanfang Database, Chinese patients with BrS who underwent SCN5A gene testing were studied.Results: A total of 27 suitable studies involving Chinese BrS patients who underwent the SCN5A gene test were included. A total of 55 SCN5A gene mutations/variations were reported in Chinese BrS patients, including 10 from southern China and 45 from northern China. Mutations/variations of BrS patients from southern China mostly occurred in the regions of the α-subunit of Nav1.5, including DIII (Domain III), DIV, DIII-DIV, C-terminus regions, and the 3'UTR region. Furthermore, we analyzed the post-transcriptional modifications (PTMs) throughout the Nav1.5 protein encoded by SCN5A and found that the PTM changes happened in 72.7% of BrS patients from southern China and 26.7% from northern China.Conclusions: SCN5A mutations/variations of BrS patients in southern China mostly occurred in the DIII-DIV to C-terminus region and the 3'-UTR region of the SCN5A gene, different from northern China. PTM changes were consistent with the mutation/variation distribution of SCN5A, which might be involved in the regulation of the pathogenesis of BrS patients.

Three new coordination compounds containing 5‑diethylamino‑2‑((4‑(phenyldiazenyl) phenylimino) methyl) phenol ligand have been synthesized and fully characterized. Single crystal structure showed that the ligand shows multiple coordination mode and the phenyl group next to azo group could rotate during the coordination process. In Mn(HDAPPP)2Cl2·CH3CN (1), the HDAPPP behaved as a mono ligand because of the N of the imine group is protonated in the keto form and does not participate in coordination. While the Cu(DAPPP)2 (2) and Ni(DAPPP)2 (3) are classic complexes containing azo-Schiff base ligand. The fluorescence emission peaks of compounds indicated that the fluorescence of the compounds are mainly derived from the π-π* charge transition of the ligand and affected by the rotation of ligand. The UV–Vis data revealed that the compound 1–3 with the maximum absorption peak at 425 nm, 440 nm and 338 nm, respectively. This clearly confirmed that the compound 1 is mainly based on the keto configuration while the compound 3 is mainly based on the enol configuration. Z-scan experiments showed that all compounds exhibited reverse saturable absorption effect and self-defocusing effect for nonlinear optical materials. The nonlinear absorption coefficients (β) of compound 1–3 are evaluated to be 6 × 10−11 m·W−1, 4.4 × 10−11 m·W−1, and 1.7 × 10−11 m·W−1 respectively, and the nonlinear refraction coefficients (n2) are −1.4 × 10−17 m2·W−1, −1.6 × 10−17 m2·W−1, −7.0 × 10−18 m2·W−1 respectively. The nonlinear optical property of compound 1 and 2 are better than compound 3, which are influenced by ligand rotation after coordination.

Loganin is an iridoid glycoside extracted from Cornus officinalis, which is a traditional oriental medicine, and many biological properties of loganin have been reported. Nevertheless, it is not clear whether loganin has therapeutic effect on cardiovascular diseases. Hence, the aim of the present study was to investigate the effect of loganin on Ang II–induced cardiac hypertrophy. In the present study, we reported for the first time that loganin inhibits Ang II–provoked cardiac hypertrophy and cardiac damages in H9C2 cells and in mice. Furthermore, loganin can achieve cardioprotective effects through attenuating cardiac fibrosis, decreasing pro-inflammatory cytokine secretion, and suppressing the phosphorylation of critical proteins such as JAK2, STAT3, p65, and IκBα. Besides, the outstanding findings of the present study were to prove that loganin has no significant toxicity or side effects on normal cells and organs. Based on these results, we conclude that loganin mitigates Ang II–induced cardiac hypertrophy at least partially through inhibiting the JAK2/STAT3 and NF-κB signaling pathways. Accordingly, the natural product, loganin, might be a novel effective agent for the treatment of cardiac hypertrophy and heart failure.

The diethylphosphonate ligand HL 1 substituted pyridylpyrrole was synthesized by treatment of 2-bromo-6-(1H'-pyrrol-2-yl)pyridine and diethylphosphite in presence of base triethylamine and catalyst Pd(PPh 3 ) 4 under refluxing toluene conditions. The HL 1 ligand was treated with bromotrimethylsilane and followed hydrolysis by methanol to afford diphosphonic acid ligand H 3 L 2 . Treatment of H 3 L 2 with [Ru(NO)Cl 3 ] in presence of triethylamine in refluxing thf was generated diruthenium nitrosyl complex [Ru(L 2 )(NO)(Cl)] 2 ·(Et 3 NH) 2 ([ 1 ]·(Et 3 NH) 2 ), which is water soluble. The ligands and metal complex were fully characterized by NMR, IR, ESI-MS and single crystal X-ray diffraction technology. The solid state structure analysis displays 1 2- is dinuclear species, of which two ruthenium atoms are linked by two PO 3 2- groups. Photorelease of nitric oxide from 1 2- was monitored by UV-Vis spectra and the amount of the NO was determined by Griess reaction and DPPH radical scavenging reaction.

// Zhenghao Zhang 1 , Shu Chen 2 , Shuang Chen 1 , Gang Chen 1 , Rui Zhang 1 , Jinhua Li 1 and Jianhua Qu 1 1 Centre of Hematology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China 2 Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China Correspondence to: Jianhua Qu, email: jhuaqu@163.com Keywords: SF3B1, chronic lymphocytic leukemia, prognosis, survival, meta-analysis Received: December 01, 2016 Accepted: May 27, 2017 Published: July 22, 2017 ABSTRACT Recent studies suggest that SF3B1 might be related to poor prognosis in CLL, but the results remain controversial. This meta-analysis was performed to clarify the relationship between SF3B1 mutation and prognosis in patients with CLL. The relevant published reports were searched in PubMed, EMBASE, and Web of Science. A total of 13 articles were included in this meta-analysis as they met the inclusion and exclusion criteria. The hazard ratios (HRs) and corresponding 95% confidence intervals (95%CIs) for progression free survival (PFS) and/or overall survival (OS) were extracted from each eligible study. The pooled HR evaluating SF3B1 mutation on PFS was 1.81(95%CI 1.33-2.46, I 2 =78.9%, P

To study the distribution of monoclonal gammopathy of undetermined significance(MGUS) in different age, sex and ethnic people over 40 years old.Five hundred and ninety-six people(over 40 years old) examened in the Health Examination center of the First Affiliated Hospital of Xinjiang Medical University from July 2017 to September 2017 were selected. Among 596 people, male 310, female 286, Han people 488, and Uygur ethnic people 108. According to age, 596 people were divided into 3 groups, (40-59 years old group, 60-79 years old group, over 80 years old group). First, all samples were screened by capillary serum protein electrophoresis. If the suspected monoclonal bands were found in the electrophoretogram, and then the specific protein types were determined by serum immunofixation electrophoresis.The total incidence of MGUS in 596 screened population was 4.027%. The incidence of MGUS in 40-59 years old group, 60-69 years old group and over 80 years old group were 1.762%, 2.929% and 10% respectively, and the differences among the groups were statistically significant(P0.05). The incidence of MGUS in male (5.806%) was significantly higher than that in female (2.097%)(χThe age increase and male may increase the incidence of MGUS, the IgG is the most common type of immunoglobcdin in pathogenesis of MGUS, so the early screening should be done.40岁以上人群中意义未明单克隆免疫球蛋白血症的发病情况分析.了解40岁以上人群中意义未明单克隆免疫球蛋白血症（MGUS）在不同年龄、性别、民族的分布情况及危险因素。.收集2017年7月到2017年9月在新疆医科大学第一附属医院健康体检中心健康体检596人（年龄≥40岁，男性310例，女性286例，汉族488例，维吾尔族108例）。根据年龄将健康体检人群分为40-59、60-79和≥80岁3组，记录所有人的年龄、性别、族别。首先采用毛细管血清蛋白电泳对所有样本筛查，如果电泳图谱发现疑似单克隆条带，再进行血清免疫固定电泳明确蛋白类型。.596例被筛查人群中MGUS发病24例（4.027%），40-59、60-79和≥80岁组人群MGUS发病率分别为1.762%、2.929%和10%，各组间差异均有统计学意义（P＜0.05）；男性发病率（5.806%）明显高于女性（2.097%）（χ年龄的增长及性别为男性可能增加MGUS的发病率，IgG是MGUS发病中最常见的免疫球蛋白类型，因此要做好早期筛查。.

To study the expression of SOX4 gene in patients with acute myeloid leukemia (AML) and its correlation with clinical features and prognosis, and to explore the role of this gene in acute myeloid leukemia.The real-time guantitative PCR was used to detect the expression level of SOX4 gene in bone marrow of 96 patients with newby diagmsed AML, and the features and prognosis was analyzed.The level of SOX4 expression in the 96 AML patients was significantly higher than that in healthy controls (P0.01), and the expression of SOX4 gene was not significanly different between M1-M5 (P0.05). The expression of SOX4 gene was no significanly different between different sex, nationality, and remission after chemotherapy (P0.05). In AML patients the SOX4 gene expression level did not significantly correlated with the white blood cell count, hemoglobin level, platelet count primitive cell count, reticulocyte count and other laboratory indexes ( P0.05), while which correlated with the overall survival (OS) (P0.01) and erent-free survival (EFS) (P0.05).The high expression of SOX4 gene affects the survival time of patients (OS, EFS), suggesting that may be one of the unfavorable prognostic factors for the AML patients.

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of monoclonal B cells expressing CD19, CD5 and CD23 together with low surface expression of B-cell receptors and related mole...

To investigate the expression of nuclear antigen Ki-67 in CLL patients and realationship of Ki-67 expression with other clinical parameters.Twenty-Six confirmed cases of CLL were analysised retrospectively. The immhnohistochemical method was carried out to examine the expression of Ki-67 in bone marrow cells, the flow cytometer was used to detect ZAP70 (Zeta chain-associated protein), CD38 and other markers, additionally, a panel of probes RB1 (13q14), ATM (11q22.3), P53 (17p13.1) and CSP12 (+12) FISH were perfomed to detect the cytogenetic abnormalities.Out of 26 patients, 15 cases (57.7%) showed positive expression of Ki-67, 11 cases (42.3%) showed negative expression of Ki-67, the average rate of Ki-67 positive expression was (10.86±7.36)%. The level of Ki-67 did not relate with sex, age, Hb, platelet, ZAP70, ATM. β2-MG, IgHV and P53, but related to the Rai staging (P=0.01, r=0.517), CD38 (P=0.02, r=0.469), 13q14 (P=0.021, r=-0.48), and there was statistically significant difference (P0.05).The Ki-67 level is higher in progressive stage of CLL and the Ki-67 expression is related with Rai staging, CD38, 13q14. The expression level of Ki-67 may be used as indicator for evaluation of CLL prognosis and guiding treatment for this disease.