[Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice].

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION: Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Post-Translational Modifications by Lipid Metabolites during the DNA Damage Response and Their Role in Cancer.

Genomic DNA damage occurs as an inevitable consequence of exposure to harmful exogenous and endogenous agents. Therefore, the effective sensing and repair of DNA damage are essential for maintaining genomic stability and cellular homeostasis. Inappropriate responses to DNA damage can lead to genomic instability and, ultimately, cancer. Protein post-translational modifications (PTMs) are a key regulator of the DNA damage response (DDR), and recent progress in mass spectrometry analysis methods has revealed that a wide range of metabolites can serve as donors for PTMs. In this review, we will summarize how the DDR is regulated by lipid metabolite-associated PTMs, including acetylation, S-succinylation, N-myristoylation, palmitoylation, and crotonylation, and the implications for tumorigenesis. We will also discuss potential novel targets for anti-cancer drug development.

Prevalence of learning disabilities among middle school students in Beijing / 中国学校卫生

Objective@#To understand the prevalence and distribution of learning disabilities among middle school students in Beijing.@*Methods@#By using stratified random cluster sampling, 6 365 students in grade one and grade two of 12 public middle schools in urban and rural in Beijing were selected. Criteria for learning disabilities included the following: on campus healthy students without serious physical and mental diseases and normal IQ assessed by combined Raven intelligence test; positive in the teacher rated Screening Scale for Middle School Students with Learning Disabilities; percentile ranking (below the bottom 10% percentile of grade) of the academic performance in the Chinese, mathematics and English tests.@*Results@#The learning disabilities of the subjects were determined by the teachers and it was found that the score of words reading, reading understanding, words spell, written expression, number calculation, mathematical reasoning and the total score of the scale were respectively (20.78±4.00, 18.16 ±4.35, 21.50±3.89, 20.06±3.92, 21.12±5.23. 18.67±5.35, 120.28±19.99) points. There were differences in the total score of learning ability between urban and rural areas, gender and grade. Urban area was better than rural area, girls were better than boys, and junior two students were better than junior one students( t=12.94, 9.94, 3.07, P <0.05). A total of 445(7%) students with learning disabilities were detected. Reading disabilities accounted for 5.0%, dysgraphia 2.7% and math disabilities 4.6%. Prevalence of learning ability differed by urban rural regions, gender and grade, with girls and students from urban areas and grade two being significantly lower( t =12.94, 9.94, 3.07, P <0.05).@*Conclusion@#The prevalence of learning disabilities in middle school students is high, which needs more attention.

Combined Associations of Smoking and Bullying Victimization With Binge Drinking Among Adolescents in Beijing, China.

Background: Binge drinking and smoking among adolescents are serious public concerns. However, very few studies have explored the reinforcement of bullying victimization by such behavior. Our study aimed at examining the individual and combined associations of smoking and bullying victimization with binge drinking among adolescents in Beijing, China. Methods: A total of 33,694 students aged 13-17 years old in Beijing, China were anonymously investigated via the cross-sectional Chinese Youth Risk Behavior Surveillance Survey from April to May 2014. A three-stage stratified sampling was used to select participants. Factors such as sociodemographic variables and indicators of smoking, bullying victimization, and binge drinking were analyzed with multiple logistic regressions, and joint and additive interaction effects were tested. Results: Overall, ever-drinking prevalence was 59.1% (boys: 64.4%; girls: 53.7%). Past 30-day binge drinking was 11.5% (boys: 15.6%; girls: 7.4%) and frequent binge drinking was 2.3% (boys: 3.3%; girls: 1.0%). Past 30-day smoking was 10.7% (boys: 16.4%; girls: 5.0%) and past 30-day bullying victimization was 48.7% (boys: 57.3%; girls: 40.1%). The combined effects of smoking and bullying victimization on occasional binge drinking (OR = 6.49, 95% CI = 5.60-7.52) and frequent binge drinking (OR = 10.32, 95% CI = 7.52-14.14) were significant, and the additive interaction effect was significant for current smoking and bullying victimization on frequent binge drinking (OR = 10.22, 95% CI = 9.43-11.07). The additive interaction effect for current smoking and bullying victimization on frequent binge drinking was significant among boys. Conclusion: Bullying victimization reinforced the association of smoking with frequent binge drinking, especially with findings specific to boys. Programs to prevent smoking or bullying or both may reduce binge drinking among adolescents in China.

Trends of dental caries in permanent teeth among 12-year-old Chinese children: evidence from five consecutive national surveys between 1995 and 2014.

BACKGROUND: Dental caries have a serious impact on general health and well-being; however, there is a lack of relevant data on the development trends of dental caries in permanent teeth among 12-year-old children in China. We aim to assess long-term trends of dental caries in permanent teeth among 12-year-old children in China and identify the susceptible subgroups based on five consecutive national surveys from 1995 to 2014. METHODS: A total of 88 972 subjects were extracted from five consecutive national surveys (1995, 2000, 2005, 2010, 2014). Standardized dental examinations were conducted and the oral health status of each subject was recorded. The prevalence of Decayed, Missing and Filled teeth (DMF%), mean Decayed, Missing, Filled teeth score (DMFT) and Caries Filling Ratio (CFR) were used as measurement indicators. Cochran-Armitage trend test was used to evaluate the trends in DMF% and CFR, and multivariate linear regression was used to evaluate the trends in DMFT. RESULTS: A V-shaped fluctuating upward trend in DMF% during 1995-2014 was observed (Z = - 13.124, P < 0.001), and the DMF% in 1995-2014 was 21.1%, 15.9%, 16.2%, 21.9% and 24.3%. The trend in DMFT was approximately consistent with DMF% (ß = 0.057, P < 0.001), but the downward volatility appeared in 2014. The DMFT in 1995-2014 was 0.38, 0.28, 0.31, 0.66 and 0.54. A continuously fluctuant trend in CFR was observed during past two decades (Z = 1.927, P > 0.05), and the CFR in 1995-2014 was 17.4%, 22.8%, 19.3%, 23.4% and 15.6%. The DMF% and DMFT of rural children had a larger absolute increase than that of urban children during 1995-2014 (DMF%-urban: Z = - 0.242, P > 0.05; DMF%-rural: Z = - 19.036, P < 0.001; DMFT-urban: ß = 0.035, P < 0.001, DMFT-rural: ß = 0.077, P < 0.001). The DMF% and DMFT in girls were higher than that in boys at each survey year (P < 0.001). CFR of urban children was higher than that of rural children at each survey year (P < 0.001). CONCLUSIONS: Over the past 20 years, DMFT and DMF% of 12-year-old children in China presented V-shaped fluctuant upward trends, with a decline trend from 1995 to 2000 and an upward trend from 2000 to 2014. CFR had no significant improvement. The rural children and girls are the more vulnerable groups in the development of dental caries and need to pay priority. Our study supports the continuation of policies to improve children' oral health.

[PI3K isoforms PI3Kß and PI3Kδ play different roles in KIT mutation-mediated cell transformation].

Objective To investigate the role of phosphatidylinositol 3-kinase (PI3K) isoforms in type III receptor tyrosine kinase KIT mutation-mediated signaling and cell proliferation. Methods The wild-type KIT and the common KIT mutations V560D and W557K558del in gastrointestinal stromal tumors (GIST) were stably expressed in BaF3 cells. The cells were treated with PI3K isoforms PI3Kα, PI3Kß and PI3Kδ specific inhibitors or pan PI3K inhibitor. The activation of KIT and its downstream signals was detected by immunoprecipitation and Western blot analysis. GIST-T1 cells were treated with the same drug, and the activation of KIT and its downstream signals was also detected by immunoprecipitation and Western blot analysis, and cell proliferation and apoptosis were detected by MTT assay and flow cytometry, respectively. Results Compared with the controls, in BaF3 cells expressing wild-type KIT and its mutants, the activation of KIT and its downstream signaling molecules AKT and ERK was inhibited the most by PI3Kδ specific inhibitor, followed by the specific inhibitors of PI3Kα and PI3Kß subtype. In GIST-T1 cells, the activation of KIT and its downstream signals was inhibited the most by PI3Kß specific inhibitor, followed by PI3Kδ and PI3Kα specific inhibitors. Conclusion In BaF3 cells, PI3Kδ subtype plays a major role in KIT activation and its downstream signal transduction, while in GIST-T1 cells, PI3Kß subtype plays a major role in KIT activation and its downstream signal transduction. These results indicate that PI3K isoforms play different roles in KIT mutation-mediated cell transformation depending on the host cells.

School health personnel in primary and secondary schools in China / 中国学校卫生

Objective@#To understand the current status of the team structure of health personnel in primary and secondary schools, and to provide suggestions and references for strengthening and optimizing school health workforce.@*Methods@#A nationwide stratified random cluster sampling method was adopted to select provinces for investigation in stratification from 2015-2016, a total of 16 provinces, autonomous regions, and municipalities directly under the Central Government, 26 survey sites, 10 027 primary and secondary schools, 9 536 questionnaires of health personnel were collected.@*Results@#Among the 9 536 school health staffs, there were various types of positions, and different types of schools had different position types construction. Elementary schools had the most part time health care teachers, accounting for 77.6%, while full time school doctors only accounting 10.0%; high schools had the most full time school doctors, accounting for 65.7%, and part time health care teachers only accounting for 15.1 %. There were various employment channels, with the most transfer jobs in schools, accounting for 70.7%. The series of professional titles were diverse, with the teaching profession accounting for 67.4%. Most of school health teachers had junior and intermediate professional titles, accounting for 42.6%, respectively. Proportion of medium, medium low, and low level of salary accounted for 39.3%, 27.9% and 21.1% respectively.@*Conclusion@#The educational background and age distribution of school health personnel is reasonable, but the proportions of medical background and full time school doctors are relatively low. School health personnel have various job types, professional titles, salary level, and limited space of career development. Top level design from the policy level, and clearly defined improve the structure of school health personnel to meet the needs of high quality development of school health work in the new era.

Factors that Influence Chinese Parents' Intentions to Use Physical Violence to Discipline Their Preschool Children.

This study explored factors affecting parents' intentions to use physical violence (PV) to discipline their children in the future. The theory of planned behavior (TPB) guided selection of variables. A sample of 1337 preschool children's parents from nine kindergartens located in a county of Henan Province, China were selected by stratified random cluster sampling. Data on parents' attitudes, subjective norms, and perceived behavioral control over PV, intentions to engage in PV to discipline their preschool children in the future, self-reported PV behavior toward their children during the past three months, and demographic characteristics were collected via a paper-based questionnaire. Multivariable logistic regression analyses examined putative predictors of parents' intentions to use physically violent discipline. Nearly three-quarters of the sample said they definitely will not use violent discipline, while 23.4% either said they would use it, or did not rule it out. Logistic regression analysis showed that parents' lower level of perceived behavioral control over using violence (OR 4.17; 95% CI: 2.659, 6.551), attitudes that support PV (OR 2.23; 95% CI: 1.555, 3.203), and having been physically violent with their children during the past three months (OR 1.62; 95% CI: 1.032, 2.556) were significantly associated with parents' tendency either to include, or not exclude, the use of violent discipline. Parents' subjective norms regarding PV had no significant impact on their intentions (p > 0.05). The influence of TPB constructs varied according to parents' gender. Intervention programs that aim to reduce violent discipline should focus both on increasing parents' perceived behavioral control over PV and changing their attitudes toward physically violent practices, especially among mothers and parents who have already used PV to discipline their children.

DNA Hypomethylation of miR-30a Mediated the Protection of Hypoxia Postconditioning Against Aged Cardiomyocytes Hypoxia/Reoxygenation Injury Through Inhibiting Autophagy.

BACKGROUND: Ischemic postconditioning (IPostC) is an endogenous protective mechanism to reduce ischemia-reperfusion (I/R) injury. However, whether IPostC protects aged cardiomyocytes against I/R injury is not fully understood. Considering the protective function of microRNA 30a (miR-30a) against ischemia-induced injury in H9C2 cells, its role in the protective effects of IPostC on I/R injury of aged cardiomyocytes was investigated further.Methods and Results:To mimic I/R and IPostC in vitro, the aged cardiomyocyte model for hypoxia postconditioning (HPostC) treatment was established by 9 days of incubation with 8 mg/mL D-galactose and then followed by exposure to hypoxic environment. HPostC significantly alleviated hypoxia/reoxygenation (H/R) injury and reduced autophagy of aged cardiomyocytes, as evidenced by decreased LC3B-II expression and increased p62 by Western blot. Quantified by quantitative real-time polymerase chain reaction (qRT-PCR), miR-30a was increased in aged cardiomyocytes treated with HPostC compared with I/R injury group. Overexpression of miR-30a by LV3-rno-miR-30a mimic promoted cardioprotective effect of HPostC in aged cardiomyocytes by suppressing BECN1-mediated autophagy, all of which was abrogated by knockdown of miR-30a expression. Epigenetic analyses demonstrated that HPostC reduced DNA methyltransferase 3b-mediated DNA hypomethylation levels at miR-30a promoter, leading to upregulation of miR-30a. CONCLUSIONS: HPostC protected aged cardiomyocytes survival against H/R injury via DNMT3b-dependent activation of miR-30a. miR-30a could be a potential therapeutic target for ischemic myocardial infarction.

Loss of PI3 kinase association improves the sensitivity of secondary mutation of KIT to Imatinib.

BACKGROUND: KIT mutations are the predominant driver mutations in gastrointestinal stromal tumors (GISTs), and targeted therapy against KIT has improved treatment outcome dramatically. However, gaining secondary mutation of KIT confers drug resistance of GISTs leading to treatment failure. RESULTS: In this study, we found that secondary mutation of KIT dramatically increases the ligand-independent activation of the receptor and their resistance to the often used KIT inhibitor Imatinib in the treatment of GISTs. PI3 kinase plays essential roles in the cell transformation mediated by the primary mutation of KIT. We found that loss of PI3 kinase association, but not the inhibition of the lipid kinase activity of PI3 kinase, inhibits the ligand-independent activation of secondary mutations of KIT, and increases their sensitivity to Imatinib, and loss of PI3 kinase association inhibits secondary mutations of KIT mediated cell survival and proliferation in vitro. The in vivo assay further showed that the growth of tumors carrying secondary mutations of KIT is more sensitive to Imatinib when PI3 kinase association is blocked while inhibition of the lipid kinase activity of PI3 kinase cannot inhibit tumor growth, indicating that PI3 kinase is important for the drug resistance of secondary mutation of KIT independent of the lipid kinase activity of PI3 kinase. CONCLUSIONS: Our results suggested that PI3 kinase is necessary for the ligand-independent activation of secondary mutations of KIT, and loss of PI3 kinase association improves the sensitivity of secondary mutations to the targeted therapy independent of the lipid kinase activity of PI3 kinase.

Trend in caries prevalence of permanent teeth and DMFT in the 7-year-old primary school students of Han nationality from 1991 to 2014 / 中国学校卫生

Objective@#To analyze the dynamic trend of caries prevalence of permanent teeth and DMFT in the 7-year-old primary school students of Han nationality from 1991 to 2014, and to provide a basis for the development of caries prevention measures for children and adolescents.@*Methods@#A total of 100 652 students from the 7yearold age group of 30 provinces, autonomous regions and municipalities in 1991, 1995, 2000, 2005, 2010 and 2014 from Physical Fitness And Health Surveillance Of Chinese School Students were selected. DMF% and DMFT were used as indicators to analyze the change trend of caries prevalence of permanent teeth and DMFT in different groups of 7-year-old primary school students of Han nationality in the past 25 years.@*Results@#During the 25 years, the DMF% of primary school students in 7 years old group showed an overall U-shaped development trend. DMF% was 7.9% in 1991, lowest at 3.2% in 2005, and 5.2% in 2014. The DMFT basically showed a steady fluctuation trend. DMFT of rural girls were higher than the other three groups.@*Conclusion@#In view of the serious caries problem among primary school students aged 7 in China, it is necessary to continue to improve oral health strategies, strengthen the publicity of prevention and treatment of caries and oral health education, increase the input of oral health resources in rural areas, reduce the prevalence of caries and protect children’s oral health.

Mental health status of students with self reported learning disabilities in Beijing / 中国学校卫生

Objective@#Understanding mental health status of students with learning disabilities in Beijing to provide a basis for mental health promotion of students with learning disabilities.@*Methods@#By means of random cluster sampling, 5 787 enrolled students in grade one and grade two of 11 public junior middle schools in Beijing were selected as the survey subjects. A self designed questionnaire was used to investigate the students’ learning disabilities and mental health status through anonymous self filling.@*Results@#About 11.6% students self reported learning disabilities. The proportions of students with learning difficulty in mathematical reasoning and calculation were higher, 44.1% and 40.7% respectively. The reported rate of mental health problems was 38.3%. The top four of the 10 symptoms were obsessive compulsive symptoms, learning pressure, emotional instability and anxiety(2.19±0.77)(2.17±0.99)(2.09±0.90)(2.07±1.08). Compared with students without learning disabilities, students with self reported learning disabilities had poorer mental health status(OR=1.47), and learning disabilities were related to most factors of mental health. Different types of learning disabilities were associated with different mental health factors.@*Conclusion@#Mental health problems of students with learning disabilities are higher than that of students without learning disabilities. It is necessary to strengthen the mental health support for students with learning disabilities and improve their mental health.

Current status and demand of health services in primary and middle school clinic in 16 provinces of China / 中国学校卫生

Objective@#To analyze the current situation and needs of primary and secondary school health clinic services, and to provide a reference for strengthening school health service in China.@*Methods@#Investigation provinces were selected according to China s three major economic zones, 1 or 2 survey centers were selected from each province, 16 provinces and 26 survey centers were selected. In each survey centers, six schools from primary and secondary schools, junior high schools and high schools in urban and rural areas were randomly selected as research sites. Each research site randomly selected 10 students in each grade(grade three, four, five from primary schools) to fill in the questionnaire anonymously. A total of 4 661 valid questionnaires were collected.@*Results@#Among the services provided by the school clinics to students, "trauma treatment" "consulting health problems" "physical examination" accounted for 49.4%, 40.5% and 39.0% respectively. Within the past one year, 45.1% students went to the school clinic for consultation or consultation 1-3 times, 6.4% for 4-5 times, and 3.7% for 6 times or more. When students were sick in school, 65.8%(primary school), 64.0%(junior high school), and 54.4%(high school) of them selected to go to the school clinic. When suddenly suffered trauma in school, 78.2%(primary school), 73.2%(junior high school) and 69.6%(high school) of the students went to the school clinic.@*Conclusion@#Primary and middle school students have a great demand for school health services, and it is necessary to continue to strengthen the construction of primary and secondary school health clinics.

[Clinical Significance of Additional Chromosomal 8 Clonal Evolution in CML Progression].

OBJECTIVES: To explore the clinical significance of clonal evolution of additional chromosomal 8 in CML progression. METHODS: An unusual case with the clonal evolution from trisomy 8 to tetrasomy 8 accompanied by 2 time of CML blast crisis (BC) was reported. RESULTS: This patient suffered from 2 time of CML blast crisis and the additional chromosome 8 aberrations were accompanied. Trisomy 8 and tetrasomy 8 were detected at first CML blast crisis and second CML blast crisis, respectively. After tetrasomy 8 was developed, the c-Myc was over-expressed and the central nervous system leukemia happened in this case. Only high dose Ara-C and MTX regimen could induce remission for a short period. CONCLUSION: These findings suggested that additional chromosome 8 aberrations are important marker for poor prognosis of CML patients and contribute to a poor prognosis.

Modulation of FABP4 hypomethylation by DNMT1 and its inverse interaction with miR-148a/152 in the placenta of preeclamptic rats and HTR-8 cells.

Inflammation and dysregulated lipid metabolism are involved in the pathogenesis of preeclampsia, and fatty acid binding protein 4 (FABP4) is known to regulate both inflammation and lipid metabolism. In the present study, we elucidated the role of FABP4 using in vitro and in vivo models of preclampsia. We found increased expression of FABP4 in the placenta of preeclamptic rats, which was further confirmed in HTR-8 cells, an extravillous trophoblast cell line, treated with L-NAME. Overexpression of FABP4 in HTR-8 cells resulted in upregulated expression of pro-inflammatory cytokines IL-6 and TNF-α, and increased lipid accumulation, suggesting that FABP4 plays a role in preeclampsia. Furthermore, downregulation of methylation in the promotor resulted in increased FABP4 expression, which was mediated by downregulated DNA methyltransferase 1 (DNMT1). Bioinformatics analysis showed that miR-148a/152 regulated the expression of DNMT1, and additional in vitro studies revealed that miR-148a/152 inhibited DNMT1 expression by directly binding to its 3'-UTR. Interestingly, DNMT1 enhanced the expression of miR-148a/152 by downregulation of methylation in its promotor. Taken together, our results showed that FABP4 may be involved in the pathogenesis of preeclampsia, and the expression of FABP4 is enhanced by miR-148a/152 mediated inhibition of DNMT1 expression.

High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE(-/-) mice.

Homocysteine (Hcy) is an independent risk factor for atherosclerosis, but the underlying molecular mechanisms are not known. We investigated the effects of Hcy on fatty acid-binding protein 4 (FABP4), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased FABP4 expression and decreased methylation. The FABP4 expression and DNA methylation was assessed in the aorta of ApoE(-/-) mice fed high-methionine diet for 20weeks. Over-expression of FABP4 enhanced accumulation of total cholesterol and cholesterol ester in foam cells. The up-regulation of DNA methyltransferase 1 (DNMT1) promoted the methylation process and decreased FABP4 expression. These data suggest that FABP4 plays a key role in Hcy-mediated disturbance of lipid metabolism and that DNMT1 may be a novel therapeutic target in Hcy-related atherosclerosis.

[Association between obesity and age at spermarche among Chinese Han boys aged 11-18 years].

OBJECTIVE: To analyze the association between obesity and age at spermarche among Chinese Han boys aged 11-18 years . METHODS: The height, weight and status of the spermarche of Chinese Han boys aged 11-18 years were selected from the data of 2010 National Physical Fitness and Health Surveillance.The body mass index (BMI), prevalence of spermarche in each age group and ages at spermarche by BMI groups were calculated. Chi square test was used to analyze the differences of prevalences of spermarche among the boys with different BMIs across ages. U-test was used to compare the differences of age at spermarche between the boys who were obese and not. RESULTS: In the boys aged 12 and 17 years in urban areas and boys aged 13 years in rural areas, the differences of prevalences of spermarche among the normal weight, overweight and obesity groups were significant (P<0.05). The age at spermarche in the obesity group (13.90 years) was 0.1 years earlier than that in the non-obesity group (14.00 years) (P<0.05). CONCLUSION: Obesity may make the age at spermarche ahead of time.

A systems biology-based approach to uncovering the molecular mechanisms underlying the effects of dragon's blood tablet in colitis, involving the integration of chemical analysis, ADME prediction, and network pharmacology.

Traditional Chinese medicine (TCM) is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB) tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME), and network pharmacology. Firstly, a rapid, reliable, and accurate ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was employed to identify 48 components of DB tablets. In silico prediction of the passive absorption of these compounds, based on Caco-2 cell permeability, and their P450 metabolism enabled the identification of 22 potentially absorbed components and 8 metabolites. Finally, networks were constructed to analyze interactions between these DB components/metabolites absorbed and their putative targets, and between the putative DB targets and known therapeutic targets for colitis. This study provided a great opportunity to deepen the understanding of the complex pharmacological mechanisms underlying the effects of DB in colitis treatment.

SIL-TAL1 rearrangement is related with poor outcome: a study from a Chinese institution.

SIL-TAL1 rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL), however its prognostic implication remains controversial. To investigate the clinical characteristics and outcome of this subtype in Chinese population, we systemically reviewed 62 patients with newly diagnosed T-ALL, including 15 patients with SIL-TAL1 rearrangement. We found that SIL-TAL1(+) T-ALL was characterized by higher white blood cell count (P = 0.029) at diagnosis, predominant cortical T-ALL immunophenotype (P = 0.028) of the leukemic blasts, and a higher prevalence of tumor lysis syndrome (TLS, P<0.001) and disseminated intravascular coagulation (DIC, P<0.001), which led to a higher early mortality (P = 0.011). Compared with SIL-TAL1(-) patients, SIL-TAL1(+) patients had shorter relapse free survival (P = 0.007) and overall survival (P = 0.002). Our NOD/SCID xenotransplantation model also demonstrated that SIL-TAL1(+) mice models had earlier disease onset, higher leukemia cell load in peripheral blood and shorter overall survival (P<0.001). Moreover, the SIL-TAL1(+) mice models exerted a tendency of TLS/DIC and seemed vulnerable towards chemotherapy, which further simulated our clinical settings. These data demonstrate that SIL-TAL1 rearrangement identifies a distinct subtype with inferior outcome which could allow for individual therapeutic stratification for T-ALL patients.

[Genetic characteristics and its prognostic significance for 217 adult patients with acute lymphoblastic leukemia].

OBJECTIVE: To evaluate cyto- and molecular genetic characteristics of adult patients with acute lymphoblastic leukemia (ALL) and its prognostic significance. METHODS: Two hundred and seventeen adult patients with ALL were analyzed for cyto- and molecular genetic characteristics with combined conventional cytogenetics, fluorescence in situ hybridization (FISH), real-time quantitative PCR (qPCR) and nested PCR. Significance of genetic findings for prognosis was evaluated. RESULTS: t(9;22)(q34;q11)/BCR-ABL has been the most frequent abnormality found in the cohort (56.3%). And 22.4% of cases with BCR-ABL detected by FISH was negative by cytogenetic analysis. Ratio of patients in high-risk group increased with age; Patients with B-ALL had a higher risk group than the average-risk group (98.40% vs. 65.70%, P=0.000). The overall survival (OS) rates at 3-month (67.30% vs. 85.10%, P=0.042), 6-month (55.1% vs. 80.4%, P=0.008), 12-month (34.0% vs. 59.1%, P=0.017) and 24-month (13.0% vs. 36.6%, P=0.010) were lower in high-risk group than in average-risk group, with medium OS time (11 months, 95% CI 8.0-13.9) being significantly shorter compared with the average-risk group (19 months, 95%CI 10.8-27.1). CONCLUSION: Adult patients with ALL have unique cyto- and molecular genetic characteristics, which has important value for prognosis and guiding treatment. Moreover, combined cytogenetic and molecular genetic techniques can precisely define sub-groups of ALL patients.