Histone lysine specific demethylase 1 (LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound (IC = 3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound (IC = 49 nmol/L, and = 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3K4me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency of compound . Compound also showed strong antiproliferative activity against four leukemia cell lines (OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, significantly inhibited colony formation and caused remarkable morphological changes. Compound induced expression of CD86 and CD11b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation. The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazole-fused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1A inhibitors.

Objective:To investigate the clinical curative effect of vitreous cavity injection combined with transconjunctival sutureless vitrectomy on the patients with poliferative diabetic retinopathy.Methods:80 patients with diabetic retinopathy were enrolled in our hospital from January 2014 to January 2016,in which contained 83 sicked eyes,and randomly divided into two groups.Group A (n=40,42 sicked eyes) accepted 25G transconjunctival sutureless vitrectomy,and Group B (n=40,41 sicked eyes) adopted intravitreal injection of conbercept based on patients in Group A.The operative conditions,best-corrected visual acuity (BCV) and retinal thickness were compared between two groups,and the incidence of adverse reactions within postoperative 1 month were recorded and analyzed.Results:The operation time of group B was significantly shorter than that of group A (P＜0.05).The percentage of using electric coagulation,operative bleeding and iatrogenic fracture space in group B were significantly lower than of those group A (P＜0.05).The percentage of neovascularization vanish in group B was significantly higher than that of group A (P＜0.05).The BVCA of patients in group B in postoperative 1 month and 3 month were higher than those of group A (P＜0.05).And the thickness of retinal in group B were significantly thinner than those of Group A (P＜0.05).The incidence of vitreous hemorrhage and hyphema in group B were significantly lower than those of Group A (P＜0.05).Conclusions:Vitreous cavity injection combined with transconjunctival sutureless vitrectomy improved the operative conditions and contributed to the recovery of postoperative visual acuity and retinal in the treatment of patients with poliferative diabetic retinopathy.

Objective:To investigate the effects of xuesaitong on the retinal microcirculation of patients with diabetic mtinopathy (DR).Methods:Ninety-five patients with DR admitted in our hospital were randomly divided into the control group and the observation group.Forty-eight patients in the control group were treated with conventional hypoglycemic agent,and those in the observation group were treated with xuesaitong.The retinal microcirculation indexes including EDV,PSV,RI,Vmax,Vmin,MV,hemorheology indexes including NBL,NBH,DE,Hct,AE,ESR,and clinical efficacy in both groups were observed and compared.Results:After treatment,the clinical efficacy of observation group was 87.8％,which was much higher than that of the control group (61.4％,P＜0.05).The EDV,Vmax,and Vmin of control group were significantly improved than those before treatment (P＜0.05),and EDV and PSV were much higher than those of control group,the RI,Vmax,Vmin,and MV were much lower (P＜0.05).Additionally,the NBL and NBH in control group were much lower compared with those before treatment,while NBL,NBH,DE,Hct,AE,and ESR in control group were improved than those in control group,which were much improved that those of control group (P＜0.05).Conclusion:Xuesaitong combined with conventional hypoglycemic therapy was effective in treating patients with diabetic retinopathy,which could significantly improved the retinal microcirculation and hemorheology.

Obesity is an independent risk factor for acute pancreatitis (AP),and the morbidity risk and severity of AP in obese patients were significantly increased than those in non-obese patients.However,the exact mechanism has not been fully elucidated.In recent years,the researches on the role of adipose tissue (AT) in AP have gradually attracted wide attention of scholars both at home and abroad.To better understand the pathogenesis and new therapeutic targets of AP,in this paper,we overviewed the recent research progress on the role of AT in AP.

Pancreatic acinar cell death modality is a significant factor which determines the course and prognosis of acute pancreatitis (AP).The severity of AP is positively correlated with acinar necrosis,while negatively correlated with acinar apoptosis.Adenosine triphosphate (ATP) level is the key to control the manner of death,and acts as a switch during the conversion of necrosis and apoptosis in a variety of pathophysiological settings:low levels of ATP can accelerate cell necrosis and high levels of ATP might promote apoptosis.Hypoxia inducible factor 1 (HIF-1) is a highly expressed transcription factor in anoxic conditions which can effectively regulate cell energy metabolism and play an important role in regulating cell death and inflammatory injury.Therefore,this review aimed to provide a reference about better understanding of the pathogenesis and new therapeutic targets of HIF-1 in AP.

Recurrent pancreatitis ( RP) can be further divided into two items , including recurrent acute pancreatitis ( RAP ) and recurrent chronic pancreatitis ( RCP ) .In recent years, with the rising incidence of pancreatitis , the incidence of RP has also been increased .During the development of pancre-atic diseases, RP may serve as a transitional disease .Thus, this article reviewed the latest research progress on RP in order to discuss its role in the development of the related pancreatic di-seases and the effects on clinical prognosis , and provide a refe-rence for preventing and treating RP and even cancer .

Borderline resectable pancreatic cancer (BRPC),characterized by low resectability rate and high postoperative recurrence rate,is a special kind of pancreatic cancer between resectable type and nonresectable one.Currently,the efficacy of neoadjuvant therapy for BRPC has become a hot topic in the field of pancreatic cancer.Although neoadjuvant therapy plays a critical role in obviously improving the R0 resectability rate and survival status of BRPC patients,the normalized therapeutic regimen has not been established.In this article,we overviewed the recent progress on the neoadjuvant therapy in treating BRPC.

The onset of acute pancreatitis (AP) is a complex pathophysiological process mediated by multifactors which are not only interdependent but also influencing each other.So far,the specific molecular mechanism remains uncertain.Autophagy widely exists in a variety of vital phenomena in eukaryotes including the growth,development and pathophysiological progression of normal cells.Autophagy plays an important role in the early damage of acinar cells as well as the development of AP.However,the mechanism is still in doubt.Thus,we overviewed the role of autophagy in the occurrence and progression of AP in order to further enrich the understanding on the pathogenesis.

BACKGROUNDCommunity-acquired pneumonia (CAP) is a common infectious disease throughout the world and the incidence continues to grow as the population ages. Aspiration is an important pathogenic mechanism for pneumonia in the elderly and the management of patients with community-acquired pneumonia with aspiration factors is a major medical problem. Our study aimed to assess whether moxifloxacin in comparison to levofloxacin plus metronidazole are effective and safe in the treatment of community-acquired pneumonia with aspiration factors.

METHODSIn this prospective, multicenter, open-label, randomized controlled trial, 77 patients with mild-to-moderate community-acquired pneumonia with aspiration factors were enrolled and randomly assigned to receive moxifloxacin or levofloxacin plus metronidazole. The primary efficacy variables were clinical outcomes in evaluable patients at a follow-up visit 7 to 14 days after the end of therapy.

RESULTSSeven days after the end of therapy a clinical cure was achieved for 76.7% (23 of 37) of efficacy-evaluable patients in the moxifloxacin group and 51.7% (15 of 40) of patients in the levofloxacin plus metronidazole group. There was a significant difference between the two groups (χ(2) = 4.002, P < 0.05). Bacteriological success rates were similar in the moxifloxacin group (93.3%) and levofloxacin plus metronidazole group (96.4%), there was no significant difference between the two groups (P > 0.05). The overall adverse event rate was 10.8% (4/37) in the moxifloxacin group versus 17.5% (7/40) in the levofloxacin plus metronidazole group, there was no significant difference between the two groups (P > 0.05). No serious adverse events were observed.

CONCLUSIONSMoxifloxacin is effective and safe for treatment of community-acquired pneumonia with aspiration factors. And the regimen of moxifloxacin monotherapy is more convenient compared with levofloxacin plus metronidazole.

Aged ; Aged, 80 and over ; Anti-Bacterial Agents ; therapeutic use ; Community-Acquired Infections ; drug therapy ; Female ; Fluoroquinolones ; therapeutic use ; Humans ; Levofloxacin ; therapeutic use ; Male ; Metronidazole ; therapeutic use ; Middle Aged ; Pneumonia ; drug therapy ; Prospective Studies