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In recent years, foundation pit construction has been rapidly developing in the direction of deep and large-scale, leading to the frequent occurrence of construction accidents. The pit construction process is characterised by a complex environment, high construction risk, and numerous coupling effects between the construction risk factors. In this paper, 23 main accident-causing factors in foundation pit construction are determined based on the six major risk accident types. In addition, the Grey-DEMATEL-Fuzzy comprehensive evaluation method of the risk evaluation model is introduced for better prediction and judgment of risk level, which combines the grey system theory with the method of decision-making experimental analysis, and in the case of inaccurate or incomplete information, the use of less data can achieve the evaluation results with a high degree of reliability, and it will effectively avoid the impact of the lack of information as well as the subjectivity in the process of risk evaluation. Through the Grey-DEMATEL method, the central degree value for each risk indicator factor is calculated, the coupling role and importance of each risk indicator are analysed, and the indicator weights are calculated. Based on the calculated weights, the fuzzy comprehensive evaluation method is used to evaluate the overall risk level. The empirical research on the deep foundation pit construction project of Haitangxi subway station in Chongqing reveals that the excessive lateral earth pressure on the pile wall is the most prominent risk factor. The overall risk level of the construction process is medium, and the risk is within the controllable range. On this basis, corresponding preventive measures can be formulated, providing a basis for risk prevention in the construction of deep foundation pit projects.
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Industria de la Construcción , Lógica Difusa , Medición de Riesgo/métodos , Humanos , Modelos Teóricos , Factores de Riesgo , ChinaRESUMEN
This study aims to decipher the mechanism of sinomenine in inhibiting platelet-derived growth factor/platelet-derived growth factor receptor(PDGF/PDGFR) signaling pathway in rheumatoid arthritis-fibroblast-like synoviocyte(RA-FLS) migration induced by neutrophil extracellular traps(NETs). RA-FLS was isolated from the synovial tissue of 3 RA patients and cultured. NETs were extracted from the peripheral venous blood of 4 RA patients and 4 healthy control(HC). RA-FLS was classified into control group, HC-NETs group, RA-NETs group, RA-NETs+sinomenine group and RA-NETs+sinomenine+CP-673451 group. RNA-sequencing(RNA-seq) was conducted to identify the differentially expressed genes between HC-NETs and RA-NETs groups. Sangerbox was used to perform the Gene Ontology(GO) function and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape was employed to build the protein-protein interaction(PPI) network. AutoDock Vina and PyMOL were used for molecular docking of sinomenine with PDGFß and PDGFRß. The cell proliferation and migration were determined by the cell counting kit-8(CCK-8) and cell scratch assay, respectively. Western blot was employed to determine the protein level of PDGFRß. Real-time quantitative polymerase chain reaction(RT-qPCR) was carried out to determine the mRNA levels of matrix metalloproteinases(MMPs). The results revealed that neutrophils in RA patients were more likely to produce NETs. Compared with HC-NETs group, RA-NETs group showed up-regulated expression of PDGFß and PDGFRß. Compared with control group, RA-NETs group showed increased cell proliferation and migration and up-regulated protein level of PDGFRß and mRNA levels of PDGFß, PDGFRß, MMP1, MMP3, and MMP9(P<0.05). Compared with RA-NETs group, RA-NETs+sinomenine group presented decreased cell proliferation and migration and down-regulated protein and mRNA level of PDGFRß and mRNA levels of MMP1, MMP3, and MMP9(P<0.05). Compared with RA-NETs+sinomenine group, the proliferation ability of RA-NETs+sinomenine+CP-673451 group decreased(P<0.05). The findings prove that sinomenine reduces the RA-NETs-induced RA-FLS migration by inhibiting PDGF/PDGFR signaling pathway, thus mitigating RA.
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Artritis Reumatoide , Movimiento Celular , Morfinanos , Factor de Crecimiento Derivado de Plaquetas , Transducción de Señal , Sinoviocitos , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Movimiento Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Morfinanos/farmacología , Sinoviocitos/efectos de los fármacos , Sinoviocitos/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptores del Factor de Crecimiento Derivado de Plaquetas/genética , Receptores del Factor de Crecimiento Derivado de Plaquetas/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Masculino , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismoRESUMEN
INTRODUCTION: Dajianzhong decoction (DJZD), a classic famous prescription, has a long history of medicinal application. Modern studies have demonstrated its clinical utility in the treatment of postoperative ileus (POI). But none of the current quality evaluation methods for this compound is associated with efficacy. OBJECTIVES: This study aimed to identify the quality markers (Q-Markers) connected to the treatment of POI in DJZD. METHODOLOGY: Ultra-performance liquid chromatography quadrupole Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was used to identify the main constituents in DJZD. Based on the qualitative results obtained by fingerprinting, chemical pattern recognition (CPR) was used to analyse the key components affecting the quality and finally to establish the network of the active ingredients in DJZD with POI. RESULTS: A total of 64 chemical components were detected. After fingerprint analysis, 13 common peaks were identified. The fingerprint similarity of 15 batches of samples ranged from 0.860 to 1.000. CPR analysis was able to categorically classify 15 batches of DJZD into two groups. And gingerenone A, methyl-6-gingerdiol, 6-gingerol, and hydroxy-ß-sanshool contributed to their grouping. Twelve common components interact with the therapeutic targets for treating POI. In addition, the mechanism of this prescription for treating POI may be related to the jurisdiction of the neurological system, the immunological system, and the inflammatory response. CONCLUSIONS: This integrated approach can accurately assess and forecast the quality of DJZD, presume the Q-Markers of DJZD for POI, and lay the foundation for studying the theoretical underpinnings and exploring the mechanism of DJZD in the treatment of POI.
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Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodos , Quimiometría , Farmacología en Red , Cromatografía de Gases y Espectrometría de MasasRESUMEN
Objective To analyze the burden and changing trend of testicular cancer in China from 1990 to 2019.Methods Based on the 2019 Global Burden of Disease Database(GBD 2019),analyze the incidence,mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs)and their variation trend of testicular cancer in Chinese population from 1990 to 2019.Evaluating changes in age standardized rate(ASR)by calculating annual estimated percentage change(EAPC).According to the age grouping,analyze the age distribution characteristics of testicular cancer disease burden by age group.Results In 2019,the incident cases,deaths,age-standardized incidence rate,and age-standardized mortality rate of testicular cancer in China were 17.17×103,1.21×103,2.39/105,and 0.16/105,respectively.Compared to 1990,incident cases,deaths,and age-standardized incidence rate increased obviously in China,which was consistent with the global change trend,while the increase was higher than the global level.However,both Chinese and global age-standardized mortality rate showed a downward trend.From 1990 to 2019,DALYs,YLLs and YLDs of testicular cancer increased by 29.66%,9.83%and 720.91%respectively in China.The two age groups,0-15 years group and 30-35 years group,were with highest incidence of testicular cancer,while the highest disease burden of testicular cancer was 30-35 years.Conclusion From 1990 to 2019,the disease burden of testicular cancer in China showed an upward trend.Adolescents and young adults should be the priority population for screening and prevention due to their higher incidence and disease burden.
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【Objective】 To analyze the disease burden of benign prostatic hyperplasia (BPH) in China, Japan and South Korea from 1990 to 2019, so as to provide scientific basis for rational allocation of health resources. 【Methods】 Data were obtained from the Global Burden of Disease Study 2019. The incidence, prevalence and years lived with disability(YLD)were used to analyze the burden, and the average annual percent change and annual percent change were calculated. 【Results】 The incidence, prevalence and YLD rate in China were much higher than those in Japan and South Korea. The crude incidence in China, Japan and South Korea increased by 2.56%, 1.49% and 3.59% per year from 1990 to 2019, the crude prevalence rate increased by 2.70%, 2.34% and 4.03%, and the crude YLD rate increased by 2.68%, 2.33% and 4.04%. After age standardization, the disease burden in China decreased with time, but the trend was not significant, and the standardized rate in Japan and Korea increased significantly with time. The disease burden of BPH increased with age, and those aged 60 to 84 years had the highest burden. In addition, the disease burden increased with the increase of socio-demographic index (SDI) in all three countries. 【Conclusion】 The disease burden of BPH was very heavy in China, Japan and South Korea, especially in China. Males aged 60 to 84 years were the high-risk group. Targeted intervention should be adopted for these population.
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Objective:To investigate the effect of luteolin(Lut)on the proliferation and ferroptosis of human adriamycin(ADR)resistant chronic myeloid leukemia(CML)K562/ADR cells and the underlying molecular mechanism. Methods:K562 and K562/ADR cells were treated with different concentrations of ADR.The sensitivity of K562 and K562/ADR cells to ADR was evaluated by CCK-8 assay;the effect of different concentrations of Lut on the proliferation of K562/ADR cells was assessed by CCK-8 assay,and the half inhibitory concentration(IC50)was calculated for subsequent experiments;the morphological changes of the cells were observed by an inverted microscope;CCK-8 assay was used to examine the sensitizing effect of Lut on ADR;FCM assay was used to study the effect of Lut on the apoptosis of K562/ADR cells;fluorescence probe DCFH-DA,Fe2+colorimetric assay and glutathione(GSH)kit were used to detect the content of reactive oxygen species(ROS),Fe2+and GSH in K562/ADR cells,respectively;Western blotting was used to examine the expression levels of glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in K562/ADR cells;the effects of Lut on the proliferation of K562/ADR cells,ROS content,GSH content,Fe2+content and GPX4 expression were studied after treatment with ferroptosis inhibitor Ferrostatin-1(Fer-1). Results:Compared with control group(cells treated with 0 μmol/L Lut),Lut significantly inhibited the proliferation of K562/ADR cells(P<0.001),improved the chemosensitivity of K562/ADR cells to ADR(P<0.05),increased apoptosis rate(P<0.001)and ROS level(P<0.05)of K562/ADR cells,reduced the GSH level(P<0.001),and increase Fe2+content(P<0.01).Compared with control group(cells treated with 0 μmol/L Lut),the protein expressions of GPX4,Nrf2 and HO-1 decreased with the increase of Lut concentration(P<0.05).Compared with the Lut treatment alone,the inhibitory effect on the proliferation of K562/ADR cells induced by Lut was partially restored by Fer-1 intervention(P<0.05),and intracellular ROS level was decreased(P<0.001),GSH level was increased(P<0.001),Fe2+content was decreased(P<0.001)and the expression of GPX4 was increased(P<0.01)in K562/ADR cells. Conclusion:Lut can inhibit the proliferation of K562/ADR cells through ferroptosis pathway,improve the chemosensitivity to ADR,and the potential mechanism may be related to the Nrf2/HO-1 signaling pathway,which provides experimental basis for the treatment of leukemia by ferroptosis.
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BACKGROUND: The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism. METHODS: C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines. RESULTS: The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866. CONCLUSION: In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.
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Nicotinamida Fosforribosiltransferasa , Sepsis , Animales , Citocinas/metabolismo , Vía de Señalización Hippo , Lipopolisacáridos , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismoRESUMEN
Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m2(range: 18.1 to 30.1 kg/m2). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ2 test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.
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Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Duodeno/cirugía , Páncreas/cirugía , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
The periodic permanent magnet electromagnetic acoustic transducer (PPM EMAT) is a sensor that can generate and receive shear horizontal (SH) waves without direct contact with the inspected medium using the Lorentz mechanism. However, the PPM EMAT experiences high signal variance on ferromagnetic steel under specific conditions, such as a change in signal amplitude when the sensor is moved in the direction of SH wave propagation. Magnetostriction effects are hypothesized to be the cause of these anomalous behaviors; the objective of this paper is to determine the relative strengths of the magnetostriction and Lorentz wave generation mechanisms for this type of EMAT on steel. This goal is accomplished through the use of a second EMAT, which induces only magnetostriction (MS-EMAT), to calibrate a novel semi-empirical magnetostriction model. It is found that magnetostriction effects reduce the amplitude of the SH wave generated by this particular PPM EMAT transmitter by an average of 29% over a range of input currents. It is also determined that magnetostriction is significant only in the investigated PPM EMAT transmitter, not the receiver. In terms of practical application, it is shown that the MS-EMAT is less sensitive to changes in the static and dynamic fields than PPM EMATs at specific operating points; this makes the MS-EMAT a viable alternative for nondestructive evaluation despite lower amplitudes.
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Objective:To investigate the drug resistance of kaempferol reversed adriamycin (ADM)-resistant K562/ADM cells in chronic myelogenous leukemia (CML) and its related mechanism.Methods:Methyl thiazolyl tetrazolium (MTT) method was used to detect the toxicity of ADM on K562 and K562/ADM cells for 24 h. The half inhibitory concentration ( IC50) of ADM and the drug resistance multiple for 24 h were calculated. MTT method was used to detect the toxicity of kaempferol on K562/ADM cells for 24 h. The 5% inhibitory concentration ( IC5) and 10% inhibitory concentration ( IC10) of kaempferol for 24 h were calculated to determine the concentration of kaempferol in the subsequent experiments. And the cells untreated by the kaempferol were selected as the control group. The cell inhibition after the treatment of ADM for 24 h of the blank control group and kaempferol intervention group was detected by using MTT method. And then the cell inhibition for 24 h and ADM IC50 for 24 h in the above groups were calculated. The ratio of IC50 in the blank control group and kaempferol group was the reversal drug resistance multiple of kaempferol. The fluorescence intensity of ADM in K562/ADM cells treated by kaempferol was detected by using flow cytometry. Western blotting was used to detect the expressions of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), phosphorylated p38 (p-p38), and total p38 (t-p38) protein in K562/ADM cells after the treatment of kaempferol, the specific inhibitor of p38-MAPK signaling pathway SB202190, and the combination of kaempferol and SB202190. Results:After the treatment of ADM for 24 h, the IC50 value of K562 and K562/ADM cells was (0.9±0.6), (28.1 ±3.5) μg/ml, respectively. The drug resistance multiple of K562/ADM cells on the treatment of ADM for 24 h was 31.16 compared with the K562 cells. MTT method showed that kaempferol inhibited the proliferation of K562/ADM cells in a dose-dependent manner. According to the IC5 and IC10, 0.5 μmol/L and 1.0 μmol/L kaempferol were determined to do the subsequent experiments. After the combined interaction of kaempferol and ADM for 24 h, the ADM IC50 of K562/ADM cells in the blank control group, 0.5 μmol/L kaempferol group and 1.0 μmol/L kaempferol group was (33.7±5.7), (21.4±0.6), (15.9±1.8) μg/ml, respectively ( F = 30.85, P < 0.05), and there was a statistical difference of pairwise comparison (both P < 0.05). The reversal drug resistance multiple of K562/ADM cells for 24 h in 0.5 μmol/L kaempferol group and 1.0 μmol/L kaempferol group was 1.58 and 2.12, respectively. Flow cytometry results showed that the mean fluorescence intensity (MFI) of ADM in the blank control group, 0.5 μmol/L kaempferol group and 1.0 μmol/L kaempferol group was 138.4±8.9, 154.3±2.2, 165.7±4.8, respectively, and the difference was statistically significant ( F = 161.48, P < 0.05). Compared with the blank control group, after treatment of K562/ADM cells with 0.5 μmol/L and 1.0 μmol/L kaempferol for 24 h, the relative expressions of P-gp, MRP1 and p-p38 protein were decreased in K562/ADM cells (all P < 0.05), but there was no statistical difference in the expression of t-p38 protein ( P > 0.05); SB202190 could reduce the relative expressions of P-gp, MRP1 and p-p38 protein (all P < 0.05); after the treatment of SB202190 combined with different concentration of kaempferol, the relative expressions of P-gp, MRP1 and p-p38 protein in K562/ADM cells did not decrease ( P > 0.05). Conclusions:Kaempferol can decrease the relative expressions of P-gp and MRP1 in K562/ADM cells by inhibiting p38-MAPK pathway, so as to increase the concentrations of ADM and to reverse the drug resistance of K562/ADM cells.
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Objective@#To investigate the drug resistance of kaempferol reversed adriamycin (ADM)-resistant K562/ADM cells in chronic myelogenous leukemia (CML) and its related mechanism.@*Methods@#Methyl thiazolyl tetrazolium (MTT) method was used to detect the toxicity of ADM on K562 and K562/ADM cells for 24 h. The half inhibitory concentration (IC50) of ADM and the drug resistance multiple for 24 h were calculated. MTT method was used to detect the toxicity of kaempferol on K562/ADM cells for 24 h. The 5% inhibitory concentration (IC5) and 10% inhibitory concentration (IC10) of kaempferol for 24 h were calculated to determine the concentration of kaempferol in the subsequent experiments. And the cells untreated by the kaempferol were selected as the control group. The cell inhibition after the treatment of ADM for 24 h of the blank control group and kaempferol intervention group was detected by using MTT method. And then the cell inhibition for 24 h and ADM IC50 for 24 h in the above groups were calculated. The ratio of IC50 in the blank control group and kaempferol group was the reversal drug resistance multiple of kaempferol. The fluorescence intensity of ADM in K562/ADM cells treated by kaempferol was detected by using flow cytometry. Western blotting was used to detect the expressions of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), phosphorylated p38 (p-p38), and total p38 (t-p38) protein in K562/ADM cells after the treatment of kaempferol, the specific inhibitor of p38-MAPK signaling pathway SB202190, and the combination of kaempferol and SB202190.@*Results@#After the treatment of ADM for 24 h, the IC50 value of K562 and K562/ADM cells was (0.9±0.6), (28.1 ±3.5) μg/ml, respectively. The drug resistance multiple of K562/ADM cells on the treatment of ADM for 24 h was 31.16 compared with the K562 cells. MTT method showed that kaempferol inhibited the proliferation of K562/ADM cells in a dose-dependent manner. According to the IC5 and IC10, 0.5 μmol/L and 1.0 μmol/L kaempferol were determined to do the subsequent experiments. After the combined interaction of kaempferol and ADM for 24 h, the ADM IC50 of K562/ADM cells in the blank control group, 0.5 μmol/L kaempferol group and 1.0 μmol/L kaempferol group was (33.7±5.7), (21.4±0.6), (15.9±1.8) μg/ml, respectively (F = 30.85, P < 0.05), and there was a statistical difference of pairwise comparison (both P < 0.05). The reversal drug resistance multiple of K562/ADM cells for 24 h in 0.5 μmol/L kaempferol group and 1.0 μmol/L kaempferol group was 1.58 and 2.12, respectively. Flow cytometry results showed that the mean fluorescence intensity (MFI) of ADM in the blank control group, 0.5 μmol/L kaempferol group and 1.0 μmol/L kaempferol group was 138.4±8.9, 154.3±2.2, 165.7±4.8, respectively, and the difference was statistically significant (F = 161.48, P < 0.05). Compared with the blank control group, after treatment of K562/ADM cells with 0.5 μmol/L and 1.0 μmol/L kaempferol for 24 h, the relative expressions of P-gp, MRP1 and p-p38 protein were decreased in K562/ADM cells (all P < 0.05), but there was no statistical difference in the expression of t-p38 protein (P > 0.05); SB202190 could reduce the relative expressions of P-gp, MRP1 and p-p38 protein (all P < 0.05); after the treatment of SB202190 combined with different concentration of kaempferol, the relative expressions of P-gp, MRP1 and p-p38 protein in K562/ADM cells did not decrease (P > 0.05).@*Conclusions@#Kaempferol can decrease the relative expressions of P-gp and MRP1 in K562/ADM cells by inhibiting p38-MAPK pathway, so as to increase the concentrations of ADM and to reverse the drug resistance of K562/ADM cells.
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Objective: To investigate the antitumor effect of osthole on human B-cell acute lymphoblastic leukemia (B-ALL) 697 cells and its possible mechanism. Methods: After B-ALL 697 cells were treated with different concentrations (8, 16, 32, 64 and 128 μmol/L) of osthole, the inhibition rate of cell proliferation was detected by CCK-8 assay. After B-ALL 697 cells were treated with 8 and 32 μmol/L osthole, the apoptosis was detected by FCM, the expressions of apoptosis-associated molecule Bcl-2 and Bax were detected by real-time fluorescent quantitative PCR and Western blotting. After B-ALL 697 cells were treated with 8 and 32 μmol/L osthole alone or in combination with autophagy inhibitor 3-methyladenine (3-MA), the intracellular mean fluorescent intensity (MFI) was detected by FCM [stained by monodansylcadaverine (MDC)] to reflect the autophagy. The expressions of autophagy-associated molecule Beclin 1 mRNA and protein was detected by real-time fluorescent quantitative PCR and Western blotting, respectively. Results: The proliferation of B-ALL 697 cells in 8, 16, 32, 64 or 128 μmol/L osthole treatment group was significantly inhibited in a dose-and time-dependent manner (all P 0.05). Conclusion: Osthole inhibits the proliferation, and induces the apoptosis and autophagy of B-ALL 697 cells. The mechanism of promoting apoptosis may be related to the up-regulation of Bax expression and the down-regulation of Bcl-2 expression. Beclin 1 participates in the autophagy.
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Electrospun polyhydroxybutyrate (PHB)/carboxyl multi-walled carbon nanotubes grafted polyhydroxybutyrate (CMWCNT-g-PHB) composite nanofibers scaffolds were fabricated by electrospinning technology. The grafted product CMWCNT-g-PHB was prepared by condensation reactions between the carboxyl groups of CMWCNT and hydroxyl groups of PHB molecules and characterized by FTIR, XRD, XPS, TG and TEM measurements. The surface morphology, hydrophilicity and tensile mechanical properties of the electrospun PHB/CMWCNT-g-PHB composite nanofibers membrane scaffolds were investigated. The values of tensile strength, breaking elongation rate, initial modulus and fracture energy of the composite nanofibers scaffolds can reach to 4.64MPa, 255.59%, 88MPa and 109.73kJ/m2, respectively. The biodegradability and cytocompatibility of the electrospun composite nanofibers scaffolds were preliminarily evaluated. The as-prepared electrospun PHB/CMWCNT-g-PHB composite nanofibers scaffolds with the characteristics of large specific area, high porosity, good biodegradability and cytocompatibility as well as sufficient mechanical properties should be more promising in the field of tissue engineering scaffolds and biological medicine.
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Materiales Biocompatibles/química , Hidroxibutiratos/química , Nanotubos de Carbono/química , Andamios del Tejido/química , Nanofibras/química , Espectroscopía Infrarroja por Transformada de Fourier , Ingeniería de Tejidos/métodosRESUMEN
Objective To explore the effect of proliferation and apoptosis of Solanine on acute T lymphocyte leukemia (T-ALL) Jurkat cells and its mechanism.Methods After treated with different concentrations of Solanine,the proliferation of Jurkat cells was detected by CCK-8 assay,and the effect of Solanine on apoptosis of Jurkat cells were detected by flow cytometry.The expression of Bcl-2 and Bax in Jurkat cells were detected by Western blot,and the expression levels of Bcl-2 mRNA and Bax mRNA were detected by real-time fluorescence quantitative polymerase chain reaction.Results CCK-8 assay showed that Solanine significantly inhibited the proliferation of Jurkat cells in a dose-and time-dependent manner.The results of flow cytometry showed that the apoptosis rates of Jurkat cells treated with Solanine for 24 h were (2.40-± 0.98) %,(28.43-± 4.86) %,(41.56-± 1.87) %,respectively,in a dose-dependent manner.Western blot showed that Solanine could increase the expression of Bax and decrease the expression of Bcl-2 in Jurkat cells,and they all were dose-dependent.Conclusion Solanine can significantly inhibit the proliferation and induce apoptosis of Jurkat cells.The mechanism is related to the up-regulation of Bax expression and down-regulation of Bcl-2 expression.
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Objective: Looking for the suitable areas of Lamiophlomis rotata based on 3S technology in Sichuan province to provide the basis for reasonable exploitation and protection of the L. rotata resource. Methods: By the ways of field researching and reviewing the related literature on L. rotata, to confirm its habitat characteristics. RS and GIS software was used to extract the environment factors such as climate, soil, topographic features, and community of L. rotata. The spatial overlay analysis on the various environmental factors were carried out to determine the distribution of L. rotata in Sichuan province. The area and combining with GPS was calculated to verify in field. Results: The result indicated that the suitable areas of L. rotata found by using 3S technology were generally consistent with the actual distribution of L. rotata. The suitable areas of L. rotata in Sichuan province were mainly distributed in 20 counties such as Aba country and Litang country. The total area of the suitable areas is about 135 200 hm2, accounting for 0.17% of the district area. Conclusion: Planting and protecting L. rotata in the suitable area will be benefit to the reasonable exploitation and protection of the L. rotata resource; This research method has the characteristics of scientificity and accuracy, which can be extended to other suitable area research of Chinese herbal medicine.
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Objective To analyze the clinical characteristics of pseudohypoparathyroidism ( PHP ) inpatients in our hospital from January 2008 to December 2017 and to gain a better understanding of this disorder. Methods 18 inpatients diagnosed as sporadic PHP in our hospital were analyzed retrospectively, as regarding the clinical manifestation, laboratory examination and imaging data. Results 18 inpatients were diagnosed sporadic PHP consisting of 12 males and 6 females, with 13 adults and 5 child participants respectively. The medium age of onset was 14 (6-57), and the average age at diagnosis was (24.9± 14.7) years old. Initial onset of symptoms reported were: 12 patients complained of tetany, 3 reported convulsions, 1 reported numbness, 1 reported dysnoesia, and 1 were asymptomatic. Among them: 3 patients were found to have short distal phalanx, 7 displayed a round face, and 3 out of 15 adults were less than 155 cm in height. 12 patients had a positive Trousseau sign, 1 had an ectopic calcification. 11 were found to have intercranial massive calcifications by head computed tomography. Serum calcium was reported at (1.58 ± 0.11) mmol/ L and parathyroid hormone was (359.5 ± 146.6) pg/ ml. 3 patients were discovered to have hypothyroidism, 2 had been misdiagnosed with epilepsy, and 1 with encephalitis. Conclusions Tetany and intracranial calcifications were the most common signs of PHP patients. A number of the PHP cases in this study lacked typical Albright's Hereditary Osteodystrophy ( AHO) appearance. The age of onset and or duration of the disease varied somewhat in the different patient populations. The heterogeneity nature of the clinical manifestations of PHP makes it difficult to diagnose. It is therefore important to make accurate differential diagnosis of PHP to avoid misdiagnosis of the condition.
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Swertia mussotii is a kind of rare medicinal materials, the relevant researches are mainly concentrated on its medicinal efficacy and medicinal value till now, researches of adaptive distribution by applying remote sensing and GIS are relatively less. This study is to analyze the adaptive distribution of S.mussotii in Sichuan province by applying remote sensing and GIS technology, and provide scientific basis for the protection and development of wild resources, artificial cultivation and adjustment of Chinese medicine industrial distribution in Sichuan province. Based on literature review and ecological factors such as altitude, annual precipitation and annual average temperature, this study extracted ecological factors, overlay analysis in GIS, as well as combining GPS field validation data by means of remote sensing and GIS, discusses the adaptive distribution of SMF sin Sichuan province. ①The area of adaptive distribution of S. mussotii in Sichuan province is 1 543.749 km², mainly in Dege county, Ganzi county, Daofu county, Kangding county, Barkam, Jinchuan county, Xiaojin county, Danba county, Daocheng county, Xiangcheng county, Xinlong county, Aba county, Muli county and other counties and cities, accounts for about 7.25% in total area. ② Combining statistical information and field validation, this study found that S. mussotii adaptive distribution gained by remote sensing and GIS is in conformity with its actual distribution. The study shows that remote sensing and GIS technology are feasible to obtain the S. mussotii adaptive distribution, they can further be applied to studies on adaptive distributions of other rare Chinese medicinal herb.
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Paris yunnanensis is a kind of rare medicinal herb, having a very high medicinal value. Studying its suitable ecological condition can provide a basis for its rational exploitation, artificial cultivation, and sustainable utilization. A practicable method in this paper has been proposed to research the suitable regional distribution of P. yunnanensis in Sichuan province. By the case study of P. yunnanensis in Sichuan province, and according to related literatures, the suitable ecological condition of P. yunnanensis such as altitude, mean annual temperature (MAT), annual precipitation, regional slope, slope ranges, vegetative cover, and soil types was analyzed following remote sensing (RS) and GIS.The appropriate distribution regionof P. yunnanensis and its area were extracted based on RS and GIS technology,combing with the information of the field validation data. The results showed that the concentrated distribution regions in counties of Sichuan province were, Liangshan prefecture, Aba prefecture, Sertar county of Ganzi prefecture, Panzhihua city, Ya'an city, Chengdu city, Meishan city, Leshan city, Yibin city, Neijiang city, Luzhou city, Bazhong city, Nanchong city, Guangyuan city and other cities and counties area.The suitable distribution area in Sichuan is about 7 338 km², accounting for 3.02% of the total study regional area. The analysis result has high consistency with the filed validation data, and the research method for P. yunnanensis distribution region based onspatial overlay analysis and the extracted the information of land usage and ecological factors following the RS and GIS is reliable.
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Objective: To investigate the effect of solanine on multidrug resistance of leukemia K562/ADR cells, and to explore its mechanism. Methods: K562/ADR cells were treated with different concentrations (5-40 μg/mL) of solanine alone or in combination with doxorubicin (DOX) for 24 h. The intracellular toxicity and DOX-sensitization effect of solanine were detected by CCK-8 assay. The cell-associated mean fluorescence intensity of DOX was detected by FCM method. The expressions of multidrug resistance-associated protein 1 (MRP1), c-Jun NH2-terminal kinase (JNK), and phosphorylated JNK (p-JNK) were determined by Western blotting. Results: Solanine at non-toxic doses (5 and 10 μg/mL) significantly enhanced the cytotoxicity of DOX (both P < 0.05), and significantly increased the mean fluorescence intensity of DOX in K562/ADR cells in a dose-dependent manner (both P < 0.05). After treatment with 5 and 10 μg/mL solanine, the expression levels of MRP1 and p-JNK proteins were significantly decreased (all P < 0.05) in K562/ADR cells. Conclusion: Solanine can reverse multidrug resistance of K562/ADR cells in vitro. The mechanism may be related to blocking JNK signaling pathway and downregulating MRP1 expression.
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Multidrug resistance (MDR) is the main reason for the failure of leukemia chemotherapy.Autophagy plays an important role in the regulation of MDR.On one hand,as a mechanism of programmed cell death,autophagy can directly induce the death of MDR cells.On the other hand,protective autophagy induced by different signaling pathways and factors such as Hedgehog (Hh) signaling pathway and p53 can promote the survival of MDR cells.Therefore,autophagy agonist or autophagy inhibitors combined with chemotherapeutics will be a new strategy for the treatment of leukemia.