Objective To investigate the possible association between two single nucleotide polymorphisms (SNPs) loci of apolipoprotein E (ApoE) gene and epileptic drug resistance in a central Chinese Han population.Methods A case control study was performed in 364 epileptic patients.According to the criteria of drug resistant epilepsy proposed by International League Against Epilepsy in 2010,143 patients were classified into drug resistant group and 221 patients into drug responsive group.The peripheral venous blood of each patient was collected for DNA extraction after clinical evaluation.The candidate ApoE SNPs loci,including rs7412 and rs769450,were genotyped by BeadChip Scanning and GoldenGate Assay following the Illumina protocols.The differences in allelic and genotypic frequency were compared between groups.Linkage disequilibrium was calculated through SHEsis platform.Results There was no significant difference for genotype or allele of rs7412 between groups.The GG genotype (OR =2.038,95％ CI 1.196-3.475,P=0.009) and G allele (OR =1.618,95％CI 1.193-2.193,P=0.002) of rs7412 were significantly more abundant in the drug resistant group.As for idiopathic epileptic patients,the GG genotype (OR =2.110,95％ CI 1.189-3.744,P =0.011) and G allele (OR =1.641,95％ CI 1.187-2.270,P =0.003) of rs7412 were still significantly more abundant in the drug resistant group.There was no linkage disequilibrium between the two loci with D' value of 0.072.Conclusion The GG genotype and G allele of ApoE rs769450 may be associated with epileptic drug resistance in a central Chinese Han population.

Artemisinin is a key anti-malarial drug and few clinically meaningful resistant cases about its application have so far been reported. The World Health Organization (WHO) officially recommended the use of ACT (Artemisinin-based Combination Therapy) as the first line antimalarial application to increase its inhibitory efficacy and prevent the likely resistance development. Based on our current understanding of artemisinin, a set of compounds were selected to study their interaction with artemisinin by using the yeast (S. cerevisiae) model, in the hope that knowledge gained might provide some references for clinical investigations. In this research, yeast strain (BY4742) was cultured in the nonfermentable YPGE solid medium with 4 μmol · L(-1) artemisinin and one of the selected compounds for 48 hours, and the combined drug efficiency was evaluated by the inhibition of yeast growth. The compounds belong to the categories of oxygenants, antioxidants, metal ions, ion chelators and uncouplers. Among them, 0.2 mmol L(-1) FeCl3, 60 μmol · L(-1) BPS, 1 mmol · L(-1) CuCl2, 0.75 mmol · L(-1) VE and 1 mmol · L(-1) VC antagonized the action of artemisinin, while 40 μmol · L(-1) DNP, 0.1 μmol · L(-1) CCCP and 0.25 mmol · L(-1) H2O2 had synergistic effects. These results suggested that redox-active and mitochondria-dysfunctional compounds could affect artemisinin's potency, supporting our prior proposed mitochondrial model for artemisinin's action. This research in addition provided a convenient method to screen likely artemisinin-interacting compounds.
Artemisinins ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Saccharomyces cerevisiae ; drug effects ; growth & development

A cobalt nanoparticles modified ITO electrode (NpCo/ITO) was prepared by casting cobalt nanoparticles onto ITO electrode and the cobalt nanoparticles were synthesized by NaHB4 reduction. The electrochemical behaviors of adriamycin (ADM) on NpCo/ITO were studied. The modified ITO electrode was characterized by cyclic voltammetry (CV), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). In a 0.01 mol L(-1) PBS (pH 8.0) buffer solution, a sensitive reduction peak of ADM was obtained. A linear relationship is held between the peak current and ADM concentration in the range of 1.0 x 10(-8) - 2.0 x 10(-6) mol L(-1) with detection of 5.0 x 10(-9) mol L(-1)- by cyclic voltammetry (CV) response. The reduction process was irreversible with adsorption at the NpCo/ITO electrode. The modified electrode showed an excellent electrocatalytic activity for the ADM electrochemical reduction.
Antineoplastic Agents ; chemistry ; pharmacology ; Clinical Laboratory Techniques ; Cobalt ; chemistry ; Doxorubicin ; chemistry ; pharmacology ; Electrochemistry ; Electrodes ; trends ; Nanoparticles ; chemistry

Objective:To investigate the outcomes of the regimen with docetaxel, cisplatin, and 5-fluorouracil (TPF regimen) in chrono-chemotherapy, and evaluate the feasibility of reducing the toxicity and immunological damage in nasopharyngeal carcinoma (NPC) patients with distant metastasis at preliminary diagnosis, then to compare the advantages and disadvantages between chrono-che-motherapy and traditional chemotherapy. Methods:A total of 46 NPC patients with distant metastasis at preliminary diagnosis (UICC 2010 stage IVc) were enrolled in this study. These NPC patients were randomly divided into chrono-chemotherapy and conventional chemotherapy groups, with 23 cases for each group. TPF neo-adjuvant chemotherapy was conducted in both groups for two cycles, with 21 days to 28 days for each cycle. The following regimen was used for the chrono-chemotherapy group:docetaxel 75 mg/m2, infu-sion, d1;cisplatin 75 mg/m2, 10:00 a.m.-10:00 p.m., continuous infusion, d1-d5;and fluorouracil 750 mg/(m2 · d), 10:00 p.m.-10:00 a. m., continuous intravenous infusion, d1-d5. The following regimen was used for the conventional chemotherapy group:docetaxel 75 mg/m2, infusion, d1;cisplatin 75 mg/m2, infusion, d1;and fluorouracil 750 mg/(m2· d), continuous infusion, d1-d5, 120 h. Patients who obtained therapeutic efficacy via induction chemotherapy were provided with intensity-modulated radiotherapy as a concurrent radio-therapy and chemotherapy (DDP 100 mg/m2, infusion, d1-d2, with 21 days each cycle and a total of two courses). One month after con-current chemoradiation, an adjuvant chemotherapy with the same regimen as the induction chemotherapy was employed for a total of two courses. Acute and late toxicities were graded in accordance with the Common Terminology Criteria for Adverse Events v3.0 scor-ing. Tumor response was evaluated using the 2000 Response Evaluation Criteria in Solid Tumors. The effective rates included complete and partial responses. Relevant data were analyzed by SPSS16.0 statistical software. Results:More emesis was observed at Grade 2 or above in the conventional chemotherapy group than in the chrono-chemotherapy group, with statistical significance between the two groups (P=0.035). After chemotherapy, the value of CD4/CD8 increased in the chrono-chemotherapy group and decreased in the con-ventional chemotherapy group, with statistical significance between the two groups (P=0.033). Conclusion:The proposed chrono-che-motherapy outperforms conventional chemotherapy in reducing the occurrence of severe vomiting. This chrono-chemotherapy may be advantageous in reducing severe bone marrow depression and may play a positive role in the immune function of NPC patients.

Objective To investigate the prevalence, etiology, rehabilitation demands and service condition of hearing disorders based on the whole population in Jilin Province, China. Methods Using the probability proportion to size (PPS) sampling, 9246 (93.3%) out of 9909 residents sampled form 36 counties were targeted for investigation from August, 2014 to January, 2015, followed the WHO Ear and Hearing Disorders Survey Protocol. The hearing loss and disability were classified as WHO recommended and Classification and Grading Criteria of Disability (GB/T 26341-2010). Results The standardized prevalence of hearing loss and disability was 16.41%and 4.78%, re-spectively. Age, sex, residence, occupation and marriage status, education level and household income were significantly associated with hearing loss prevalence, while nationality was not. The main etiologies included non-infectious disease (47.33%), ear disease (14.17%), un-known causation (13.89%), and noise (8.59%). Among all people with hearing loss, those who accepted intervention service accounted for 11.02%. Among all people with hearing disability, those who used hearing aids accounted for 5.58%, and 0.67%used artificial cochlea. Con-clusion Demographics and socioeconomic factors are significantly associated with the prevalence of hearing loss. The main etiology con-tains non-infectious disease, ear disease and noise. Both the rate of service utilization among people with hearing loss and the rate of adopt-ing hearing aids among people with hearing disability are low. It is needed to do more in prevention and rehabilitation of hearing impairment.

AIM:To investigate the effect of irbesartan on the fatty liver of db/db mice and whether autophagy is involved in the process.METHODS:Male db/db mice(n=24)were randomly divided into model group and irbesar-tan group,and 12 db/m mice with similar age and weight were selected as normal control group.After 16 weeks of inter-vention respectively,the fatty liver-related parameters including body weight, liver index, blood lipid, liver function and pathological changes in the liver were observed.The protein levels of p-PI3K,p-Akt,and p-mTOR,as well as Atg-7,bec-lin-1 and LC3B in the liver tissues were detected by Western blot,and the autophagosomes in the liver were observed under electron microscope.RESULTS:Compared with the model group,the body weight,liver index,blood lipids,alanine and aspartate aminotransferase were decreased in irbesartan group(P<0.05).Moreover,the pathological changes in the liver were significantly ameliorated in irbesartan group than that of model group.Importantly, the protein levels of p-PI3K, p-Akt and p-mTOR were decreased with irbesartan administration,while the expression of Atg-7,beclin-1 and LC3B-Ⅱwas increased(P<0.05),which resulted in a distinct increase in autophagosomes.CONCLUSION:Irbesartan alleviates he-patic steatosis in db/db mice by inhibiting the PI3K/Akt/mTOR signaling pathway and upregulating the protein expression of Atg-7,beclin-1 and LC3B-Ⅱ,thereby inducing autophagy in hepatocytes.

Objective To study the anti thrombotic effect of Ligustrazine injection combined with aspirin,clopidogrel in rabbits.Methods Forty-two healthy Japanese white rabbits were randomly divided into 7 groups:blank group,control A group,control B group,control-low dose herb group,control-high dose herb group,combined A group,combined B group.Blank group was given equal volume normal saline,control A group was given aspirin 5.13 mg· kg-1,control B group was given clopidogrel 3.85 mg · kg-1,control-low,high doses herb groups were given Ligustrazine injection 6.54,26.16 mg · kg-1,combined A group was given Ligustrazine injection 26.16 mg· kg-1 and aspirin 5.13 mg · kg-1,combined B group was given Ligustrazine injection 26.16 mg · kg-1 and clopidogrel 3.85 mg · kg-1.Ligustrazine injection was given for ten days through ear marginal vein and aspirin,clopidogrel were given for seven days through intragastric administration.On the last day of administration,heart blood was taken at 1 h after administration.Thrombus length and wet weight were measured by extracorporeal thrombus forming apparatus.The effect on the platelet aggregation rate induced by platelet activating factors (PAF) was measured by platelet aggregation instrument.And the content of platelet activating factors (PAF),cluster of differentiation 62 platelet (CD62p) and platelet factor-4 (PF-4) were detected by enzyme-linked immunosorbent assay.Results The throrobus length in combined B group was (7.4 ± 4.6) cm,which significantly reduced compared with that of blank group (22.8 ±2.3) cm (P ＜0.01).The wet weights of thrombus of control A,B group,control-high dose herb group and combined A,B group were (0.31 ± 0.04),(0.30 ± 0.05),(0.35 ±0.14),(0.28 ±0.08),(0.16 ±0.07) g,compared with that of blank group (0.55 ±0.10) g with significantly reduced(P ＜ 0.01).The platelet aggregation rates of control-low,-high doses herb groups and combined A,B groups induced by PAF were (43.3 ± 4.7) ％,(37.2 ± 4.7) ％,(35.5 ± 4.1) ％,(35.0 ± 3.2) ％,when compared with that of blank group (52.9 ± 4.4) ％,they reduced significantly (P ＜ 0.01).The platelet aggregation rates of combined A,B group were significantly lower than that of control-low dose herb group (P ＜ 0.05).The PAF contents of control-low,-high doses herb groups and combined A,B groups were (1043 ± 162),(1010 ± 189),(973 ± 159),(959 ± 178) ng · L-1,significantly lower than that of blank group (1510 ± 319) ng · L-1 (P ＜ 0.01).The CD62P contents of control A,B groups,control-low,-high doses herb groups and combined A,B groups were (156 ± 13),(130 ±21),(101 ±17),(85 ±8),(107 ± 18),(107 ± 19) ng · mL-1,significantly lower than that of blank group (234 ±69) ng · mL-1(P ＜ 0.01).The PF-4 content of control A,B groups,control-high dose herb group and combined A,B groups were (148 ± 14),(255 ± 14),(322 ±69),(242 ±26),(266 ±36) ng· mL-1,which significantly reduced compared with that of blank group (478 ±91) ng · mL-1 (P ＜0.05,P ＜0.01).Conclusion Ligustrazine injection combined with aspirin and clopidogrel can play a synergistic anti-thrombosis effect.

To construct a recombinant replication-defective human adenovirus type 5 expressing Cap protein of PCV2 and test the immunological efficacy in mice. In this study, the recombinant replication-defective human adenovirus type 5, named as rAd5-Cap (wt-rAd5), was constructed through homologous recombination internally in the HEK293AD cells after co-transfection of the Pac I-linearized backbone plasmid and the shuttle plasmid pacAd5CMV-Cap containing the open reading frame (ORF2) of the porcine circovirus type 2 (PCV2) cap protein or pacAd5CMV without inserted fragment. Furthermore, the rAd5-Cap could induce the expression of PCV2 cap protein in the HEK293AD cells with high efficacy evaluated by the RT-PCR and indirect immunofluorescence assay (IFA). The virus titer of rAd5-Cap could reach up to 10(8.5) TCID50/mL similarly to that of wt-rAd5, indicating that there was little affect on the virus proliferation after the insertion of PCV2 cap protein gene. The humeral immune responses could be activated and detected 14 days after the inoculation of the mice with 10(7) TCID50 rAd5-Cap intramuscularly, and constantly in crease in another 14 days. These molecular biological and animal experiments results demonstrated that the PCV2 cap protein could be efficiently expressed by the recombinant adenovirus rAd5-Cap in eukaryotic cells and induce robust immune responses in mice, which laid a good foundation for the development of new type vaccine against porcine circovirus.
Adenoviruses, Human ; genetics ; Animals ; Antibodies, Viral ; blood ; Capsid Proteins ; genetics ; immunology ; Circovirus ; immunology ; Defective Viruses ; genetics ; HEK293 Cells ; Humans ; Mice ; Recombinant Proteins ; biosynthesis ; immunology ; Virus Replication

OBJECTIVETo compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC).

METHODSSeventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle.

RESULTSSixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group (P=0.040). Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono-chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+ /CD8+ ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group (P<0.05). The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group.

CONCLUSIONSCompared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Carcinoma ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; Drug Chronotherapy ; Fluorouracil ; administration & dosage ; Humans ; Induction Chemotherapy ; methods ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Nausea ; Neoplasm Staging ; Radiotherapy, Intensity-Modulated ; Taxoids ; administration & dosage ; Treatment Outcome

Objective To retrospectively analyze the research on the integrated medical and elderly care in China in re-cent ten years,and explore the research hotspots and future research trend of the integrated medical and elderly care.Methods Using the method of literature research,the journal articles with the theme of combination of medical care and nursing,integration of medical care and nursing or medical care and nursing service from 2013 to 2023 were searched in CNKI.The sources were lim-ited to Peking University Core,CSSCI,CSCD and AMI,and the selected articles were analyzed by CiteSpace.Results This ar-ticle takes 896 literatures as research objects,we found that the number of articles reached a peak in 2018,the higher number of articles issued by the institutions are medicine-related institutions.The high-frequency keywords are the integrated medical and elderly care,elderly services,senior citizens,elderly care institutions and elderly care model.The strongest emergent word de-tected is health care integration.Conclusion In the past ten years,domestic research on the integration of medical care and eld-erly care has shown diversification and innovation.Policy tools,pension insurance,community and rural pension,quality evalua-tion index system,influencing factors were the research focus of scholars.Future research needs to focus on the application of quantitative methods,empirical and practical analysis.