1.Correlation of gut microbiota and neurotransmitters in a rat model of post-traumatic stress disorder
Zhou QIN ; Sun TIANSHI ; Wu FENGZHI ; Li FENG ; Liu YAN ; Li WEIHONG ; Dai NING ; Tan LIBO ; Li TENGHUI ; Song YUEHAN
Journal of Traditional Chinese Medical Sciences 2020;7(4):375-385
Objective: To determine the effect of gut microbiota on a rat model of post-traumatic stress disorder(PTSD)and explore the correlation of gut microbiota with behavior and neurotransmitters.Methods: We established a single prolonged stress(SPS)model to examine the pathogenesis of PTSD on rat behavior,gut microbiota,and neurotransmitter levels.Rats were separated into control and model groups,and neurotransmitter levels were measured using enzyme linked immunosorbent assay.Then,16 S rRNA sequencing was used to compare the gut microbiota between the control and model groups.Results: Compared with those in the control group,freezing time significantly increased,while number of standing upright,crossing frequency,time spent in the central arena,and total distance traveled were significantly reduced in the model group after exposure to SPS(all P<.05).Meanwhile,serotonin,or 5-hydroxytryptamine,levels in the brain in the model group were significantly lower than those the control group(P=.0332).In addition,changes were observed in the gut microbiota diversity and relative abundances of bacterial phyla,orders,families,and genera in the model group.Especially,changes in Firmicutes,Bacteroidetes,Cyanobacteria,and Proteobacteria levels were most pronounced after SPS exposure.Correlation analysis showed that the strongest positive correlation was found between Bac-teroidaceae and 5-HT(P =.0009).Moreover,RF32 abundance was the most negatively related to 5-HT(P=.0009),crossing frequency(P=.0007),and total distance(P=.0003).Conclusion: Our results suggest that SPS model rats showed differences in behavior,neurotransmitter levels,and gut microbiota with control rats.Moreover,Firmicutes,Bacteroidetes,Cyanobacteria,and Proteobacteria were most relevant to the exhibited fear-like and anxiety-like behaviors and significant serotonin content reduction in SPS model rats.
2.Development of the triazole-fused pyrimidine derivatives as highly potent and reversible inhibitors of histone lysine specific demethylase 1 (LSD1/KDM1A).
Zhonghua LI ; Lina DING ; Zhongrui LI ; Zhizheng WANG ; Fengzhi SUO ; Dandan SHEN ; Taoqian ZHAO ; Xudong SUN ; Junwei WANG ; Ying LIU ; Liying MA ; Bing ZHAO ; Pengfei GENG ; Bin YU ; Yichao ZHENG ; Hongmin LIU
Acta Pharmaceutica Sinica B 2019;9(4):794-808
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.
4.The role of adipose tissue in the progress of acute pancreatitis
Fengzhi QU ; Pengyu DUAN ; Gang WANG ; Bei SUN
Chinese Journal of Hepatobiliary Surgery 2017;23(7):499-502
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.
5.Clinical Curative Effect of Vitreous Cavity Injection Combined with Transconjunctival Sutureless Vitrectomy on the Patients with Poliferative Diabetic Retinopathy
Lianyi SUN ; Meisheng ZHAO ; Fengzhi LI ; Qian YAO ; Zhongqiao ZHU ; Xinguang YANG
Progress in Modern Biomedicine 2017;17(23):4579-4582
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.
6.Effects of Xuesaitong on the Retinal Microcirculation of Patients with Diabetic Retinopathy
Lianyi SUN ; Meisheng ZHAO ; Fengzhi LI ; Juan ZHU ; Xiaoqin LEI ; Hua AI
Progress in Modern Biomedicine 2017;17(27):5309-5311,5353
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.
7.Research updates on recurrent pancreatitis
Fengzhi QU ; Chengliang CAO ; Gang WANG ; Bei SUN
Chinese Journal of Hepatobiliary Surgery 2016;22(6):422-424
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 .
8.Role of hypoxia inducible factor-1 in the development of acute pancreatitis
Chengliang CAO ; Fengzhi QU ; Gang WANG ; Bei SUN
Chinese Journal of Hepatobiliary Surgery 2016;22(10):718-720
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.
9.Updates on neoadjuvant therapy in borderline resectable pancreatic cancer
Fengzhi QU ; Gang WANG ; Bei SUN ; Hongchi JIANG
Chinese Journal of Hepatobiliary Surgery 2015;21(3):206-209
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.
10.Role of autophagy in occurrence and development of acute pancreatitis
Fengzhi QU ; Gang WANG ; Bei SUN ; Hongchi JIANG
Chinese Journal of Hepatobiliary Surgery 2015;21(7):497-499
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.

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