Objective To investigate the serum levels of CXC, CC and C chemokines, and to esti-mate the relationship among the three kinds of chemokines as well as that between these chemokines and other Th1 and Th2-related cytokines, in patients with atopic dermatitis (AD). Methods Fifty-one patients with atopic dermatitis, including 35 males and 16 females with an average age of 17 years and disease course of 13.6 years were enrolled into this study together with 34 normal human controls. ELISA was used to measure the serum levels of monokine induced by IFN-γ (Mig), thymus and activation-regulated chemokine (TARC), cutaneous T cell-attracting chemokine (CTACK) and lymphotactin (Ltn) in these subjects. Severity of AD was assessed according to SCORAD. Results The serum levels were 79.6±28.0 ng/L for Mig, 349.9±91.5 ng/L for TARC, 747.4±359.4 ng/L for CTACK and 141.0±68.4 ng/L for Ltn in patients, significantly higher than those in the normal controls (63.8±26.5 ng/L, 219.4±82.1 ng/L, 294.3± 64.9 ng/L, 80.9±54.2 ng/L, P < 0.05, 0.01, 0.01, 0.01 respectively). A significant correlation was observed between the serum level of CTACK and SCORAD score in patients (r = 0.343, P < 0.05). Similarly, the percentage of body surface area (BSA) involved positively correlated with the serum levels of Mig, TARC, CTACK and Ltn. Furthermore, there was a significant correlation between the serum level of Ltn and TARC (r=0.444, P< 0.01) as well as CTACK (r=0.572, P< 0.01), between that of CTACK and TARC (r=0.524, P< 0.01), and between that of TARC and Mig (r=0.313, P< 0.05). Conclusion The CXC, CC and C chemokines might be involved in the pathogenesis of AD. Further more, CTACK level could serve as a good indicator for the severity of AD.

OBJECTIVE To analyze impulsive-like behaviors of SD rats induced by pramipexole in Y-maze avoidance tasks. METHODS Behaviors of SD rats in Y-maze avoidance tasks were recorded with a camera and analyzed by Noldus Etho Vision XT8 software after acute subcutaneous injection of pramipexole(0.1,1 and 10 mg · kg-1),including right reaction numbers of 20 consecutive avoidance tasks,shuttle number of times between the three arms of Y-maze, distance covered in Y-maze and time spent in safe arms during 20 consecutive avoidance tasks. Then,the prepulse inhibition(PPI)of the startle reflex test was used to assess the effect of pramipexole on sensorimotor gating (SG). Effects of pramipexole on the dialyzed content of monoamine neurotransmitter and its metabolites in the striatum and amygdala of SD rats were measured by microdialysis in vivo. RESULTS Compared with normal control group,the rats of pramipexole group showed a significant increase in the shuttle number of times and distance covered in Y-maze between Y-maze avoidance tasks(P<0.01),but a statistically significant decrease in the time spent in safe arms(P<0.01),while the number of right reactions in Y-maze avoidance tasks was not changed. Such premature responses were quite similar to certain impulsive-compulsive behaviors in rodent models,such as five-choice serial reaction time tasks. In the PPI test,pramipexole displayed an impairing effect on SG(P<0.01). The microdialysis results showed that there was an increase of dopamine and 5-hydroxytryptamine in the striatum of pramipexole group, but not statistically significant. Monoamine neurotransmitters and their metabolites were not significantly changed in the amygdala. CONCLUSION Pramipexole can induce impulsive-compulsive behaviors in Y-maze avoidance tasks,which might be attributed to impaired SG.

BACKGROUND:It is particularly important to establish an ideal animal model of pulmonary fibrosis to investigate the underlying pathogenesis and screen effective drugs to prevent and control pulmonary fibrosis. OBJECTIVE: To establish a modified scheme of establishing mouse models that can reflect pulmonary fibrosis formation in humans. METHODS: Fifty-six male C57BL/6 mice were randomly divided into two groups: A (a single large-dose injection) and B (multiple smal-dose injections). Mice in group A were subjected to a single intravenous injection of bleomycin 200 mg/kgviathe tail vein; and mice in group B received intravenous injections of bleomycin 50 mg/kg via the tail vein per week, totaly for 6 weeks. 

Objective To investigate the clinical significance of compensatory angiogenesis and the angiosome-based revascularization strategy for endovascular procedures in treating infrapopliteal critical limb ischemia in elderly diabetic patients.Methods A retrospective study of 194 patients with diabetic feet (Fontaine Ⅳ) who had undergone endovascular procedures at our hospital from January 2005 to December 2014 was performed.Based on the angiosome concept,all subjects were classified into the direct revascularization group (DR group),the indirect revascularization through collaterals group (IR-tc group) and the indirect revascularization without collaterals group (IR-wc group).After one-year follow-up,the therapeutic effects were analyzed and compared between the three groups.Results During the one-year follow-up,the rate of unhealed ulcers,the re-intervention rate and the rate of major adverse limb events (MALE) were higher in the IR-wc group than in the DR and IR-tc groups (P=0.000 and 0.000,P=0.025 and 0.013,P=0.014 and 0.023,respectively).The IR-wc group presented a lower limb salvage rate as compared with those in the DR and IR-tc groups (P=0.011 and 0.027).Patients with a single recanalized branch had a higher rate of unhealed ulcers than those with multiple recanalized branches in the IR-wc group (93.9％ vs.71.0％,P=0.015).Conclusions The angiosome-based revascularization strategy has shown important value in guiding endovascular procedures for patients with diabetic foot disease and,in particular,the compensatory angiogenesis approach appears to be critical in generating favorable short-term clinical outcomes in the treatment of diabetic foot disease.

The change of drug development pattern pushes the innovation of drug valuation methods. The pharmacokinetic research of traditional Chinese medicines (TCM) is an important part of TCM modernization and plays a key role in novel drug development of TCM. However, the research methods and techniques are in consistent with the specific characteristics of TCM, i.e., multiple-components is still in the infant. This review makes a brief summary of current pharmacokinetic exploration of TCM, metabonomics and complex network, and puts forward a new strategy based on complex network and metabonomics to study TCM pharmacokinetic in order to disclose the active components and mechanism of TCM.
Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Humans ; Medicine, Chinese Traditional ; Metabolic Networks and Pathways ; Metabolomics ; Plants, Medicinal ; chemistry

Objective To study the role of Anopheles anthropophagus in malaria transmission and transmission threshold so as to provide basis for vector surveillance and malaria control strategy. Methods Parasitological and entomological methods were used in the investigation at 5 villages of Xinyang City, Henan Province. Results From July to August, 1999, 74 febrile cases (10\^9% of the total population) were examined. Among them 50 were infected, the incidence in the population of surveyed spots was 7\^4%. Active detection was made in another randomly selected two villages and found that the parasite rate in the inhabitants was 2\^0%, and the positive rate of IFA was 8\^4%. Only vivax malaria was detected. An.anthropophagus and An.sinensis were collected, with An.anthropophagus as the predominant one in human dwellings. The estimated man\|biting rate and the human blood index were 4\^9388 and 0\^7858 respectively. The vectorial capacity of An. anthropophagus was 5\^5296. The critical man\|biting rate of An.anthropophagus was 0\^2407 as calculated by the formula (ma=-rlnP/abP\+n) according to Macdonald′s model.The local man\|biting rate was 20 times higher than that of the critical man\|biting rate. Conclusion The results demonstrated that An.anthropophagus is the principal vector in malaria transmission in the area. The findings imply that the critical man\|biting rate is of practicable importance in vector surveillance.

AIM:To investigate the efficiency of 2-methoxyestradiol (2-ME) as radiosensitizing agent for the treatment of lung cancer cells. METHODS:Cell line A549 and GLC-82 originated from human non-small cell lung cancer were cultured in vitro. Study group (2-ME in different concentrations) and control group without 2-ME were set up. Cell proliferation was measured by MTT assay that lung cancer cells were treated with 2-ME for 24 h,then the cells were exposed from 0 to 8Gy radiation,and the survival fraction was determined by clone forming test. Flow cytometry was used to measure the effects of 2-ME on cell cycle distribution. RESULTS:MTT assay showed minimum effective concentration value was 0.15625×10~(-6) mol/L in GLC-82 and 1.25×10~(-6) mol/L in A549 cells. Compared to control group,exposed GLC-82 cells or A549 cells to minimum effective concentration of 2-ME for 24 h before irradiation resulted in an enhancement of radiation. The protection enhancement factor was 1.98 and 2.06 in GLC-82 and A549 cells,respectively. Flow cytometry analysis of cell cycle progression demonstrated G_2/M phase arrest in both cells in a dose dependent manner. No obvious change of CDK2 activity in both GLC-82 cells and A549 cells was observed. CONCLUSION:2-ME enhances radiosensitivity by G_2/M phase arrest in the cell cycle.

OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hyp-notics.To explore the mechanism of LCX001 on protection against respiratory depression,a novel AMPA receptor modulator LCX001,synthesized by our Institute of Medicinal Chemistry,is expected to relieve suppressed respiration. METHODS LCX001 was tested to alleviate respiratory depression triggered by opioid(fentanyl and TH-030418),propofol and pentobarbital in the plethysmography recording.The acetic acid writhing and hot-plate tests were conducted to evaluate analgesic effect of LCX001.Binding assay and whole-cell recording were used to analyze the property of LCX001 on positive modulation. The function of AMPA receptors were determined by location of receptors in the membrane and state of channel opening, and both processes were impressed by AMPA receptor regulatory proteins. Ac-cording to the theory,the effect of LCX001 on the expression of stargazin was measured firstly by west-ern blotting. The variation of receptor surface location was observed by live cell imaging. The regula-tion on neuronal Ca2+and cell function was investigated intensively by Ca2+imaging to clarify mecha-nism of LCX001. RESULTS LCX001 effectively rescued and prevented opioid (fentanyl and TH-030418), propofol, and pentobarbital-induced respiratory depression by strengthening respiratory fre-quency and minute ventilation in rats. The acetic acid writhing test and hot-plate test revealed potent anti-nociceptive efficacy of LCX001,in contrast to some ampakines that did not affect analgesia. Fur-thermore,LCX001 potentiated[3H]AMPA and L-glutamate binding affinity to AMPA receptors,and facili-tated glutamate-evoked inward currents in HEK293 cells stably expressing GluA2(R).Importantly,appli-cation of LCX001 generated a significant increase in GluA2(R) surface expression in a mechanism of stargazin up-regulation,and restrained opioid-induced abnormal intracellular Ca2+load,which might par-ticipate in breathing modulation. CONCLUSION The novel pharmacological effect and potential new mechanism of LCX001 might promote ampakines to be a therapeutic option for protection against respi-ratory depression.

Objective To construct the recombinant plasmid of YTH domain family 2(YTHDF2)and express it in E.coli in order to obtain YTHDF2 fusion protein that was capable of binding m 6A-modified RNA.Methods The coding region of YTHDF2 gene was amplified by RT-PCR.The recombinant plasmid pET-28a-YTHDF2 was constructed and expressed in E.coli.The fusion protein was purified by Ni2+-NTA resin affinity chromatography, while the fusion protein activity was analyzed by Ni2+-NTA magnetic spheres.Results and Conclusion The recombinant YTHDF2 protein was expressed in E.coli BL21(DE3)and purified.YTHDF2 fusion protein was capable of binding RNA with m 6A-modification. The preparation of YTHDF2 fusion protein provides an essential tool to study the biological function of RNA with m6A-modification.

Objective:To stablish of chemiluminescent Southern blot detection system for examining HBV DNA replication intermediates in HepG2.2.15,and analyse the inhibition of HBV replication with three kind of drugs with different targets.Methods:The HBV DNA replication intermediates were extracted and analyzed by Southern blot with HBV probe,which(pTHBV1047) was labelling with digoxigenin.The results of the hybridization were detected by chemiluminescent,and the condition of hybridization was optimized.After treated with lamivudine,Bay41-4109,?-Galcer in different concentration,the HBV DNA from the HepG2215 cells were detected with the system.Results:the sensitivity of the system was 1pg of pTHBV1047,and HBV specific positive signals was detected with the DNA from HepG2.2.15.The three kinds of drugs can inhibit the HBV replication obviously with chemiluminescent Southern blot detection system,the IC50 were 1.53?mol/L,0.41?mol/L,0.01?mol/L.Conclusion:The HBV replication intermediates from the cell of HepG2.2.15 can reflect the antiviral effect accurately with different targets drugs and this mothod would be used in the study of Chinese-midicine.