Humans ; Integrative Medicine ; Medicine, Chinese Traditional ; trends

Tumor cells can metabolize glucose through glycolysis to intermediates for biomacromolecule synthesis by inhibiting the activity of the pyruvate dehydrogenase complex (PDC) in mitochondria. In this process, pyruvate dehydrogenase kinases (PDKs) play a key role. The inhibition of the activity of PDKs can effectively block this metabolic pathway, activate mitochondrial oxidative metabolism, and induce tumor cell apoptosis. PDK inhibitors have become a research hotspot in medicinal chemistry, and novel structures targeting classical binding sites have been synthesized. In this paper, recent research progress on PDK inhibitors is reviewed to provide information on these latest entities and to explore their clinical applicability.

Objective To describe the manifestations of the inferior phrenic arteries(IPA)supply to the pulmonary hemorrhagic lesions and to evaluate the safety and efficacy of transcatheter arterial embolization(TAE)of the IPA.Methods The clinical data and imaging findings of eighteen patients with the additional blood supply to the pulmonary hemorrhagic lesions from the IPA were evaluated retrospectively.The causes of the bleeding were lung malignancies in 9,bronchiectasis in 7,and chronic inflammation in 2 patients.TAE supplementally was performed in patients with IPA supply to the pulmonary lesions,using polyvinyl alcohol particles,gelatin sponge particles,and microcoils.Results Selective arteriogram demonstrates an enlarged IPA,with numerous branches and hypervascularity in all 18 cases, with tumor staining in 9,the contrast material extravasation in 6,and non-specific staining in 2 cases.In addition,IPA-to-pulmonary shunting was found in 9 cases.All the lesions supplying by IPA were adjacent to the pleurae,including adjacent to the diaphragmatic pleura in 11,the mediastinal pleura in 5,and the lateral pleura of the lower lobe in 2 cases.Technical success of IPA embolization was achieved in the 18 cases.Embolization of other nonbronchial systemic arteries(the internal thoracic artery in 7 and intercostal artery in 3)was performed at the same session.All bleeding ceased immediately after supplemental IPA embolization.Follow-up time ranged from 8 months to 4 years.Mild recurrent hemoptysis occurred in 3 patients at 1,2,6 months respectively,after the embolization.These patients were responsive to conservative management.Recurrent bleeding did not occur in 15 patients during the follow-up. Conclusion The pulmonary hemorrhagic lesions,especially adjacent to the diaphragmatic and mediastinal pleurae,can be supplied by IPA,and may result in clinical failure following BAE.Supplemental TAE of IPA is a safe and effective adjunct to BAE in the management of bronchial bleeding supplied by IPA.

Objective To evaluate the efficacy of disinfection and isolation measures in a hospital that received and treated the first case of imported Middle East respiratory syndrome(MERS)in China.Methods The first MERS case in China was admitted in the negative pressure room of the intensive care unit in a hospital on May 28,2015,a series of disinfection and isolation measures were taken for controlling and preventing MERS coronavirus (MERS-CoV)infection.Results One case of MERS confirmed by Guangdong Provincial Center for Disease Control and Pre-vention (CDC)and Chinese CDC were admitted in a hospital at 2:30 of May 28,2015,throat swabs and blood specimens of patients were detected as positive for MERS-CoV by real-time polymerase chain reaction.On the 3rd day,8th day,2 week after admission,and on June 21 ,throat swabs,blood,stool,and sputum specimen culture were negative respectively;before patient’s discharge,throat swabs,sputum,blood,and stool specimen culture were all negative for consecutive two times,there was no fever for 10 consecutive days,clinical symptoms were im-proved,patient finally recovered and was discharged on June 26.Detection of MERS-CoV were all negative for nasal swabs,throat swabs,and blood specimens from all health care workers (HCWs)participated in the treatment for MERS;all HCWs were performed physical examination from June 26 to July 10,none of them felt discomfort, there was no infection occurred among them.On the 7th,13th day of admission,and following terminal disinfec-tion,specimens of environment and object surface were taken and performed detection of MERS-CoV,all were negative.Conclusion Strict implementation of disinfection and isolation measures can effectively cut off the routes of MERS-CoV transmission and protect the safety of HCWs.

Animals ; Cardiomegaly ; Constriction ; Heart ; Mice

OBJECTIVETo investigate the synergistical killing effect of docetaxel combined with ABT-737 on human prostate cancer cell line PC-3 by inducing apoptosis and further to determine the mechanism underlying such effect.

METHODSPC-3 cells were treated with various concentrations of docetaxel or (and) ABT-737. Cell viability was determined using MTT assay. Apoptosis was assessed by fluorescence microscopy analysis of cells with condensed and segmented nuclei following staining with 4',6-diamidino-2-phenylindole (DAPI). Cellular DNA was stained with propidium iodide and flow cytometric analysis was performed to analyze the cell cycle distribution. Bcl-2, Bax, Bcl-xL and Mcl-1 protein changes were detected by Western blot. The activity of caspase-3 was measured using a colorimetric assay.

RESULTSDocetaxel (20 nmol/L) combination with ABT-737 (400 nmol/L) for 48 hours, the cell viability was decreased to 19.7% ± 3.2% to compare with 44.2% ± 4.4% (t = 4.45) of docetaxel and 93.2% ± 1.8% of ABT-737 separately and there was a synergistic effect between the two drugs (CI = 0.8). Apoptosis rate of the combination group was higher than other two drugs. Docetaxel increased the cell number arrested in G(2)/M phase compared with control group (P < 0.05), but the combination treatment resulted in a significant arrest in the G(0)/G(1) phase. The combination treatment could significantly reduced the Bcl-2, Bcl-xL and Mcl-1 expression (F = 369.53, 57.89 and 32.77, all P < 0.05) and enhanced the activity of caspase-3 (419.7% ± 15.6%) (F = 207.33, P < 0.05).

CONCLUSIONSThe combination of ABT-737 with docetaxel can synergistically inhibit the proliferation of PC-3 cells through inducing apoptosis, which may be associated with cell cycle arrest, down-regulation of Bcl-2, Bcl-xL and Mcl-1 expression and activation of caspase-3.

Apoptosis ; drug effects ; Biphenyl Compounds ; pharmacology ; Caspase 3 ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Drug Synergism ; Humans ; Male ; Myeloid Cell Leukemia Sequence 1 Protein ; metabolism ; Nitrophenols ; pharmacology ; Piperazines ; pharmacology ; Prostatic Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Sulfonamides ; pharmacology ; Taxoids ; pharmacology ; bcl-X Protein ; metabolism

Aged ; Animals ; China ; epidemiology ; Disease Outbreaks ; Female ; Humans ; Male ; Middle Aged ; Orientia tsutsugamushi ; Scrub Typhus ; epidemiology

Objective To evaluate the development of the sphincter muscle complex(SMC)and defecation function in pediatric patients with congenital anorectal malformations(ARM).Methods A total of 64 children underwent MRI,among whom 39 were patients with ARM,and the others were patients without ARM undergoing MRI because of other dieases.The dimensions of the SMC in different planes were evaluated with different sequences and coils.The relationship between the SMC development and the defecation function was investigated.Results In control group,the absolute value of SMC width was (3.63?0.22)mm,which had a high correlation with age(r=0.998,P0.05).The SMCs in intermediate ARM patients[muscle index(MI)=0.47?0.05]and low ARM patients(MI=0.49? 0.05)were well developed.The SMCs in a portion of patients with high ARM(MI=0.28?0.06)were poorly developed,when MI≤0.18,anorectal contraction pressurewas significantly lower(t=3.55, P0.18[(0.85?0.20)vs(2.24?1.02)kPa].The length of anal canal with high-pressure[(10.88?3.64)vs(20.26?4.34)mm]was shorter(t=5.18,P0.18,the anorectal angle was less than 90 degrees,and normal continent function was found in 21 of 23 cases(91%).Conclusion MRI can be employed to evaluate the development of SMC in patients with ARM,MI was an objective criteria to evaluate the development of SMC.When MI≤0.18, maldevelopment of SMC will be highly suspected.

Alzheimer disease (AD) is one of the most common types of dementia.Serotonin (5-HT) plays an important role in the pathogenesis of AD,causing alterations in patients' cognitive abilities,as well as learning and memory capabilities,by regulating the cholinergic and glutamatergic neurotransmission through the signal transduction pathway.Patients suffer from emotional disorders including depression and apathy and clinical manifestations such as unrestrained diet,which are all related to the signaling function of 5-HT receptors.Strengthening the 5-HT receptor-mediated transduction pathway and increasing the concentration of synaptic 5-HT have been used as a novel therapy for delaying the progression of AD.This articles reviews the AD therapies targeting 5-HT transduction pathway.

Objective To explore the changes in neuroglobin(NGB)expression in rat cerebral cortex induced by acute and chronic hypoxia at high altitude.Methods Seventy SD rats were randomly divided into normal control and experimental groups,and in the latter group,the rats kept in a high-altitude research base in Kekexili(4600 m),while the control rats were kept in a facility at the altitude of 2295 m.The rats in the experimental group were divided into 6 groups with the exposure time of 12,24,48,72 h,1 week and 1 month.An oximeter was used to measure the SaO2 level.Semi-quantitative PCR and Western blotting were performed to detect the expression levels of NGB mRNA and protein in the cortical neurons of the rats after the exposure.Results After explosure of the rats to hypoxia at high altitude for 12h,the SaO2 was lowered to(70.70±2.83)%and increased gradually as exposure time prolonged,but remained lower than that in the control group throughout the exposure.RT-PCR showed a rapid increase of NGB mRNA expression after 24-h exposure to hypoxia,followed by gradual decrease till recovery of the normal level at 1 week;the expression slowly increased after 1 week and maintained a high level till 1 months.showing significant difference from that in the control group(P＜0.05).Western blotting showed an identical pattem of NGG protein expression alterations during the experiment.Conclusion NGB expressions in the cerebral cortex increase significantly after acute and chronic hypoxia at an altitude of 4600 m to enhance the tolerance to hypobaric hypoxia,suggesting the possible role of NGB as an important endogenous mechanism for protecting the neural tissues against hypoxic injuries.