Objective To analyze the effect of community physicians' following-up on type 2 diabetes management in community.Methods A total of 99 local patients with type 2 diabetes,who were selected randomly and divided into management group (49 cases) and control group(50 cases).The patients in management group were accepted diabetes management in community with community physicians' following-up.The patients in control group were followed to see the doctor in endocrinology clinic based ontheir consciousness.The changes of related indicators between two groups after 10 months of different kinds of diabetes management were compared.Results After management,the levels of body mass index (BMI),fasting blood glucose (FBG),triacylglycerol (TG),total cholesterol (TC),etc in management group were significantly better than those in control group,and there were significant differences (P ＜ 0.05).The medical compliance rate of diabetes-related behavior in management group was significantly better than that in control group,and there was significant difference (P ＜ 0.05).The multi-factor analysis showed that high level of BMI,FPG,TG,TC were risk factors of blood glucose control in type 2 diabetes (P ＜ 0.05),while high level of success rate of blood pressure,prescribed rate of medication,adherence rates of diabetes diet had promotion to blood glucose control of type 2 diabetes.Conclusion Type 2 diabetes management in community with community physicians'following-up is useful for improving diabetes management effectiveness and quality.

Objective To evaluate the risk of locoregional recurrence (LRR) and the influencing factors for long-term survival in patients with epithelial-myoepithelial carcinoma (EMCa).Methods A retrospective analysis was performed for 18 EMCa patients, who received initial therapy or initial adjuvant therapy in our hospital from 1999 to 2015, to investigate their survival.Among these patients, 8(44%) underwent surgery alone, 9(50%) received adjuvant radiotherapy, and 1(6%) received radical concurrent chemoradiotherapy.Locoregional recurrence-free survival (LRFS) and overall survival (OS) rates were compared between these groups.The Kaplan-Meier mtthod was used to calculated survival rates and log-rank test was used to compare the LRFS.Results With a median follow-up time of 46 months, 5 patients developed LRR, and the 5-year LRFS and OS rates were 69% and 93%, respectively.The patients treated with radiotherapy had a significantly higher 5-year LRRFS rate than those not treated with radiotherapy (71% vs.57%, P=0.569).Conclusions LRR is the main failure mode of EMCa treatment, and further improving local control is the key to improved survival.

OBJECTIVETo investigate the apoptosis inducing effects of ponicidin (PON) on leukemic K562 cells and its mechanisms of action.

METHODK562 cells in culture medium in vitro were given different concentrations of PON (10-50 micromol x L(-1)) for 24, 48 and 72 h. The inhibitory rate of the cells was measured by MTT assay, cell apoptotic rates were detected by flow cytometry (FCM) using Annexin V staining after K562 cells were treated with different concentrations of PON for 72 hours, and cell morphology was observed by Wright-Giemsa staining. Western blot was used to detect caspase-3 and poly(ADP-ribose) polymerase (PARP) expression, and the protein levels in mitogen-activated protein kinase signaling pathways (MAPKs, p-P38, p-ERK and p-JNK) as well as p-AKT and p-P85 in PI3K/AKT signaling pathways were also detected.

RESULTPON (over 30 micromol x L(-1)) could inhibit the growth of K562 cells in both time- and dose-dependent manner. FCM analysis revealed that apoptotic cells were gradually increased in a dose-dependent manner after treatment for 72 hours, and that marked morphological changes of cell apoptosis such as condensation of chromatin was clearly observed by Wright-Giemsa staining after treatment by 50 micromol x L(-1) PON. Western blot showed cleavage of the caspase-3 zymogen protein (32 kD), with the appearance of its 17 kD subunit, and a cleaved 89 kD fragment of 116 kD PARP was also found. Furthermore, Western blotting also showed that expression of p-AKT and p-P85 in PI3K/AKT signaling pathways was downregulated dramatically whereas the expression of p-P38 as well as p-ERK and p-JNK remained unchanged after the cells were treated by PON for 48 h.

CONCLUSIONThe results demonstrate that PON exhibits in vitro anti-leukemia effect by induction of apoptosis in K562 cells, and that PON induced apoptosis in K562 cells mainly related to activation of caspase-3 as well as inactivation of PI3K/AKT signaling pathway via down regulation of the expression of p-AKT and p-P85 protein levels. These results provide strong laboratory evidence for further anti-leukemia trials of PON.

Apoptosis ; drug effects ; Blotting, Western ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Diterpenes ; pharmacology ; Humans ; Poly(ADP-ribose) Polymerases ; metabolism ; Signal Transduction ; drug effects

Objective: To observe the vascular and bronchial abnormalities in subsolid nodules on high resolution CT (HRCT), and analyze its correlations with the classification and subtypes of lung adenocarcinoma. Methods: Pathological and radiographic data of 315 surgically resected subsolid nodules (226 were pure ground-glass opacities, and 89 were part solid nodules with tiny solid components ≤ 6 mm) were retrospectively reviewed. The morphologic changes of the blood vessels and bronchia/bronchioles in ground-glass opacity on HRCT were evaluated, and their correlations with histopathology classification were analyzed. Chi-square test was performed for analysis of correlations with categorical variables, whereas the one-way ANOVA analysis was performed for analysis of correlations with continuous variables (e.g., lesion dimension). Results: Forty-eight pre-invasive lesions (PILs), 29 minimally invasive adenocarcinomas (MIAs), and 238 invasive adenocarcinomas (IACs) were analyzed. IACs were divided into 2 groups according to the percentage of lepidic pattern: lepidic predominant (lepidic pattern ≥ 50%, n=145), and non-lepidic predominant (lepidic patten<50%, n=93). The prevalence of vascular and bronchial abnormalities was higher in IACs (59.24% & 18.49% in IACs, 13.79% & 3.45% in MIAs, and 0% & 0% in PILs). The abnormalities of vessels and bronchi in nodules on HRCT were correlated with the PIL/MIA/IAC classifications (χ²=69.797, P<0.001, χ²=14.213, respectively). Moreover the prevalence of valcular and bronchial abnormalities significantly increased from non-lepidic predominant IACs (78.49%, 26.88%) compared to lepidic predominant IACs (46.90%, 13.10%), these morphologic abnormalities correlated with a higher percentage of non-lepidic pattern, which were considered with higher invasiveness, in IACs (P<0.001, χ²=22.139, P=0.012, χ²=6.253, respectively). Conclusion The morphologic changes of blood vessels and bronchia/bronchioles within the subsolid nodules on HRCT help to differentiate IAC from PIL and MIA, also correlate with the proportion of non-lepidic pattern in IACs, even when the solid component undeveloped or very tiny.

The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes. Progestin and adipoQ receptor 3 (PAQR3), a key regulator of inflammation and metabolism, can negatively regulate the PI3K/AKT signaling pathway. Here, we report that gentiopicroside (GPS), the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa, decreased lipid synthesis and increased glucose utilization in palmitic acid (PA) treated HepG2 cells. Additionally, GPS improved glycolipid metabolism in streptozotocin (STZ) treated high-fat diet (HFD)-induced diabetic mice. Our findings revealed that GPS promoted the activation of the PI3K/AKT axis by facilitating DNA-binding protein 2 (DDB2)-mediated PAQR3 ubiquitinated degradation. Moreover, results of surface plasmon resonance (SPR), microscale thermophoresis (MST) and thermal shift assay (TSA) indicated that GPS directly binds to PAQR3. Results of molecular docking and cellular thermal shift assay (CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH₂-terminus including Leu40, Asp42, Glu69, Tyr125 and Ser129, and spatially inhibited the interaction between PAQR3 and the PI3K catalytic subunit (P110α) to restore the PI3K/AKT signaling pathway. In summary, our study identified GPS, which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway, as a potential drug candidate for the treatment of diabetes.

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.