10.3969/j.issn.2095-4344.2013.23.006

OBJECTIVE: To compare all published sodium valproate population pharmacokinetic models of epileptic children in China and assess them by external validation to determine their predictive performance. METHODS: The published population pharmacokinetic model of sodium valproate in children with epilepsy in China was collected by database retrieval. By retrospectively collecting patients' information, we performed an external validation to evaluate the power of prediction. RESULTS: Four sodium valproate models were published before. The external validation of 101 samples showed that the MPE, MAE, RMSE of the four model were similar. All of them showed good adequacy between predicted concentrations and observed concentrations. Comparing with other models, the model established by Ding has better prediction error coincidence rate in most interval, which is more targeted for the prediction of individualized dosage regimen for epileptic children in our hospital. However, the overall prediction accuracy of the four models is not significantly different. CONCLUSION: By the evaluation of four published population pharmacokinetic models of sodium valproate model B performs better than others, while the overall accuracy of the four models did not differ much. Racial difference may be an important factor affecting the accuracy of the model, which needs to be further explored in subsequent studies.

Background: We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. Objective: To explore the role and mechanism of miR-1246 in severe AA. Methods: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+ IL-17+ cells proportion. ELISA was used to measure cytokine levels. Results: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples.NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+ IL-17+ cells proportion and the IL-17F level. Conclusion miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.

Targeted therapeutic drugs for acute myeloid leukemia (AML) are showing immense development, thereby laying a solid foundation for the precise treatment of AML patients. The paper reviews four types of targeted drugs that have progressed rapidly for AML treatment (by targeting genes or signaling-pathway alterations, targeting apoptosis-related pathways, targeting cell-surface antigens, and targeting immune-related substances). We look forward to the future development directions of targeted drugs, providing references for hematologists and developers of new drugs for AML.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

OBJECTIVE: To investigate the composition of gut microbiota and its correlation with the severity of behavior symptoms in children with autism spectrum disorder (ASD). METHODS: A total of 30 children with ASD were enrolled as the ASD group, and 20 healthy children matched for age and sex were enrolled as the healthy control group. Related clinical data were analyzed. The V3-V4 hypervariable regions of the bacterial 16S rRNA gene in fecal samples were sequenced. The severity of behavior symptoms in children with ASD was assessed using the autism behavior checklist. The Spearman's correlation analysis was used to investigate the correlation between gut microbiota and the severity of behavior symptoms in children with ASD. RESULTS: There was a significant difference in the composition of gut microbiota between the two groups. Compared with the healthy control group, the ASD group had significant reductions in Shannon index and Shannoneven index (P<0.05), as well as a significant reduction in the percentage of Firmicutes and a significant increase in the percentage of Acidobacteria in feces (P<0.05). In the ASD group, the dominant bacteria were Megamonas, Megasphaera, and Barnesiella, while in the healthy control group, the dominant bacteria were Eubacterium_rectale_group, Ezakiella, and Streptococcus. In the children with ASD, the abundance of Megamonas was positively correlated with the scores of health/physical/behavior and language communication (P<0.05). CONCLUSIONS The development of ASD and the severity of behavior symptoms are closely associated with the composition of gut microbiota.
Autism Spectrum Disorder ; Bacteria ; Child ; Feces ; Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S

This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.
Animals ; Disease Models, Animal ; Leukemia, Biphenotypic, Acute ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Fusion ; genetics ; Retroviridae ; genetics ; Transfection

OBJECTIVETo evaluate postoperative glottic area and vocal quality of three various surgical techniques for treating bilateral vocal cord paralysis, including laser arytenoidectomy (Group A, 24 cases), reinnervation of the posterior cricoarytenoid muscle by phrenic nerve (Group B, 9 cases) and arytenoidectomy accompanying lateral cordopexy by extralaryngeal approach (Woodman's procedure, Group C, 13 cases).

METHODS46 cases suffered from bilateral recurrent laryngeal nerve injury were included in our study. The pre-postoperative glottic measurement and vocal acoustic parameters were analyzed.

RESULTSThe decannulated cases in group A and group B and group C were 22, 8, 13 respectively. The post-operative mean maximal glottic area was (47.2 +/- 7.4) mm2, (78.3 +/- 16.0) mm2, (48.1 +/- 6.5) mm2 respectively. Group B cases glottic area was larger than that of group A and group C (t value were 4.46 and 3.85, P value were 0.000 and 0.001). No significant difference was found between group A and group C (t = 1.68, P = 0.101). After surgery, in group A, 17 cases voice quality was the same compared with that of before surgery, and 7 cases voice quality had become worse; In group B, the voice quality had become better in 5 cases, completely recovered in 1 case, and had not change in 3 cases; In group C, the voice quality had become deteriorated in 10 cases and no change in 3 cases. And in group B, ipsilateral diaphragm paralysis in 9 cases after surgery, whose vital capacity and forced vital capacity had decreased to 72%-84%, 76%-84% of that before the surgery respectively; and the diaphragm mobility had recovered by 35%-76% respectively, while vital capacity and forced vital capacity had become 93%-97%, 91%-98% of that before the surgery. In Group B, all cases' pulmonary function was normal half a year postoperatively.

CONCLUSIONSReinnervation of the posterior cricoarytenoid muscle by phrenic nerve seems to be best procedure with better post-operative voice and larger glottic area. Although the sufficient airway for decannulation can be acquired in Group A and Group C, but most of patients in Group A had pre-operative vocal level and badly abnormal in Group C.

Adult ; Aged ; Arytenoid Cartilage ; surgery ; Female ; Glottis ; physiopathology ; Humans ; Laser Therapy ; Male ; Middle Aged ; Phrenic Nerve ; surgery ; Treatment Outcome ; Vocal Cord Paralysis ; physiopathology ; surgery ; Voice Quality ; Young Adult

To measure particle size distribution of phenols in mainstream cigarette smoke aerosol,the particles of cigarette smoke aerosol were divided into 12 stages using single channel smoking machine coupled electrical low-pressure impactor (ELPI) and collected by 12 polyester films.The collected particles were weighted and then analyzed by ultra-high performance liquid chromatography-fluorescence detection (UPLC-FLD) to determine the 14 phenols in the different size particles.The results showed that the aerosols collecting method had good stability with relative standard deviation (RSD) of collected particles mass less than 10%.The analyzing results of 14 phenols by UPLC-FLD showed that the linear correlation coefficients(R2) were greater than 0.9959,with detection limits were less than 1.2 ng/cig and recoveries were 80.1%-115.0%.The distributions of 14 phenols with respect to smoke aerosol particle size were investigated.The results indicated that except 4-ethyl-2-methoxy-phenol not detected,the other 13 phenols were detected in mainstream cigarette smoke aerosol.The content of 13 phenols appeared increasing at first and then decreasing with increase of the particle size which distributed in a pattern similar to that of particle mass.All of 13 phenols were present in higher amounts in the medium size particles (0.261-0.722 μm) with peak content in particles 0.431 μm.The distribution of concentrations (ratio of content to particle mass) of 13 phenols in different size particles was different.The concentrations of phenol and mono-substituted phenol appeared to first increase and then decrease with increasing smoke aerosol particle size and were higher in medium size particles (0.261-0.772 μm).The concentrations of benzenediol and mono-substituted benzenediol were uniformly distributed in medium size particles (0.144-1.166 μm),and the concentration of disubstituted phenol was uniform throughout the particles of varying sizes.

Cholangiocarcinoma is a malignant tumor originating from bile duct epithelium, with insidious onset and high degree of malignancy. Most of the patients were diagnosed at the middle and late stages and the survival rate is very poor. The etiology of cholangiocarcinoma is still unknown. Billary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, biliary mucinous cystic neoplasm and intraductal tubular/tubulopapillary neoplasm of the bile duct are considered as precancerous lesions of cholangiocarcinoma. Improving the understanding of precancerous lesions of cholangiocarcinoma, and early treatment of these lesions are important for enhancingthe patients’ quality of life. However, the current understanding of precancerous lesions of cholangiocarcinoma is limited. Development of molecular diagnostic technology is deeply needed. And sensitive and specific biomarkers are urgently needed for the early diagnosis of the high-risk persons accurately, so as to achieve " early detection, early diagnosis and early treatment" . This article reviews how to recognize and deal with precancerous lesions of cholangiocarcinoma.