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BACKGROUND: One of the effects of Steamed Panax notoginsen (SPN) is to replenish blood, which is mostly used to treat anemia in clinic. SPN has the effect of treating anemia and Alzheimer's disease (AD) in clinical and basic research. In traditional Chinese medicine, anemia and AD have the same characteristics, and their symptoms are qi and blood deficiency. METHODS: First, data analysis was carried out through network pharmacology to predict the action targets of SPN homotherapy in the treatment of AD and anemia. Specifically, TCMSP and relevant literature were used to screen the main active ingredients of Panax notoginseng, and SuperPred was used to predict the action targets of the active ingredients. Disease targets related to AD and anemia were collected through Genecards database, and STRING and protein interaction (PPI) was used for enrichment analysis, Analyze the characteristics of the active ingredient target network on the Cytascape 3.9.0 platform, and use Metascape to enrich the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment (KEGG pathway). Then Drosophila was used as the AD animal model, and the effects of SPN on the climbing ability, olfactory memory and brain Aß, with rats as anemia animal models, the improvement effect of SPN on blood routine and organ index of rats with blood deficiency induced by CTX and APH was analyzed to further explain the therapeutic effect of SPN on these two diseases. Finally, the regulatory effect of SPN on the key active target of allotherapy for AD and anemia was verified by PCR. RESULTS: After the screening, 17 active components and 92 action targets of SPN were obtained. The degree values of components and the first 15 targets are NFKB1, IL10, PIK3CA, PTGS2, SRC, ECFR, CASP3, MTOR, IL1B, ESR1, AKT1, HSP90AA1, IL6, TNF, and Toll-like receptor, it is mainly related to inflammatory response, immune regulation and antioxidation. SPN improved the climbing ability, olfactory memory ability, and Aß42 content in the brain of Aß flies, and significantly reduced the expression of TNF and Toll-like receptor in the brain after treatment. SPN can significantly improve the blood routine index and organ index of anemia rats, and also significantly reduce the expression of TNF and Toll-like receptor in the brain after treatment. CONCLUSION: SPN can regulate the expression of TNF and Toll-like receptor to achieve the same treatment of AD and anemia.
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Doença de Alzheimer , Anemia , Medicamentos de Ervas Chinesas , Panax notoginseng , Animais , Ratos , Doença de Alzheimer/tratamento farmacológico , Receptores Toll-Like , Encéfalo , Anemia/tratamento farmacológico , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
Objective@#To explore the factors associated with the transplant outcomes after the treatment of preimplantation genetic testing (PGT) for infertile patients.@*Methods@# A retrospective analysis of data of frozen⁃thawed embryo transfers in PGT for structural rearrangements/PGT for monogenic ( PGT⁃SR/PGT⁃M) cycles was performed. According to the transplant outcomes , it was divided into the pregnancy group (74 cases) and the nonpregnancy group (74 cases) . The factors including male age , female age , duration of infertility , number of abortion , female BMI , follicle⁃stimulating hormone (FSH) , luteinizing hormone ( LH) , estradiol( E2) , progesterone(P) , blood glucose , insulin , albumin , total cholesterol , triglycerides , high⁃density lipoprotein( HDL) , parents ′causes of infertility , type of chromosomal abnormality , number of retrieved oocyte , number of meiosis II( MII) , number of fertilization , number of two pronuclei(2PN) , endometrial thickness on embryo transfer day , endometrial preparation , day of embryo development , presence of a top quality embryo ( TQE) or not were analyzed by the Mann⁃Whitney U test and Pearson ′s chi⁃square test. The probability of transplant outcomes in correlation with the relevant parameters analyzed was measured with multivariate logistic regression analysis.@*Results@#Univariate analysis indicated that E2 , insulin , total cholesterol , triglycerides and endometrial preparation were significantly associated with transplant outcomes in PGT⁃SR , PGT⁃M cycles (P < 0. 05) . Multiple logistic regression analysis revealed that lower levels of insulin ( OR = 0. 14 , 95% CI = 0. 03 - 0. 27) and triglycerides ( OR = 1. 38 , 95% CI = 0. 14 -2. 78) in women were beneficial to transplant outcomes in PGT cycles. For endometrial preparation , compared with natural cycles , hormone replacement therapy (HRT) cycles ( OR = 3. 52 , 95% CI = 2. 54 - 4. 65) were another factor to improve transplant outcomes.@*Conclusion@#There is a correlation between the levels of insulin and triglycerides , endometrial preparation and transplant outcomes in PGT cycles. In detail , lower levels of insulin and triglycerides , and the HRT cycle can lead to a better transplant outcome.
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Objective:To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy.Methods:A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis.Results:A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included“original_ngtdm_Strength”(0.49 vs. -0.61, P=0.006), “wavelet-HLH_glszm_ZonePercentage”(0.67 vs. -0.22, P=0.024),“wavelet-LHL_ngtdm_Strength”(1.20 vs. -0.51, P=0.002), “wavelet-HLL_gldm_LargeDependenceEmphasis”(-0.84 vs. 0.19, P=0.002), “wavelet-HLH_glcm_Id” (-0.30 vs. 0.43, P=0.037),“wavelet- HLH_glrlm_RunPercentage”(0.45 vs. -0.01, P=0.032),“wavelet-LHH_firstorder_Skewness”(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95% CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95% CI 0.817-0.997) according to ROC curve analysis. Conclusions:Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.
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Objective:To investigate the value of quantitative parameters of magnetic resonance imaging (MRI) in predicting the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy for children and adolescents with mature aggressive B-cell non-Hodgkin lymphoma (NHL).Methods:It was a retrospective multicenter study.Clinical data of 44 children and adolescents diagnosed with mature aggressive B-cell NHL between January 2016 and January 2023 in Henan Cancer Hospital, Beijing Gaobo Boren Hospital, and the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed.Patients were divided into complete response (CR) group and non-CR group based on the international criteria for the diagnosis of pediatric NHL.Quantitative parameters of MRI, including T2 signal intensity, the minimal apparent diffusion coefficient (ADCmin), maximal ADC (ADCmax), and the mean ADC (ADCmean) were measured before and within 2 weeks after CAR-T infusion.The correlation between the above parameters and the achievement of CR was analyzed.The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement among observers in measuring quantitative parameters of MRI.Differences between groups were analyzed using the independent sample t-test.Factors influencing CR were identified through the binary Logistic regression analysis, and a prediction model was established.Model performance was evaluated by plotting receiver operating characteristic (ROC) curves. Results:Significant differences were observed between the CR group and non-CR group in T2 signal intensity before CAR-T infusion (267±152 vs.364±160, P=0.048), and ADCmin (0.94±0.38 vs.0.53±0.28, P<0.05), ADCmax (1.73±0.69 vs.0.84±0.43, P<0.05), ADCmean (1.28±0.48 vs.0.67±0.33, P<0.05), and T2 signal intensity within 2 weeks after CAR-T infusion (198±139 vs.345±168, P=0.004). A univariate prediction model was created by introducing the above quantitative parameters.The area under the curve (AUC), specificity, sensitivity, and accuracy of T2 signal intensity before CAR-T infusion in predicting the efficacy on children and adolescents with mature aggressive B-cell NHL were 0.800, 84.0%, 57.9%, and 72.7%, respectively.The AUC, specificity, sensitivity, and accuracy of ADCmax within 2 weeks of CAR-T infusion were 0.958, 88.0%, 78.9%, and 84.1%, respectively.The AUC, specificity, sensitivity, and accuracy of T2 signal intensity within 2 weeks of CAR-T infusion were 0.869, 84.0%, 68.4%, and 77.3%, respectively. Conclusions:Quantitative parameters of MRI, including ADC values and T2 signal intensity, are of great significance in the early prediction of CAR-T therapy efficacy on children and adolescents with mature aggressive B-cell NHL.Among these parameters, ADCmax presents the strongest predictive performance and serves as a valuable indicator for predicting a complete response with CAR-T treatment.
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Reflux esophagitis (liver-stomach disharmony, Spittoon-Qi interties, Qi and blood stasis syndrome, turbid poison intrinsic) and nonalcoholic fatty liver disease (liver depression, spleen deficiency, phlegm and blood stasis syndrome, hot and humid embodiment, phlegmy wet resistance) and functional dyspepsia (liver depression syndrome, liver stomach with spleen deficient, spleen deficiency cold syndrome, in a word, fever) is a common disease and frequently encountered disease of digestive system. The course of disease is prolonged and the prevalence is high. The successful establishment of animal model combining disease and syndrome is the premise of exploring the mechanism of traditional Chinese medicine(TCM) effect and the foundation of the development of new preparations. At the same time, mastering the complex relationship network among disease, syndrome and prescription is the prerequisite of effective treatment. When the same syndrome occurs between different diseases, the concept of "treating different diseases with the same treatment" in TCM suggests that methods can be cross-referenced for the shortage of some syndrome models. TCM intervention of digestive diseases has the characteristics of multi-path, multi-target, multi-dimension and multi-level. Therefore, this article through the literature review, summarizes the reflux esophagitis, nonalcoholic fatty liver disease and functional dyspepsia is a common disease such as the combined operation method of the model and the intervention mechanism of TCM, so as to diseases of the digestive system of different syndrome types provides the theory basis for the objective of research, and the basic research of TCM prescription and achievements provide methodological guidance.
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Reflux esophagitis (liver-stomach disharmony, Spittoon-Qi interties, Qi and blood stasis syndrome, turbid poison intrinsic) and nonalcoholic fatty liver disease (liver depression, spleen deficiency, phlegm and blood stasis syndrome, hot and humid embodiment, phlegmy wet resistance) and functional dyspepsia (liver depression syndrome, liver stomach with spleen deficient, spleen deficiency cold syndrome, in a word, fever) is a common disease and frequently encountered disease of digestive system. The course of disease is prolonged and the prevalence is high. The successful establishment of animal model combining disease and syndrome is the premise of exploring the mechanism of traditional Chinese medicine(TCM) effect and the foundation of the development of new preparations. At the same time, mastering the complex relationship network among disease, syndrome and prescription is the prerequisite of effective treatment. When the same syndrome occurs between different diseases, the concept of "treating different diseases with the same treatment" in TCM suggests that methods can be cross-referenced for the shortage of some syndrome models. TCM intervention of digestive diseases has the characteristics of multi-path, multi-target, multi-dimension and multi-level. Therefore, this article through the literature review, summarizes the reflux esophagitis, nonalcoholic fatty liver disease and functional dyspepsia is a common disease such as the combined operation method of the model and the intervention mechanism of TCM, so as to diseases of the digestive system of different syndrome types provides the theory basis for the objective of research, and the basic research of TCM prescription and achievements provide methodological guidance.
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With the global pandemic of COVID-19, cytokine storms in critical patients with pneumonia is really a problem and need to be solved immediately.Low dose radiation therapy (LDRT) has been temporarily used to treat pneumonia.In the past decades, researchers were dedicated to clarify the biological mechanism of LDRT.LDRT plays a unique role in the suppression of inflammation, preliminary outcomes have been acquired in critical patients with COVID-19 pneumonia, and radiotherapy community is paying attention to this treatment strategy.This review summarizes the application of LDRT in pneumonia, its biological mechanism, the result of LDRT in COVID-19 pneumonia, the existing problems and prospective in clinic.
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Objective:To observe the effect of Buzhongyiqi Decoction on the expression of transforming growth factor β-3(TGFβ-3)and microRNA-30d(miR-30d)in uterosacral ligament tissues in a rat model of pelvic organ prolapse.Methods:According to the number lottery, 16 rats in the blank control group were divided into 2 groups: the A1 group(feeding 4 weeks, n=8)and the A2 group(undergoing the ovariotomy with normal saline gavage for 8 weeks, n=8). The 64 rat models of pelvic organ prolapse were randomly divided into 8 groups(8 rats in each group): the B1 group(feeding 4 weeks), the B2 group(given normal saline via gavage for 8 weeks), the C1 and C2 groups(given Buzhongyiqi Decoction via gavage, 3.5 ml·kg -1·d -1, for 4 and 8 weeks, respectively), the D1 and D2 group(given Buzhongyiqi Decoction via gavage, 7.0 ml·kg -1·d -1, for 4 and 8 weeks, respectively), the E1 and E2 group(given Buzhongyiqi Decoction via gavage, 14.0 ml·kg -1·d -1, for 4 and 8 weeks, respectively). Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the expression of collagen COL1A1, COL3A1, TGF β-3 and miR-30d in uterosacral ligament tissues. Results:Compared with A1 group, the B1 group showed that the expression of COL1A1 and COL3A1 was decreased and the expression of TGFβ-3 and miR-30d was increased( P<0.01). After 4 weeks treament of Buzhongyiqi Decoction, the expression of COL1A1 was higher in E1 group than in C1 group ( P<0.01), The expression of COL3A1 in group D1 was singificantly higher than that in group C1, The expression of COL3A1 in group E1 was also singificantly higher than that in group D1 .The expression of TGF β-3 was higher in the D1 and E1 groups than in the C1 group( P<0.01). The expression of miR-30d was lower in the D1 and E1 groups than in the C1 group( P<0.01). After 8 weeks of Buzhongyiqi Decoction treatment, the expression of COL1A1 was higher in the D2 group than in the C2 group( P<0.01), while was lower in the E2 group than in the D2 group( P<0.01). The expression of COL3A1 and TGFβ-3 was higher in the D2 group than in the C2 group( P<0.01)and the expression of TGFβ-3 was lower in the E2 group than in the D2 group( P<0.01). The expression of miR-30d was lower in the D2 group than in the C2 group( P<0.01)and was higher in the E2 group than in the D2 group( P<0.01). Compared with the B1 group, the expression of COL1A1, COL3A1 and TGF β-3 was increased in the D1 and E1 groups( P<0.01), the expression of miR-30d was decreased in the C1, D1 and E1 groups( P<0.01). Compared with the B2 group, the expression of COL1A1 and COL3A1 was increased in the D2 and E2 groups, the expression of TGF β-3 was increased and the expression of miR-30d was decreased in the C2, D2 and E2 groups( P<0.01). Conclusions:Buzhongyiqi Decoction can increase the synthesis of collagen COL1A1 and COL3A1 in uterosacral ligament tissues of rats with pelvic organ prolapse, which may be related to the up-regulation of TGF β-3 expression and the down-regulation of miR-30d expression in rat uterosacral ligament tissues.
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Objective@#To investigate the clinicopathologic characteristics, immunophenotypes, and differential diagnostic features of extra-pleural solitary fibrous tumor (SFT) with uncommon histology.@*Methods@#Seven cases of extra-pleural SFT with uncommon histology were collected during January 2015 and December 2016 in Zhejiang Provincal People′s Hospital; the clinical and radiologic features, histomorphology, immunophenotype and prognosis were analyzed. EnVision method was used for immunohistochemical staining of STAT6, CD34 and other differential diagnosis associated markers.@*Results@#There were five male and two female patients, age from 23 to 54 years (mean=39 years). Three tumors were located in the soft tissue of head and neck, two in trunk subcutaneous soft tissue, one in sella region, and one in the kidney. Grossly the tumors ranged from 0.4 to 8.0 cm (mean=3.1 cm). Microscopically, all three head and neck cases resembled giant cell angiofibroma/giant cell subtype SFT, and one case showed sheet-like pattern of the multinucleated syncytial cells, creating a biphasic arrangement similar to myofibroma. Both truncal tumor resembled lipomatous type SFT, with one similar to dermatofibrosarcoma protuberans and the other to atypical spindle cell lipomatous tumor. The sella tumor showed morphology of a conventional SFT with high grade sarcomatous transformation. The renal tumor demonstrated a malignant SFT with entrapped benign renal tubules, mimicking a biphase synovial sarcoma or a malignant mixed epithelial and stromal tumor. By immunohistochemistry, all seven SFTs showed diffuse and strong nuclear reactivity to antibody against STAT6.@*Conclusions@#Extra-pleural SFTs show a significant heterogeneity of morphology and biological behavior which could cause differential confusion.Careful attention to its characteristic histomorphology with the use of STAT6 immunohistochemistry can help distinguish this tumor from its many mimickers.
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Objective@#To explore the clinical application value of prognostic nutritional index(PNI) for predicting overall survival(OS) in patients with advanced non-small cell lung cancer (NSCLC).@*Methods@#123 patients with histologically confirmed non-small cell lung cancer were enrolled in this study, and their clinical and laboratory data were reviewed. The PNI was calculated as 10×serum albumin value+ 5×total lymphocyte countin peripheral blood.Univariate and multivariate analyses were used to identify the potential prognostic factors for advanced NSCLC.@*Results@#PNI of the 123 NSCLC patients was 46.24±6.56. PNI was significantly associated with age, weight loss and pleural effusion (P<0.05). However, it showed no relationship with sex, smoking, hemoptysis, chest pain, dyspnea, histological type, clinical stage, and administration of chemotherapy (P>0.05). The median OS of the 123 patients was 19.5 months. The median OS in the higher PNI group (PNI≥46.24) and lower PNI group(PNI<46.24) were 25.2 months and 16.4 months, respectively.The 1-year survival rates were 80.6% and 63.9%, and 2-year survival rates were 54.8% and 19.6%, respectively (P<0.01). Univariate analysis showed that PNI, age, dyspnea, and weight loss were related to the OS of the advanced NSCLC patients (P<0.05). Multivariate analysis identified PNI as an independent prognostic factor for OS of advanced NSCLC (P<0.001).@*Conclusion@#PNI can be easily calculated, and may be used as a relatively new prognostic indicator for advanced NSCLC in clinical practice.
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Objective To determine the difference in blood microcirculation recovery between normal frostbite and high-altitude frostbite during the wound healing.Methods Twenty four male rats were randomly divided into control group (n=8), normal frostbite group (n=8), and high-altitude group (n=8). The normal frostbite group rats were frozen to produce mid-degree frostbite models by controlling the freezing time with liquid nitrogen penetration equipment. The high-altitude frostbite group rats were acclimated to a hypoxic and low-pressure environment for 1 week, and then the high-altitude frostbite models were constructed by the same way with liquid nitrogen penetration apparatus. On days 3, 7, 11, 15, 19, and 23 after modeling, the recovery situation of blood circulation of each group was observed with contrast ultrasonography by injecting SonoVue micro-bubble into rats' tail. Finally, the micro-bubble concentration (MC) was calculated to confirm the blood circulation recovery with software Image Pro. ResultsAt different time points, the wound area of the high-altitude frostbite group was bigger than that of the normal frostbite group, and the MC of control group was always about (27±0.2)×109/ml. On day 3, 7, 11, 15, 19, and 23, the MC was significantly lower in the high-altitude frostbite group than in the control group and normal frostbite group (P<0.05). The MC of normal frostbite group was significantly lower than that of the control group on day 3, 7, 11, 15 and 19 (P<0.05). In addition, no obvious difference in MC was found between normal group and control group on the 23th day (P<0.05).Conclusion The blood microcirculation recovery after high-altitude frostbite is significantly slower than the normal frostbite.
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Objective To investigate the correlation between chronic kidney disease (CKD) and long-term outcomes in a large cohort of unselected patients with acute cerebral infarction.Methods Consecutive acute cerebral infarction patients hospitalized in Department of Neurology,General Hospital of Jinan Military Region were prospectively recruited from August 2010 to November 2013.The baseline data including age,sex,the National Institute of Health Stroke Scale (NIHSS) scores,type of Oxfordshire Community Stroke Project (OCSP:total anterior circulation infarct,partial anterior circulation infart,posterior circulation infarct and lacunar infarct),serum creatinine were recorded.Estimated glomerular filtration rate (eGFR) was calculated according to CKD epidemiology collaboration (CKD-EPI) equation.CKD was defined as eGFR < 60 ml · min-1 · 1.73 m-2 body surface area.Patients were divided into eGFR≥60 ml · min-1 · 1.73 m-2 group and eGFR < 60 ml · min-1 · 1.73 m-2 group.Recovery was assessed by modified Rankin Scale (mRS) 180 days after stroke by telephone interview (mRS≤2 reflected good prognosis,and mRS > 2 reflected unfavorable prognosis).Multinominal Logistic regression analysis,Kaplan-Meier curve and log rank test were used.Results Eight hundred and fifty-two patients were enrolled,among them 93 patients were with CKD.Compared to patients without CKD,acute ischemic patients with CKD were older ((70.56 ± 11.86) years vs (63.11 ± 12.15) years,t =5.60,P =0.000),more likely with NIHSS ≥7 (59.14% (55/93) vs 32.54% (247/759),x2 =25.61,P =0.000),more likely with hypertension (89.25% (83/93) vs 77.34% (587/759),x2 =6.99,P =0.007),more likely with atrial fibrillation (29.03 % (27/93) vs 9.5 % (72/759),x2 =30.82,P =0.000),more likely with congestive heart failure (13.98% (13/93) vs 3.03% (23/759),x2 =24.54,P =0.000),more likely with tumour (6.50% (6/93) vs 2.24% (17/759),x2 =5.59,P =0.031).CKD was a independent prognostic factor for long-term poor outcome (OR =2.034,95% CI 1.194-3.468) and long term mortality (OR =2.657,95% CI 1.450-4.870).Kaplan-Meier estimate of patients without CKD for cumulative 180 days survival function for all-cause mortality was higher than those with CKD (79.57% (74/93) vs 93.54% (710/759),Log rank test:x2 =23.602,P =0.000).Conclusions Acute ischemic stroke patients with CKD are with more comorbidities.CKD is a independent prognostic factor for long-term poor outcomes and long term mortality in patients with acute cerebral infarction.
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Objective To explore the effect of non-invasive labor analgesia on postnatal depression among primipara. Methods Three hundred primipara of spontaneous labor in our hospital from February 2014 to April 2014 were assigned as control group and another 300 primiparas of spontaneous labor from May 2014 to August 2014 as experiment group. In the control group, one-to-one responsibility system was conducted for the delivery with an accompanying midwife and in the experiment group, non-invasive labor analgesia was done apart from one-to-one responsibility system. The two groups were compared in terms of analgesic effect at three stages of labor, postnatal depression scores and incidence of postnatal depression. Result The analgesic effect of the experiment group was better than that of the control group during the three stages of labor (all P<0.01), and postnatal depression scores and the incidence of postnatal depression in the experiment group were significantly lower than those in the control group (both P<0.05). Conclusion Non-invasive labor analgesia can relieve the labor pains and decrease the incidence of postnatal depression among primiparas.
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Objective To investigate the mechanisms underlying intedeukin-22 (IL-22)-induced expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in HaCaT cells.Methods Some HaCaT cells were divided into several inverention groups treated with IL-22 at concentrations of 12.5,25,50,100 μg/L,respectively and a control group treated with phosphate buffer saline (PBS).After 24-hour culture,total proteins were extracted from the HaCaT cells,and Western blot was performed to measure the expression of phosphorylated extracellular signalregulated kinase 1/2 (P-ERK1/2) in the mitogen-activated protein kinase (MAPK)-ERK1/2 pathway,as well as phosphorylated-JAK2 (P-JAK2) and phosphorylated-signal transducer and activator of transcription 3 (P-STAT3) in the JAK2/STAT3 pathway.In a blocking experiment,some HaCaT cells were divided into 4 groups to be treated with PBS,IL-22,PD98059 (an inhibitor of MAPK-ERK1/2) combined with IL-22 (PD98059 group),AG490 (an inhibitor of JAK2/STAT3) combined with IL-22 (AG490 group),respectively.After 24-hour treatment,total proteins and mRNAs were extracted from the HaCaT cells followed by Western blot and real-time quantitative reverse transcription-PCR for the measurement of protein and mRNA expressions of HB-EGF respectively.Statistical analysis was carried out with the software SPSS 16.0 by one-way analysis of variance (ANOVA) for intergroup comparisons and by Bonferroni's test for multiple comparisons.Results After treatment with IL-22 at the above 4 concentrations,the expressions of P-ERK1/2,P-JAK2 and P-STAT3 in HaCaT cells were all increased compared with the control group (all P < 0.05).The protein and mRNA expression levels (expressed as the HB-EGF/β-actin ratio and 2-△△Cr respectively) of HB-EGF were both significantly decreased in the PD98059 group and AG490 group than in the IL-22 group (protein:0.183 ± 0.020 and 0.199 ± 0.011 vs.0.924 ± 0.032,F =37.700,36.400,respectively,both P < 0.05; mRNA:1.034 ± 0.072 and 0.989 ± 0.038 vs.1.844 ± 0.135,F =11.271,13.429,respectively,both P < 0.05).Conclusions IL-22 can activate the MAPK-ERK1/2 and JAK2/STAT3 signaling pathways in HaCaT cells,which may contribute to IL-22-induced expression of HB-EGF in HaCaT cells.
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Objective To evaluate the effects of interleukin-22(IL-22)on the expression of tazarotene-induced gene 3(TIG3)in HaCaT cells. Methods Cultured HaCaT cells were randomly divided into several groups to be treated with different concentrations (12.5, 25, 50, 100 μg/L)of IL-22 alone, or the combination of 50 μg/L IL-22 with the MAPK-ERK1/2 inhibitor PD98059 or the JAK/STAT inhibitor AG490 for 24 hours. Those HaCaT cells treated with phosphate buffered saline served as the control group. Subsequently, total proteins and mRNAs were extracted from the HaCaT cells. An immunofluorescence assay, Western blot and enzyme-linked immunosorbent assay (ELISA) were performed to determine the protein expression level of TIG3, and real-time fluorescence-based quantitative PCR to quantify the mRNA expression of TIG3 in HaCaT cells. Results The immunofluorescence assay showed that TIG3 protein was mainly expressed in the cytoplasm of HaCaT cells. As Western blot revealed, the protein expression level of TIG3 was 0.743 ± 0.035, 0.678 ± 0.040, 0.582 ± 0.041 and 0.328 ± 0.032 in HaCaT cells treated with IL-22 of 12.5, 25, 50 and 100μg/L, respectively, significantly lower than that in the control group (0.839 ± 0.045, all P<0.05). ELISA also showed a decrease in the protein expression of TIG3 in IL-22-treated HaCaT cells, which was consistent with Western blot results. Further more, the mRNA expression level (2-△△Ct)of TIG3 was significantly weaker in HaCaT cells treated with IL-22 of 12.5, 25, 50 and 100μg/L than in the control group (0.838 ± 0.036, 0.686 ± 0.061, 0.565 ± 0.047 and 0.457 ± 0.033 vs. 1.000, all P< 0.05). The decrease in TIG3 mRNA and protein expressions was significantly attenuated in HaCaT cells treated with the combination of 50 μg/L IL-22 with PD98059 or AG490 compared with those treated with 50 μg/L IL-22 alone. Conclusion IL-22 can dose-dependently inhibit the expression of TIG3 in HaCaT cells, likely through the MAPK-ERK1/2 and JAK2/STAT3 signaling pathways.
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<p><b>OBJECTIVE</b>To investigate the role of β-catenin and caspase-3 in amentoflavone-induced apoptosis of human colorectal cancer SW480 cells.</p><p><b>METHODS</b>MTT assay was used to detect the viability of SW480 cells exposed to amentoflavone, and flow cytometry was employed to assess the cell apoptosis. Western blotting was performed to determine the protein expressions of β-catenin and caspase-3 in the exposed cells.</p><p><b>RESULTS</b>Amentoflavone dose-dependently inhibited the viability of SW480 cells, and a high concentration of amentoflavone (150 µmol/L) obviously induced apoptosis of the cells. Amentoflavone exposure caused significantly increased expression of caspase-3 and suppressed β-catenin expression in the cells.</p><p><b>CONCLUSION</b>Amentoflavone-induced apoptosis in SW480 human colorectal cancer cells is associated with altered expressions of β-catenin and caspase-3.</p>
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Humanos , Apoptose , Biflavonoides , Farmacologia , Caspase 3 , Metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais , Patologia , beta Catenina , MetabolismoRESUMO
Objective To explore the developmental characteristics of different functional levels of autism and the diffe-rence in children. Methods A total of 159 autistic children aged 13-71 months including 85 high-functioning autistic (HFA) chil-dren and 74 low-functioning autistic (LFA) children were evaluated for their developmental characteristics by the development scales from the psycho-educational profile-revised (PEP-R). Results Within the same age group, both HFA and LFA children had obvious unbalance in individual ability development (H=41.68~113.51, P<0.01). Impaired cognitive performance is most common in HFA children. The development of cognitive performance was inconsistent with cognitive expression while the gross motor development was normal. The ability development in LFA children were all impaired, especially in imitation, cogni-tive performance and cognitive expression. With increasing age, the scores of imitation, perception, cognitive performance, cog-nitive expression and overall development quotient were increased gradually in HFA children (P<0.05) while the scores of cogni-tive performance and overall development quotient were decreased in LFA children. Conclusions Autistic children tend to have abnormal developmental progress and order, and individual ability development varies by functional level in autistic children with increasing age.
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Objective To investigate the clinical diagnostic evidences of pleural tuberculosis (PT).Methods One hundred and eighty patients with pleural effussion, whom were admited into our hospital from December 2007 to December 2009 ,were enrolled into this study. The clinical data of patients confirmed with PT ( n = 90) or Non-PT ( n = 90) were analyzed retrospectively. The likelihood ratios( LR), sensitivity, specificity,positive predictive value,and nagative predictive value of six indices including pleural ADA, IFN-γ, sIL-2R ,TB-antibody in blood and pleural effusion, age and fever status were calculated. Results The variable with the hightest LR+ was ADA optimal threshold, followed by TB-antibody, IFN-γ, age, sIL-2R, fever status, If all six variables reached the optimal threshold,the probabilities of PT exceeded 99.9%. However,if all variables didn't reached the optimal threshold, the probabilities of PT were less than 1%. Among all the six variables, any four or over four variables reached the optimal threshold, the probabilities of PT exceeded 97%. Conclusion The combination use of these six variables can aid the clinical analysis, early detection, and therapy instruction,complication prevention of PT.
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Objective To explore the expression and clinical significance of Twist. E-cadherin and N-cadherin in gallbladder carcinoma. Methods From 2000 to 2008, in Zhejiang Provincial People's Hospital, the expression of Twist, E-cadherin and N-cadherin protein were detected in 79 surgically removed gallbladder carcinoma tissue specimens in paraffin blocks and 20 normal gallbladder tissue specimens by tissue microarray technique and immunohistochemistry. Results Compared with normal gallbladder tissues, the expression of Twist and N-cadherin was up-regulated in gallbladder carcinoma tissues and the positive percentage was 68.3% and 49.4% respectively, while which both were 1/20 in normal gallbladder tissues. The percentage of high E-cadherin expression in gallbladder carcinoma tissues was only 27.8 %, which was significantly lower than that in normal gallbladder tissues (20/20;X2 =29.31, P<0. 05). The expression of Twist was correlated with T classification, lymph node metastasis, distant organ metastasis, hepatoduodenal ligament invasion, lymphatic invasion and UICC stage of gallbladder carcinoma (P<0.05). The expression of E-cadherin was correlated with T classification, distant organ metastasis, hepatoduodenal ligament invasion, differentiation degree and UICC stage of gallbladder carcinoma (P<0.05). The expression of N-cadherin was only correlated with lymphatic invasion of gallbladder carcinoma (P <0.05 ). There was significant negative correlation between Twist and E-cadherin expression (P<0. 01). All the 79 gallbladder carcinoma patients were followed up after the surgery, the mean follow-up time was 30.6±14.3months. The 3-year survival rates of patients with low or high Twist expressions were 66% and 7% respectively,there was significant difference between the two groups(P<0. 01). The 3-year survival rates of patients with low or high E-cadherin expressions were 25 % and 86 % respectively, the difference of two groups was significant(P<0.01). The 3-year survival rates of patients with low or high Ncadherin expressions were 39% and 41% respectively, there was no significant difference between the two groups(P>0.05). The multivariate analysis indicated that the Twist expression was one of independent prognostic factors of gallbladder carcinoma. Conclusion The abnormal expression of Twist and E-cadherin was correlated with the development and progression of gallbladder carcinoma,and Twist expression was one of the independent prognostic factors of gallbladder carcinoma.
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Objective To set up a multiplex real time quantitative PCR method to detect the expression of WT1 and MDR1 gene simultaneously in acute leukemia patient. Methods Total RNA was extracted from k562 cell line and was reverse transcribed to cDNA by the outer primers of WT1 and MDR1 respectively. The cDNA of WT1 and MDR1 were purified and digested by Bam H Ⅰ and Bgl Ⅱ , and then the two fragments were ligated to form the recombinant fragment WT1 + MDR1. The outer forward primer of WT1 and outer reverse primer of MDR1 were used to amplify the recombinant fragment WT1 + MDR1. The PCR product was purified and cloned into pMD18-T vector, and then transferred into E. coli DH-5α. A new kind of WT1-MDRl-contained standard plasmid was obtained from the positive colony. The recombinant plasmid was verified by digestion with restriction enzyme and PCR amplification. A multiplex real time quantitative PCR method was set up with FAM-labeled MDR1 probe and VIC-labeled WT1 probe in one reaction tube. The WT1 and MDR1 gene expression was detected in forty-seven AL patients and thirty-two controls by this method. Seven patients were followed-up to elucidate the relationship between the gene expression levels and clinical prognosis. Results The recombinant plasmid was confirmed by EcoR1 digestion and PCR amplification. The multiplex real time quantitative PCR technique could reach the sensitivity of WT1 and MDR1 gene up to 102 copy/μl. The standard curve slopes were 0. 999 and 0. 998. The WT1 [ 37 000( 163-6 370 000 )copies/μg RNA ] and MDR1 [ 76 200( 179-18 000 000 )copies/μg RNA ]expression levels of AL patients were significantly higher as compared to the controls [ 258( 0-643 ) copies/μg RNA and 333( 0-779 )copies/μg RNA ]( Z= 6. 755,6. 736, P < 0. 01 ). Following up seven patients with similar regimen of chemotherapy, the WT1 and MDR1 expression correlated to the clinical course. Three AL patients with WT1 and MDR1 expression levels (2 170 and 86 900, 1 130 and 5 860, 1 170 and 586 copies/μg RNA )significantly decreased after chemotherapy and kept in the low range ( 370 and 560,138 and 980, 150 and 690 copies/μg RNA ), and had a favorable outcome. Three AL patients with WT1 and MDR1 expression levels ( 1 600 and 11 800, 24 800 and 968, 48 200 and 1 100 000 copies/μg RNA )decreased after initial chemotherapy, but increased significantly afterwards (20 314 and 25 660,184 364 and 31 530, 15 680 and 878 000 copies/μg RNA ),and suffered clinical relapse. One patient with high WT1 and MDR1 expression levels ( from 81 600 and 1 200 000 copies/μg RNA to 124 100 and 7 632 400 copies/μg RNA )showed the persistence of disease. Conclusions A multiplex real time quantitative PCR method to detect WT1 and MDR1 gene simultaneously is constructed successfully. The expression of WT1 and MDR1 may provide useful information for AL patients prognosis.