Objective To prepare paclitaxel-natural borneol complex,and to explore the prescription and preparation process of paclitaxel-natural borneol complex drug-loaded submicroemulsion,and its in vitro anti-tumor effect.Methods The Paclitaxel-natural borneol complex was prepared by grinding method and identified by Fourier Transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC).The compound drug-loaded submicroemulsion was prepared using a two-step high-pressure emulsification method.The single-factor investigation and the orthogonal experimental design were applied to optimize the formulation and preparation process.MTT assay,cell cloning assay,and cell scratch assay were used to evaluate the effect of this preparation on HCT-116 cells.Results The infrared spectral absorption peaks of taxol-natural borneol complex at 3 312.76 cm-1 and 3 513.92 cm-1 disappeared,and DSC analysis showed that a new absorption peak of taxol-natural borneol complex appeared at 154.56 ℃,indicating that taxol be coupled with natural borneol to form a new complex.The optimal prescription was 0.44％active pharmaceutical ingredient[paclitaxel-natural borneol(1∶3)],10％medium chain triglyceride,3％emulsifier[egg yolk lecithin-Poloxam 188(1∶2)],2％glycerol,0.3％oleate.The optimal process was emulsification at 80 ℃,60 MPa high pressure homogenization 10 times.The half inhibitory concentration(IC50)was 0.75 μg·mL-1 by MTT asssy in cell.In the cell cloning assay,the scratch healing area of blank control group,paclitaxel raw material and paclitaxel/natural borneol submicroemulsion were(36.44±3.35)％,(13.59±9.28)％,(8.30±4.09)％,respectively.The results were statistically significant(P＜0.05).In the plate cloning experiment,the cell cloning rates of blank control group,paclitaxel bulk drug group and submicroemulsion group were(37.92±0.729)％,(9.16±1.335)％and(3.36±1.065)％,respectively,the differents were statistically significant(P＜0.05).Conclusion This submicroemulsion has reasonable prescription,feasible process and good stability.Cell experiments showed that the submicronemulision effectively inhibits the proliferation and migration of HCT-116 cells,suggesting its potential as a promising antitumor agent.

Objective To observe the effect of quercetin on mechanical allodynia,astrocyte activation,and upregulation of pain-related transient receptor potential vanilloid 1(TRPV1)and P2X purinoceptor 3(P2X3)in mice with paclitaxel-induced peripheral neuropathy.Methods Twenty-four C57BL/6 mice were divided randomly into control,model,and model+quercetin groups(n=8 mice per group).Paclitaxel(total dose 8 mg/kg)was injected intraperitoneally into mice in the model and model+quercetin groups to establish the model.Mice in the control group were injected intraperitoneally with the same volume of vehicle.On day 8 after the first injection,mice in the model+quercetin group were injected with 60 mg/kg quercetin solution orally and mice in the other groups were injected with the same volume of vehicle.Mechanical pain was measured by the von Frey test.Activation of astrocytes in the spinal dorsal horn was detected by immunofluorescence.Expression levels of TRPV1 and P2X3 in dorsal root ganglia were detected by immunofluorescence and Western Blot.Results(1)Compared with model group,the mechanical pain of mice in model+quercetin group were relieved.(2)Compared with model group,the activation of astrocytes and the expressions of TRPV1 and P2X3 in mice of model+quercetin group were alleviated(P＜0.05).Conclusions Quercetin can significantly reduce mechanical pain in mice with paclitaxel-induced peripheral neuropathy.This mechanism maybe related to alleviating the activation of astrocytes in the spinal dorsal horn and reducing expression of TRPV1 and P2X3 in the dorsal root ganglia.

Background As a group of environmental pollutants, polycyclic aromatic hydrocarbons (PAHs) are neurotoxic and may cause mild cognitive impairment (MCI) by inducing inflammation. Whether neutrophil-lymphocyte ratio (NLR), an inflammatory indicator, plays a mediating role in the relationship between PAHs exposure and MCI is unclear yet. Objective To investigate a potential mediating role of NLR in the association between exposure to PAHs and MCI in coke oven plant workers. Methods Eleven urine hydroxylated PAHs (OH-PAHs) of 530 coke oven plant workers were determined by high performance liquid chromatography tandem mass spectrometry. NLR was derived from participants' routine blood examination results using a fully automated haematology analyser. The associations between urinary OH-PAHs and MCI were analyzed by binary logistic regression, the associations between urinary OH-PAHs and NLR were analyzed by multiple linear regression, and the role of NLR in the relationship between urinary OH-PAHs and MCI was evaluated by mediating effect analysis. Results After controlling for confounding factors and other OH-PAHs, the results of binary logistic regression showed that for every e-fold (e is the base of the natural logarithm) increase in the concentration of 2-hydroxynaphthalene (2-OHNap) and 1-hydroxyphenanthrene (1-OHPhe), the OR (95%CI) values of reporting MCI positive were 1.21 (1.02, 1.43) and 1.25 (1.04, 1.51) respectively. For each unit increase of NLR, the OR (95%CI) of reporting MCI positive was 1.56 (1.12, 2.18). The results of multiple linear regression showed that each unit increase in natural log-transformed levels of 1-OHPhe was associated with 0.05 (95%CI: 0.01, 0.10) increase of NLR. The results of mediating effect analysis showed that the association between urinary 1-OHPhe and MCI was partially mediated by peripheral blood NLR, with a mediation ratio of 9.8%. Conclusion Exposure to PAHs in coke oven plant workers may increase the risk of reporting MCI positive partially through increased NLR in peripheral blood.

Background As a complex organic pollutant, polycyclic aromatic hydrocarbons (PAHs) exposure shares the common exposure characteristics of multiple hydroxyl metabolites. Most studies have analyzed independent effect of each PAHs metabolite and have adjusted for the potential confounding effects induced by other metabolites concomitantly, without considering possible interactions among them. Proper statistical methods are needed to study their toxic effects. Objective To explore the applicability of logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) in evaluating the correlation between mixed exposures to exogenous chemicals and health outcomes, compare the advantages and limitations of the three models, and propose analytical strategies for evaluating the health effects of mixed chemical exposure for application in the analysis of the association between PAHs exposure and cognition. Methods Urine samples were collected of workers from a coke oven plant and a water treatment plant in Shanxi Province, who participated in their routine employee healthexamination. Mono-hydroxylated PAHs were detected by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). A cut-off value of MoCA less than 26 was considered mild cognitive impairment (MCI). According to a predetermined inclusion and exclusion criteria, 1 051 cases were included in the final data analysis. Logistic regression, WQS regression, and BKMR were used to analyze the relationship between PAHs metabolites and MCI. Results The prevalence rate of reporting MCI among the 1 051 workers was 21.7% (228/1 051). The concentration of 2-hydroxynathalene (2-OHNAP) was the highest among the 11 PAHs metabolites with a median concentration of 0.30 μg·L⁻¹, followed by 9-hydroxyphenanthrene (9-OHPHE) (0.26 μg·L⁻¹). There were significant differences between the two groups in 2-OHNAP, 1-hydroxynaphthalene (1-OHNAP), 2-hydroxyfluorene (2-OHFLU), 9-OHPHE, 1-hydroxyphenanthrene (1-OHPHE), and 1-hydroxypyrene (1-OHPYR) (all Ps<0.05). In the logistic regression, 2-OHNAP and 2-OHPHE were associated with MCI, and the OR (95%CI) for reporting MCI was 1.28 (1.01-1.67) and 1.27 (1.00-1.72) for each 10-fold increase in 2-OHNAP and 2-OHPHE concentrations, respectively. In the WQS regression analysis, the WQS index was positively correlated with the prevalence rate of reporting MCI (OR=1.37, 95%CI: 1.10-1.72). In the BKMR analysis, compared with the median exposure levels of all chemicals, the overall effect was statistically significant when all PAHs metabolites concentrations were at or above their 30th percentile; when all exposures were at the 75th percentile, the risk of reporting MCI increased by 6%. Conclusion Based on the results of these three models, 2-OHNAP and 2-OHPHE are the most important factors related to cognitive. It is recommended to use a combination of traditional logistic regression and either WQS or BKMR to study the association between PAHs and MCI.

Objective:To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development.Methods:In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old.Results:The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points.Conclusion:Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.

Objective:To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development.Methods:In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old.Results:The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points.Conclusion:Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.

Objective: To understand the needs of primary and secondary school students, parents and teachers for comprehensive sexuality education content, and to explore the applicability of comprehensive sexuality education content in China. Methods: By using the method of stratified cluster sampling, 5 571 primary and middle school students and 4 835 parents from Beijing, Chongqing, Heilongjiang (Harbin and Jiamusi) and Hubei (Wuhan and Xiaogan) were selected for questionnaire survey. Depending on the physical health monitoring points of various provinces and cities, 176 sexuality education related teachers in nine regions were surveyed. The development of the questionnaire was based on the content framework of comprehensive sexuality education proposed in the International Technical Guidelines for Sexuality Education. Results: Students had a higher demand for knowledge on the concepts of "relationship" (53.4% for primary school students, 57.6% for junior high school students) and "health and well-being skills" (71.1% for primary school students, 55.9% for junior high school students). Parents had higher demand for most comprehensive sexuality education content with the exception of lower need for "sex and sexual behavior (74.7% of primary school parents, 80.8% of junior high school parents)" and "sexual and reproductive health (primary parents 74.3%, junior high school parents 75.8%)". Teachers had a high demand for most comprehensive sexuality education content, but primary school teachers had a lower need for "values, rights, culture and sex(65.9%)", "sex and sexuality(60.1%)" and "sexual and reproductive health(66.8%)". The results of correspondence analysis showed that junior middle school teachers had the highest demand for comprehensive education content, followed by primary school parents, junior middle school parents, primary school teachers, junior middle school students and primary school students. Conclusion Teachers and parents have a higher demand for most comprehensive sexuality education content, while lower demand for some relatively sensitive content. Students have a relatively low demand for comprehensive sexuality education content. It is recommended to further improve the content of school sexuality education based on the actual needs of China.

Abstract Sexuality education policy is an important part of guiding and guaranteeing the implementation of sexuality education. At present, China has not formulated an independent sexuality education policy, but stipulates the content of sexuality education into the health education standard, namely the guidelines for health education in primary and secondary schools. globally, International Technical Guidance on Sexuality Education (revised edition) formulated by UNESCO provides a reference for countries around the world to carry out sexuality education. This research adopts the basic method of comparative pedagogy to make an in-depth comparative analysis of the above two programs, in order to understand their similarities and differences in the goals, contents, implementation and evaluation of sexuality education, and to provide reference for further improving the content of sexuality education in China and promoting the implementation of sexuality education in schools.

Objective: To explore the related factors and working way of adolescent injury,and to provide a basis for the effective prevention and intervention of adolescent injury. Methods: The framework of the questionnaire in this study was developed based on the Social Ecology Model. A cross-sectional survey was conducted on a valid sample of 4 309 students from 8 junior high schools and 8 senior high schools in Beijing and Zhongshan city respectively, using stratified random cluster sampling method. Students from grade 7 to grade 12 were invited to participate and investigated with injury prevalence. Results: The incidence of adolescent injury by person and by person-time was 15.53% and 22.49% respectively, and there were differences by sex, age and regions(χ2=15.92，11.45，20.33，P<0.05). The occurrence of adolescent injury was affected by adolescent psychological behavior and social environment through different underlying pathways. The intrapersonal factors and perception of environmental safety showed direct effects on the adolescents’ injuries (effect size was 0.29 and 0.05 respectively, P<0.05). Conclusion Adolescent injury is associated with diverse factors and pathways in a synergistic and complex manner, suggesting that a three-dimensional and diverse strategy should be taken to intervene the injures.

Objective: To understand the awareness of sexual knowledge among primary and secondary school students, as well as their attitudes towards school sex education and to provide a reference for school-based sex education. Methods: A total of 5 531 primary and secondary school students were selected from Beijing, Chongqing, Heilongjiang (Harbin and Jiamusi) and Hubei (Wuhan and Xiaogan) by stratified cluster sampling and were investigated with self-reported questionnaire. Results: Sex-related knowledge scored 62.33±19.35, with a pass rate of 61.9%, and the excellent rate 17.5%. Sexual knowledge of junior high school students scored 64.30±19.07, with the pass rate of 64.7%, and the excellent rate 22.0%. A large proportion of primary students reported unaware of pubertal growth and HIV/AIDS-related knowledge, and a large proportion of junior high students unaware of reproductive physiology. Multivariate Logistic regression analysis showed region, grade, gender, and suburban areas were related to the level of sexual knowledge(P<0.05). More than 76.0% primary students and 85.9% middle school students agreed on the importance of school sexuality education. 59.7% of primary school students and 73.3% of junior high school students hoped to include school sexuality education in compulsory education courses; 59.8% of primary school students and 68.3% of junior high school students felt that school sexuality education should be equipped with specialized teachers. Conclusion Chinese primary and secondary school students are lack of sexual knowledge. As students have strong wills to get more information on sexual knowledge, schools should provide them with more comprehensive and effective sex education through appropriate courses and activities.