Objective To study the effects of alpinetin on apoptosis of Hep3B cells and explore the related mechanism.Methods Hep3B cells were cultured in vitro,treated with alpinetin; RT-PCR and Western blot was used to detect the mRNA and protein levels of Bcl-2; MTT assay was used to detect the cellular growth inhibitory rate; Annexin V-FITC/PI double staining was used to detect the apoptosis rate of cells; Mitochondrial membrane potential was analyzed by flow cytometry; Western blot was used to detect protein expression of Caspase-3,9 and Cytochrome C ; the experiment was carried out in four groups:control group,high dosage of alpinetin group,middle dosage of alpinetin group and low dosage of alpinetin group.Results The expression of Bcl-2 in Hep3B cells were decreased by alpinetin.After treated with different dosages of alpinetin (40,80,120 μmol/L),the apoptotic inhibitory rate detected by MTT were 6.38％ ± 1.32％,21.58％ ± 1.97％ and 43.18％ ± 3.89％,significantly higher than those in control group (tlowdose =13.01,tmiddle dose =15.12,thighdose =14.79,average P ＜ 0.01) ; the expression of mitochondrial membrane potential green fluorescence protein (GFP) were 18.93％ ± 2.3％,31.11％ ± 2.67％ and46.06％ ± 2.95％,significantly higher than those in control group (tlow dose =16.70,tmiddle dose =31.38,thigh dose =48.15,average P ＜ 0.01).Western blot analysis showed that the expression of Caspase-3,9 andCytochrome C in cytoplasm significantly was higher than those in control group(Caspase-3:llow dose =11.94,tmiddle dose =10.18,thigh dose =18.82,average P ＜0.01; Caspase-9:tlow dose =15.11,tmiddle dose =20.41,thish dose =21.25,average P ＜0.01; Cytochrome C:tlow dose =15.11,tmiddle dose =28.47,thigh dose =16.01,average P ＜ 0.01).while that Cytochrome C in mitochondria significantly lower than those in control group (tlow dose =16.70,tmiddle dose =12.00,thighdose =27.61,average P ＜ 0.01).Conclusions Alpinetin promotes apoptosis of human hepatic cancer cells Hep3B by down-regulating Bcl-2,probably through mitochondrial pathway.

BACKGROUND: The introduction of cyclosporin A (CsA) has greatly enhanced the early survival rate of kidney graft, but the long-term graft survival rate is still limited. Whether tacrolimus prevents chronic allograft nephropathy (CAN) and prolongs survival time is now becoming a hot spot in field of renal transplantation.OBJECTIVE: To investigate the feasibility and safety of converting CsA to tacrolimus (FK506) in preventing progression of CAN. DESIGN: Observation and controlled trial.SETTING: Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital, Central South University.PARTICIPANTS: A total of 73 patients who had received kidney transplantation at the Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital of Central South University from April 2001 to October 2005, and had been diagnosed as CAN by graft biopsy (42 male patients and 31 female patients; age ranged 19-69 years), were enrolled in the study approved by the ethics committee of this hospital after their written informed consents. CsA soft capsules (Hangzhou Zhongmei Huadong Pharmaceutical Limited Company or Huabei Pharmaceutical Limited Company); mycophenolate mofetil capsules (Shanghai Roche Pharmaceutical Limited Company); prednisone acetate tablets (Second Xiangya Hospital of Central South University); tacrolimus capsules (Fujisawa Pharmaceutical Limited Company).METHODS: Seventy-three patients voluntarily participated in CsA group (n =30) or FK506 group (n =43). The two groups were homogenous regarding patients' sex, age and general data (P > 0.05). Patients in the CsA group were continued on their initial immunosuppression protocol, which consisted of CsA, mycophenolate mofetil and prednisone acetate. In the FK506 group, CsA was stopped, and FK506 was started at a dose of 0.08-0.1 mg/(kg·d) 24 hours later, twice daily, administered 2 hours after breakfast and supper. Three days later, the blood trough concentration of FK506 was tested and adjusted to a target range of 5-8μg/L. FK506 dosage adjustment was based on the blood trough concentration, serum creatinine (SCr) and its side effects. All 73 patients were treated for 12 months. MAIN OUTCOME MEASURES: SCr, glomerular filtration rate (GFR), 24-hour urine protein excretion, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) and the toxic side effects of calcineurin inhibitors (incidences of tremor, hyperglycemia and hypertension) were monitored during a follow-up of over 12 months. RESULTS: A total of 73 patients were involved in the result analysis.①12 months after conversion, the level of SCr was statistically reduced and GFR levels were markedly elevated in the FK506 group compared with the CsA group (P < 0.01). TC, TG and LDL levels in the FK506 group were significantly lower than those in the CsA group (P < 0.01).②Compared with the CsA group, the incidence of tremor was obviously increased [30% (9/30), 5% (2/43), P < 0.01] and the incidence of hypertension was obviously decreased [56% (24/43), 83% (25/30), P < 0.05] in the FK506 group.CONCLUSION: Conversion from CsA to FK506 can postpone renal dysfunction, reduce proteinuria and improve hyperlipidemia. FK506 treatment is an effective therapy in slowing the progression of CAN.

Objective To explore the prevention and treatment strategies for the infectious renal artery rupture after renal transplantation of organ donation after citizens death (DCD).Methods The clinical data of 5 donors and their corresponding recipients with infectious renal artery rupture after renal transplantation were retrospectively analyzed with review of the literature.Results The corresponding donors of 5 recipients had the potential risk factors for donor-transmitted infection (DTI):1 case of traumatic rupture of small intestine,2 cases of digestive tract injury when resecting the donor kidney from DCD donors,1 case of severe pneumonia and 1 case of multiple renal contusion.The pathogenic microorganisms were found in the culture of kidney preservation solution,including klebsiella pneumoniae in 1 case,candida albicans in i case,enterococcus.No pathogens were detected in 1 case,and kidney preservation solution taken from the external hospital was not cultured in 1 case.The pathological examination on the resected renal grafts revealed the necrosis of the arteries and the infiltration of lymphocytes.The culture of bacteria and fungi in the removed vessel walls of renal grafts and the iliac tissues showed there were 2 cases positive for candida albicans (case 2 and case 4),1 case for cryptococcus neoformans (case 1),1 case for klebsiella pneumonia (case 5).No pathogenic bacteria were detected in 1 case,but the possibility of fungal infection was more likely.In case 1,the second kidney transplantation was performed 10 months later after artery re-transplantation,and the kidney function was normal during the follow-up period.In case 4,the second kidney transplantation was performed 2 months later after transplant nephrectomy due to the refractory rejection,the transplanted kidney experienced a rapid loss of graft function,and the blood dialysis was given continuously.The remaining 3 patients survived so far,waiting for re-transplantation.No case of bleeding occurred again in the 5 recipients.Conclusion Renal graft artery rupture is one of most severe complications after renal transplantation.It is the key for preventing infectious renal artery rupture to screen strictly infection of donors and recipients,and to use sensitive and wide coverage antimicrobial to the donors before the removal of donor kidney and during the perioperative period after renal transplantation.Early detection and operation as soon as possible is the only treatment to save the lives of the recipients.

OBJECTIVETo investigate the correlation between the coping style and mental health of patients with lumbar intervertebral disc herniation.

METHODSThe simplified coping style questionnaire and SCL-90 were used to conduct a survey of 106 patients with lumbar intervertebral disc herniation, and the scores were compared with the national norms.

RESULTSThe patients had a positive coping style score of 1.51-/+0.58 and negative coping style score of 1.13-/+0.58. The SCL-90 scores were significantly higher than the national norms. A significant correlation was found between the negative coping style and mental health of the patients.

CONCLUSIONNegative coping style is an important factor influencing the mental health of patients with lumbar intervertebral disc herniation.

Adaptation, Psychological ; Adult ; Female ; Humans ; Intervertebral Disc Displacement ; psychology ; Low Back Pain ; etiology ; psychology ; Male ; Middle Aged ; Quality of Life ; Stress, Physiological ; Surveys and Questionnaires

Objective To assess the differences in carotid artery stiffness properties and endothelium-independent dilation (EID)between elderly and young patients,and evaluate the echotracking (ET)system for vascular stiffness at different ages.Methods A total of 79 outpatients with multiple cardiovascular risks were recruited.Clinical data including medical history,height,weight,blood pressure,fasting blood glucose and blood lipid were collected.We evaluated the arterial stiffness parameters of carotid artery and EID using an ultrasonic ET system in 46 elderly subjects,compared with 33 sex-matched non-elderly subjects.The impaired EID function was defined as brachial artery nitroglycerin mediated dilation (NMD)below 4％.Results All stiffness parameters including pressure-strain elasticity modulus stiffness index β (Ep),pulse wave velocity β (PWVβ)and augmentation index (AI)were significantly increased in elderly group compared with the non-elderly group [(138.9±64.7)kPa vs.(100.6±30.8)kPa,(10.9±4.7)vs.(8.2±2.3),and (6.9±1.4)m/s vs.(6.1±0.9)m/s,P＜0.05 respectively],while the exception of arterial compliance (AC)was reduced (0.9±0.3)mm2/kPa vs.(1.0±0.5)mm2/kPa(P＜0.05).The incidence of impaired EID in elderly group was higher than in non-elderly group [56.5％ (26 cases) vs.33.3％ (11 cases),P＜0.05].ET parameters including Ep,stiffness index β,PWVβ,AC and AI were related to age (r=-0.44,-0.45,-0.40,-0.40,0.34,all P＜0.01)； Ep,stiffness index β,PWVβ and AC were also related to impaired EDI (r=-0.38,-0.40,-0.34,-0.29,all P＜0.01).Conclusions Arterial stiffness properties and EID measured by ET system was more serious in elderly with multiple cardiovascular risks than in non-elderly subjects.As a convenient and accurate assessment of stiffness parameters,ET system is optimal option for measuring arterial stiffness and EID in elderly people.

Signal transduction in cells plays an important role in the process of cellular metabolism, segmentation, differentiation, biological behaviors and cell death. Direct and indirect involvement of kinases in tumor growth, metastasis and apoptosis make them the most promising targets for anticancer discovery. Most of the kinase inhibitors in clinical use or in late development stages are multi-target kinase inhibitors (MTKIs). These MTKIs are demonstrated to exert potent anti-tumor effects through several different pathways. This review presents in the view of a medicinal chemistry point, a brief account and analysis of transduction pathways of representative MTKIs in clinical use or in late development stages.
Antineoplastic Agents ; therapeutic use ; Clinical Trials, Phase III as Topic ; Drug Delivery Systems ; methods ; Humans ; Neoplasms ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; Signal Transduction

The poly(ADP-ribose) polymerases (PARPs) is an important group of enzymes in DNA repair pathways, especially the base excision repair (BER) for DNA single-strand breaks (SSBs) repair. Inhibition of PARP in DNA repair-defective tumors (like those with BRAC1/2 mutations) can lead to cell death and genomic instability, what is so called "synthetic lethality". Currently, PARP inhibitors combined with cytotoxic chemotherapeutic agents in the treatment of BRCA-1/2 deficient cancers are in the clinical development. In this review, we will be focused on the development of combination application of PARP inhibitors with other anticancer agents in clinical trials.
Animals ; Antineoplastic Agents ; therapeutic use ; Benzimidazoles ; therapeutic use ; Breast Neoplasms ; drug therapy ; genetics ; DNA Repair ; Drug Therapy, Combination ; Enzyme Inhibitors ; therapeutic use ; Female ; Humans ; Indoles ; therapeutic use ; Melanoma ; drug therapy ; Mutation ; Ovarian Neoplasms ; drug therapy ; genetics ; Phthalazines ; therapeutic use ; Piperazines ; therapeutic use ; Poly(ADP-ribose) Polymerase Inhibitors

Among those enzymes that regulate gene expression, histone deacetylases (HDACs) play important roles in cell cycles. Extensive studies were carried out in the field of HDACs and the applications of HDAC inhibitors (HDACIs) as chemotherapeutic interventions for diverse diseases. HDACIs have moved from laboratories to clinic uses. Huge bodies of related research results were well documented and dispersed in literature. According to our understanding, HDACIs can be broadly classified as hydroxamic acids, cyclic tetrapeptides, short chain fatty acids, benzamides and electrophilic ketones. Herein, we are going to review the design and their structure-activity relationships of HDACIs and according to their structural catalogs.
Antineoplastic Agents ; chemistry ; pharmacology ; Benzamides ; chemistry ; Fatty Acids ; chemistry ; Histone Acetyltransferases ; metabolism ; Histone Deacetylase Inhibitors ; chemistry ; pharmacology ; Histone Deacetylases ; metabolism ; Humans ; Hydroxamic Acids ; chemistry ; Molecular Structure ; Peptides, Cyclic ; chemistry ; Structure-Activity Relationship

OBJECTIVETo investigate the characteristic and effect of cadmium on ATP-activated currents (I(ATP)) mediated by P2X4 purinoceptors.

METHODSTranscribe cDNA coding for the rat P2X4 receptor to cRNA in vitro. Inject the cRNA to oocytes of an xenopus laevis using the microinjection technique. Reveal the effect of cadmium on I(ATP) mediated by P2X4 receptor using the two-electrode whole-cell voltage clamp technique.

RESULTS(1) Within a certain concentration range, cadmium was found to reversibly magnify I(ATP) mediated by P2X4 receptors expressed in oocytes of an xenopus. When the concentration of cadmium reached 30 micromol/L, the increase of I(ATP) was the most significant. I(ATP) turned to decrease when the concentration of cadmium was more than 30 micromol/L; (2) The concentration-response curve was shifted to left by applying cadmium at 10 micromol/L; the EC50 was reduced from (17.1 +/- 1.5) micromol/L to (9.8 +/- 1.8) micromol/L (n = 6, P < 0.01) and the Hill coefficient was increased from 1.14 +/- 0.13 to 1.57 +/- 0.36; (3) The effect of cadmium on I(ATP) showed no dependence on membrane voltage; (4) The magnifying effect on I(ATP) reached maximum when preincubating cadmium for 120 seconds.

CONCLUSIONThe increase I(ATP) by cadmium is reversible, concentration-dependent, time-dependent, and voltage-independent. One reason of this augment effect could be the allosteric modulation on P2X4 receptors.

Adenosine Triphosphate ; metabolism ; Animals ; Cadmium ; toxicity ; Microinjections ; Oocytes ; drug effects ; metabolism ; physiology ; Rats ; Receptors, Purinergic P2X4 ; metabolism ; Xenopus laevis

OBJECTIVETo investigate the qualifications and current situations of the medical and health institutions and certified doctors for providing occupational disease diagnosis in China and to provide a reference for developing relevant policies.

METHODSWork reports and questionnaires survey were used to investigate the qualifications of all medical and health institutions and certified doctors for providing occupational disease diagnosis in China and their acceptance and diagnosis of occupational disease cases from 2006 to 2010. The rate for the work reports was 100%, and the response rate for the questionnaires was 71.0%.

RESULTSBy the end of 2010, in the 31 provincial-level regions (excluding Hong Kong, Macao, and Taiwan) in China, there had been 503 medical and health institutions which were qualified for providing occupational disease diagnosis, including 207 centers for disease control and prevention, accounting for 41.2%, 145 general hospitals, accounting for 28.8%, 69 enterprise-owned hospitals, accounting for 13.7%, and 64 institutes or centers for occupational disease prevention and control, accounting for 12.7%; 4986 certified doctors got the qualification for providing occupational disease diagnosis, with 9.4 certified doctors on average in each institution, and there was 0.65 certified doctor per 100 000 employees. In addition, 16.5% of the institutions got all the qualifications for diagnosing 9 occupational diseases, and 17.1% of the institutions got the qualification for diagnosing one occupational disease. Each certified doctor accepted diagnosis of 16.8 cases of occupational diseases on average every year.

CONCLUSIONA national occupational disease diagnosis network has been established in China, but the imbalance in regional distribution and specialty programs still exists among the qualified medical and health institutions and certified doctors. It is essential to further strengthen the development of regional qualified medical and health institutions and training of qualified doctors.

Accountable Care Organizations ; standards ; China ; Occupational Diseases ; diagnosis ; Physicians ; standards