China ; Diabetes Mellitus ; diagnosis ; metabolism ; Glycated Hemoglobin A ; metabolism ; Humans

Objective To explore the effectiveness and safety of totally laparoscopic distal gastrectomy (TLDG)and laparoscopically assisted distal gastrectomy (LADG)for gastric cancer.Methods The comparative studies of TLDG and LADG published between 2008 and 2014 were searched from PubMed,EMBASE,Chinese Biomedical Literature Database (CBM),China National Knowledge Infrastructure (CNKI). After screening for inclusion, data extraction,and quality assessment,RevMan 5.3 software was used for Meta-analysis.Results Ten studies of 2 212 patients were included in the Meta-analysis,among whom 930 cases underwent TLDG and 1 282 cases underwent LADG.The results of Meta-analysis indicated that compared with LADG,TLDG had the advantages of less blood loss (WMD= - 20.70,95%CI:- 30.81 - - 10.59,P <0.01),less usage of analgesic (WMD=-0.38,95%CI:-0.74 - -0.02,P =0.04),more retrieved lymph nodes (WMD= 2.98,95%CI:0.71 -5.26,P =0.01).However,the Meta-analysis showed no statistically significant differences in the operation time, postoperative time-to-first flatus and oral intake,postoperative hospital stay,length of proximal resection margin, C reaction protein (CRP)level at postoperative day 1,incidence of overall complications and anastomosis-related complications.Conclusion TLDG is safe and effective with less blood loss, less pain than those of LADG. Moreover,it has comparable results to conventional LADG,with no increase of postoperative complications.

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents ; Benzamides ; chemistry ; DNA Repair ; Drug Design ; Humans ; Molecular Docking Simulation ; Poly(ADP-ribose) Polymerase Inhibitors ; chemical synthesis ; chemistry ; Poly(ADP-ribose) Polymerases

Acupuncture Therapy ; Adult ; Eye Movements ; Humans ; Male ; Miller Fisher Syndrome ; physiopathology ; therapy

Objective To explore the apoptosis and proliferation of peripheral blood lymphocytes(PBLs) from primary nephrotic syndrome(PNS) and effects of dexamethasone(Dex) on them.Methods Minimal change NS(MCNS), non-minimal change NS(NMCNS) and healthy children were involved in this study. PBLs were cultured in vitro with Dex or PHA+Dex or without PHA and Dex. Apoptosis of PBLs was measured by propidium iodide(PI) staining; The effects of Dex at different concentrons on PBLs′proliferation were investigated by 3H-TdR incorporation.Results The apoptotic rate of vacuity group in MCNS was lower compared with NMCNS and healthy controls(P

Objective To explore the effect of systemic subhypothermia and erythropoietin combined treatment on neonatal hypoxic-ischemic brain damage(HIBD).Methods Sixty-five asphyxiated newborns enrolled in this study were divided randomly into combination group(n=16),hypothermia group(n=24)and conventional group(n=25).Subhypothermia was adepted in hypotheria group as well as conventional therapy.Subhypotheria and erythropoietin were both applied in combination group excepy for conventional therapy.The short-term effect was evaluated by neonatal neurological score as well as neonatal behavioral neurological assessment(NBNA)on postnatal days of 7,14 and 28,and the long-term effect was evaluated by using intellectual development table made by Children's Development Center of China(CDCC)at 3 and 6 month of age.Results The neonatal neurological score in combination group at 24,48,72 and 80 h were lower than that of 0 and 12 h.NBNA evaluation was much higher on 14 d and 28 d in combination group and hypothermia group than that in conventional group(Pa0.05).Conclusions Combination therapy with systemic subhypothermia and erythropoietin exerts obvious short and longer-time neuroprotective effect on HIBD,but there are no differences compared with hypothermia alone.

Objective To investigate the acute effect of dialysate calcium concentration on calcium balance and blood pressure(BP) of maintenance hemodialysis(MHD) patients with normal serum tCa,and to provide scien- tific basis for individualized calcium concentration dialysate formula.Methods For 4 weeks,dialysate with different calcium concentrations as DCa 1.25,DCa 1.5 and DCa 1.75 was used in 15 stable MHD patients.Arterial blood pressure was measured before and after each dialysis session,and every 30 minutes during hemodialysis session.Serum total calcium and ionized calcium were assessed before and after each dialysis session with different calcium concen- trations dialysate.Results With the DCa 1.2.5,BP,serum tCa and iCa decreased as compared with pre-dialysis val- ues(P

Objective To investigate the relationship and mechanism of the serum vitamin D levels with insulin sensitivity and adipokines APN,RBP4,visfatin and TNF-α in patients with gestational diabetes mellitus(GDM). Methods A total of 101 patients with gestational diabetes( GDM group) and 50 pregnant women with normal blood sugar( control group) were recruited to detect the serum levels of correlative biochemical indexes,APN,RBP4,visfatin,TNF-α and 25OHD3 using an HPLC method. Twenty-four patients in the GDM group diagnosed with vitamin D deficiency(<25 nmol·L-1 ) were randomized to receive either 1,25(OH) 2D3(0. 25 μg·d-1) orally or no treatment. Serum levels of correlative biochemical indexes were detected after 1 month. Results GDM patients had 25OHD3 levels significantly lower than the control group(P<0. 05),APN levels lower than the control group,and RBP4,visfatin,TNF-α levels significantly higher than the control group(all P<0. 05). After 1 month of 1,25(OH) 2D3 treatment,HOMA-IR increased,while HOMA-β decreased. APN levels was positively correlated(r= 0. 526) with 25OHD3;RBP4,visfatin,TNF-α decreased and were negatively correlated with 25OHD3( r values were -0. 272,-0. 153,-0. 072). Conclusion Vitamin D can reduce the adipokines RBP4,visfatin,TNF-α,increase APN,and thus play a protective role for gestational diabetes.