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OBJECTIVES@#To study the distribution characteristics of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in children with primary hypertension, and to explore the association between MTHFR C677T gene polymorphism and H-type hypertension in children.@*METHODS@#A total of 121 children with primary hypertension who were hospitalized in the department of cardiovascular medicine from January to July 2021, newly diagnosed, and untreated were retrospectively selected as the subjects. The children were divided into three groups: CC genotype (19 children), CT genotype (51 children), and TT genotype (51 children). According to the serum homocysteine (Hcy) level, they were divided two groups: H-type hypertension (47 children) and simple hypertension (74 children). The medical data were compared between the groups. The association between MTHFR C677T gene polymorphism and H-type hypertension was evaluated.@*RESULTS@#The mutation frequency of T allele in children with primary hypertension was significantly higher than that in healthy adults in Beijing and Chinese Han adults (P<0.001). The serum Hcy level in the TT genotype group was significantly higher than that in the CC and CT genotype groups (P<0.001). The serum Hcy level in the H-type hypertension group was significantly higher than that in the simple hypertension group (P<0.001), and MTHFR C677T was mostly TT genotype, which was associated with the risk of H-type hypertension (OR=12.71, P<0.001). There was no significant difference in the incidence rate of target organ damage between the H-type hypertension and simple hypertension groups (P>0.05). However, multiple organ involvement was observed in the H-type hypertension group at diagnosis, accounting for 11% (5/47).@*CONCLUSIONS@#The mutation rate of MTHFR C677T T allele in children with primary hypertension is high and associated with the serum Hcy level. TT genotype is an independent risk factor for H-type hypertension in children, and it may be related to the severity of early target organ damage.
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Niño , Humanos , Alelos , Genotipo , Hipertensión/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Estudios RetrospectivosRESUMEN
@#BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the used devices, pain score, and complications between intraosseous (IO) access and central venous catheterization (CVC) in critically ill Chinese patients. METHODS: In this prospective clustered randomized controlled trial, eight hospitals were randomly divided into either the IO group or the CVC group. Patients who needed emergency vascular access were included. From April 1, 2017 to December 31, 2018, each center included 12 patients. We recorded the data mentioned above. RESULTS: A total of 96 patients were enrolled in the study. There were no statistically significant differences between the two groups regarding sex, age, body mass index, or operator satisfaction with the used devices. The success rates of the first attempt and the procedure time were statistically significant between the IO group and the CVC group (91.7% vs. 50.0%, P<0.001; 52.0 seconds vs. 900.0 seconds, P<0.001). During the study, 32 patients were conscious. There was no statistically significant difference between the two groups regarding the pain score associated with insertion. There were statistically significant differences between the two groups regarding the pain score associated with IO or CVC infusion (1.5 vs. 0.0, P=0.044). Complications were not observed in the two groups. CONCLUSIONS: IO access is a safe, rapid, and effective technique for gaining vascular access in critically ill adults with inaccessible peripheral veins in the emergency departments.
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Typical symptoms of peripartum cardiomyopathy(PPCM)are heart failure and dyspnea.Echocardiography is the first choice.Bromocriptine and oral drugs for heart failure are the main treatments.For pregnant women with heart failure with hemodynamic instability,pregnancy should be terminated regardless of the size of the gestational age.The predictors of maternal mortality are NYHA class Ⅲ/Ⅳ and left ventricular ejection fraction(LVEF)<40%.
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Positive cardiopulmonary resuscitation is a guarantee for successful rescue.To remove pulmonary hypertension as soon as possible is the key to successful treatment.Dobutamine and milrinone have the effect of strengthening the heart and expanding the pulmonary artery,which is the drug of first choice for treatment.
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Objective To investigate the feasibility of multiple real-time PCR for the detection of Fritillariae Cirrhosae Bulbus and adulterants. Methods Based on the analysis of interspecies variation, genetic distance and phylogenetic relationship of ITS, psbA-trnH, rbcL and matK gene sequences, the genes with fast evolution rate, big interspecies variation and small intraspecies variation were selected as target genes. Fritillariae Cirrhosae Bulbus and adulterants specific primers and Taqman probes were designed to establish a multiplex real-time PCR assay. Methods were evaluated by comparison of specificity, sensitivity and mixed sample detection and sequencing. Results The ITS and psbA-trnH mutations were higher than rbcL and matK, and rbcL and matK were significantly lower than ITS and psbA-trnH genes by genetic distance analysis. And the sensitivity of the establish multiple real-time PCR using ITS as the target gene was 0.01 ng. Four samples of adulterants were detected in 18 samples, and the results were consistent with the results of NJ tree clustering analysis. Conclusion Based on the IIS region sequence as the target gene to establish multiple real-time fluorescence PCR detection method can successfully identify Fritillariae Cirrhosae Bulbus and its counterfeit goods, which provides a new basis for the authenticity of identification.
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The specific PCR primer was designed base on ITS2 sequence in GenBank, and we developed a SYBRGreen real-time fluorescence quantitative PCR system for identification of Crocus sativus and Carthamus tinctorius source. Compared with Chinese herbal medicine DNA barcode technique, this method showed characteristics of shorter time, higher specificity and sensitivity. Using this method to detect 15 samples, 4 were C. sativus, 8 were C. tinctorius, and the other 3 samples were none of them. The result was in accordance with Chinese herbal medicine DNA barcode. This study lays the foundation for identification of related Chinese medical materials.
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Carthamus tinctorius , Crocus , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
The paper analyzes the building demands of outpatient clinical path information system.By introducing system design from aspects like idea,architecture and key technology,it elaborates on concrete functional realization,including subsystems like clinical path management,outpatient doctor station,nursing path,patient path,quality control management and system management,pointing out that application of the system is able to make patients accessible to better outpatient diagnosis and treatment service.
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Objective To elucidate the characteristics of vascular remodeling in pregnant hypertensive rats. Methods Pregnant rats were induced by L-nitro-arginine methylester (L-NAME) to build hypertension models and normal pregnant rats were used as control. Using a programmable sphygmomanometer, the blood pressure was recorded with the tail-cuff method to ensure the hypertension model was successfully replicated. The changes of mean shear stress in left common carotid artery were determined after the blood viscosity, the average blood flow and the inner diameter were measured. To analyze the degree of arterial remodeling, the protein expression levels of Collagen I (Col I) and III (Col III) were detected by Western blotting and the media thickness, the inner diameter, the opening angel were determined in both thoracic aorta and carotid artery. Results The mean shear stress of common carotid artery in pregnant hypertensive rats was reduced by (28.52 ± 3.08)% with the blood viscosity increasing and the average blood flow decreasing in pregnant hypertensive rats. Compared with control groups, the ratio of media thickness and inner diameter was significantly increased in thoracic aorta and carotid artery, while the opening angel decreased in carotid artery while increased in thoracic aorta. With the expression of COL I decreasing and COL III increasing, the ratio of Col I and Col III went an apparent decline. Conclusions The mean shear stress is descending, and the remodeling of thoracic aorta and carotid artery are found in pregnant hypertensive rats. These results may provide new experimental references for further illustrating the pathogenesis of pregnant hypertension.
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Objective To elucidate the characteristics of vascular remodeling in pregnant hypertensive rats.Methods Pregnant rats were induced by L-nitro-arginine methylester (L-NAME) to build hypertension models and normal pregnant rats were used as control.Using a programmable sphygmomanometer,the blood pressure was recorded with the tail-cuff method to ensure the hypertension model was successfully replicated.The changes of mean shear stress were determined after the blood viscosity,the average blood flow and the inner diameter in left common carotid artery were measured.To analyze the degree of arterial remodeling,the protein expression levels of collagen Ⅰ (Col Ⅰ) and Ⅲ (Col Ⅲ) were detected by Western blotting,and the media thickness,the inner diameter,the opening angel both in thoracic aorta and carotid artery were determined.Results The mean shear stress of common carotid artery was reduced by (28.52 ± 3.08) ％ with the blood viscosity increasing and the average blood flow decreasing in pregnant hypertensive rats.Compared with control groups,the ratio of media thickness and inner diameter significantly increased in thoracic aorta and carotid artery,while the opening angel decreased in carotid artery and increased in thoracic aorta.With the expression of Col Ⅰ decreasing and Col Ⅲ increasing,the ratio of Col Ⅰ and Col Ⅲ went an apparent decline.Conclusions The mean shear stress is descending in pregnant hypertensive rat,with the remodeling of thoracic aorta and carotid artery.These results may provide new experimental references for further illustrating pathogenesis of pregnant hypertension.
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Objective To elucidate the characteristics of vascular remodeling in pregnant hypertensive rats.Methods Pregnant rats were induced by L-nitro-arginine methylester (L-NAME) to build hypertension models and normal pregnant rats were used as control.Using a programmable sphygmomanometer,the blood pressure was recorded with the tail-cuff method to ensure the hypertension model was successfully replicated.The changes of mean shear stress were determined after the blood viscosity,the average blood flow and the inner diameter in left common carotid artery were measured.To analyze the degree of arterial remodeling,the protein expression levels of collagen Ⅰ (Col Ⅰ) and Ⅲ (Col Ⅲ) were detected by Western blotting,and the media thickness,the inner diameter,the opening angel both in thoracic aorta and carotid artery were determined.Results The mean shear stress of common carotid artery was reduced by (28.52 ± 3.08) ％ with the blood viscosity increasing and the average blood flow decreasing in pregnant hypertensive rats.Compared with control groups,the ratio of media thickness and inner diameter significantly increased in thoracic aorta and carotid artery,while the opening angel decreased in carotid artery and increased in thoracic aorta.With the expression of Col Ⅰ decreasing and Col Ⅲ increasing,the ratio of Col Ⅰ and Col Ⅲ went an apparent decline.Conclusions The mean shear stress is descending in pregnant hypertensive rat,with the remodeling of thoracic aorta and carotid artery.These results may provide new experimental references for further illustrating pathogenesis of pregnant hypertension.
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Renal tubulointerstitial fibrosis is the common ending of progressive renal disease. It is worth developing new ways to stop the progress of renal fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been studied to treat diabetic nephropathy, cisplatin-induced acute renal injury, ischemia reperfusion injury and adriamycin nephropathy. In this study, unilateral ureteral obstruction (UUO) was used to establish a different renal fibrosis model. PPAR? agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14th day after the operation, mice were sacrificed for fibrosis test and T lymphocytes subsets test. Unexpectedly, through MASSON staining, immunohistochemistry for α-SMA, and Western blotting for a-SMA and PDGFR-β, we found that pioglitazone failed to attenuate renal fibrosis in UUO mice. However, flow cytometry showed that pioglitazone down-regulated Th1 cells, and up-regulated Th2 cells, Th17 cells and Treg cells. But the Th17/Treg ratio had no significant change by pioglitazone. Real-time PCR results showed that TGF-β and MCP-1 had no significant changes, at the same time, CD4(+) T cells associated cytokines were partially regulated by pioglitazone pretreatment. Taken together, pioglitazone failed to suppress renal fibrosis progression caused by UUO.
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Animales , Masculino , Ratones , Quimiocina CCL2 , Metabolismo , Fibrosis , Riñón , Patología , Enfermedades Renales , Quimioterapia , Ratones Endogámicos C57BL , PPAR gamma , Subgrupos de Linfocitos T , Tiazolidinedionas , Farmacología , Usos Terapéuticos , Factor de Crecimiento Transformador beta , Metabolismo , Obstrucción UretralRESUMEN
Renal tubulointerstitial fibrosis is the common ending of progreβsive renal disease. It is worth developing new ways to stop the progreβs of renal fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been studied to treat diabetic nephropathy, cisplatin-induced acute renal injury, ischemia reperfusion injury and adriamycin nephropathy. In this study, unilateral ureteral obstruction (UUO) was used to establish a different renal fibrosis model. PPAR? agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14th day after the operation, mice were sacrificed for fibrosis test and T lymphocytes subsets test. Unexpectedly, through MASSON staining, immunohistochemistry for α-SMA, and Western blotting for a-SMA and PDGFR-β, we found that pioglitazone failed to attenuate renal fibrosis in UUO mice. However, flow cytometry showed that pioglitazone down-regulated Th1 cells, and up-regulated Th2 cells, Th17 cells and Treg cells. But the Th17/Treg ratio had no significant change by pioglitazone. Real-time PCR results showed that TGF-β and MCP-1 had no significant changes, at the same time, CD4(+) T cells associated cytokines were partially regulated by pioglitazone pretreatment. Taken together, pioglitazone failed to suppress renal fibrosis progression caused by UUO.
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No abstract available.
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Anciano de 80 o más Años , Humanos , Masculino , Antibacterianos/farmacología , Proteínas Bacterianas/genética , China , Farmacorresistencia Bacteriana Múltiple , Metiltransferasas/genética , Pruebas de Sensibilidad Microbiana , ARN Ribosómico 16S/genética , Serratia marcescens/efectos de los fármacos , Infecciones Urinarias/diagnósticoRESUMEN
Objective To study the role of cyclic strain-modulated tumor necrosis factor-α (TNF-α) played in the quantity and intercellular cell adhesion molecule-1(ICAM-1) expression of endothelial microparticles (EMPs). Methods The endothelial cells (ECs) primarily cultured from rat aorta were applied with 5% cyclic strain (to simulate normal physiological condition) and 18% cyclic strain (to simulate hyper-tension condition), respectively, by using FX-4000T cyclic stain loading system for 24 hours at the loading frequency of 1.25 Hz. The mRNA expression of TNF-α under different amplitudes of cyclic strain was determined by real time-PCR. The TNF-α was then used to stimulate the ECs from rat aorta, and the supernatants were collected and ultracentrifuged to get endothelial microparticles (EMPs), which were then identified by lipophilic styryl membrane staining and transmission electron microscope for morphological identification. The quantities of Annexin V positive EMPs under TNF-α stimulation were counted by flow cytometer and ICAM-1 expression on EMPs was detected as well. Results Compared with the 5% normal cyclic strain, under 18% high cyclic strain condition,the mRNA expression of TNF-α in ECs increased significantly. TNF-α could then significantly up-regulate the production of Annexin V positive EMPs and promote the expression of ICAM-1 on EMPs. Conclusions The over-expression of TNF-α in ECs under high cyclic strain might mediate the high production of EMPs and over-expression of ICAM-1 on EMPs. The research findings will provide new experiment evidence for further studying the role of EPCs in the mechanobiological mechanism of vascular remodeling.
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<p><b>OBJECTIVE</b>To investigate the effect of the selective PI3K inhibitor and MEK inhibitor on KRAS and PTEN co-mutated non-small cell lung cancer cell line NCI-H157 and the relevant mechanisms.</p><p><b>METHODS</b>NCI-H157 was cultured routinely and treated with different concentrations of the two inhibitors. Cell proliferation was detected by MTT cell cycle assay. Based on the MTT results the cells were divided into four groups: the control group, PI3K inhibitor group (GDC-0941, 0.5 and 5.0 µmol/L), combination group I (0.5 µmol/L AZD6244 + 0.5 µmol/L GDC-0941) and combination group II (5.0 µmol/L AZD6244 + 5.0 µmol/L GDC-0941). Colony formation assay was performed to detect colony formation efficiency. The cell cycle and apoptosis were analyzed by flow cytometry. The expression of protein related to apoptosis was tested with Western blot.</p><p><b>RESULTS</b>Cell growth was inhibited by the two inhibitors. Combination groups led to stronger cell proliferation inhibition: combination group Ishowed synergistic effect of their actions and combination group II showed an additive effect; in both groups, there were decreased colony number [(77.2 ± 1.54)/well vs (61.50 ± 2.12)/well, P < 0.01] and [(51.00 ± 4.00)/ well vs (22.50 ± 3.53)/well, P < 0.01]; and enhanced apoptotic ratios [(18.30 ± 0.82)% vs (21.32 ± 0.56)%, P < 0.01] and [(27.14 ± 1.58)% vs (42.45 ± 4.42)%, P < 0.01]. In addition, compared to the PI3K inhibitor alone group, the NCI-H157 cells in the combination groups showed increased G0/G1 phase and decreased S phase (P < 0.01). Western blotting showed that the combination groups demonstrated significantly decreased expression of cyclin D1 and cyclin B1, increased p21 and cleaved PARP and decreased bcl-2/bax ratio, compared to the PI3K inhibitor only group.</p><p><b>CONCLUSION</b>The combined inhibition of PI3K (AZD6244) and MEK (GDC-0941) has synergistic effects on the proliferation of NCI-H157 cells, but such effects appear to be in a dose-dependent manner.</p>
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Humanos , Apoptosis , Bencimidazoles , Farmacología , Carcinoma de Pulmón de Células no Pequeñas , Genética , Patología , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Ciclina B1 , Metabolismo , Ciclina D1 , Metabolismo , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Indazoles , Farmacología , Neoplasias Pulmonares , Genética , Patología , Quinasas de Proteína Quinasa Activadas por Mitógenos , Metabolismo , Mutación , Fosfohidrolasa PTEN , Genética , Fosfatidilinositol 3-Quinasas , Metabolismo , Poli(ADP-Ribosa) Polimerasas , Metabolismo , Proteínas Proto-Oncogénicas , Genética , Proteínas Proto-Oncogénicas c-bcl-2 , Metabolismo , Proteínas Proto-Oncogénicas p21(ras) , Metabolismo , Transducción de Señal , Sulfonamidas , Farmacología , Proteína X Asociada a bcl-2 , Metabolismo , Proteínas ras , GenéticaRESUMEN
An HPLC method for determination of scoparone and ayapin was established for investigating the distributed patterns of scoparone and ayapin in 37 species of Dendrobium. The contents of scoparone and ayapin in varied collected samples were determined by the established HPLC method. The pseudo-bulbs sampled were collected according to different growth age of D. thyrsiflorum. The results showed that the contents of scoparone and ayapin were much differently distributed in species of Dendrobium. Only D. thyrsiflorum and D. densfilorum contained both scoparone and ayapin, the content decreased with the growth age. A fewer amount of ayapin was tested in D. loddigesii from Wenshan. The scoparone and ayapin were not determined in the rest species of Dendrobium. The method was concise, sensitive, accurate and reproducible. It could be applied to assay scoparone and ayapin in populations of herbal Dendrobium.
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China , Cromatografía Líquida de Alta Presión , Cumarinas , Dendrobium , Química , Medicamentos Herbarios Chinos , SesquiterpenosRESUMEN
<p><b>OBJECTIVE</b>To evaluate the inhibitory effect and its mechanism of celecoxib combined with capecitabine on the growth of implanted H22 hepatoma in mice.</p><p><b>METHODS</b>Tumor model was established by hypodermical injection of H22 cells in BALB/c nude mice. Forty mice were equally randomly divided into 4 groups: control group, celecoxib group (receiving 100 mg/kg celecoxib), capecitabine group (receiving 755 mg/kg capecitabine), and combined treatment group (receiving 100 mg/kg of celecoxib and 755 mg/kg of capecitabine). From the third post-implantation day, each mouse was given relevant drug (or normal saline) by oral gavage. Fifteen days later, all mice were sacrificed and the tumor tissues were measured. The mRNA and protein levels of nuclear factor kappa-B (NF-ΚB) p65 and cyclooxygenase (COX)-2 in tumor tissues were detected by the quantitative polymerase chain reaction (qPCR)and Western blotting, respectively.</p><p><b>RESULTS</b>The tumor inhibition rate was 30.2% in celecoxib group and 49.9% in capecitabine group, which was significantly lower than that (75.4%) in the combined treatment group (P<0.01,P<0.05, respectively). qPCR showed a significant decrease of the mRNA expression of COX-2 in celecoxib group and combined treatment group when compared with control group (P<0.001), but no significant change in NF-ΚB p65.Capecitabine had no significant effects on the mRNA expression of COX-2 and NF-ΚB p65. Western blotting showed that celecoxib and combined treatment significantly inhibited the protein expression of COX-2 and NF-ΚB p65(P<0.05), but not capecitabine.</p><p><b>CONCLUSION</b>Celecoxib can enhance the antitumor effect of capecitabine by inhibiting the expressions of COX-2 and NF-ΚB p65 in mice bearing H22 implanted tumor.</p>
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Animales , Ratones , Capecitabina , Celecoxib , Línea Celular Tumoral , Ciclooxigenasa 2 , Metabolismo , Desoxicitidina , Usos Terapéuticos , Sinergismo Farmacológico , Fluorouracilo , Usos Terapéuticos , Neoplasias Hepáticas , Quimioterapia , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Pirazoles , Usos Terapéuticos , Sulfonamidas , Usos Terapéuticos , Factor de Transcripción ReIA , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To analyze the clinical and SLC2A1 gene mutation characteristics of glucose transporter type 1 deficiency syndrome.</p><p><b>METHOD</b>The detailed clinical manifestations of six cases were recorded. The laboratory tests including EEG, MRI, blood chemistry, and lumbar puncture were performed. SLC2A1 gene mutations were analyzed by PCR, DNA sequencing and multiplex ligation-dependent probe amplification (MLPA).</p><p><b>RESULT</b>Patient 1, 2 and 3 had classical clinical symptoms including infantile onset seizures, development delay. Patient 4, 5 and 6 had non-classical clinical symptoms including paroxysmal behavior disturbance, weakness, ataxia, lethargy, especially after fasting or exercise, without severe seizures. The plasma glucose levels were normal. The CSF glucose levels decreased in all the six cases, ranged from 1.10 mmol/L to 2.45 mmol/L, the mean level was 1.68 mmol/L. The CSF glucose/plasma glucose ratios decreased, ranged from 0.16 to 0.51, the mean ratio was 0.34. Four patients had normal EEG. Two patients had focal and diffuse epileptiform discharge, and one of them also had paroxysmal occipital or generalized high-amplitude slow waves during awake and sleep time. MRI abnormalities were found in three patients, patient 1 with mild brain atrophy, patient 3 with bilateral ventricle plump, and patient 4 with high signals in T2 in the frontal and occipital white matter, interpreted as hypomyelination. SLC2A1 gene mutations were found in six cases. Patient 1 has large scale deletion in exon 2. In patient 2 to 6, the mutations were c.741 G>A (E247K), 599delA, 761delA, c.1148 C>A (P383H), c.1198 C>T (R400C) respectively. Two patients were treated with ketogenic diet. The seizures disappeared and development became normal. Three patients responded to frequent meals with snacks. One patient refused any treatments, the symptoms continued to exist.</p><p><b>CONCLUSION</b>The clinical manifestations of glucose transporter type 1 deficiency syndrome are varied. The common symptoms included infantile onset seizures and various paroxysmal events. These neurologic symptoms generally fluctuated and were influenced by factors such as fasting or fatigue. This feature could be a very important clue for the diagnosis of GLUT1-DS. Lumbar puncture is recommended in patients with episodic CNS symptoms especially after fasting. GLUT1-DS is a treatable neurometabolic disorder, early diagnosis and treatment may improve the prognosis of the patients.</p>
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Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Biomarcadores , Encéfalo , Diagnóstico por Imagen , Patología , Errores Innatos del Metabolismo de los Carbohidratos , Diagnóstico , Genética , Terapéutica , Análisis Mutacional de ADN , Dieta Cetogénica , Electroencefalografía , Epilepsia , Diagnóstico , Genética , Terapéutica , Estudios de Seguimiento , Transportador de Glucosa de Tipo 1 , Genética , Imagen por Resonancia Magnética , Proteínas de Transporte de Monosacáridos , Genética , Trastornos del Movimiento , Diagnóstico , Genética , Terapéutica , Mutación , Genética , RadiografíaRESUMEN
<p><b>OBJECTIVE</b>To observe the anti-remodeling effect of acupuncture on asthma and to explore the mechanism of T-type calcium channel protein in airway smooth muscle cell in airway remodeling effect in asthma.</p><p><b>METHODS</b>Thirty-two rats were randomly divided into a normal group, a model group, an acupuncture group and a sham acupuncture group, 8 rats in each group. The rats in the latter three groups were sensitized for consecutive 14 days by single peritoneal injection of aqueous suspension 1 mL of 10 mg ovalbumin (OVA), 200 mg aluminum hydroxide and saline together with 1 mL inactivated pertussis vaccine. From the 15th day, asthma was induced for 30 minutes by ultrasonic atomizing inhalation of 1% OVA for consecutive 14 days in the model group. The acupuncture group was treated with acupuncture at "Dazhui" (GV 14), "Fengmen" (BL 12) and "Feishu" (BL 13) for 30 minutes before the ultrasonic atomizing inhalation, once every two days for consecutive 14 days. The same acupoints selection and the course of treatment as the acupuncture group were produced in the sham acupuncture group and they were treated with acupuncture at 1 mm acupoint skin without retaining needles. The normal group remained unhandled. The respiratory function and the airway remodeling were evaluated by airway resistance and pulmonary histopathology, respectively, and the T-type calcium channel protein expression of Ca(v)3.1, Ca(v) 3.2, Ca, 3.3 in airway smooth muscle cell were detected by immunohistochemistry technique.</p><p><b>RESULTS</b>(1) The airway resistance in the model group was higher than that in the normal group and in the acupuncture group (both P < 0.05), and the airway resistance in the acupuncture group was lower than that in the sham acupuncture group (P < 0.05). (2) The ratios of the airway wall thickness to the basement membrane perimeter (Awt/Pbm) and the airway outer perimenter to the airway internal perimeter (Po/Pi) in the model group were higher than those in the normal group and in the acupuncture group (all P < 0.05), and the ratios of Awt/Pbm and Po/Pi in the acupuncture group were lower than those in the sham acupuncture group (both P < 0.05). (3) The average optical of Ca(v) 3.1 and Ca(v) 3.2 in airway smooth muscle cell in the model group were higher than that in the normal group and in the acupuncture group (both P < 0.05), and the average optical of Ca(v) 3.3 in airway smooth muscle cell in the model group was higher than that in the normal group (P < 0.05) and it was lower than that in the sham acupuncture group (P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture can inhibit the airway remodeling and the accrementition of the airway smooth muscle and can reduce the airway resistance. The mechanism may be related to the inhibition of T-type calcium channel protein in airway smooth muscle cell, especially in relation to the protein expression of Ca(v) 3.1.</p>
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Animales , Humanos , Masculino , Ratas , Terapia por Acupuntura , Remodelación de las Vías Aéreas (Respiratorias) , Asma , Genética , Metabolismo , Canales de Calcio Tipo T , Genética , Metabolismo , Miocitos del Músculo Liso , Metabolismo , Ratas Sprague-Dawley , Sistema Respiratorio , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate synergistically killing effect of histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) combined with imatinib on human chronic myeloid leukemia (CML) cell line.</p><p><b>METHODS</b>K562 cells were co-treated with SAHA and imatinib. Cell growth was measured by MTT assay. Apoptosis was determined using Hoechst staining apoptosis detection kit and flow cytometric analysis. Activation of Caspase pathway, expression of Bcr-Abl and its downstream target genes, and expression of anti-apoptotic proteins were detected by Western blot.</p><p><b>RESULTS</b>SAHA synergized the cytotoxicity of imatinib against leukemia K562 cells, concomitantly with increased apoptosis and enhanced activation of Caspase-3, -8 and PRAP. The combination therapy resulted in significantly lower levels of Bcr-Abl,phosphorylated Bcr-Abl compared to treatment with either SAHA or imatinib alone. Furthermore,the co-treatment resulted in down-regulation of anti-apoptotic protein Mcl-1 expression. Also,marked down-regulated expression of JAK2,STAT5,and phosphorylated STAT5 was detected in the combination therapy.</p><p><b>CONCLUSION</b>Combining HDAC inhibitor SAHA with imatinib can kill CML cells synergistically by inhibiting cell growth and inducing apoptosis, which is associated with activation of Caspase pathway and regulation of anti-apoptotic proteins.</p>