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Novel two-dimensional melamine lead iodide perovskite (2D-C3H8N6PbI4) is synthesized to investigate its crystallinity, optical band gap and broadband emission properties and to make comparisons with 2D-C3H8N6PbCl4/2D-C3H8N6PbBr4 perovskites. Both experimental and density functional theory (DFT) interrogations on 2D-C3H8N6PbX4 (X = Cl, Br and I) are conducted. The crystal structure, morphology and percentile of Pb and halide elements are confirmed using scanning electron microscope (SEM), and energy dispersive spectrum (EDS), powder/single crystal X-ray diffraction (PXRD/SXRD), DFT and X-ray crystallography simulations. The optical band gaps of 2D-C3H8N6PbX4 perovskites are determined from the Tauc plot fitting of absorbance and DFT studies. Distinct broadband emission of 2D-C3H8N6PbX4 perovskites between 300 and 800 nm is observed, which can be fitted with multiple Gaussian distributions. The fittings of broad PL spectra from 2D-C3H8N6PbCl4/2D-C3H8N6PbBr4 perovskites confirm the involvement of both Dexter energy transfer from melamine cation and self-trapped excitons (STEs). However, the broadband emission of 2D-C3H8N6PbI4 is attributed only to the Dexter energy transfer from melamine cation and the absence of STEs is attributed to the larger lattice deformation of 2D-C3H8N6PbI4. Moreover, the involvement of spin-orbit coupling (SOC) in the energy transfer is clarified to attest that the broadband emission of 2D-C3H8N6PbI4 is distinct among its halide family.
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OBJECTIVE: Laparoscopic box simulation training is widely recognized as an assessment tool to facilitate psychomotor skills especially for novice surgeons. However, current commercialized training modules including pegs, gauze, clips, pins etc. are generally costly and relatively inaccessible. We introduce a simple and pioneer surgical training drill, the Origami Box Folding Exercise (OBFE), based on the validated evaluating system of objective structured assessment of technical skills (OSATS) constructed with the scoring system of procedure-specific checklist (PSC) and global rating scale (GRS). MATERIALS AND METHODS: Face and content validation of the OBFE and OSATS are evaluated by five endoscopic experts from two medical centers in Taiwan. This is a prospective observational study analyzing the pre-test/post-test result of OBFE from 37 participants in two individual workshops as training and evaluating method for laparoscopic psychomotor skills. Both the pre and post tests are video recorded with a time limit of 5 min graded by two independent evaluators based on the OSATS scoring system. RESULTS: The reliability of PSC, GRS, and intergroup value between PSC and GRS were 0.923, 0.926 and 0.933, respectively. Inter-rater reliability of PSC, GRS, and both were 0.985, 0.932 and 0.977, respectively. Construct validity of PSC and GRS were statistically significant, with p-value 0.006 and 0.001, respectively. CONCLUSION: OBFE enhances laparoscopic psychomotor skills with requirement of a single piece of paper. The associated OSATS tool for a 5-min OBFE test was validated. OBFE training is an efficient training and assessment system to promote psychomotor skills in laparoscopic box simulation drill which requires simple and economical preparation.
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Internato e Residência , Laparoscopia , Treinamento por Simulação , Humanos , Reprodutibilidade dos Testes , Laparoscopia/métodos , Treinamento por Simulação/métodos , Estudos ProspectivosRESUMO
STUDY OBJECTIVE: Although a pericervical tourniquet helped reduce blood loss in myomectomy [1], a technique of triple tourniquets was more influential in occluding the uterine vessel networks [2,3]. This video demonstrates the procedures of laparoscopic triple-tourniquet constriction with the number 1 suture around the uterine isthmic portion and bilateral infundibulopelvic ligaments [4] in a case of robotic myomectomy. DESIGN: A step-by-step, narrated video demonstration. SETTING: A university hospital. INTERVENTIONS: Robotic myomectomy was scheduled for a patient with menorrhagia. Magnetic resonance imaging revealed 8 uterine myomas; the maximal one was 9.1 × 8.4 × 8.6 cm in dimension. Our robotic settings included 3 ports: fenestrated bipolar in the left lower quadrant, spatula or mega needle holder in the right lower quadrant, and an umbilical glove port accessible for lens and assisted instruments. A number 1 Monocryl (Ethicon, Bridgewater, NJ) was introduced from the suprapubic area extracorporeally; then, the needle penetrated through bilateral avascular zones of broad ligaments at the isthmic level and with a sliding tie made anteriorly to the uterus. The isthmic tourniquet-we also named it as the hangman's tourniquet-was tightened by manually tensioning the suture extracorporeally and pushing down the knot intracorporeally. Bilateral infundibulopelvic tourniquets were placed by using sliding ties of 1-0 Monocryl as well. With the total occlusion of uterine vessel networks, the uterus should retain only minimal blood flow. During the enucleation of uterine myomas, the tourniquet may loosen because of newly developed, unoccupied space with increasing bleeding; therefore, the tourniquet should be tightened up regularly throughout the surgery. After the repair of all the uterine wounds, we removed the 3 tourniquets. CONCLUSION: The convenient and adjustable triple-tourniquet constriction is a safe and feasible laparoscopic technique to block the vessel networks temporally in uterine-preserving surgery.
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Laparoscopia , Leiomioma , Mioma , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Humanos , Miomectomia Uterina/métodos , Torniquetes , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/patologia , Constrição , Leiomioma/cirurgia , Leiomioma/patologia , Laparoscopia/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Constrição Patológica/cirurgia , Mioma/cirurgiaRESUMO
Liver disorders are a major health concern. Saikosaponin-d (SSd) is an effective active ingredient extracted from Bupleurum falcatum, a traditional Chinese medicinal plant, with anti-inflammatory and antioxidant properties. However, its hepatoprotective properties and underlying mechanisms are unknown. We investigated the effects and underlying mechanisms of SSd treatment for thioacetamide (TAA)-induced liver injury and high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in male C57BL/6 mice. The SSd group showed significantly higher food intake, body weight, and hepatic antioxidative enzymes (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) and lower hepatic cyclooxygenase-2 (COX-2), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and fibroblast growth factor-21 (FGF21) compared with controls, as well as reduced expression of inflammation-related genes (nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS)) messenger RNA (mRNA). In NAFLD mice, SSd reduced serum ALT, AST, triglycerides, fatty acid-binding protein 4 (FABP4) and sterol regulatory element-binding protein 1 (SREBP1) mRNA, and endoplasmic reticulum (ER)-stress-related proteins (phosphorylated eukaryotic initiation factor 2α subunit (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). SSd has a hepatoprotective effect in liver injury by suppressing inflammatory responses and acting as an antioxidant.
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Anti-Inflamatórios não Esteroides/farmacologia , Doença Hepática Induzida por Substâncias e Drogas , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Alanina Transaminase/análise , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspartato Aminotransferases/análise , Catalase/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Saponinas/uso terapêutico , Superóxido Dismutase/análise , Tioacetamida/toxicidadeRESUMO
Imipramine is a tricyclic antidepressant that has been approved for treating depression and anxiety in patients and animals and that has relatively mild side effects. However, the mechanisms of imipramine-associated disruption to metabolism and negative hepatic, renal, and retinal effects are not well defined. In this study, we evaluated C57BL6/J mice subjected to a high-fat diet (HFD) to study imipramine's influences on obesity, fatty liver scores, glucose homeostasis, hepatic damage, distribution of chromium, and retinal/renal impairments. Obese mice receiving imipramine treatment had higher body, epididymal fat pad, and liver weights; higher serum triglyceride, aspartate and alanine aminotransferase, creatinine, blood urea nitrogen, renal antioxidant enzyme, and hepatic triglyceride levels; higher daily food efficiency; and higher expression levels of a marker of fatty acid regulation in the liver compared with the controls also fed an HFD. Furthermore, the obese mice that received imipramine treatment exhibited insulin resistance, worse glucose intolerance, decreased glucose transporter 4 expression and Akt phosphorylation levels, and increased chromium loss through urine. In addition, the treatment group exhibited considerably greater liver damage and higher fatty liver scores, paralleling the increases in patatin-like phospholipid domain containing protein 3 and the mRNA levels of sterol regulatory element-binding protein 1 and fatty acid-binding protein 4. Retinal injury worsened in imipramine-treated mice; decreases in retinal cell layer organization and retinal thickness and increases in nuclear factor κB and inducible nitric oxide synthase levels were observed. We conclude that administration of imipramine may result in the exacerbation of nonalcoholic fatty liver disease, diabetes, diabetic retinopathy, and kidney injury.
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Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1ß, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor ß (TGF-ß), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Animais , Apoptose , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fluoruracila/administração & dosagem , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In Taiwan, freshwater clams (Corbicula fluminea) and hard clams (Meretrix lusoria) are the most frequently raised shellfish in land-based pond aquaculture, but research on the accumulation of organochlorine pesticides (OCPs) in these shellfish is limited. We detected the levels of 14 OCPs in 62 shellfish from Taiwanese aquafarms by performing gas chromatography-tandem mass spectrometry. OCP residues were detected in 4.84% of the samples including readings of 0.04 mg/kg chlordane (in a freshwater clam), 0.03 mg/g p,p'-DDE (in a freshwater clam), and 0.02 mg/g p,p'-DDE (in a hard clam). However, the associated estimated daily intake values were less than the acceptable daily intake levels of chlordane and p,p'-DDE Therefore, the consumption of these shellfish presents no immediate health risks. Our findings contribute to food safety and serve as a reference for OCP screenings for aquatic shellfish.
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Hidrocarbonetos Clorados , Praguicidas , Poluentes Químicos da Água , Cromatografia Gasosa-Espectrometria de Massas , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Medição de Risco , Frutos do Mar , Taiwan , Poluentes Químicos da Água/análiseRESUMO
Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozapine have less severe side effects and may positively affect obesity and blood glucose level. However, no systematic study of clozapine's adverse metabolic effects-such as changes in kidney and liver function, body weight, glucose and triglyceride levels, and retinopathy-was conducted. This research investigated how clozapine affects weight, the bodily distribution of chromium, liver damage, fatty liver scores, glucose homeostasis, renal impairment, and retinopathy in mice fed a high fat diet (HFD). We discovered that obese mice treated with clozapine gained more weight and had greater kidney, liver, and retroperitoneal and epididymal fat pad masses; higher daily food efficiency; higher serum or hepatic triglyceride, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels; and higher hepatic lipid regulation marker expression than did the HFD-fed control mice. Furthermore, the clozapine group mice exhibited insulin resistance, poorer insulin sensitivity, greater glucose intolerance, and less Akt phosphorylation; their GLUT4 expression was lower, they had renal damage, more reactive oxygen species, and IL-1 expression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were lower. Moreover, clozapine reduced the thickness of retinal cell layers and increased iNOS and NF-κB expression; a net negative chromium balance occurred because more chromium was excreted through urine, and this influenced chromium mobilization, which did not help overcome the hyperglycemia. Our clozapine group had considerably higher fatty liver scores, which was supported by the findings of lowered adiponectin protein levels and increased FASN protein, PNPLA3 protein, FABP4 mRNA, and SREBP1 mRNA levels. We conclude that clozapine can worsen nonalcoholic fatty liver disease, diabetes, and kidney and retinal injury. Therefore, long-term administration of clozapine warrants higher attention.
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Cromo/deficiência , Clozapina/farmacologia , Intolerância à Glucose/metabolismo , Nefropatias/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Doenças Retinianas/metabolismo , Adipócitos/metabolismo , Animais , Biomarcadores , Pesos e Medidas Corporais , Modelos Animais de Doenças , Proteínas de Ligação a Ácido Graxo/genética , Imunofluorescência , Expressão Gênica , Regulação da Expressão Gênica , Imuno-Histoquímica , Insulina/metabolismo , Nefropatias/etiologia , Fígado/metabolismo , Camundongos , Camundongos Obesos , Óxido Nítrico Sintase Tipo II , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doenças Retinianas/etiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
Liver disorders have been recognized as one major health concern. Fucoidan, a sulfated polysaccharide extracted from the brown seaweed Fucus serratus, has previously been reported as an anti-inflammatory and antioxidant. However, the discovery and validation of its hepatoprotective properties and elucidation of its mechanisms of action are still unknown. The objective of the current study was to investigate the effect and possible modes of action of a treatment of fucoidan against thioacetamide (TAA)-induced liver injury in male C57BL/6 mice by serum biochemical and histological analyses. The mouse model for liver damage was developed by the administration of TAA thrice a week for six weeks. The mice with TAA-induced liver injury were orally administered fucoidan once a day for 42 days. The treated mice showed significantly higher body weights; food intakes; hepatic antioxidative enzymes (catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD)); and a lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and C-reactive protein (CRP) levels. Additionally, a reduced hepatic IL-6 level and a decreased expression of inflammatory-related genes, such as cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA was observed. These results demonstrated that fucoidan had a hepatoprotective effect on liver injury through the suppression of the inflammatory responses and acting as an antioxidant. In addition, here, we validated the use of fucoidan against liver disorders with supporting molecular data.
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Anti-Inflamatórios , Antioxidantes , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Polissacarídeos , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Citocinas/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Tioacetamida/toxicidadeRESUMO
In this letter, we successfully explored a cascade Pd/Cu-catalyzed intermolecular C(sp3)-H arylation of amides and intramolecular C-N coupling reaction. This method provides a one-pot strategy to synthesize 3,4-2 H-quinolinone with good regioselectivity of C-H arylation and C-N coupling from C-I and C-X bonds from readily available starting materials.
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The volume concentration of peroxyacetyl nitrate (PAN) and O3 in the atmosphere were measured at the Tianjin Meteorological Tower in summer 2017 by using the online instrument with meteorological parameters and back trajectory analysis to analyze the delivery characteristics of PAN and O3. The average volume concentrations of PAN and O3 during the observational period are (0.73±0.56)×10-9 and (53±25)×10-9, respectively. The hourly maximum concentrations of PAN and O3 are 3.49×10-9 and 137×10-9. The volume concentrations of PAN and O3 show pronounced diurnal profiles, which are both characterized by much higher values at daytime than at nighttime. In addition, the correlation coefficient between PAN and O3 at daytime (R2=0.52) is notably higher than that at nighttime (R2=0.21). The air masses originating from the south show the highest volume concentration of PAN and O3, with the lowest volume concentration originating from the east. The wind rose plot and cluster analysis of the back trajectories show that the highest concentration of pollutants mainly originates in the southwest. The air massess originating from the east and circulating through the Bohai Sea and coastal areas of the Hebei and Liaoning provinces show the lowest volume concentrations of PAN and O3. The transportation within the boundary layer plays an important role in the concentration distribution of PAN and O3.
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Objective To summarize regularities in acupoint prescriptions for acupuncture treatment of stroke disorders by using data mining techniques to analyze 150 ancient acupuncture books from the Han dynasty to the end of Qing dynasty. Method A standard database and a ancient book database were established by a manual entry and proofreading method. The sentences containing stroke disorders, acupoints, meridians and needling moxibustion method in the ancient books were selected according to the key words in the standard database using a variety of data mining techniques and a regular relation to establish corresponding disease, acupoint, needling moxibustion method and meridian databases. They were classified into two types: prescriptions for stroke disorders and acupoint indications containing stroke disorders. The results from selection were reviewed manually and standardized. A multilevel analysis of regularities in acupuncture prescriptions for stroke disorders in the ancient books was performed by statistical analysis and apriori algorithm on association rules with support degree and confidence level. Result There were a total of 536 records on acupuncture point prescription for stroke disorders. Single acupoint prescriptions accounted for 34.89% of the total number of prescriptions. The single acupoint that was used most frequently was Baihui(GV20). Thedouble acupoints that were combined most frequently were Quchi(LI11) and Baihui. In three acupoint combination, Quchi and Fengshi(GB31) were separately combined most frequently with Baihui, Jianyu(LI15) and Xuanzhong(GB39). The three meridians that were used most frequently were the Du Meridian, the Large Intestine Meridian of Hand-Yangming and the Gallbladder Meridian of Foot-Shaoyang. The two meridians that were combined most frequently were the Gallbladder Meridian of Foot-Shaoyang and the Stomach Meridian of Foot-Yangming. Crossing points and Five-Shu points were selected most frequently in specific points. He-Sea points were used most frequently in Five-Shu points. Conclusion The prescriptions for stroke disorders in ancient acupuncture books focus on selecting the confluence of all yang meridians and yang meridian points. Specific points are the important composition of the prescriptions. Crossing points and He-Sea points are mainly used in specific points.
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BACKGROUND: High prevalence rates of delirium have been found in intensive care units (ICUs), ranging from 20% to 80%. The development of delirium may prolong length of stay, impair cognition, and result in placement in a nursing home for the patient. PURPOSE: There is a lack of research focused on the aging population, so the purpose of this study was to establish the incidence rate of delirium among ICU elderly patients and to identify its risk factors. METHODS: An observational design with repeated measures was used. Subjects older than 65 years who had been admitted to the ICU within 24 hours were recruited. The Confusion Assessment Method for the Intensive Care Unit and Richmond Agitation-Sedation Scale were used twice a day to identify subjects experiencing delirium by RA. The demographic data, history of illness, Acute Physiology and Chronic Health Evaluation II scores, and laboratory data of the participants were recorded. RESULTS: Ninety participants were included from a medical ICU. The incidence rate of delirium was 75.6% (n = 68). Average age was 78.28 ± 7.6 years; Acute Physiology and Chronic Health Evaluation II scores ranged from 7 to 35. Most participants were diagnosed with respiratory failure (73.3%), and 86.76% of participants developed delirium within 24 hours. The most frequently experienced type of delirium was the mixed subtype (47.05%); the second most frequently experienced was hypoactive next. The risk factors were analyzed using logistic regression. The number of anesthetic analgesics used, total number of medications prescribed, duration of dehydration, use of corticosteroids before admissions, and shock were identified and explained 31.3% of variance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Delirium is a severe problem among elderly patients in the ICU. Healthcare professionals should pay more attention to elderly patients at greater risk for experiencing delirium.
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Envelhecimento/psicologia , Delírio/diagnóstico , Delírio/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
<p><b>OBJECTIVE</b>To observe the efficacy of regular or intermittent inhalation of salmeterol/fluticasone propionate (SM/FP) in the treatment of bronchial asthma and its effects on growth and development in children.</p><p><b>METHODS</b>A total of 112 children diagnosed with bronchial asthma between September 2012 and October 2013 were assigned to standardized treatment (standard group, n=56) and non-standardized treatment (intermittent group, n=56). Comparisons of clinical symptom scores and main pulmonary function indicators between the two groups were carried out before treatment and at 6 and 12 months after treatment. The growth velocity and changes in body mass index (BMI) were observed in the two groups.</p><p><b>RESULTS</b>At 6 and 12 months after the treatment, the standard group had significantly reduced clinical symptom scores and significantly increased pulmonary function indicators (percentage of predicted peak expiratory flow, PEF%; percentage of forced expiratory volume in 1 second, FEV1%) (P<0.05); the intermittent group had significantly reduced clinical symptom scores and significantly increased FEV1% (P<0.05), but PEF% was significantly increased only at 6 months after treatment (P<0.05). At 12 months after treatment, the standard group had significantly lower clinical symptom scores and significantly higher PEF% and FEV1% when compared with the intermittent group (P<0.05). The growth velocity and BMI showed no significant differences between the two groups at 6 and 12 months after treatment (P>0.05).</p><p><b>CONCLUSIONS</b>Compared with intermittent inhalation, long-term regular inhalation of SM/FP performs better in controlling clinical symptoms and enhancing pulmonary function in children with asthma. Inhalation of SM/FP for one year reveals no apparent effect on the growth and development of these children.</p>
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Criança , Pré-Escolar , Feminino , Humanos , Masculino , Administração por Inalação , Corticosteroides , Asma , Tratamento Farmacológico , Índice de Massa Corporal , Desenvolvimento InfantilRESUMO
Glycine N-methyltransferase (GNMT) is a folate binding protein commonly diminished in human hepatoma yet its role in tumor development remains to be established. GNMT binds to methylfolate but is also inhibited by it; how such interactions affect human carcinogenesis is unclear. We postulated that GNMT plays a role in folate-dependent methyl group homeostasis and helps maintain genome integrity by promoting nucleotide biosynthesis and DNA repair. To test the hypothesis, GNMT was over-expressed in GNMT-null cell lines cultured in conditions of folate abundance or restriction. The partitioning of folate dependent 1-carbon groups was investigated using stable isotopic tracers and GC/MS. DNA damage was assessed as uracil content in cell models, as well as in Gnmt wildtype (Gnmt(+/+)), heterozygote (Gnmt(+/-)) and knockout (Gnmt(-/-)) mice under folate deplete, replete, or supplementation conditions. Our study demonstrated that GMMT 1) supports methylene-folate dependent pyrimidine synthesis; 2) supports formylfolate dependent purine syntheses; 3) minimizes uracil incorporation into DNA when cells and animals were exposed to folate depletion; 4) translocates into nuclei during prolonged folate depletion. In conclusion, loss of GNMT impairs nucleotide biosynthesis. Over-expression of GNMT enhances nucleotide biosynthesis and improves DNA integrity by reducing uracil misincorporation in DNA both in vitro and in vivo. To our best knowledge, the role of GNMT in folate dependent 1-carbon transfer in nucleotide biosynthesis has never been investigated. The present study gives new insights into the underlying mechanism by which GNMT can participate in tumor prevention/suppression in humans.
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Carcinoma Hepatocelular/patologia , Dano ao DNA , Ácido Fólico/farmacologia , Glicina N-Metiltransferase/fisiologia , Hepatócitos/patologia , Neoplasias Hepáticas/patologia , Fígado/patologia , Adenosina/metabolismo , Animais , Radioisótopos de Carbono , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Metilação de DNA , Suplementos Nutricionais , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Hepatócitos/metabolismo , Homocisteína/metabolismo , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Camundongos , Camundongos Knockout , Antígenos de Histocompatibilidade Menor , Transporte Proteico , Purinas/metabolismo , Pirimidinas/metabolismo , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Tetra-Hidrofolatos , Uracila/metabolismoRESUMO
Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated diseases in pigs. The sole structural capsid protein of PCV2, Cap, consists of major antigenic domains, but little is known about the assembly of capsid particles. The purpose of this study is to produce a large amount of Cap protein using Escherichia coli expression system for further studying the essential sequences contributing to formation of particles. By using codon optimization of rare arginine codons near the 5'-end of the cap gene for E. coli, a full-length Cap without any fusion tag recombinant protein (Cap1-233) was expressed and proceeded to form virus-like particles (VLPs) in normal Cap appearance that resembled the authentic PCV2 capsid. The N-terminal deletion mutant (Cap51-233) deleted the nuclear localization signal (NLS) domain, while the internal deletion mutant (CapΔ51-103) deleted a likely dimerization domain that failed to form VLPs. The unique Cys108 substitution mutant (CapC/S) exhibited most irregular aggregates, and only few VLPs were formed. These results suggest that the N-terminal region within the residues 1 to 103 possessing the NLS and dimerization domains are essential for self-assembly of stable Cap VLPs, and the unique Cys108 plays an important role in the integrity of VLPs. The immunogenicity of PCV2 VLPs was further evaluated by immunization of pigs followed by challenge infection. The Cap1-233-immunized pigs demonstrated specific antibody immune responses and are prevented from PCV2 challenge, thus implying its potential use for a VLP-based PCV2 vaccine.
Assuntos
Proteínas do Capsídeo/imunologia , Infecções por Circoviridae/veterinária , Circovirus/imunologia , Doenças dos Suínos/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Montagem de Vírus , Motivos de Aminoácidos , Animais , Anticorpos Antivirais/imunologia , Proteínas do Capsídeo/administração & dosagem , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Infecções por Circoviridae/imunologia , Infecções por Circoviridae/prevenção & controle , Infecções por Circoviridae/virologia , Circovirus/genética , Circovirus/fisiologia , Suínos , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/química , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas Virais/administração & dosagem , Vacinas Virais/química , Vacinas Virais/genética , Vacinas Virais/imunologiaRESUMO
BACKGROUND: Ovarian cancer is commonly fatal and incidence has persistently risen in Taiwan over the past 20 years. Prevention strategies, however, are limited. Pelvic inflammatory disease (PID) has been suggested to increase the risk of developing ovarian cancer, but the results of studies have been inconsistent. Therefore, we investigated whether PID increases the risk of developing ovarian cancer in a large, nationwide cohort. METHODS: From the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan, we obtained data for women aged 13-65 years for whom a diagnosis of PID, confirmed by multiple episodes, had been recorded between Jan 1, 2004, and Dec 31, 2005. We also obtained data for two controls per patient, matched for age and the year of first entry into the LHID2005. All patients were followed up from the date of entry in the LHID2005 until they developed ovarian cancer or to the end of 2006, whichever was earlier. We used Cox's regression models to assess the risk of developing ovarian cancer, with adjustment for age, comorbid disorders, and socioeconomic characteristics. FINDINGS: We identified 67,936 women with PID and 135,872 controls. Among these 90 had developed ovarian cancer during the 3-year follow-up period (42 patients with PID and 48 controls, incidence 2·78 and 1·44 per 10,000 person-years, respectively). The adjusted hazard ratio for ovarian cancer in patients with PID was 1·92 (95% CI 1·27-2·92) compared with controls, which rose to 2·46 (1·48-4·09) in women who had had at least five episodes of PID. The adjusted hazard ratio was slightly higher for women aged 35 years or younger with PID than in older women with PID (2·23, 1·02-4·79 vs 1·82, 1·10-3·04). INTERPRETATION: We found an association between PID and ovarian cancer. PID might, therefore, be a useful marker for ovarian cancer, and early treatment could help to improve prognosis. Whether pelvic inflammation itself accelerates the growth of ovarian cancers or affects cancer-cell differentiation in ways that adversely alter prognosis needs to be investigated. FUNDING: None.
Assuntos
Neoplasias Ovarianas/epidemiologia , Doença Inflamatória Pélvica/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Comorbidade , Bases de Dados como Assunto , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores Socioeconômicos , Taiwan/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated diseases in pigs. To analyze whether the PCV2 nonstructural protein ORF3 is able to induce apoptosis in nature target cells, transient expression of ORF3 in porcine peripheral blood mononuclear cells (PBMC) was performed, and apoptosis was confirmed by terminal dexoynucleotidyl transferase (TdT)-mediated BrdUTP-nick end labeling (TUNEL) assay. The apoptotic responses induced by the full length or the C-terminal half of ORF3 were significantly higher (p < 0.001) than that of cells transfected with the control plasmid. In contrast, the N-terminal half of ORF3 restrictively localized in the cytoplasm and remarkably reduced its ability to induce apoptosis, the apoptotic activity might be correlated with the nuclear localization of ORF3. Furthermore, two clusters of basic residues on the C-terminal half region at the amino acid residues 53-68 and 85-104 could mediate the nuclear localization of fusion protein, confirming their potential role as a nuclear localization signal.
RESUMO
<p><b>OBJECTIVE</b>To investigate the mechanism of loss of human esophageal cancer-related gene 4 (ECRG4) expression in esophageal squamous cell carcinoma (ESCC.)</p><p><b>METHODS</b>PCR-SSCP and DNA sequencing analysis were used to detect the mutation of ECRG4 exons in esophageal cancer and matched adjacent normal tissues of 80 patients. DNA bisulfite-modifying ssPCR sequencing assay was used to examine the methylation status of ECRG4 promoter in human esophageal squamous cell carcinoma EC9706 cells. The re-expression of ECRG4 mRNA was examined by RT-PCR in EC9706 cells, after treatment with either demethylation drug 5-aza-2'-deoxycytidine or arsenic trioxide.</p><p><b>RESULTS</b>No mutation in the four ECRG4 exons was found in all the ESCC and matched normal adjacent tissues. RT-PCR showed that 11 of 16 CpG islands of ECRG4 promoter were hypermethylated, while ECRG4 mRNA expression level was undetectable in the EC9706 cells. The ECRG4 mRNA was re-expressed after treatment with either demethylation drug 5-aza-2'-deoxycytidine or arsenic trioxide.</p><p><b>CONCLUSION</b>The epigenetic mechanism of methylation is a reason of loss of ECRG4 gene expression in the ESCC cell line EC9706.</p>
Assuntos
Humanos , Antimetabólitos Antineoplásicos , Farmacologia , Antineoplásicos , Farmacologia , Arsenicais , Farmacologia , Azacitidina , Farmacologia , Carcinoma de Células Escamosas , Genética , Metabolismo , Patologia , Linhagem Celular Tumoral , Ilhas de CpG , Genética , Metilação de DNA , Epigênese Genética , Neoplasias Esofágicas , Genética , Metabolismo , Patologia , Éxons , Regulação Neoplásica da Expressão Gênica , Mutação , Proteínas de Neoplasias , Genética , Metabolismo , Óxidos , Farmacologia , Regiões Promotoras Genéticas , RNA Mensageiro , MetabolismoRESUMO
Ambient O3, NOx, NOy, and CO were measured at the Shangdianzi regional background station from 26 March to 9 October 2008, and VOCs samples were taken and analyzed. This paper uses the data to obtain the ozone production efficiency (OPE) at Shangdianzi and studies the relationship of OPE with NO, and VOCs. In addition, the potential impact from the dry deposition of NOx oxidation products on the calculated OPE was estimated and tentatively corrected. Based on this study, the daily OPE varied in the range of 0.2-21.1, with an average of 4.9 +/- 3.6. An overall OPE average of 4.3 +/- 1.5 can be obtained. The dependence of OPE on the NO, concentration can be described using an empirical parabolic function. If the concentration of NOx is lower than 14 x 10(-9), OPE increases with NO,; while if the concentration of NOx is higher than 14 x 10(-9), OPE decreases with NOx. The correlation analysis indicates that the concentrations of aromatics and OVOCs are positively correlated to OPE. Dry deposition of HNO3 and other NO, oxidation products may significantly impact the calculated OPE values, leading to overestimate. It is possible to correct such overestimate using the NOy/CO ratios obtained at an urban site and at Shangdianzi. However, this correction is less rigorous and the corrected OPE data remain to be validated. The uncorrected data can be viewed as the upper limit of the real OPE.