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ObjectiveTo investigate the risk factors and construct a predictive model for severe myelosuppression due to chemotherapy in triple negative breast cancer (TNBC). MethodsPatients with TNBC who received anthracycline combined with cyclophosphamide sequential paclitaxel chemotherapy regimen at the Second Affiliated Hospital of Nanchang University from September 2, 2016 to September 2, 2021 were selected and assigned to severe myelosuppression group and no/mild myelosuppression group. The χ2 test and binary logistic regression were used to analyze the risk factors for severe myelosuppression due to chemotherapy and to develop a prediction model. Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were used to evaluate the predictive efficiency of the regression model. Kappa consistency test was used to verify the regression model externally. ResultsA total of 207 patients who met the inclusion were enrolled and 106 patients (51%) had severe myelosuppression. Binary logistic regression multivariate analysis showed that age 40 to 60 years (OR = 3.463, 95% CI: 1.144 to 10.486, P = 0.028), age >60 years (OR = 3.474, 95% CI: 1.004 to 12.020, P = 0.049), body mass index (BMI) 18.5 to 24.0 (OR = 1.445, 95% CI: 0.686 to 3.087, P = 0.328), BMI <18.5 (OR = 3.582, 95% CI: 1.260 to 10.182, P = 0.017), tumor TNM stage Ⅱ (OR = 1.698, 95% CI: 0.831 to 3.468, P = 0.146), tumor TNM stage Ⅲ (OR = 2.943, 95% CI: 1.199 to 7.227, P = 0.019), previous diabetes (OR = 2.441, 95% CI: 1.076 to 5.539, P = 0.033), low pre-treatment albumin level (OR = 2.759, 95% CI: 1.141 to 6.669, P = 0.024) and low pre-treatment lymphocytes (OR = 3.428, 95% CI: 1.689 to 6.958, P = 0.001) were independent risk factors for severe myelosuppression due to chemotherapy. The χ2 value for the logistic regression model Hosmer-Lemeshow test was 11.507, P= 0.175, the area under the ROC curve was 0.763, standard error 0.033, 95% CI: 0.698-0.828, P=0.000. External validation showed that the prediction model had a specificity of 88% and a sensitivity of 80%; the kappa value was 0.679, standard error 0.081, P=0.000. conclusionThis logistic regression model had high predictive efficacy and is useful for clinicians to predict whether patients with TNBC develop severe myelosuppression.
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In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
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Mice , Animals , Hedgehog Proteins/genetics , Receptors, G-Protein-Coupled/metabolism , Cilia/metabolism , Cartilage/metabolism , RegenerationРеферат
The volatile oil of Chuanxiong Rhizoma(CX) is known as an effective fraction. In order to seek a suitable method for processing CX and its decoction pieces, this study selected 16 volatile components as indices to investigate how different processing methods such as washing/without washing, sun-drying, baking, oven-drying and far-infrared drying at different temperatures affected the quality of CX and its decoction pieces(fresh CX was partially dried, cut into pieces, and then dried) by headspace gas chromatography-mass spectrometry(GC-MS), cluster analysis, principal component analysis and comprehensive weighted scoring. The results showed that the rapid washing before processing did not deteriorate the volatile components of CX. Considering the practical condition of production area, oven-drying was believed to be more suitable than sun-drying, baking, and far-infrared drying. The CX decoction pieces with a thickness of 0.3-0.4 cm were recommended to be oven-dried at 50 ℃. The integrated processing(partial drying, cutting into pieces, and drying) did not cause a significant loss of volatile components. For the fresh CX, the oven-drying at 60 ℃ is preferred. The temperature should not exceed 60 ℃, and drying below 60 ℃ will prolong the processing time, which will produce an unfavorable effect on volatile components. This study has provided the scientific evidence for field processing of CX, which is conducive to realizing the normalization and standardization of CX processing in the production area and stabilizing the quality of CX and its decoction pieces.
Тема - темы
Desiccation , Gas Chromatography-Mass Spectrometry/methods , Oils, Volatile , Principal Component Analysis , Rhizome/chemistry , Volatile Organic Compounds/analysisРеферат
OBJECTIVES@#This study aimed to explore the short-term clinical efficacy and factors influencing low-dose superficial X-ray for treating infantile maxillofacial hemangioma.@*METHODS@#Retrospective analysis was conducted on 161 cases of infants with maxillofacial hemangioma treated with superficial X-ray in the Laser Center of Dermatology Department of Sichuan Provincial People's Hospital from January 2015 to December 2017. Clinical efficacy was analyzed by comparing the photos before and after treatment. Patients were further divided into groups according to different genders, age at the start of treatment, preterm birth or low birth weight, hemangioma site, longest diameter of hemangioma, and type of hemangioma to analyze whether differences existed in clinical efficacy and therapeutic dose between different groups.@*RESULTS@#Twelve months after the end of treatment, the overall cure rate was 93.8%, and the significant efficiency was 97.5%. The clinical efficacy was related to the age of children at the beginning of treatment and the type of hemangioma (@*CONCLUSIONS@#Low-dose superficial X-ray is safe and effective for the treatment of infantile maxillofacial hemangioma. Age and type of hemangioma at the time of treatment are the factors influencing therapeutic dose and clinical efficacy.
Тема - темы
Child , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , Hemangioma , Premature Birth , Retrospective Studies , Skin Neoplasms , Treatment Outcome , X-RaysРеферат
At present, there is little research on the new teaching mode for the practice course of epidemiology. Based on the situation, this paper mainly discussed how the MOOC (Massive Open Online Course)-based multi-teaching mode was applied to the practice course of Epidemiology. The structure of this multi- teaching mode consisted of case base construction, class preparation, class presentation and learning evaluation. Thus, MOOC, flipped Class Mode and other new teaching modes were integrated into traditional face-to-face teaching. In addition, this paper also demonstrated the implementation of the multi-teaching mode in the teaching of preventive medicine. It is worth exploring how to integrate MOOC into the teaching of the practice course of epidemiology in the future.
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There were significant differences in phenolic acid content between fresh and dried Salvia miltiorrhiza before and after drying. That is to say, the content of phenolic acid in S. miltiorrhiza significantly increased with the increase of dehydration during the drying process.In order to investigate the differences and transformation of free and bound phenolic acids before and after the drying process of S.miltiorrhiza, we studied hydrolysis method, hydrolysates and hydrolysis regularity of phenolic acids in S.miltiorrhiza. UPLC method was used to determine four main hydrolysates of bound phenolic acids, namely danshensu, caffeic acid dimer(SMND-309), caffeic acid, przewalskinic acid A(prolithosperic acid), and three main free phenolic acids in S.miltiorrhiza, namely rosmarinic acid, lithospermic acid, salvianolic acid B. The results of the acid-base hydrolysis experiment of salvianolic acid showed that the alkaline hydrolysis effect was significantly better than acid hydrolysis. The optimal alkaline hydrolysis condition was hydrolysis at 70 ℃ for 4 h with 2 mol·L~(-1) NaOH solution containing 1% ascorbic acid(Vit C). The hydrolysates of free phenolic acids were the same with the hydrolysates of bound phenolic acids. Fresh S.miltiorrhiza contains a low level of free phenolic acids and a high level of bound phenolic acids, which were exactly opposite to dried S.miltiorrhiza. It was suggested that a large amount of bound phenolic acids was accumulated during the growth of S.miltiorrhiza. These bound phenolic acids were coupled with polysaccharides on the cytoderm through ester bonds to form insoluble phenolic acids, which was not easy to be detected by conventional methods. However, during drying and dehydration processes, the bound phenolic acids were converted to a large amount of free phenolic acids under the action of the relevant enzyme.
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Desiccation , Hydroxybenzoates/analysis , Salvia miltiorrhiza/chemistryРеферат
Objective@#To examine the prevalence of multiple anxiety disorder of adolescents in Lushan, Sichuan and to provide the scientific reference for a long-term psychological intervention and rehabilitation for adolescents after earthquake.@*Methods@#In May 2016, 3 741 students were sampled in two middle schools and two high schools in Lushan county. Self-report questionnaice regarding exposure to earthquake, Screen for Child Anxiety Related Emotional Disorders (SCARED), and negative life events questionnaire (ASLES) were administered to the subjects.@*Results@#The prevalence of anxiety symptoms of adolescents in Lushan, Sichuan was 42.3%, among which panic disorder was 36.3%; generalized anxiety was 29.5%, separation anxiety was 40.3%, social anxiety was 26.1%, school fear was 32.4%. Junior school students resported more symptoms of separation anxiety than high school students (χ2=33.09, P<0.01). The results of Logistic regression showed that girls (OR=2.34, 95%CI=2.00-2.74, P<0.01), high negative life events (OR=2.87, 95%CI=2.60-3.17, P<0.01), trapped in earthqnakes (OR=1.77, 95%CI=1.18-2.67, P<0.01), parents injured (OR=1.22, 95%CI=1.03-1.43, P=0.02), experienced extreme fear (OR=1.78, 95%CI=1.52-2.08, P<0.01) were associated with higher risk of anxiety disorder.@*Conclusion@#High prevalence of anxiety disorder among adolescent following disaster need to be alerted. Adolescents among female victim or those experienced extreme fear emotion or high frequencies of negative life events, need specific intervention.
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BACKGROUND@#Adjuvant (chemo)radiotherapy (A(C)RT) may be an important supplement to surgery for extrahepatic cholangiocarcinoma (EHCC). However, whether all patients would achieve benefits from A(C)RT and which adjuvant regimen, adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT), would be preferred, are still undetermined. The low incidence of EHCC makes it difficult to carry out randomized controlled trials (RCTs); therefore, almost all clinical studies on radiotherapy are retrospective. We have conducted a meta-analysis of these retrospective studies.@*METHODS@#We conducted a meta-analysis of current retrospective studies using PubMed, Embase, and ClinicalTrials databases. All studies published in English that were related to A(C)RT and which analyzed overall survival (OS), disease-free survival (DFS), or locoregional recurrence-free survival (LRFS) were included. Estimated hazard ratios (HRs) were calculated for OS, DFS, and LRFS.@*RESULTS@#Data from eight studies including 685 patients were included. Our analysis showed that A(C)RT significantly improved OS (HR 0.69, 95% confidence interval (CI) 0.48-0.97, P=0.03), DFS (HR 0.60, 95% CI 0.47-0.76, P<0.0001), and LRFS (HR 0.27, 95% CI 0.17-0.41, P<0.00001) of EHCC overall. In subgroups, patients with microscopically positive resection margin (R1) could achieve a benefit from A(C)RT (HR 0.44, 95% CI 0.27-0.72, P=0.001). No statistically OS difference was observed in negative resection margin (R0) subgroup (HR 0.98, 95% CI 0.30-3.19, P=0.98).Significant OS benefit was found in patients who received concurrent ACRT (HR 0.40, 95% CI 0.26-0.62, P<0.0001), while the result of ART without chemotherapy showed no significant benefit (HR 1.14, 95% CI 0.29-4.50, P=0.85). In the distal cholangiocarcinoma subgroup, no significant difference was seen when ACRT and ART were included (HR 0.61, 95% CI 0.14-2.72, P=0.52), but a significant difference was seen when analyzing the concurrent ACRT only (HR 0.29, 95% CI 0.13-0.64, P=0.002).@*CONCLUSIONS@#A(C)RT may improve OS, DFS, and LRFS in EHCC patients, especially in those with R1 resection margins. ACRT may be superior to ART especially in distal patients.
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Objective To analyze the mechanism of the influencing factors of myopia for junior high school students in China. Methods Based on the follow-up to 7 119 students in the 3 waves of questionnaire survey of the Chinese Education Panel Survey in junior high school stage, and the variables on students’ myopia status, myopia influencing factors, and two kinds of risk behaviors of myopia including near visual activities and outdoor activities, the mediation effects of the myopia risk behaviors were tested by Logistic regression model. Results The myopia prevalence of 9th graders before junior high school graduation was 66.36%. Time on writing homework significantly increased the risk of myopia,the odds ratio (OR) was 1.17,the 95% confidence interval (CI) was 1.13-1.21, and the time on outdoor sports significantly decreased the risk of myopia (OR=0.80,95% CI:0.75-0.86). Before and after including the risk behaviors into the model, the myopia risk OR(95% CI) of female centralized from 1.84(1.66-2.04) to 1.69(1.51-1.88), the myopia risk OR(95% CI) of urban students’centralized from 1.19(1.03-1.37) to 1.16(1.00-1.34), the myopia risk OR(95% CI) of only children’centralized from 1.20(1.06-1.36) to 1.18(1.04-1.33). With reference to not myopic for both parents, the myopia risk OR(95% CI) of students having one myopic parent centralized from 2.47(2.12-2.88) to 2.44(2.09-2.85), the myopia risk OR(95% CI) of students having parent without myopic centralized from 4.25(3.09-5.86) to 4.13(3.00-5.69). Conclusions Gender, urban and rural, only child, and myopic parents are influencing factors of myopia. These factors have effects on myopia via two kinds of risk behaviors including outdoor activities and near visual activities.
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There is no consensus on the drying methods of Salvia miltiorrhiza in ancient and modern times,especially on the content of phenolic acid in fresh S. miltiorrhiza. In order to further explore the content of main components in fresh S. miltiorrhiza and study the dynamic changes during the drying process,the content of main components was used as the index in this study to evaluate the processing method,drying method,correlation between dehydration rate and component content for fresh S. miltiorrhiza. In addition,the sealed and unsealed parallel control groups were set to carry out verification test during the drying process. UPLC method was used for determination of seven main components including rosmarinic acid,lithosperic acid,salvianolic acid B,cryptotanshinone,tanshinoneⅠ,methylene salianolate and tanshinone ⅡAin S. miltiorrhiza. The results showed that the fresh S. miltiorrhiza contained low levels of phenolic acid,and the content of phenolic acid increased significantly with the increase of dehydration rate during drying process,while the change of tanshinone was not obvious. In the comparison of three drying methods,we found that drying at 50 ℃ was better than drying in the sun,and drying in the sun was superior to drying in the shade. So,drying at 50 ℃ was the best drying method. The correlation between dehydration and phenolic acid content of S. miltiorrhiza was analyzed by verification test and SPSS software,which further proved that the dehydration rate was significantly positively correlated with the content of phenolic acid components. This study provides reference for the production processing and drying methods of S. miltiorrhiza medicinal materials,which is of great significance for improving the quality of S. miltiorrhiza.
Тема - темы
Abietanes , Desiccation , Plant Roots , Salvia miltiorrhizaРеферат
We analyzed the clinicopathological data of 3 cases of primary intraosseous hematopoietic pseudotumor (IHPT), which had been previously misdiagnosed as malignancies or metastases both clinically and pathologically. Two of the patients received close follow-up for 132 and 100 months, and one patient was lost to follow-up, and the tumors were confirmed to be benign in all the 3 cases. IHPT is a rare benign intraosseous solid lesion consisting of tissues resembling normal hematopoietic tissue, and can be easily misdiagnosed as malignancy. Understanding the clinicopathological features and the outcomes of the disease can facilitate the clinical decisions on individualized diagnosis and therapeutic regimens.
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Humans , Bone Marrow , Follow-Up Studies , Hematopoietic Stem Cell TransplantationРеферат
OBJECTIVE@#To obtain cancer stem cells (CSCs) from surgically resected colorectal cancer specimens and identify their stem cell characteristics.@*METHODS@#Colorectal cancer tissue specimen obtained from a patient undergoing radical resection of colorectal cancer were implanted in nude mice, and the xenograft was harvested 1 month later to obtain purified tumor cells by enzyme digestion and adherent culture. The CSCs were screened by limiting dilution method and serum-free culture to identify their phenotypes. Soft agar colony assay was used to assess the proliferative ability of the CSCs and human colorectal cancer cell line SW480. The tumorigenic ability of the isolated CSCs and SW480 cells was evaluated by observing their subcutaneous tumor formation in nude mice. Western blotting and immunofluorescence assay were used to detect the immunophenotype of the CSCs and SW480 cells.@*RESULTS@#The primary cultured CSCs from clinical specimens of colorectal cancer underwent differentiation in the presence of serum in the culture. Soft agar colony formation assay showed that the CSCs had a colony formation rate above 50%, significantly higher than the rate of colorectal cancer SW480 cells (4.41%; < 0.01). In nude mice, subcutaneous injection of 500 CSCs was sufficient to result in subcutaneous tumor formation, while the injection of 500 SW480 cells failed to form any subcutaneous tumors. The CSCs expressed CD133 and CD44 but not CK7, while SW480 cells expressed CK7 but not CD133 or CD44.@*CONCLUSIONS@#CSCs can be derived by primary culture of cancer cells obtained from surgically resected colorectal cancer tissue followed by serum-free culture, and the CSCs obtained have self-renewal and differentiation abilities.
Тема - темы
Animals , Humans , Mice , Cell Culture Techniques , Cell Differentiation , Cell Line, Tumor , Colorectal Neoplasms , Mice, Nude , Neoplastic Stem CellsРеферат
Objective To explore the consistency of different physicians in diagnosis of malignant breast lesions with breast CEUS predictive model.Methods Totally 953 patients with solitary breast nodule from multicenter who underwent ultrasound and CEUS were collected.The research team was composed by the initial group (one junior physician from each hospital),check group (one or two physicians who had at least two-year experience of CEUS examination from each hospital),research group (two senior physicians from Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) and cross-blinded group (one or two vice directors or chief physicians from each hospital).At first,the lesions were classified according to the breast imaging reporting and data system (BI RADS) by the initial group and the check group,then new BI RADS classifications were performed by research group and cross blind group with breast CEUS predictive model.The consistency of different physicians in diagnosis of malignant breast lesions was analyzed.Results Among 953 patients,benign lesions were found in 451 patients (451/953,47.32%),malignant lesions were found in 435 patients (435/953,45.65%),and precancerous lesions were found in 67 patients (67/953,7.03%).The accuracy of the initial group,check group,research group and cross-blinded group was 71.67%(683/953),74.92%(714/953),80.17% (764/953) and 83.42 % (795/953),respectively.The consistency of different physicians for diagnosis of malignant breast lesions between initial group and check group was good (Kappa =0.82,P<0.001),while between initial group and crossblinded group,initial group and research group were both moderate (Kappa =0.56,0.41;all P<0.001).The consistency of different physicians for diagnosis of malignant breast lesions between cheek group and cross-blinded group,between check group and research group were both moderate (Kappa =0.68,0.51;all P<0.001).The consistency between research group and cross-blinded group with breast CEUS predictive model was moderate (Kappa =0.74,P< 0.001).Conclusion The consistency of different physicians in diagnosis of malignant breast lesions with breast CEUS predictive model was moderate.
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The present study was to investigate the role of the interaction between canonical transient receptor potential channel 1 (TRPC1) and calcium release-activated calcium modulator 1 (Orai1) in extracellular Ca-sensing receptor (CaR)-induced extracellular Ca influx and nitric oxide (NO) production. Human umbilical vein endothelial cells (HUVECs) were incubated with CaR agonist Spermine [activating store-operated calcium channels (SOC) and receptor-operated calcium channels (ROC)] alone or in combination with the following reagents: CaR negative allosteric modulator Calhex231 plus ROC analogue TPA (activating ROC and blocking SOC), Ro31-8220 (PKC inhibitor that activates SOC and blocks ROC) or Go6967 (PKCs and PKCµ inhibitor that activates SOC and blocks ROC). The protein expressions and co-localization of TRPC1 and Orai1 were determined using immunofluorescent staining. The interaction between TRPC1 and Orai1 was examined by co-immunoprecipitation. We silenced the expressions of their genes in the HUVECs by transfection of constructed TRPC1 and Orai1 shRNA plasmids. Intracellular Ca concentration ([Ca]) was detected using Ca indicator Fura-2/AM, and NO production was determined by DAF-FM staining. The results showed that TRPC1 and Orai1 protein expressions were co-located on the cell membrane of the HUVECs. Compared with Spermine+Ca group, Calhex231+ TPA+Spermine+Ca, Ro31-8220+Spermine+Ca and Go6976+Spermine+Ca groups exhibited down-regulated protein expressions of TRPC1 and Orai1 in cytoplasm and decreased co-localization on the cell membrane. Co-immunoprecipitation results showed that the interaction between TRPC1 and Orai1 was reduced by Calhex231 plus TPA, Ro31-8220 or Go6976 addition in the Spermine-stimulated HUVECs. Double knockdown of Trpc1 and Orai1 genes significantly decreased [Ca] level and NO production in all of the Spermine+Ca, Calhex231+TPA+Spermine+Ca, Ro31-8220+Spermine+Ca and Go6976+Spermine+Ca groups. These results suggest that TRPC1/Orai1 may form a complex that mediates Ca influx and No production via SOC and ROC activation.
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Objective To analyze the implement value of hierarchical management mode for nurses in intensive care unit. Methods The hospital implemented a hierarchical management mode in the intensive care unit from December 2016. We randomly selected 60 patients before and 60 patients after hierarchical management from intensive care unit as study subjects. Satisfaction of nursing work were collected using the self-made nursing satisfaction scale in our hospital. Psychological condition of nurses was assessed using SAS and SDS scales before and after implementation of the hierarchical management mode. At the same time, the incidence of adverse nursing events in different periods was counted. The implement value of hierarchical management mode for nurses in intensive care unit was analyzed. Results The satisfaction rate of patients was 93. 33% after the implementation of the hierarchical management mode, and 80. 00% before implementation, the difference was statistically significant before and after the implementation of management (P<0. 05). The SAS and SDS scores of the nurses were all lower than those before the implementation of hierarchical management (P<0. 05). The incidence of various types of adverse nursing events was 6. 67%(4 cases) after the implementation of hierarchical management and 20. 00% before the implementation, and the difference was statistically significant before and after implementation (P<0. 05). Conclusion Hierarchical management to nurses in the intensive care unit will help improve the satisfaction of patients and quality of nursing, reduce the incidence of adverse care events, and increase nurses' working enthusiasm.
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Objective To investigate and analyze the effect of pantoprazole and omeprazole in the treatment of gastric ulcer.Methods a total of 100 patients with gastric ulcer treated in Shizuishan First People's Hospital from January 2014 to June 2016 were selected and randomly divided into the control group and the experimental group, with 50 patients in each group.The control group was treated with omeprazole, and the experimental group was treated with pantoprazole.After taking one course of treatment, the clinical efficacy, treatment cost, eradication rate of Helicobacter pylori and recurrence rate of gastric ulcer were compared between the 2 groups.Results The total effective rate of the experimental group was 94%, which was significantly higher than that of the control group(72%), and the difference was statistically significant(P<0.05).After the corresponding treatment, the experimental group of 50 cases, Helicobacter pylori eradication rate was 72%, the recurrence rate of gastric ulcer was 12%.In the control group of 50 cases, the eradication rate of Helicobacter pylori was 52%, and the recurrence rate of gastric ulcer was 36%.As a result, the eradication rate of H.pylori in the experimental group was significantly higher than that in the control group.The cost of treatment in the control group was(499.78±74.81)yuan, and the treatment cost of the experimental group was(413.26±56.39)yuan.The treatment cost and gastric ulcer recurrence rate in the control group were significantly higher than those in the experimental group, with statistical difference(P<0.05).Conclusion Pantoprazole in the treatment of gastric ulcer is much better than omeprazole, high treatment efficiency, is the preferred drug for the treatment of gastric ulcer, after the treatment of gastric ulcer recurrence rate is low, the cost of treatment is low and high eradication rate, with the further promotion and application in clinic significance.
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OBJECTIVE To make a comparison of sensitivity and specificity between serum miR-122 and traditional biomarkers of drug-induced liver injury. METHODS Acetaminophen (APAP, 1250 mg · kg-1, ig), α-naphthylisothiocyanate (ANIT, 150 mg · kg-1, ig), methionine-choline deficient diet (MCDD, free feeding) and carbon tetrachloride (CCl4, 50%, ip) were used to establish hepatocellular injury, cholestasis, steatosis and fibrosis models, respectively, which were used to evaluate the sensitivity of serum miR-122 as a biomarker of drug-induced liver injury, when compared with the traditional biomarkers. Isoprenaline hydrochloride (IH) and gentamicin (GM) were used to establish myocardial and renal injury models, respectively, which were used to evaluate the specificity of serum miR-122, when compared with the tradi-tional biomarkers. Serum and liver tissues were collected at different time points during the study. Tradi-tional biomarkers such as glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT) and total bilirubin (TBIL) were measured with an automatic biochemistry analyzer. MiR-122 was detected with real- time quantitative PCR. Histopathological examination with HE staining was performed for liver tissues. RESULTS Serum miR-122 increased significantly earlier [miR-122 was signifi-cantly increased (>2 fold) at 1.5 h, 3 h, 2 weeks and 4 weeks after treatment in the four models respec-tively, while no significant increase (<2 fold) was observed for GPT, GOT and TBIL at 6 h, 12 h, 3 weeks and 6 weeks after treatment in the four models respectively] and more signficantly (the maximum fold change for miR-122 was 235.8, 202.7, 73.8 and 600.3 for the four models, respectively. For the GPT, the maximum fold change was 9.5, 3.9, 2.5 and 6.6, respectively; 6.0, 2.4, 1.4 and 3.5 respectively for GOT; 2.6, 2.3, 1.2 and 1.8 respectively for TBIL) than that of traditional biomarkers in hepatocellular injury, cholestasis, steatosis and fibrosis models, when compared with the control group. In the myocar-dial injury model, a significant increase of GOT was observed after IH treatment (2.1 fold), while no change was observed for serum miR-122. In the renal injury model, no false positive results were observed for serum miR-122. CONCLUSION Serum miR-122 can be used as a biomarker of drug-induced liver injury and serum miR-122 is more sensitive and specific than traditional biomarkers (such as GPT, GOT and TBIL).
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Objective@#To investigate the interaction of Ca2+ protein TRPC1 and STIM1 in extracellular Ca2+ -sensing receptor (CaR)-induced extracellular Ca2+ influx and the production of nitric oxide (NO).@*Methods@#Human umbilical vein endothelial cells (HUVECs) were cultured and incubated with CaR agonist spermine (activating store-operates cation channels (SOC) and receptor-operated channels (ROC)), CaR negative allosteric modulator Calhex231 (blocking SOC, activating ROC) and ROC analogue TPA (activating ROC, blocking SOC), protein kinase C (PKC) inhibitor Ro31-8220, PKCs and PKCμ inhibitor Go6967(activate SOC, blocking ROC), respectively. The interaction of TRPC1 and STIM1 was determined using the immunofluorescence methods. The interaction between TRPC1 and STIM1 were examined by Co-immuno precipitation. The HUVECs were divided into: TRPC1 and STIM1 short hairpin RNA group (shTRPC1+ shSTIM1 group), vehicle-TRPC1+ vehicle-STIM1 group and control group. The cells were incubated with four different treatments under the action of above mentioned interventions, intracellular Ca2+ concentration ([Ca2+ ]i) was detected using the fluorescence Ca2+ indicator Fura-2/AM, the production of NO was determined by DAF-FM.@*Results@#(1) The expression of TRPC1 and STIM1 proteins levels in HUVECs: Under the confocal microscope, TRPC1 and STIM1 protein expression showed masculine gender, both located in cytoplasm in the normal control group. Post incubation with Calhex231+ TPA, Ro31-8220 and Go6967, TRPC1 and STIM1 positioned in cytoplasm was significantly reduced, and the combined TRPC1 and STIM1 was also significantly reduced. (2) The interaction of TRPC1 and STIM1 in HUVECs: The relative ratios of Calhex231+ TPA+ Spermine+ Ca2+ group, Ro31-8220+ Spermine+ Ca2+ group and Go6976+ Spermine+ Ca2+ group STIM1/TRPC1 and TRPC1/STIM1 were as follows: (25.98±2.17)% and (44.10±4.01)%, (20.85±1.01)% and (46.31±3.47)%, (23.88±2.05)% and (39.65±2.91)%, which were significantly lower than those in the control group (100.00±4.66)% and (100.00±6.40)% and in the Spermine+ Ca2+ group (106.04±2.45)% and (107.78±2.66)% (all P<0.05). (3) The influence of joint TRPC1 and STIM1 transfection to four different drugs treated HUVECs on [Ca2+ ]i and NO generation: The changes of two excitation fluorescence intensity ratio and NO net fluorescence intensity values were consistent, [Ca2+ ]i and NO net fluorescence intensity values were significantly lower in the experimental group than the control group and the vehicle group (all P<0.05), while which were similar between the vehicle group and control group (all P>0.05).@*Conclusions@#Our results indicate that TRPC1 and STIM1 jointly regulate CaR-mediated Ca2+ influx and nitric oxide generation in HUVECs in the form of binary complex.
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Objective To investigate the differences in the expression of PHF20 and Bax and their correlations in non-small cell lung cancer before chemotherapy.Methods An immunohistochemical method was used to detect the expression of PHF20 and Bax in non-small cell lung cancer,and to analyze the clinical significance of PHF20 and the possible correlation between PHF20 and Bax proteins.Results PHF20 protein is expressed in the cytoplasm of non-small cell lung cancer cells.Moreover,it is highly expressed in squamous cell carcinoma,less expressed in adenocarcinoma,and closely related with cell differentiation,TNM staging,and lymph node metastasis.The expression of PHF20 and Bax was positively correlated with squamous cell lung carcinoma.Conclusion The expression of PHF20 in non-small cell lung cancer is closely associated with tumor progression and the expression of Bax.PHF20 may be a new target for the treatment of non-small cell lung cancer.
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Objective this research mainly analysis in the treatment of patients with ischemic cerebrovascular disease by comparison of clinical therapeutic effect of endovascular treatment and simple drug treatment. Methods 60 cases of patients with ischemic cerebrovascular disease admitted in our hospital from January 2016 to January 2017, and were randomly divided into control group and observation group, 30 cases in each group. The control group were treated by endovascular treatment, the observation group were treated with simple drug treatment, the two groups of patients treated for 6 months, 12 months to improve blood flow, the incidence of cerebrovascular events, mortality, prognosis Quality of life scores as a comparison basis.Results The patients in the observation group were treated for 6 months, 12 months after the blood flow improved superior to the patients in the control group (P<0.05); the patients in the observation group were treated for 6 months, 12 months of cerebrovascular disease incidence rate lower than that of the control group (P<0.05); the observation group after 6 months treatment and mortality of patients in the control group had no significant difference; the patients in the observation group after 12 months of treatment the mortality rate lower than that of the control group (P<0.05). The patients in the observation group survival quality scores were excellent in the control group (P<0.05). Conclusion The study proves that, in the treatment of patients with ischemic cerebrovascular disease in the treatment can effectively improve the treatment effect of endovascular intervention, improve the blood flow status of patients, reduce the events in patients with cerebrovascular disease incidence and mortality.