OBJECTIVE: To establish a high-performance liquid chromatographic(HPLC)-fluorometric method for the concentration determination of itraconazole (ITZ) and its metabolite hydroxy-itraconazole(HITZ) in rabbit plasma simultaneously.METHODS: Separation was achieved with Agilent Eclipse C18,the mobile phase consisted of acetonitrile(adjusted to pH=2.5 with 85% phosphoric acid)-water(63∶37),and the flow rate was 1.0 mL?min-1.The excitation and emission wavelengths were 260 nm and 365 nm.The analysis was performed at room temperature..RESULTS: The linear concentration range of ITZ and HITZ were 7.4～296 0 ng?mL-1(r=0.999 1)and 5.4～216 0 ng?mL-1(r=0.999 3), respectively.The limit of detection was 0.518 and 0.318 ng?mL-1,respectively.The extraction and method recovery rate of ITZ and HITZ were more than 80%.The intra-day and inter-day RSD of ITZ and HITZ were less than 4.47%. CONCLUSIONS: The method is simple,sensitive,accurate and reliable for monitoring ITZ and HITZ in rabbit plasma and pharmacokinetic studies.

High mobility group box-1(HMGB1)distributed widely.It exists in many organs.HMGB1 locates in nuclei and cytoplasm in normal condition.It involves in many activity of life(i.e.,duplication of DNA,cellular differentiation,gene expression).The immunocytes(i.e.,mononuclear macrophage and dendritic cells)secrete HMGB1 into the extracellular milieu when stimulated with LPS and cytokines.It acts as proinflammatory cytokines,activates inflammatory and immunological responses.As a late mediators of inflammation and last long,HMGB1 plays an important role in sepsis,so it may be a convenient and practical index in evaluating severity of sepsis and may be an important and new therapeutic target in sepsis.It has been initially proved in experimental and clinical study.

Objective To investigate the effects of DLXNP on hemorrheology and bulbar conjunctiva microcirculation (BCM) in rabbit and to explore its effects of activating the blood and eliminating the stagnant. Methods The blood stagnant syndrome model was reproduced by injecting dextran 500 into the marginal ear vein. The BCM and the hemorrheology properties were detected and compared. Results Compared with the normal group, the model group's indexes of whole blood relative and whole blood reducing viscosity improved (P

Objective To study effects ofDanlong Xingnao Formula (DLXNF) on proliferation of neural stem cells (NSCs) and the expressions of Hes1 and Hes5 in sub ventricular zone (SVZ) in cerebral ischemia-reperfusion injury model rats; To explore the mechanism of promoting the proliferation of NSCsMethods Eighty male SD rats were randomly divided into sham-operation group, model group, edaravone group andDLXNF group. The focal cerebral ischemia reperfusion injury models were prepared by suture method, and 7 d after reperfusion, the SVZ brain tissue of ischemia side was taken. The proliferation of cells was detected by Brdu labeling fluorescence immunocytochemistry; Hes1, Hes5 mRNA and protein expressions were detected by fluorescence real-time quantitative PCR and Western blot method in each group.Results Compared with the sham-operation group, Brdu positive cell rate in other groups increased more obviously, and the expressions of Hes1, Hes5 mRNA and protein also increased significantly (P<0.01). Compared with the model group, Brdu positive cell rate increased significantly in edaravone group and DLXNF group, and the expressions of Hes1, Hes5 mRNA and protein increased significantly (P<0.01). The expression of Hes1 mRNA in DLXNF group was superior to that in edaravone group (P<0.01), and other indexes had no significant difference.Conclusion DLXNF can promote the proliferation of NSCs in SVZ in cerebral ischemia-reperfusion injury model rats, and up-regulate the expressions of Hes1 and Hes5, whose mechanism may be related to the activation of Notch signaling pathway.

Objective To study the relationship of proliferation of neural stem cells (NSCs) in SVZ and the expressions of c-jun and c-myc in rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury model administrated byDanlong XingnaoFormula.Methods The focal cerebral ischemia reperfusion injury models were prepared by longa method. Totally 150 male SD rats were randomly divided into sham-operation group, cerebral model group,Danlong XingnaoFormula low-, medium-, and high-dose groups. The treatment groups were given corresponding dose ofDanlong XingnaoFormula, while the sham-operation group and model group were given the same amount of distilled water 24 h after modeling by gavage, once a day, 7 days in a row. 1 d, 3 d and 7 d after reperfusion, modified Neurological Severity Scores (m-NSS) was used to grade neurologic impairment. 7 d after reperfusion taken to the SVZ brain tissue of ischemia side, Brdu immunohistochemical method was used to record the BrdU positive cells number. The hippocampal c-jun, c-myc mRNA and protein expressions were determined respectively by RT-qPCR method and Western blot method.Results Grades of neurologic impairment in others groups were improved obviously than sham-operation group (P<0.01); 3 d, and 7 d after reperfusion, grades of neurologic impairment inDanlong XingnaoFormula groups were obviously lower compared with model group (P<0.05,P<0.01). Brdu positive cell rates in others groups increased obviously compared with sham-operation group; Compared with model group, Brdu positive cell rates inDanlong XingnaoFormula groups increased obviously (P<0.01). The expressions of c-jun and c-myc protein and mRNA inDanlong XingnaoFormula groups improved obviously than sham-operation group and model group (P<0.01).ConclusionDanlong Xingnao Formula can improve the neural function after cerebral ischemia and stimulate the proliferation of NSCs, and the mechanism may be related to activating the expression of c-jun and c-myc and extending the duration.

Objective To analyze the medication rules of the treatment of stroke in Gu Jin Ming Yi Lin Zheng Jin Jian Zhong Feng Juan; To provide references for the clinical treatment. Methods Prescriptions with confirmed efficacy of famous TCM doctors in the history in Gu Jin Ming Yi Lin Zheng Jin Jian Zhong Feng Juan was searched. Excel2003 was used to establish database to analyze medication frequency. SPSS17.0 statistical software was used to conduct cluster analysis, and tree view was used to show results. Results Totally 112 prescriptions for the treatment of stroke of 36 famous TCM doctors were included in the study, including 204 kinds of Chinese materia medica and 1169 times of medication frequency. The high-frequency medicines (>10 times) were Paeoniae Radix Alba, Achyranthis Bidentatae Radix, Angelicae Sinensis Radix, Pinelliae Rhizoma Praeparatum, and Poria. The high-frequency medicine categories were tonifying deficiency medicine (22.58％), pacifying liver and wind medicine (12.31％), activating blood and dispelling stasis medicine (11.89％), clearing heat medicine (11.46％) and dissipating phlegm, cough and asthma medicine (8.72％). Cluster analysis showed that high-frequency medicine (>10 times) could be clustered as 6 categories. Conclusion Gu Jin Ming Yi Lin Zheng Jin Jian Zhong Feng Juan focuses on tonifying deficiency medicine, accompanied with pacifying liver and wind medicine, activating blood and dispelling stasis medicine, clearing heat medicine and dissipating phlegm, cough and asthma medicine, which can be used to guide clinic.

Objective:To analyze the correlation between the volume of irradiated pelvic bone marrow and acute hematologic toxicity (HT), in order to provide clinical data to reduce the risk of acute HT and optimize the radiotherapy plan.Methods:From October 2017 to May 2019, 41 LARC patients who received neoadjuvant concurrent chemoradiotherapy (CCRT) were retrospectively reviewed in our center. All patients were treated with 5-field intensity-modulated radiotherapy (IMRT), and the prescription dose delivered to PTV was 45-50.4 Gy in 25-28 fractions. Capecitabine or 5-fluorouracil (5-FU) wasadministered daily 5 days a week during radiotherapy. Different HTswere recorded according to National Cancer Institute Common Toxicity Criteria Version 5.0 (NCI-CTC.V5.0) based on laboratory tests. The volume of PBM or each site (coxal, sacrum, femoral) receiving more than x Gy refers to as TVx, CVx, SVx, and FVx, respectively. Logistic regression was performed to evaluate the association between the volume of irradiated pelvic bone marrow and different HT. Generalized additive model (GAM) and piecewise regression were used to further analyze the possible nonlinear relationship and threshold effect between them. Results:Multivariate logistic regression analysis showed that low-dose of irradiated total pelvic bone marrow volume ( TV5) and coxal bone marrow volume ( CV5, CV10) were significantly correlated with Grade ≥2 leukopenia( P<0.05). There was a significant negative correlation between the sacrum bone marrow volume ( SV5, SV10) and Grade ≥2 leukopenia ( P<0.05). A thresholdeffect has been observed between CV10 and Grade ≥2 leukopenia by Generalized additive model (GAM) and piecewise linear regression. The threshold between CV10 and Grade ≥2 leukopenia was 575 ml, OR (95% CI) was 1.85 (1.08, 3.16). Conclusions:In neoadjuvant IMRT of rectal cancer, CV is a better predictor of acute HT induced by CCRT than TV. The irradiated volume of CV associated with acute HT was mainly low-dose levels ( CV5, CV10). The thresholds of our study ( CV10= 575 ml) could be a good reference for the optimization of the radiotherapy plan.

Objective To explore the compound compatibility regulation of oral traditional Chinese medicines (TCM) for the prevention and treatment of infantile repeated respiratory infection.Methods The oral TCM compound literatures for the prevention and treatment of infantile repeated respiratory infection were collected from four databases,including China Biology Medicine disc,CNKI,VIP Periodical and Wanfanf Data.The retrieval time was from January 2006 to July 2006.Then the TCM oral compound prescriptions meeting the requirements were obtained by the literature arrangement and performed the terms standardized processing for extracting the information and establishing Excel table.Then the Kaiyuan software package R i386 3.3.0 was used to conduct the drug frequency,association rules analysis and clustering analysis.Results A total of 311 prescriptions were screened out and 208 kinds of traditional Chinese medicine were analyzed.It was found that the higher compatibility frequencies of TCM were atractylodes,radix glycyrrhizae,windproof,radix astragali,radix pseudostellariae,poria cocos,dried tangerine or orange peel,etc.;the strong association rules prompted that modified Yupinfeng Powder composed of core medicines such as astragalus,atractylodes and windproof was the basic formula for prevention and treatment of infantile repeated respiratory infection;the clusters analysis found some TCM societies such as emembranous Astragalus mongholicus-keel-oysters,Atractylodes-Poria cocos-licorice-Astragalus mongholicus-dangshen.Conclusion The drug frequency,association rules analysis and clustering analysis can reveal the compatibility rules of TCM prescriptions for preventing and treating infantile repeated respiratory to provide reference basis for optimizing the clinical prescription and improving the curative effect.

Objective To evaluate the implementation and effectiveness of syphilis prevention and control in Hubei Province from 2011 to 2020, to summarize the experience and practice, to analyze the existing problems and causes, and to study and put forward policy and strategy suggestions, so as to provide reference for formulating the national ^“14th five-year plan^” and carrying out the next step of prevention and control work. Methods The National STD Prevention and Control Management Information System, STD Prevention and Control New Media Health Service Platform, National AIDS Comprehensive Prevention Information System, and National Management Information System for the Prevention of AIDS, Syphilis, and Mother-to-Child Transmission of Hepatitis B were used to analyze and evaluate the completion of main prevention and control indicators in Hubei Province. Results Among the 16 evaluation indexes, 10 indexes including the effectiveness of syphilis promotion and training for various groups of people, the proportion of pregnant women undergoing syphilis testing in the monitoring and testing work, and the effectiveness of syphilis prevention and treatment, all met the requirements of the plan. In addition, some of the 5 indexes failed to meet the requirements of the plan. Conclusion Hubei Province has fairly fulfilled the work requirements of the Plan. It is still necessary to strengthen the syphilis prevention and control to ensure the urban pregnant women infected with syphilis and their infants to receive standardized STD diagnosis and treatment services, and the drug users in the drug maintenance treatment clinic to receive free syphilis testing, and to provide referral services for the syphilis antibody positive patients at AIDS voluntary counseling and testing points.