Efficacy of Children Neuropsychological and Behavioral Scale in Screening for Autism Spectrum Disorders through a Combination of Developmental Surveillance.

OBJECTIVE: This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) for Autism Spectrum Disorder (ASD) screening in the presence of developmental surveillance. METHODS: All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules (GDS). Spearman's correlation coefficients and Kappa values were obtained. Taking GDS as a reference assessment, the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic (ROC) curves. The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). RESULTS: In total, 150 children aged 12-42 months with ASD were enrolled. The developmental quotients of the CNBS-R2016 were correlated with those of the GDS (r=0.62-0.94). The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays (Kappa=0.73-0.89), except for Fine Motor. There was a significant difference between the proportions of Fine Motor, delays detected by the CNBS-R2016 and GDS (86.0% vs. 77.3%). With GDS as a standard, the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor, which was 0.70. In addition, the positive rate of ASD was 100.0% and 93.5% when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used, respectively. CONCLUSION: The CNBS-R2016 performed well in developmental assessment and screening for children with ASD, especially by Communication Warning Behaviors subscale. Therefore, the CNBS-R2016 is worthy of clinical application in children with ASD in China.

Long noncoding RNA MIR210HG is induced by hypoxia-inducible factor 1α and promotes cervical cancer progression.

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play essential roles in various types of cancer, especially the ability of tumor cells to adapt to hypoxia conditions. However, only a few of them have been experimentally validated in cervical squamous cell carcinoma (CSCC). In the current study, we identified a hypoxia-induced lncRNA MIR210HG was excessively expressed in CSCC tissues and regulated by human papillomavirus (HPV) type 16 E6 and E7 via hypoxia-inducible factor 1α (HIF-1α). Functional assays revealed the role of MIR210HG in promoting proliferation, migration and invasion of CSCC cells in vitro under normoxia as well as hypoxia conditions. Meanwhile, stable MIR210HG silencing dramatically repressed tumor growth and pulmonary metastasis in vivo. Mechanistically, the depletion of MIR210HG or HIF-1α decreased each other's expression level, while silencing MIR210HG or HIF-1α respectively downregulated the expression levels of phosphoglycerate kinase 1 (PGK1), one of key metabolic enzymes in the glycolysis pathway. Furthermore, decreased expression of PGK1 by HIF-1α knockdown was reversed through the overexpression of MIR210HG. Also, we demonstrated HIF-1α can activate the transcription of MIR210HG via binding its promoter. Taken together, these results expand our understanding of the cancer-associated functions of hypoxia-induced lncRNAs, and highlight MIR210HG forms a feedback loop with HIF-1α contributing to cervical carcinogenesis, with potential implications for therapeutic targeting.

Exploring lived experiences of informal caregivers for pregnant women seeking scheduled antenatal care during the COVID-19 lockdown in China: A phenomenological study.

OBJECTIVE: We aimed to explore the lived experiences of informal caregivers for pregnant women seeking scheduled antenatal care during the early stage of China's COVID-19 lockdown and potential measures to address the challenges. DESIGN: This is a phenomenological qualitative study. SETTING: The study was carried out in a leading teaching hospital in Southwest China. PARTICIPANTS: We recruited 15 informal caregivers for healthy pregnant women on routine antenatal visits about six months after China launched the city-wide lockdown and other control measures for COVID-19, including 10 males and 5 females with diverse demographic backgrounds. MEASURES AND FINDINGS: The research team developed a demographic form and an interview outline with key questions, conducted semi-structured interviews with the informal caregivers, and analyzed the data using the Colazzie's method. Five themes of lived experiences were revealed, i.e., increased caregiving burdens, disruption of routines in family life, lack of accurate information and knowledge, active role adjustment, and positive attitudes and coping in a difficult time. Some caregivers reacted positively to the lockdown experience and saw it as an opportunity to rethink their lives and improve family relations. KEY CONCLUSIONS: The informal caregivers experienced increased physical and psychological burdens. Strategies such as adoption of a less frequent prenatal visit schedule, use of tele-medicine technologies, and provision of accurate information and knowledge may help to ease the increased informal caregiving burdens. Psychological counseling, community services and disaster response policies specially targeting pregnant women and their informal caregivers may also be valuable resources. IMPLICATIONS FOR PRACTICE: Attention should be drawn to the group of informal caregivers for pregnant women during a COVID-19 lockdown, including professional assistance delivered by nursing and other related professionals. Measures are called for to minimize exposure opportunities such as adoption of a new prenatal care schedule and tele-medicine technologies. Patient education with reliable information should be provided, preferably by nursing staff and physicians. Social support efforts including professional mental counseling may added and work with other resources such as community services and policy makers.

Myosin 1b promotes migration, invasion and glycolysis in cervical cancer via ERK/HIF-1α pathway.

BACKGROUND: Increasing evidence indicated that metabolic reprograming is essential and has been regarded as a hallmark of cancer. Although the biological functions of Myosin 1b (Myo1b) have been reported in several malignancies, the correlation between Myo1b and cancer metabolism, and its underlying mechanisms remain elusive, particularly in cervical cancer (CC). METHODS: Myo1b and other glycolytic enzymes expression levels were examined in CC cells and tumor tissues from xenograft models by quantitative real-time PCR, Western blot and immunohistochemistry. The biological impacts and regulatory mechanisms of Myo1b on cell migration, invasion and glycolysis were explored. Also, the effects of Myo1b on carcinogenesis and metastasis in nude mice were investigated. RESULTS: Upregulation of Myo1b was found in CC tissues and associated with poor prognosis. Overexpressed Myo1b not only significantly elevated CC cell glycolysis, migration and invasion in vitro, but also promoted tumorigenesis and metastasis in vivo. Conversely, Myo1b knockdown had opposite consequences. Moreover, our study suggested that Myo1b stimulated ERK/HIF-1α pathway and its downstream glycolysis associated genes to modulate the glycolysis, migration and invasion of CC. CONCLUSION: These findings provide evidence that Myo1b regulates migration, invasion and glycolysis in CC through ERK/HIF-1α pathway, suggesting a promising remedial target in treatment of CC.

Clinical and survival analysis of nasopharyngeal carcinoma with consistently negative Epstein-Barr virus DNA.

BACKGROUND: To assess the clinical and survival features of nasopharyngeal carcinoma (NPC) with consistently negative Epstein-Barr virus (EBV) DNA level. METHODS: Propensity score matching (PSM) method was used to create well-balanced cohorts. Kaplan-Meier method and Cox proportional hazards models were performed to conduct survival analysis. RESULTS: Four hundred and eighty patients were enrolled. Patients with consistently negative plasma EBV DNA level had a greater chance to present a relatively earlier T and N classification compared with those with positive EBV DNA level (p < .001; p = .015). And patients with consistently negative EBV level were significantly associated with preferable 3-year DFS (95.0% vs. 84.4%, p = .004), DMFS (98.3% vs. 89.4%, p = .009), and OS (100% vs. 97.6%, p = .004). CONCLUSIONS: NPC patients with consistently negative EBV DNA level performed an earlier clinical stage and negative EBV DNA level was related to preferable survival outcomes.

Ghrelin Affects Gastric Cancer Progression by Activating AMPK Signaling Pathway.

As the endogenous ligand for the GH secretagogue receptor (GHSR), Ghrelin is aberrant expressed in multiple malignant carcinoma, and involved in regulating a number of progression of cancer, especially in metastasis and proliferation. However, the precise role of Ghrelin in tumorigenesis of gastric cancer (GC) is still poorly understood. In this study, we extensively investigated the roles and mechanisms of Ghrelin in human gastric cancer. Ghrelin levels in cancer tissues and cell lines were analyzed by immunohistochemistry, qRT-PCR, and Western blot. Functional studies were performed after Ghrelin overexpressed or knockdown in AGS cell line. Cell proliferation was evaluated in by MTT and clone formation assays. The wound healing and Transwell system were used to assess the cell migration and invasive ability of GC cells. Cell apoptosis was detected by flow cytometry, and metabolic assays were performed to reveal the function of Warburg effect in the process. Ghrelin was lowly expressed in gastric cancer tissues and cell lines. Overexpression of Ghrelin inhibited gastric cancer cell proliferation, migration, invasion, and promoted apoptosis by activating the AMPK pathway, while D-[lys3]-GHRP-6 (a GHSR agonist) treatment relieved the effect, promoting tumorigenesis. Ghrelin knockdown increased the glucose uptake and lactic acid release, suggesting that Ghrelin elicited an anti-Warburg effect via AMPK pathway to inhibit gastric tumorigenesis. Ghrelin inhibits cell proliferation, migration, and invasion by eliciting an anti-Warburg effect via AMPK signaling pathway in gastric cancer cells.

Solvent-assisted planar structure of a stilbene-based salicylhydrazone compound: crystal structure, solvent- and aggregation-induced emission, and switchable luminescence colouration.

A novel stilbene-based salicylhydrazone compound {systematic name: (E)-4,4'-(ethene-1,2-diyl)bis[(N'E)-N'-(2-hydroxybenzylidene)benzohydrazide] dimethyl sulfoxide disolvate, C30H24N4O4·2C2H6OS or L·2DMSO} was synthesized and characterized by single-crystal X-ray diffraction, powder X-ray diffraction and luminescence spectroscopy. The title compound crystallizes in the monoclinic space group P21/c, with half a symmetry-independent L molecule and one dimethyl sulfoxide (DMSO) solvent molecule in the asymmetric unit. The L molecule adopts an almost planar structure, with a small dihedral angle between the planes of the stilbene and salicylhydrazone groups. There are multiple π-π stacking interactions between adjacent L molecules. The DMSO solvent molecules act as proton donors and acceptors, forming hydrogen bonds of various strengths with the L molecules. In addition, the geometry optimization of a single molecule of L and its luminescence properties either in solution, as a solvated solid or as a desolvated solid were studied. The compound shows an aggregation-induced emission (AIE) effect and exhibits switchable luminescence colouration in the solid state by the simple removal or re-addition of the DMSO solvent.

Experience of Clinical Management for Pregnant Women and Newborns with Novel Coronavirus Pneumonia in Tongji Hospital, China.

Based on the New Diagnosis and Treatment Scheme for Novel Coronavirus Infected Pneumonia (Trial Edition 5), combined with our current clinical treatment experience, we recently proposed a revision of the first edition of "Guidance for maternal and fetal management during pneumonia epidemics of novel coronavirus infection in the Wuhan Tongji Hospital". This article focused on the issues of greatest concern of pregnant women including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnostic criteria, inspection precautions, drug treatment options, indications and methods of termination of pregnancy, postpartum fever, breastfeeding considerations, mode of mother-to-child transmission, neonatal isolation and advice on neonatal nursing, to provide valuable experience for better management of SARS-CoV-2 infection in pregnant women and newborns.

Long noncoding RNA SNHG12 modulated by human papillomavirus 16 E6/E7 promotes cervical cancer progression via ERK/Slug pathway.

Recently, long noncoding RNA SNHG12 has been reported to be dysregulated in various types of cancer. This study investigated its biological function and the underlying molecular mechanism in cervical squamous cell carcinoma (CSCC). We found that SNHG12 was significantly overexpressed in CSCC tissues. Further evidence showed that human papillomavirus (HPV) type 16 E6 and E7 might regulate the expression level of SNHG12 by modulating transcription factor c-Myc. Functional experiments suggested that SNHG12 knockdown dramatically repressed CSCC cells proliferation, migration, and invasion while induced apoptosis in vitro as well as suppressed tumor growth in vivo. In addition, SNHG12 could facilitate epithelial-mesenchymal transition through ERK/Slug/E-cadherin pathway at least in part. Our findings highlight SNHG12 functions as an oncogenic long noncoding RNA in malignant phenotype and tumorigenesis of CSCC, which implicate it may be a potential target for CSCC treatment.

A series of pure-blue-light emitting Cu(i) complexes with thermally activated delayed fluorescence: structural, photophysical, and computational studies.

Four mononuclear Cu(i)-halide complexes containing phosphines and pyridine ligands with strong electron donor substituents, [CuCl(PPh3)2(4-NMe2py)] (1), [CuI(PPh3)2(4-NH2py)] (2), [CuI(POP)(4-NH2py)] (3), and [CuI(POP)(4-NMe2py)]·0.5(Et2O) (4), (PPh3 = triphenylphosphine, 4-NMe2py = 4-(dimethylamino)pyridine, POP = bis[(2-diphenyl-phosphino)phenyl]ether, 4-NH2py = 4-aminopyridine, Et2O = diethyl ether) were synthesized and studied with regard to their structural, photophysical properties and theoretical calculations. The complexes exhibit pure blue thermally activated delayed fluorescence (λmax = 442 (1), 436 (2), 464 (3), and 448 nm (4)) in crystalline at room temperature. Emission lifetime analyses and density functional theory (DFT) calculations show that the blue-light emission at room temperature is the singlet (metal + halide)-to-ligand charge transfer state, (1(M + X)LCT), while that at 77 K is the state of 3(M + X)LCT transition character, owing to the small singlet-triplet energy gaps (ΔE = 660-1680 cm-1). X-ray diffraction structure analysis, photophysical studies and theoretical calculations suggest that the much larger torsion angle between the N-heterocyclic rings and N-Cu-X planes of complex 3 than that of 1, 2 and 4 might causes the bathochromic shift of luminescence, although these complexes containing similar heterocycle ligands.

[Simulation Study of Dynamic Color Modulation Based on Tunable Micro/Nano-Structure Array].

With the development of nanotechnology, it has been accessible to display colors by artificial micro/nano-structure, and then the study of structure coloring has become a hot subject, opening a new space for inkless printing. In this paper, a dynamic color modulation method based on tunable micro/nano-structure array is proposed. To tune colors on the same device, a periodic micro/nano-structure array is designed with functional material inside, which could alter the height difference between up and bottom surface precisely by applying an external voltage. It is modeled, and simulated by the Finite Difference Time Domain (FDTD) method in this work. In simulations, perpendicular incident linearly polarized light source is applied, and parameters of surface height difference and period are swept. Series reflective spectra of the devices are obtained, and their corresponding colors are calculated and marked on the CIE 1931 chromaticity diagram. Simulation results demonstrate that when the period is in the range of 100-300 nm, full-color modulation could be realized by varying the height of functional material film via applied voltage, and the peak intensities of reflective spectra are at about 60%, having high energy efficiency. This method is innovative and provides a theoretical basis for the dynamic color modulation micro/nano device, which is quite promising in fields like inkless printing and display technology.

Factors Related to Complicated Grief among Bereaved Individuals after the Wenchuan Earthquake in China.

BACKGROUND: The Wenchuan earthquake in China caused shock and grief worldwide. Sudden bereavement caused by the earthquake led to physical disorders as well as psychological disturbances in the bereaved individuals. The bereaved had a high risk for complicated grief (CG), which may have led to significant distress and impairment in their health. However, there was few available studies on CG among disaster-bereaved individuals in China after the disaster. The aim of this study was to identify factors (demographic characteristics and disaster-related variables) associated with symptoms of CG among the bereaved 18 months after the Wenchuan earthquake. METHODS: This study was conducted with a cross-sectional design and a convenience sample of 271 bereaved individuals from three of the hardest hit areas. Data were collected by questionnaires and the instruments used in the study were: General questionnaire and Inventory of CG (ICG). Multivariate linear regression analysis was used to identify factors associated with symptoms of CG. RESULTS: The mean score on ICG was 52.77 (standard deviation: 10.00). Being female and loss of a child were related to higher level of CG while having another child after the disaster and receiving psychological counseling experience were associated with lower level of CG. Forty-nine percent of the variance of CG was explained by these identified factors. CONCLUSIONS: Eighteen months after the Wenchuan earthquake, the symptoms of CG among the bereaved were higher than the previous studies with bereaved individuals. This study uncovers a vulnerable population of the bereaved at high risk for CG. Early assessments, targeted interventions, and policy support tailored for the disaster-bereaved individuals are necessary to identify and alleviate symptoms of CG and to improve their well-being.

Altered thyroid hormone profile in offspring after exposure to high estradiol environment during the first trimester of pregnancy: a cross-sectional study.

BACKGROUND: The increasing number of babies conceived by in vitro fertilization and embryo transfer (IVF-ET) shifts concern from pregnancy outcomes to long-time health of offspring. Maternal high estradiol (E2) is a major characteristic of IVF-ET and lasts throughout the first trimester of pregnancy. The fetal thyroid develops during this period and may thus be affected by exposure to the supra-physiological E2. The aim of this study is to investigate whether the high E2 maternal environment in the first trimester increases the risk of thyroid dysfunction in children born following IVF-ET. METHODS: A cross-sectional survey design was used to carry out face-to-face interviews with consecutive children attending the hospital. A total of 949 singletons born after fresh embryo transfer (ET) (n=357), frozen ET (n=212), and natural conception (NC) (n=380), aged 3 to 10 years old, were included. All children were thoroughly examined. Meanwhile, another 183 newborns, including 55 fresh ET, 48 frozen ET, and 80 NC were studied. Levels of serum T3, FT3, T4, FT4, and TSH and levels of maternal E2 at different stages of the first trimester were examined. RESULTS: The mean serum E2 levels of women undergoing fresh ET during the first trimester of pregnancy were significantly higher than those of the women undergoing frozen ET or following NC. The thyroid hormone profile, especially the levels of T4, FT4, and TSH, were significantly increased in 3- to 10-year-old children conceived by fresh ET compared to NC. The same tendency was confirmed in newborns. However, levels of T4 and TSH in the frozen ET group were nearer to that of the NC group. Furthermore, levels of T4 and FT4 in fresh ET were positively correlated with maternal serum levels of E2 during early pregnancy. CONCLUSIONS: The maternal high E2 environment in the first trimester is correlated with increased risk of thyroid dysfunction. Frozen ET could reduce risks of thyroid damage in children conceived by IVF. Further studies are needed to confirm these findings and to better determine the underlying molecular mechanisms and clinical significance. TRIAL REGISTRATION: ChicCTR-OCC-14004682 (22-05-2014).

Learning needs of Chinese patients before undergoing elective percutaneous coronary intervention.

Abstract This study aimed to determine the learning needs of Chinese patients going for elective percutaneous coronary intervention (PCI), in order to design nurse-led education programs. A self-administered survey was completed by a total of 395 patients prior to the procedure. Face-to-face communication was chosen by 343 (86.8%) patients as the most preferred way of education. Doctor-in-charge was ranked as the most wanted educator by 372 (94.2%) patients, including 191 (45.4%) patients who chose both doctor-in-charge and nurse-in-charge. Interventional cardiologist was preferred by patients with higher education more than those with lower education (63.6 vs. 48.1%, P < 0.05). Learning items such as self-rescue on heart attack, efficiency of PCI and post-procedural medication were regarded as the most important, which could be affected by age, gender and educational level. These findings would help to develop patient preferred programs that involve brief communications with doctors and more structured education activities led by nurses.

Enantioselective synthesis of a chiral coordination polymer with circularly polarized visible laser.

Circular dichroism is known to be the feature of a chiral agent which has inspired scientist to study the interesting phenomena of circularly polarized light (CPL) modulated molecular chirality. Although several organic molecules or assemblies have been found to be CPL-responsive, the influence of CPL on the assembly of chiral coordination compounds remains unknown. Herein, a chiral coordination polymer, which is constructed from achiral agents, was used to study the CPL-induced enantioselective synthesis. By irradiation with either left-handed or right-handed CPL during the reaction and crystallization, enantiomeric excesses of the crystalline product were obtained. Left-handed CPL resulted in crystals with a left-handed helical structure, and right-handed CPL led to crystals with a right-handed helical structure. It is exciting that the absolute asymmetric synthesis of a chiral coordination polymer could be enantioselective when using CPL, and provides a strategy for the control of the chirality of chiral coordination polymers.

Learning Need of Chinese Patients before Undergoing Elective Percutaneous Coronary Intervention.

Abstract This study aimed to determine the learning needs of Chinese patients going for elective percutaneous coronary intervention (PCI) in order to design nurse led education programs. A self-administered survey was completed by a total of 395 patients prior to the procedure. Face-to-face communication was chosen by 343 (86.8%) patients as the most preferred way of education. Doctor-in-charge was ranked as the most wanted educator by 372 (94.2%) patients, including 191 (45.4%) patients who chose both doctor-in-charge and nurse-in-charge. Interventional cardiologist was preferred by patients with higher education more than those with lower education (63.6% vs. 48.1%, p<0.05). Learning items such as self-rescue on heart attack, efficiency of PCI and post-procedural medication were regarded as the most important, which could be affected by age, gender and educational level. These findings would help to develop patient preferred programs that involve brief communications with doctors and more structured education activities led by nurses.

[Role of macrophage migration inhibitory factor in hepatic stellate cells activation].

OBJECTIVE: To investigate the role of macrophage migration inhibitory factor (MIF) in activation of primary hepatic stellate cells (HSC), and to explore the blocking effect of specific antisense oligonucleotides (ASONs) targeting MIF on the activation of primary HSCs. METHODS: Rat primary HSC were isolated from SD rats by in situ perfusion of collagenase and pronase and single-step Nycodenz density gradient centrifugation, and then cultured and activated. The expression of alpha-smooth muscle actin (alpha-SMA), the marker of HSC activation, was assessed by RT-PCR and immunocytochemistry (ICC). The expression of MIF was detected by RT-PCR, enzyme-linked immuno sorbent assay (ELISA), immunofluorescence (IF) or ICC. Completely activated primary HSC were transfected with MIF-specific antisense oligonucleotide (MIF-ASONs), mis-sense oligonucleotides of MIF, or blank liposome (negative-control). RESULTS: Quiescent HSC expressed very low level of MIF, while MIF gene and protein expression increased significantly during the process of HSC activation. Positive correlation was found between the expression of alpha-SMA and MIF (r = 0.944, P < 0.01). Compared with the control, activated primary Gen HSC transfected with MIF-ASONs showed lower MIF and alpha-SMA expressions at gene and protein profiles (P < 0.05). CONCLUSION: The expression of MIF was up-regulated in the process of HSC activation. Activation in culture of primarily isolated rat HSC could be inhibited by MIF-ASONs, suggesting at least in part that, MIF might be a novel and important factor involved in HSC activation and hepatic fibrosis.

[Family function and depression in relatives of earthquake victims: a survey conducted one year after China's Wenchuan Earthquake].

BACKGROUND: The Wenchuan Earthquake that hit Sichuan, China in 2008 not only caused huge losses in terms of human life and economic damage. It also caused psychological trauma in survivors, especially those who had lost relatives and close friends (bereaved). In the aftermath of earthquakes, bereaved individuals require family and spiritual renewal in addition to material assistance. PURPOSE: This study investigated the status of and relationship between family function and depression in bereaved individuals living in areas devastated by the Wenchuan Earthquake. Results provide baseline information for post-disaster family reconstruction. METHODS: This cross-sectional study surveyed 264 qualified bereaved individuals who lived in an area hard hit by the Wenchuan Earthquake. Face-to-face interviews were administered based on the family APGAR(adaptation, partnership, growth, affection, resolve) index and Hamilton depression (HAMD) scale. RESULTS: The mean family function score for participants was 6.52 ± 2.65. Results for half (50.0%) of participants indicated "good" family function. Results indicated marital status, family structure and status of having another baby as factors that significantly influence family function (p < .05). Participants' mean depression score was 40.41 ± 9.35, with all (100%) of participants demonstrating symptoms of depression. The 5 most prevalent depressive symptoms were: depressed mood, decreased interest in work, mental anxiety, diminished capacity and agitation. Results showed marital status, leisure frequency, economic status, and having another baby as factors that significantly influenced family function (p < .05). A Pearson's correlation analysis indicated no significant relationship between level of depression and family function (p >.05). CONCLUSION: Family functions of the bereaved living in areas hard hit by the Wenchuan Earthquake were all undermined to varying degrees. Although participants all exhibited depressive symptoms, this study found no affect of such symptoms on family functions. Interventions delivered in the months and years after an earthquake should be tailored to address each individual's depression status. Interventions should also help these individuals learn to improve and enhance family functions to effectively reduce negative behaviors and reactions in order to better promote physical and mental health.

[Effect of hypoxia on the expression of macrophage migration inhibitory factor (MIF) in rat vascular smooth muscle cells].

OBJECTIVE: To investigate whether hypoxia could induce the expression of MIF in vascular smooth muscle cells (VSMCs). METHODS: Rat vascular smooth muscle cells (A7r5 from ATCC) were cultured under hypoxia condition (37 degrees C, 5% CO2, 1% O2) and normoxia condition (37 degrees C, 5% CO2, 20% O2) for 2, 4, 12, 24 or 48 hours respectively. MIF mRNA expression was detected by reverse transcriptase and polymerase chain reaction (RT-PCR). MIF protein expression was determined by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Expression of MIF mRNA was up-regulated as early as 2 hours in VSMCs after being exposed to hypoxia condition, which remained the elevated level up to 48 hours. Meanwhile, MIF protein level increased after hypoxia treatment for 2 hours, and maintained elevated status up to 48 hours. CONCLUSION: Hypoxia could significantly induce MIF expression in VSMCs. MIF might be an important factor in the patho-physiological response of VSMCs to hypoxia.

Simultaneous determination of docetaxel and ketoconazole in rat plasma by liquid chromatography/electrospray ionization tandem mass spectrometry.

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed and validated for simultaneous quantification of docetaxel and ketoconazole in rat plasma with paclitaxel as internal standard (IS). The analytes were extracted from rat plasma by using a liquid-liquid extraction technique with ethyl acetate and the LC separation was performed on a Cosmosil-C(18) analytical column (150 mm x 2.0 mm i.d., Nacalai Tesque Inc., Japan). The extracted samples were analyzed with LC/MS/MS, operating in selected reaction monitoring (SRM) mode. The SRM transitions of precursor ions to product ions were 830.3-->549.1 (m/z) for docetaxel, 531.2-->489.3 (m/z) for ketoconazole, and 876.7-->307.9 (m/z) for the IS. The calibration curves were linear over the range of 2-500 ng/mL for docetaxel and 50-20 000 ng/mL for ketoconazole, with coefficients of correlation above 0.999. The limits of quantification for docetaxel and ketoconazole were both 2 ng/mL. The limit of detection for each analyte was 1 ng/mL. The intra- and inter-day precision (CV) of analysis were within 7%, and the accuracy ranged from 95 to 110%. The overall recoveries for docetaxel and ketoconazole were about 89.0% and 91.1%, respectively. The total analysis time was only 9.0 min. This quantitation method was successfully applied to the simultaneous determination of docetaxel and ketoconazole in rat plasma and some potential interaction was found in the current coadministration pharmacokinetic study. This established method was also utilized in the in vitro and in vivo drug-drug interaction study of docetaxel and ketoconazole (to be published).