OBJECTIVE: To establish an LC-MS/MS method for simultaneous determination of blonanserin and its metabolite blonanserin C in the plasma of healthy volunteers. METHODS: After adding saturated aqueous solution of sodium bicarbonate as the basification reagent, blonanserin and blonanserin C were extracted from plasma by ethyl acetate-dichloromethane (4;1). Then blonanserin and blonanserin C were determined by LC-MS/MS using blonanserin B and blonanserin D as internal standards respectively. Separation was carried on an Agilent Eclipse plus C18 column(4.6 mm×150 mm, 5 μm)with a mobie phase of acetonitrile-0.005 mol·L-1 ammonium formate aqueous solution containing 0.1% formic acid (87;13) at the flow rate of 0.5 mL·min-1. The column temperature was set at 40°C. ESI source was applied and operated in positive ion mode. Quantitative determination was performed using selective reaction monitoring (SRM) at m/z 368.2→297.2 for blonanserin, m/z 396.3→297.2 for blonanserin B, m/z 340.2→297.1 for blonanserin C and m/z 356.2→313.3 for blonanserin D. RESULTS: Blonanserin and blonanserin C showed good linearity in the range of 10-2000 ng·L-1(r2=0.997). The extraction recoveries for blonanserin and blonanserin C were more than 93.5% and 74.5% respectively, while the intra-day and inter-day RSDs were lower than 9.0% and 16.4% respectively. CONCLUSION: The method is simple, rapid, accurate and sensitivie for simultaneous determination of blonanserin and blonanserin C in human plasma, which can be applied to the clinical pharmacokinetic study and therapeutic drug monitoring of blonanserin.

Objective To evaluate the treatment of current status and prognosis in childhood APL with APL2008 ,which was administrated since 2008 in our center .Methods A total of 43 children with newly diagnosed APL between 2008 to 2014 were studied retrospectively .Treatment options and current status were summarized from 28 patients who received APL2008 therapy . Results Studied 43 patients were at median age of 8 years and 4 months ,with 28 boys and 15 girls .The main clinical manifestations were infection ,anemia ,bleeding ,fever ,hepatomegaly ,splenomegaly and lymphadenopathy .The proportions of low ,intermediate and high risk groups were 27 .9% ,48 .8% and 23 .3% ,respectively .Eleven cases could be diagnosed as DIC .Bone marrow morphology showed abnormal elevation of promyelocyte .37 patients had distinctive immunophenotype such as frequent expression of CD33 , CD117 and MPO .PML/RARαfusion gene positive rate was 100% in 43 children and cytogenetic analysis were positive in 37 cases , of which specific genetic lesion in APL cells with t (15 ;17)(q22 ;q12) was found in 28 cases ,and karyotypes was found in 9 cases as infrequent chromosomal abnormalities .In 43 patients ,4 cases were early dead from intracranial hemorrhage at early stage ,and 11 cases were given up early .There were only 2 cases dead ,2 cases relapsed and 1 case lost among 28 APL children ,which enabled ef‐ficacy analysis possible .96 .4% of these 28 cases achieved HCR .The 2 year Kaplan Meier estimates of OS and EFS were 85 .9% ± 7 .6% and 80 .4% ± 8 .8% .But OS and EFS would be 94 .7% ± 5 .1% and 88 .9% ± 7 .4% if 3 patients who had non standard treat‐ment were excluded .Conclusion Childhood APL were characterized by anemia ,bleeding ,fever and infiltration .APL′s coincidence rate between PML/RARa fusion gene and morphology ,immunology and cytogenetics were 95 .3% ,90 .2% and 86 .5% ,respective‐ly .APL2008 significantly improved the prognosis of APL .

Objective To investigate the relationship between EVI1 gene expression and clinical features and prognosis of children with acute myeloid leukemia (AML). Methods EVI1 gene was detected in AML children, correlation of clinical and lab features, prognosis of AML children with EVI1 gene were analyzed. Results EVI1 expression is positive in 38 of 145 children with AML. There were no significant differences in age, gender, hemoglobin concentration, leukocytes and platelet count, subtype of morphology, ratio of chromosomal anomaly and complex karyotypes between EVI1 positive and EVI1 negative group (P>0.05); coexist genes were detected in 9 cases (23.68%) of EVI1 positive group. Rate of complete remission (CR) was 91.67% in 24 cases of EVI1 positive patients received chemotherapy. Relapse rate was 64.29% and 14.29% in EVI1 positive patients who received chemotherapy and allo-hematopoietic stem cell transplantation (allo-HSCT), retrospectively and significant differences were found (P<0.05). There was no significant difference in CR but significant difference was found in event free survival (P<0.05) for EVI1 positive and EVI1 negative patients who received chemotherapy. EVI1 gene kept negative when bone marrow relapse occurred in two patients with EVI1 positive at diagnosis. Conclusion EVI1 gene may play adverse role in pediatric AML; prognosis of EVI1 positive AML patients can be improved by allo-HSCT; follow-up of EVI1 transcript levels is insufficient to monitoring of minimal residual disease.

Objective To evaluate the effect of the difficult embryo transfer on the clinical pregnancy outcome of in vitro fertili-zation-embryo transfer(IVF-ET) .Methods There were 209 fresh cycles of difficultly transferring and 2 489 fresh cycles of easily embryo transferring between January 2011 and December 2012 .The clinical outcome was compared .Results There were statistical-ly significant differences in the catheter blood staining rates (51 .20% vs 27 .68% ,P< 0 .05) ,implantation rate(31 .14% vs 35 . 54% ,P<0 .05) ,and clinical pregnancy rate (46 .41% vs 55 .56% ,P<0 .05)between the two groups .There was no significant difference in the rates of ectopic pregnancy and miscarriage between the two groups (P>0 .05) .Conclusion Difficulty ET will in-fluence the clinical pregnancy .Therefore ,all efforts should be made to avoid the difficult transfer in order to increase the pregnant rate .

OBJECTIVETo study the therapeutic effects of posterolateral depression fractures of the tibial plateau through a modified anterolateral approach.

METHODSFrom February 2011 to January 2012,13 patients with posterolateral depression fractures of the tibial plateau were treated through a modified anterolateral approach. There were 8 males and 5 females, ranging in age from 28 to 59 years old (49.2 years old on average). Data from patients were collected retrospectively as follows: X-ray, time of fracture healing and the complications of fracture healing. The patients were evaluated both clinically and radiologically according to the Rasmussen score system.

RESULTSAll the patients were followed up, and the duration ranged from 6 to 18 months (mean 13.7 months). All the patients got bony union. The average radiographic bony union time was 15.1 weeks (ranged, 11 to 17 weeks). No case of secondary articular depression was found. No complications such as malunion or joint stiffness were found. But 1 patient had superficial infection and 1 patient had common peroneal nerve injury. According to the Rasmussen score system,the mean radiological score was 16.50 ± 0.67 (ranged, 13 to 18), and the mean functional score was 25.20 ± 2.21 (ranged, 13 to 30). The mean range of knee motion was (125.3 ± 9.3)° (ranged, 0° to 135°).

CONCLUSIONTreatment of depression fractures of posterolateral tibial plateau with a modified anterolateral approach is a safe method with effective exposure, due to its stable fixation and relatively good outcome with minimal soft-tissue complications. It is regarded as an ideal procedure for depression fractures of posterolateral tibial plateau.

Adult ; Female ; Fracture Fixation, Internal ; methods ; Fracture Healing ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Tibial Fractures ; surgery

Objective To study the clinical and electrophysiological features of myasthenia gravis (MG)accompanied by myogenic lesion.Methods The data of the patients who were diagnosed MG accompanied by myogenic lesion from 1998 to 2006 were collected in EMG Room, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and were retrospectively analyzed.Results In this group of 53 patients, myogenic lesion was found more often in patients with early-onset MG than those with late-onset(69.81% vs 30.20%), and among the early-onset patients the frequency of female was significantly higher than male(26 vs 11,X~2=5.281, P

Objective To summarize and analyze prenatal ultrasound and postnatal autopsy ifndings in fetuses with urorectal septum malformation sequence (URSMS). Methods An analysis of prenatal ultrsound ifndings and postnatal autopsy features was performed on eleven cases of fetuses with URSMS that were identiifed by ultrasonography at Shenzhen Maternity&Child Healthcare Hospital in the period of January 2003 to December 2012. Results Prenatal ultrasonography showed a large abdominal cystic mass concomitant with imperforate anus in eleven fetuses with URSMS. The cyst contained unilocular or bilocular cystic structures in two fetuses, and trilocular cystic structures in nine fetuses. The cyst was demonstrated as clear acoustic transmission in three fetuses and unclear in eight fetuses. Out of them, seven fetuses had kidney abnormalities, six had ascites, and three had enterolithiasis. The associated systemic abnormalities included tethered cord in two fetuses, single umbilical artery in two fetuses, sacrococcygeal dysplasia in one fetus, and myocardial noncompaction in one fetus. 21-trisomy was found in one fetus by chromosome examination. Eleven cases were all identiifed as female fetuses by autopsy ifndings, including a single perineal opening and ambiguous genitalia with clitoral hypertrophy and labial fusion. The internal genital abnormalities included double vagina or longitudinal vaginal septum in nine fetuses, double uterus or uterus bicornis in ten fetuses and vaginal dysplasia in one fetus. Conclusions URSMS is a complex congenital malformation, which includes abnormalities of the urinary system, reproductive system and gastrointestinal track. An abdominal cystic mass visualized by prenatal ultrasonography might be the distinctive lesion in female with URSMS, and have an important diagnostic value. The kidney abnormalities and ambiguous genitalia can contribute to the diagnosis of URSMS.

The α4β2-nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that is distributed throughout the nervous system. It is involved in the regulation of various neurotransmitters including acetylcholine, dopamine, γ-aminobutyric acid, and norepinephrine. α4β2-nAChR plays an important role in learning, memory, cognition, attention, inflammation, and pain. A large number of studies have shown that α4β2-nAChR is an important therapeutic target for neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, depression, nicotine dependence, pain, etc. It is an important target in the early diagnosis and curative effect detection of neurodegenerative diseases including Alzheimer's disease. This review summarizes the role, mechanisms and related drug research advances on α4β2-nAChR ligand drugs in neurological diseases, as well as providing a theoretical basis for identifying and developing more suitable α4β2-nAChR-related compounds.

Objective: To understand the behavioral characteristics of vaccination of human papillomavirus (HPV) vaccine based on diffusion of innovation theory, and to put forward suggestions for improving the vaccination willingness. Methods: The women who had made an appointment or received at least one dose of HPV vaccine in two community health service centers with HPV vaccination qualification in Hangzhou were recruited by convenience sampling method. A questionnaire survey was conducted according to cervical cancer risk factors, HPV vaccine knowledge and the time of vaccination. The diffusion of HPV vaccination and the characteristics of vaccinees in different stages was analyzed. Results: A total of 448 women, aged from 18 to 45 years old, with a median of 30.5 years old, were investigated. The spread of HPV vaccine were divided into five stages: April 2017 and before was the initial stage, with 8 leaders, accounting for 1.79%; October 2017 to February 2018 was the slowly rising stage, with 59 early vaccinees, accounting for 13.17%; April 2018 to April 2019 was the rising stage, with 160 most early vaccinees, accounting for 35.71%; May to August 2019 was the rapidly rising stage, with 170 most late vaccinees, accounting for 37.95%; September 2019 to the end of the survey was the standstill stage, with 51 laggards, accounting for 11.38%. All of the leaders had participated in cervical cancer screening, voluntarily vaccinated, and knew the susceptible population of cervical cancer, the targeted HPV types and the suitable population of vaccine. The median age of the first pregnancy was 27 years old. Six of them had three pregnancies. The early vaccinees and the most early vaccinees were recommended by doctors or friends to get HPV vaccine. The median age of first pregnancy was 26 and 28 years old, respectively. Their other characteristics were similar to those of the leaders. The characteristics of most late vaccinees were similar to those of the laggards. They were were mainly students who were recommended by their friends to receive HPV vaccination, did not participate in cervical cancer screening, did not know the susceptible population of cervical cancer, the targeted HPV types and the suitable population of vaccine. Conclusions People with high risk of HPV exposure, awareness of cervical cancer and screening are more likely to receive HPV vaccination at the early stage. It is necessary to strengthen the health education of HPV vaccination, and make full use of the influence of doctors and early vaccinees, which is helpful to promote the early vaccination of HPV vaccine among the right age population.

This study is to investigate the protection effect of schisandrin B (Sch B) against oxidation stress of HK-2 cells induced by cisplatin and the mechanisms involved. HK-2 cells were cultured and divided into different groups: solvent control group, cisplatin exposure group, positive group, Sch B treatment group. Cell viability and toxicity were evaluated by MTT and LDH assay. GSH level and SOD enzymes activities were also measured. DCFH-DA as fluorescence probe was used to detect ROS level by fluorescence microplate reader. Nrf2 translocation was detected by Western blotting. Real time Q-PCR was used to detect expressions of NQO1, HO-1 and GCLC mRNA level. The results showed that Sch B could significantly inhibit the decline of cell viability induced by cisplatin treatment (P < 0.05) and the protective effect was in a dose dependent manner. Furthermore, Sch B treatment significantly inhibited the increase of ROS level induced by cisplatin and reversed the decrease of GSH level (P < 0.05). When Sch B concentration was up to 5 micromol x L(-1), SOD enzyme activities were also enhanced significantly compared with that of the cisplatin group (P < 0.05). It was shown that Sch B could cause nuclear accumulation of Nrf2 in association with downstream activation of Nrf2 mediated oxidative response genes such as GCLC, NQO1 and HO-1. These results suggested Sch B could protect against the oxidative damage of HK-2 cells induced by cisplatin via the activation of Nrf2/ARE signal pathway.
Antineoplastic Agents ; toxicity ; Antioxidants ; isolation & purification ; pharmacology ; Cell Line ; Cell Survival ; drug effects ; Cisplatin ; toxicity ; Cyclooctanes ; isolation & purification ; pharmacology ; Glutamate-Cysteine Ligase ; genetics ; metabolism ; Glutathione ; metabolism ; Heme Oxygenase-1 ; genetics ; metabolism ; Humans ; Kidney Tubules, Proximal ; cytology ; metabolism ; L-Lactate Dehydrogenase ; metabolism ; Lignans ; isolation & purification ; pharmacology ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; metabolism ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Polycyclic Compounds ; isolation & purification ; pharmacology ; RNA, Messenger ; metabolism ; Reactive Oxygen Species ; metabolism ; Schisandra ; chemistry ; Signal Transduction ; Superoxide Dismutase ; metabolism