ABSTRACT
Objective: To assess the clinical features and relative factors of left ventricular hypertrophy (LVH) in children with primary hypertension. Methods: In this retrospective cohort study, 430 children diagnosed with primary hypertension in Children's Hospital, Capital Institute of Pediatrics from January 2019 to September 2022 were enrolled. Their clinical data was analyzed and LVH was assessed by echocardiography. According to left ventricular geometry, these children were assigned to the LVH group and normal geometry group. General conditions, laboratory indicators and ambulatory blood pressure parameters between two groups were compared by independent sample t-test or Mann-Whitney U test. Spearman correlation coefficient was used to analyze the correlation between LVH and clinical indicators including blood pressure, biochemical and metabolic indicators. The independent risk factors of LVH were analyzed by multivariable logistic regression. The receiver operating characteristic (ROC) curve was used to explore the value of risk factors in the diagnosis of LVH. Results: Among the 430 children with primary hypertension, 342 (79.5%) were males and 88 (20.5%) females. Their age was (12.6±2.3) years, and 123 children (28.6%) of them had LVH. Body mass index (BMI) ((30.0±5.2) vs. (26.2±4.3) kg/m2), ratio of stage 2 hypertension (75.6% (93/123) vs. 59.6% (183/307)), 24-hour systolic blood pressure (24 h SBP)((131±10) vs. (128±10) mmHg,1 mmHg=0.133 kPa), daytime systolic blood pressure (SBP) ((135±11) vs. (131±11) mmHg), nighttime SBP ((128±11) vs. (123±10) mmHg), cholesterol level ((4.0±0.7) vs. (3.9±0.7) mmol/L), serum uric acid level ((447±81) vs. (426±91) μmol/L) and incidence of hyperinsulinemia (69.9% (86/123) vs.59.0% (181/307)) were significantly elevated in the LVH group compared with those in the normal geometry group (all P<0.05). There were more patients with a disease course over 5 years in the LVH group than in the normal geometry group, with a statistically significant difference (χ2=8.90,P=0.031). Spearman correlation analysis showed that BMI, 24 h SBP, daytime SBP, nighttime SBP, triglyceride, uric acid, and serum sodium level were positively correlated with LVMI (r=0.43, 0.20, 0.18, 0.18, 0.18, 0.16, and 0.12, all P<0.05). BMI, hyperinsulinemia, and cholesterol level were positively correlated with relative wall thickness (RWT) (r=0.22, 0.12, and 0.16, all P<0.05). The multivariate logistic regression analysis showed that BMI (OR=1.17, 95%CI 1.10-1.25) and 24 h SBP (OR=1.04, 95%CI 1.01-1.08) were the independent risk factors for LVH (both P<0.05). The area under the receiver operator characteristic curve, combined with BMI and 24 h SBP, was 0.72 (95%CI 0.67-0.77, P<0.05), with a sensitivity and specificity of 71.5% and 64.8%, respectively. Conclusions: BMI and 24 h SBP are the independent risk factors for LVH in children with primary hypertension, and the combination of BMI and 24 h SBP has an acceptable diagnostic value for LVH. Early monitoring of these indexes is necessary to predict preclinical cardiac damage.
Subject(s)
Male , Female , Humans , Child , Adolescent , Hypertension/diagnosis , Hypertrophy, Left Ventricular/etiology , Uric Acid , Blood Pressure Monitoring, Ambulatory , Retrospective Studies , Blood Pressure/physiology , Risk Factors , Essential Hypertension , Hyperinsulinism , CholesterolABSTRACT
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.
Subject(s)
Child , Humans , Alleles , Genotype , Hypertension/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic , Retrospective StudiesABSTRACT
@#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.
ABSTRACT
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%.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Carthamus tinctorius , Crocus , Real-Time Polymerase Chain ReactionABSTRACT
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.
ABSTRACT
Objective: To explore the expression and prognostic significance of miR-223 in patients with mantle cell lymphoma (MCL) and to investigate the possible mechanism. Methods: Twenty-one newly diagnosed MCL patients with bone marrow involvement were enrolled in the present study, 20 healthy donors as normal control. The expression level of miR-223 and SOX11 mRNA was determined by RQ-PCR. CCK-8 and flow cytometer assays were used to analyze cell proliferation, cell cycle and apoptosis of the constructed miR-223 overexpressing MCL cell line, Granta519 cells. SOX11 protein expression level was determined by Western blot. The target gene of miR-223 was confirmed by dual luciferase reporter assay. Results: ①Of the 21 newly diagnosed MCL patients, 15 were male and 6 female, the median age was 58 (37-72) years. The expression level of miR-223 was significantly down regulated in MCL patients compared with that of healthy donors (14.7±10.5 vs 1 244.1±1 935.2, P<0.001). The lower expression of miR-223 was inversely correlated with high-risk mantle international prognostic index (P=0.001), elevated LDH (P=0.001), ECOG score ≥2 (P=0.035). ②Using the median relative expression level of miR-223 as the cutoff value, 21 MCL patients were divided into high-expression group (n=10) and low-expression group (n=11) and found that the high-expression group had a significantly superior OS (median OS: 36 vs 12 months, P=0.021). ③In vitro results showed that compared with the control group, the proliferation of miR-223 overexpressed Granta519 cells was inhibited (the most significant reduction on 96h, P<0.001), manifested by lower proportion of cells in G2/M phase (P<0.001) and increased apoptosis (P<0.001), and the expression level of SOX11 protein in Granta519 cells was significantly lower than that of the control group. ④miR-223 could inhibited the 3' untranslated region of SOX11, and the expression level of miR-223 was significantly negatively correlated with mRNA level of SOX11 in MCL patients (r=-0.81, P<0.001). Conclusions: The expression of miR-223 was repressed in MCL and was associated with poor clinical outcomes, which may be probably attributed to its direct targeting SOX11.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Lymphoma, Mantle-Cell , MicroRNAs , Prognosis , RNA, Messenger , SOXC Transcription FactorsABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Animals , Male , Mice , Chemokine CCL2 , Metabolism , Fibrosis , Kidney , Pathology , Kidney Diseases , Drug Therapy , Mice, Inbred C57BL , PPAR gamma , T-Lymphocyte Subsets , Thiazolidinediones , Pharmacology , Therapeutic Uses , Transforming Growth Factor beta , Metabolism , Urethral ObstructionABSTRACT
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.
ABSTRACT
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.
ABSTRACT
No abstract available.
Subject(s)
Aged, 80 and over , Humans , Male , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , China , Drug Resistance, Multiple, Bacterial , Methyltransferases/genetics , Microbial Sensitivity Tests , RNA, Ribosomal, 16S/genetics , Serratia marcescens/drug effects , Urinary Tract Infections/diagnosisABSTRACT
<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>
Subject(s)
Animals , Mice , Capecitabine , Celecoxib , Cell Line, Tumor , Cyclooxygenase 2 , Metabolism , Deoxycytidine , Therapeutic Uses , Drug Synergism , Fluorouracil , Therapeutic Uses , Liver Neoplasms , Drug Therapy , Mice, Inbred BALB C , Neoplasm Transplantation , Pyrazoles , Therapeutic Uses , Sulfonamides , Therapeutic Uses , Transcription Factor RelA , MetabolismABSTRACT
<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>
Subject(s)
Humans , Apoptosis , Benzimidazoles , Pharmacology , Carcinoma, Non-Small-Cell Lung , Genetics , Pathology , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Cyclin B1 , Metabolism , Cyclin D1 , Metabolism , Dose-Response Relationship, Drug , Drug Synergism , Indazoles , Pharmacology , Lung Neoplasms , Genetics , Pathology , Mitogen-Activated Protein Kinase Kinases , Metabolism , Mutation , PTEN Phosphohydrolase , Genetics , Phosphatidylinositol 3-Kinases , Metabolism , Poly(ADP-ribose) Polymerases , Metabolism , Proto-Oncogene Proteins , Genetics , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Proto-Oncogene Proteins p21(ras) , Metabolism , Signal Transduction , Sulfonamides , Pharmacology , bcl-2-Associated X Protein , Metabolism , ras Proteins , GeneticsABSTRACT
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.
Subject(s)
China , Chromatography, High Pressure Liquid , Coumarins , Dendrobium , Chemistry , Drugs, Chinese Herbal , SesquiterpenesABSTRACT
<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>