Nucleotide binding oligomerization domain (NOD)-like receptor protein 3, NLRP3) inflammasomes regulate the secretion of caspase-1, interleukin-18 (IL-18), IL-1β, and other cytokines, and participates in aging. In recent years, it has been found that NLRP3 inflammasomes are abnormally activated in aging heart and vessels, and inhibition of NLRP3 inflammasomes can alleviate heart aging and vascular aging. This review summarizes the research of NLRP3 inflammasome in heart and vascular aging, and the related drugs to promote the discovery of the mechanism of NLRP3 inflammasome in heart and vascular aging and the development of related drugs.

E2F transcription factor 1 (E2F1) is a major member of the E2F transcription factor family and participates in a wide range of physiological regulatory processes, such as cell cycle, survival, apoptosis, and metabolism. It is proved that the activity of E2F1 is related to the G1/S phase regulation of the cell cycle dependent on tumor suppressor retinoblastoma protein (RB). Recent studies have shown that E2F1 is highly expressed in prostate cancer cells, manifested as an oncogene, and its expression level is closely related to the occurrence, development, and poor clinical prognosis of prostate cancer. Androgen receptor (AR) is the main driving factor for the growth and progression of prostate cancer, and the changes of AR pathway play a key role in the pathological progression of prostate cancer. This article provide a systematic and comprehensive summary on recently published articles to review the role of the E2F1 pathway in prostate cancer.

OBJECTIVETo evaluate the efficacy and safety of wuling Capsule combined with Pinaverium Bromide in treatment of irritable bowel syndrome (IBS).

METHODSSixty-four IBS patients were randomized into two groups, the treatment group and the control group, 32 in each group. Patients in the treatment group took wuling Capsule (0. 33 g/capsule, 3 times per day) and Pinaverium Bromide (50 mg/tablet, one tablet each time, 3 times per day) , while those in the control group only took Pinaverium Bromide (50 mg/tablet, one tablet each time, 3 times per day). The therapeutic course for all was 6 weeks. IBS symptom score questionnaire, IBS-Quality of Life (IBS-QOL) , Self-Rating Depression Scale (SDS) , and Self-Rating Anxiety Scale (SAS) were assessed before and after treatment. Adverse reactions were also observed.

RESULTSThe improvement of abdominal pain, stool frequency, and stool properties, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). The improvement of dysphoria, body image, concerns for health, and dietary restriction of IBS-QOL, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). The improvement of SDS and SAS, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). No severe adverse reaction occurred in either group.

CONCLUSIONCombination therapy of wuling Capsule and Pinaverium Bromide could improve abdominal pain and defecation, attenuate depression and anxiety of IBS patients with higher safety.

Anxiety ; Anxiety Disorders ; Biomedical Research ; Capsules ; Defecation ; Depression ; Depressive Disorder ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Irritable Bowel Syndrome ; drug therapy ; Morpholines ; therapeutic use ; Quality of Life ; Surveys and Questionnaires

Vascular endothelial growth factor 121 (VEGF121) was expressed as inclusion bodies by recombinant Escherichia coli. High concentrations of both biomass (46 g dry cell/L) and VEGF121 inclusion bodies (4.5 g/L) were obtained by applying a high-cell-density culture. After the inclusion bodies were washed and dissolved, VEGF121 was refolded at 0.2 mg/ml by ultrafiltration in refolding buffer with a yield of 81%. Renatured VEGF121 was purified by anion chromatography and Sephacry S-100 chromatography with purity higher than 95% and fnal purification yield of 31%. The purified VEGF121 could stimulate the proliferation of human umbilical vein endothelial cells as demonstrated by a biological activity assay.

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) 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

Objective To investigate the current dyslipidemia profiles and correlation with etiological factors in early stage post-transplantation, and the impact of lipid metabolic disorder on renal function. Methods The clinical data of 1032 renal allografts from eight hospitals in Beijing between 2004 and 2008 were collected and evaluated retrospectively. Before and at the 1st, 3rd, 6th and 12th month post-transplantation, the changes in blood total cholesterol (TC), triglycerides (TG),low density lipoprotein (LDL)-cholesterol and high density lipoprotein (HDL)-cholesterol were analyzed. The difference in the blood lipid disorder at different stages stratified by time and different age group, the effects of immunosuppressive agents on blood lipid, and the impact of blood lipid disorder on the blood creatinine were studied. Results Except HDL-cholesterol, TC, LDL-cholesterol and TG levels were increased gradually at the first year, especially LDL-cholesterol and TG. The TC and LDL-choleaterol abnormalities were obviously related with age (P<0. 01 ). The effect of Tacrolimus (Tac)-based immunosuppressive regimen on the lipid metabolic disorder was less than cyclosporine (CsA). At the first year, there was no significant difference in blood creatinine between lipid-lowering treatment and non-lipid-lowering treatment (P>0. 05). For the recipients not subject to lipid-lowering treatment and their TG level higher than the normal at the first month after operation, the creatinine level at the first year was significantly higher than in those with normal TG level (P< 0. 05). Conclusion The lipid metabolic disorder following renal transplantation is a common complication after the first transplant year, and was related with age and immunosuppressive agent regimen. Tac-based immunosuppressive regimen has little effects on the blood lipid metabolism.

OBJECTIVETo compare the difference in the clinical efficacy on posterior circulation ischemia between acupuncture at stellate ganglion and conventional acupuncture as well as the impacts on blood pressure.

METHODSEighty cases of posterior circulation ischemia were randomized into an observation group (40 cases) and a control group (40 cases). In the observation group, acupuncture was applied to the bilateral stellate ganglions on the neck, stimulated with reinforcing technique by rotating the needles. In the control group, the acupuncture of reducing technique was applied to Fengchi (GB 20), Baihui (GV 20), Neiguan (PC 6) and Taichong (LR 3) in the excess syndrome. The even needling or reinforcing technique was applied to Fengchi (GB 20), Baihui (GV 20), Ganshu (BL 18), Shenshu (BL 23) and Zusanli (ST 36) for the deficiency syndrome. The treatment was given once every 3 days and 4 treatments were required totally in the two groups. The changes in total syndrome score, peak Systolic blood flow velocity (Vp) of vertebral artery and basilar artery, systolic and diastolic blood pressures were compared before and after treatment in the two groups. The clinical efficacy was compared between the two groups.

RESULTSThe total syndrome score was reduced apparently after treatment compared with that before treatment in the two groups (P < 0.01), and the reducing was more obvious in the observation group as compared with that in the control group (P < 0.01). The total effective rate was 87.5% (35/40) in the observation group, higher than 67.5% (27/40, P < 0.05) in the control group. After treatment, the reduced Vp of vertebral artery was not improved apparently as compared with that before treatment in the control group, Vp in blood velocity abnormality (including vascular spasm, stenosis or reduced velocity) of vertebral artery and basilar artery was all improved as compared with that before treatment in the two groups (P < 0.01), and the improvements in the observation group were more obvious than those in the control group (P < 0.01). After treatment, the systolic and diastolic pressures were reduced as compared with those before treatment in the two groups, and the reduced systolic and diastolic pressures in the observation group were more apparent than those in the control group (P < 0.01).

CONCLUSIONAcupuncture at stellate ganglion achieves the satisfactory efficacy in the treatment of posterior circulation ischemia and the significant efficacy of reducing blood pressure, more advanced than the conventional acupuncture.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Blood Pressure ; Brain Infarction ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Stellate Ganglion ; physiopathology ; Treatment Outcome

Objective To evaluate the effectiveness of arthroscope-assisted surgical technique in treating knee fractures and knee peripheral fractures.Methods From September 2000 to December 2005,there were 46 cases with knee or knee peripheral fractures,in whom artbroseope-assisted surgical technique was performed in 36 cases including 24 males and 12 females,with mean age of 30.5 years (18-52 years).Of 36 cases,26 cases with patella fractures were treated by internal fixation of tension band using cancellous bone screws,four with distal end femoral fractures by retrograde interlocking using intramedullary nail and six with fractures of tibial plateau and tibial condyle crista by internal fixation u- sing cancellous bone screws.Results The mean hospitalization was eight days.A follow up for 3-36 months(average 14 months)in 36 cases showed fracture healing.Of 36 cases,32 cases regained full knee range of motion,four left with terminal flexion,with mean loss of 15?,and had thigh circumference (10 cm above knee)1.1 cm(range 0.6-2.0 cm)shorter than health side and two had slight pain in the knee joint.Lysholm knee joint function score was 86.5+7.6 for patellar fractures,tibial plateau frac- tures and condylar crista fractures.Conclusion As for knee or knee peripheral fractures,arthroscope- assisted surgical technique can provide fine monitoring,decrease trauma and complications,fixate inter- nally and help early ground exercise.

Objective To analysis and determine the possibility of the Citellus undulatus infected with Yersinia pestis surviving the winter in an experimental study, and to provide scientific experimental basis for the study on the mechanism of Yersinia pestis preservation. Method In 2006,09 to 2007,04 and 2007,09 to 2008,04 in Xinjiang Wusu-Gurtu natural foci of plague, under natural conditions, the over the winter process of Citellus undulatus carrying the plague bacteria was simulated, and 178 Citellus undulatus were infected with Yersinia pestis (1×107 Bacteria/mouse) using artificial injection method. One hundred seventy-eight Citellus undulatus infected with Yersinia pestis were kept into a construction of the black (1-5 ℃) basement (2 meters under the ground) in the plague focus. In doing so, these Citellus undulatuses almost simultaneously stepped into hibernation. After waking up from hibernation in following year in April, the survived mice carrying the plague bacteria were observed. Results Sixty-eight mice survived among the 178 infected with Yersinia pestis after 6 months of hibernation (through October to the following year in April), and the remaining 110 were all dead without pulling through the hibernation period. The survival rate was 38.2% (68/178). The organ culture of Yersinia pestis of the 110 dead mice(Citellus undnlatus) were tested, 67 were negative(-), 43 positive(+), with a positive rate of 39.1%(43/110). Among the rats with positive plague bacteria, the congestive pulmonary edema and the pathological changes of the hemorrhagic inflammation of the heart, liver, spleen, kidney and injection site could be seen clearly; the plague-free mice were not found to have any pathological changes. The survived 68 mice over the winter were autopsied and observed after being fed up for 20 days. No any pathological changes were found among these mice, and culturing of Yersinia pestis of the heart, liver, spleen, lungs and the tissue of injection site of these mice were all negative (-). Conclusions Citellus undulatus can carry Yersinia pestis during hibernation, but some fail to carry the bacteria through the entire process of hibernation persistently. Yersinia pestis was negative in the survived mice at the end of hibernation. The results showed that Citellus undulatus can not carry Yersinia pestis over the winter.