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Objective:To study the feasibility and value of applying organ dose modulation technique in computed tomography(CT)scanning on eyes.Methods:A total of 330 patients who admitted to Beijing Friendship Hospital affiliated with Capital Medical University from August 2021 to August 2023 and underwent CT examination on eyes were selected.They were divided into modulation group,conventional group and low-dose group based on the control methods of tube current in scanning.The modulation group used organ dose modulation technique with intelligent automatic tube current of 70-150 mA,and the conventional dose group used a fixed tube current of 100 mA,and the low-dose group used a fixed tube current of 70 mA.The differences in radiation dose and CT imaging quality among 3 groups were compared.Results:The dose length product(DLP),volume CT dose index(CTDIvol)and effective dose(ED)of cross-sectional scan of the modulation group were respectively 62.37,12.83 and 0.143 mSv,which were significantly lower than 115.23,18.93 and 0.265mSv of conventional dose group,respectively,with statistically significant(F=2544.944,6009.596,2544.944,P<0.05).The DLP,CTDIvol and ED of coronary scan of the modulation group were 68.19,13.15 and 0.156,respectively,which were significantly lower than 122.41,19.20 and 0.282 mSv of the conventional dose group,respectively,with statistically significant(F=1232.413,3813.940,1232.413,P<0.05).The excellent rates of cross-sectional scans among the modulation group,conventional group and lower-dose group were respectively 98.83%,86.15%and 47.69%,and the difference among three groups was statistically significant(x2=53.908,P<0.05).The excellent rates of image qualities of the modulation group,conventional group and low-dose group were respectively 96.61%,80.70%and 48.28%,and the difference among three groups was statistically significant(x2=20.992,P<0.05).Conclusion:The application of organ dose modulation technique in CT scanning on eyes can significantly reduce radiation dose on patient under ensures imaging quality can meet diagnostic needs when undergoes cross-sectional and coronal scans,which has higher clinical feasibility and application value.
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ObjectiveTo investigate the impact of cancer-associated fibroblasts （CAFs） on immunotherapy and liver metastasis in colorectal cancer （CRC）. MethodsThe single-cell sequencing data （GSE205506） of CRC patients with mismatch repair deficiency （MMRd） were downloaded from the gene expression omnibus database， and R software was used to preprocess the original sequencing data and establish the umap of fibroblast subpopulations， with each subpopulation named based on signature genes. GraphPad was used for the statistical analysis of the proportion of each fibroblast subpopulation， and the key subpopulations with significant differences were analyzed among CRC patients before and after PD-1 immunotherapy， as well as between the patients with pathological complete response （pCR） and those without pCR （non-pCR） after treatment. The analysis of differentially expressed genes and the gene pathway enrichment analysis were performed for the key subpopulations. The TCGA database was used to perform a prognostic and survival analysis of the signature genes of key CAF subpopulations， and RNA sequencing data were used to score and calculate the proportion of key CAF subpopulations in the primary lesions of CRC patients with liver metastasis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Kaplan-Meier method was used to plot survival curves， and the log-rank test was used to calculate survival rates. CellPhoneDB software was used to analyze the receptor-ligand interaction between fibroblast subpopulations and tumor cells， and in vitro cell experiments were used to validate the effect of NRG1， a key ligand molecule， on the migration and invasion abilities of CRC cells. ResultsAfter PD-1 immunotherapy for CRC patients， there was a significant reduction in the proportion of F6_MMP1+CAFs （P<0.001）， which was only observed in patients achieving complete remission after immunotherapy. F6_MMP1+CAFs were upregulated， as well as the genes and signaling pathways associated with tumor migration and invasion， and in addition， there was a significant increase in F6_MMP1+CAFs in the tumor tissue of CRC patients with liver metastasis （P<0.000 1）. As a ligand， NRG1 expressed by F6_MMP1+CAFs interacted with ERBB3 receptor expressed by tumor cells， and the in vitro experiments confirmed that NRG1 promoted the migration and invasion abilities of tumor cells by activating the ERBB signaling pathway （P<0.05）. ConclusionF6_MMP1+CAFs may affect the efficacy of PD-1 immunotherapy in CRC patients and play an important role in promoting liver metastasis in CRC. F6_MMP1+CAFs， along with NRG1 that is produced by them and can promote tumor metastasis， can be used as potential therapeutic targets and prognostic markers for CRC.
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Objective:To investigate the application value of standardized outcomes in nephrology hemodialysis (SONG-HD) scale in evaluating the fatigue level of patients undergoing maintenance hemodialysis (MHD) patients and the factors that affect fatigue.Methods:A total of 201 patients undergoing regular MHD who received treatment in the Department of Nephrology, The First Affiliated Hospital of Xiamen University in April 2021 were included in April, 2021. The SONG-HD scale was used to evaluate patient's fatigue level. Fatigue was assessed using face-to-face interview questionnaire. Clinical and laboratory indicators were analyzed. Univariate logistic regression analysis and multivariate logistic regression analysis were performed to analyze the factors that affect fatigue of patients undergoing MHD.Results:Among the 201 MHD patients, 73.1% (147/201) had fatigue. The high-sensitivity C-reactive protein and parathyroid hormone levels in patients with fatigue were 0.91 (0.30, 3.63) mg/L and 216.00 (141.00, 347.00) ng/L, respectively, which were significantly higher than 0.40 (0.30, 2.01) mg/L and 153.00 (96.73, 308.50) ng/L in patients who had no fatigue ( Z = 2.12, 2.17, both P < 0.05). The pre-dialysis carbon dioxide binding capacity and blood albumin levels in patients who had fatigue were (21.03 ± 2.65) mmol/L and (36.76 ± 3.20) g/L, respectively, which were significantly lower than (22.68 ± 3.01) mmol/L and (38.61 ± 2.85) g/L in patients who had no fatigue ( t = 3.77, 3.73, both P < 0.05). Univariate logistic regression analysis showed that high-sensitivity C-reactive protein, pre-dialysis carbon dioxide binding capacity, serum albumin level, and parathyroid hormone level were related to the occurrence of fatigue in patients undergoing MHD ( Wald = 4.32, 12.39, 12.23, 4.66, all P < 0.05). Additionally, in a multivariate model adjusted for confounding factors, the independent risk factors for fatigue in patients undergoing MHD were relatively low pre-dialysis carbon dioxide binding capacity and serum albumin level ( Wald = 12.41, 11.67, both P < 0.05). Conclusion:The incidence of fatigue is high in patients undergoing MHD. The SONG-HD scale is convenient to use in assessing the fatigue level of patients undergoing MHD. After adjusting for confounding factors, fatigue in patients undergoing MHD is associated with reduced levels of pre-dialysis carbon dioxide binding capacity and serum albumin.
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Objective:To correlate peripheral blood neutrophil-to-lymphocyte ratio with the occurrence of restless legs syndrome (RLS) in patients undergoing maintenance hemodialysis (MHD).Methods:This is a cross-sectional study. A total of 203 patients who underwent long-term MHD at the Blood Purification Center, Department of Nephrology, The First Affiliated Hospital of Xiamen University from May to June 2021 were included in this study. The counts of peripheral blood neutrophils and lymphocytes were determined and the neutrophil-to-lymphocyte ratio was calculated. These patients were divided into a RLS group and a non-RLS group according to whether they developed RLS. RLS-related factors were evaluated using face-to-face interview questionnaires. Various clinical and laboratory parameters were analyzed. The influential factors of RLS in patients undergoing MHD were analyzed through univariate regression analysis and multivariate logistic regression analysis.Results:A total of 203 patients undergoing MHD were enrolled, 30 individuals were determined as current RLS cases (14.78%). The levels of NLR and PTH in the RLS group were 4.86 (3.39, 5.82) L/L and 244.50 (143.25, 406.50) ng/L, respectively, which were significantly higher than those in the normal group [3.51 (2.60, 5.24) L/L, 147.00 (94.80, 263.50) ng/L, Z = -3.38, -2.64, both P < 0.05]. Univariate logistic regression analysis showed that NLR, PTH, uric acid, and neutrophil count were correlated with RLS (Wald χ2 = 7.96, 4.99, 4.76, 8.33, all P < 0.05). NLR was the independent risk factor of RLS (Wald χ2 = 6.14, P < 0.05) in multivariate models adjusting for confounding factor. Conclusion:The prevalence of RLS is high in patients undergoing MHD. RLS is assicuated with NLR among patients undergoing MHD after adjusting for confounding factor. RLS is likely associated with systemic inflammatory diseases.
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Neuroendocrine tumors(NET) originating in the kidney account for less than 1% of renal epithelial malignancies, and are rarer when combined with horseshoe kidney. This article reported a patient of NET with horseshoe kidneys. The patient was admitted to hospital because of the pain of left waist and back for more than 1 month. Enhanced CT examination showed that horseshoe kidney, left kidney mass, about 5.0 cm × 4.0 cm, and about 2 cm from the gorge. There was a separate blood supply in the gorge. The patient underwent laparoscopic radical left nephrectomy. Intraoperatively the canyon was separated, and the tumor and left kidney were completely removed. The postoperative pathological results was NET. No auxiliary treatment was given after surgery. After 15 months of follow-up, no tumor recurrence and metastasis was seen.
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Objective:To evaluate the relationship between Karyopherin β2 (Kapβ2)-mediated nuclear translocation of nuclear inhomogeneous ribonucleoprotein A2/B1 (hnRNPA2/B1) and sevoflurane-induced brain neurotoxicity in a cellular experiment.Methods:The mouse hippocampal neuronal cell line HT22 cells were inoculated in confocal culture dishes and 6-well culture plates at a density of 2×10 5 cells/well and 1×10 6 cells/well and divided into 4 groups( n=12 each) by a random number table method: control group (GFP-C group) carrying green fluorescent protein (GFP) with empty adenovirus transfection, sevoflurane group (GFP-Sev group) carrying GFP with empty adenovirus transfection, control group (GFP-Sev group) transfected with Kapβ2 gene-overexpressing adenovirus, and sevoflurane group (Kapβ2-Sev group) transfected with Kapβ2 gene-overexpressing adenovirus. After 48 h of conventional incubation, empty adenovirus-carrying GFP (GFP-C and GFP-Sev groups) and Kapβ2 gene-overexpressing adenovirus (Kapβ2-C and Kapβ2-Sev groups) were transfected. After 48 h of transfection, the cells were conventionally incubated continuously in GFP-C and Kapβ2-C groups, and the cells were incubated for 3 h with 3% sevoflurane and then were conventionally incubated for 48 h in GFP-Sev and Kapβ2-Sev groups. The expression of Kapβ2, synaptophysin (SYP), postsynaptic density protein 95 (PSD95) and hnRNPA2/B1 nucleoplasmic ratio were measured in cells by Western blot. Immunofluorescence assay was used for hnRNPA2/B1 subcellular localization. Results:Compared with GFP-C group, the expression of SYP and PSD95 was significantly down-regulated, hnRNPA2/B1 nucleoplasmic ratio was decreased, and cytoplasmic hnRNPA2/B1 expression was up-regulated in GFP-Sev group, and Kapβ2 expression was significantly up-regulated in Kapβ2-C group ( P<0.05). Compared with Kapβ2-C group, the expression of SYP and PSD95 was significantly down-regulated, hnRNPA2/B1 nucleoplasmic ratio was decreased, and cytoplasmic hnRNPA2/B1 expression was up-regulated in Kapβ2-Sev group ( P<0.05). Compared with GFP-Sev group, the expression of Kapβ2, SYP and PSD95 was significantly up-regulated, hnRNPA2/B1 nucleoplasmic ratio was increased, and cytoplasmic hnRNPA2/B1 expression was down-regulated in Kapβ2-Sev group ( P<0.05). Conclusions:Kapβ2-mediated hnRNPA2/B1 nuclear translocation may be the endogenous protective mechanism against sevoflurane-induced brain neurotoxicity.
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OBJECTIVE@#To explore the role of the Notch signaling pathway in regulating neuronal differentiation and sensorimotor ability in a zebrafish model of fetal alcohol spectrum disorder.@*METHODS@#Zebrafish embryos treated with DMSO or 50 μmol/L DAPT (a Notch signaling pathway inhibitor) were examined for mortality rate, hatching rate, malformation rate, and body length at 15 days post fertilization (dpf). The mRNA expression levels of sox2, neurogenin1 and huc in the treated zebrafish embryos were detected using in situ hybridization and qRT-PCR, and their behavioral responses to strong light and vibration stimulation were observed. The zebrafish embryos were then exposed to DMSO, 1.5% ethanol, DAPT, or both ethanol and DAPT, and the changes in mRNA expression levels of sox2, neurogenin1, huc, and the Notch signaling pathway genes as well as behavioral responses were evaluated.@*RESULTS@#Exposure to 50 μmol/L DAPT significantly increased the mortality rate of 1 dpf zebrafish embryos (P < 0.01), decreased the hatching rate of 2 dpf embryos (P < 0.01), increased the malformation rate of 3 dpf embryos (P < 0.001), and reduced the body length of 15 dpf embryos (P < 0.05). DAPT treatment significantly downregulated sox2 mRNA expression (P < 0.01) and increased neurogenin1 (P < 0.05) and huc (P < 0.01) mRNA expressions in zebrafish embryos. The zebrafish with DAPT treatment exhibited significantly shortened movement distance (P < 0.001) and lowered movement speed (P < 0.05) in response to all the stimulation conditions. Compared with treatment with 1.5% ethanol alone, which obviously upregulated notch1a, her8a and NICD mRNA expressions in zebrafish embryos (P < 0.05), the combined treatment with ethanol and DAPT significantly increased neurogenin1 and huc mRNA expression, decreased sox2 mRNA expression (P < 0.01), and increased the moving distance and moving speed of zebrafish embryos in response to strong light stimulation (P < 0.05).@*CONCLUSION@#Ethanol exposure causes upregulation of the Notch signaling pathway and impairs neuronal differentiation and sensorimotor ability of zebrafish embryos, and these detrimental effects can be lessened by inhibiting the Notch signaling pathway.
Sujet(s)
Animaux , Danio zébré , Amyloid precursor protein secretases , Diméthylsulfoxyde , Antiagrégants plaquettaires , Antinéoplasiques , Éthanol/effets indésirables , Transduction du signalRÉSUMÉ
【Objective】 To investigate the efficacy of autologous ozoneized blood transfusion(AOBT) in improving consciousness and motor function in convalescent stroke patients. 【Methods】 A total of 44 patients who were diagnosed as convalescent cerebral apoplexy and received treatment in Rehabilitation Department of our hospital from August 2016 to September 2021 were randomly divided into the experimental group and control group by blind method. The experimental group (n=22) received general rehabilitation training (such as exercises, occupational therapy, acupuncture and transcranial magnetic stimulation) plus AOBT (200 mL venous phlebotomy at the median elbow), once every 2 to 3 days and 12 occasions as a course of treatment; the control group solely recieved general rehabilitation training. The consciousness (GCS score) and ability of daily living (Barthel index score) score of the two groups before and after treatment were statistically compared, and Ueda motor function grade, Brunnstrom stage and muscle tone grade were observed and evaluated. 【Results】 After the treatment, the experimental group and the control were compared as follows: 1) the GCS score and Barthel score was 14.82±0.39 vs 12.41±2.52, 61.14±12.24 vs 52.05±11.72(P<0.05); 2) The recovery rate of motor function was 95.45% (21/22) vs 63.64% (14/22) (P<0.05); 3) The total recovery rate of muscle tone was 90.91% (20/22) vs 63.64% (14/22) (P<0.05). 【Conclusion】 AOBT, with somewhat high safety and effectiveness, can improve the state of consciousness, motor function and muscle tone in convalescent patients with stroke.
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Objective:To investigate the effect of visual preconditioning on emergence agitation in ophthalmic surgery among preschool children.Methods:A total of 156 preschool children who underwent elective ophthalmic surgery in Qilu Hospital of Shandong University from February to September 2021 were selected as the research subjects, and they were divided into the control group and the intervention group by random number table method, there were 78 cases in each group. The control group was given normal nursing 1 hour before surgery while the intervention group accepted visual preconditioning by covering the affected eye. Chinese Version of the Modified Yale Preoperative Anxiety Scale (Cm-YPAS) was used to evaluate the grade of anxiety for the patients during the process of anesthesia induction. Pediatric Anesthesia Emergence Delirium (PAED) was used to compare the score of emergence agitation and the incidence rate of emergence agitation of the two groups.Results:Finally, 75 cases were included in the intervention group and 75 cases in the control group. During anesthesia induction, the intervention group scored (39.78±4.84) and the control group scored (41.07±5.09) with Cm-YPAS, and there was no statistical difference between the two groups ( P>0.05). Furthermore, compared the PAED score of the intervention group 5(4,8) with the control group 8(5, 11), there were statistically significant differences between the two groups ( Z=-3.07, P<0.01). Emergence agitation incidence in the intervention group was 14.67%(11/75), which was lower than that in the control group 38.67%(29/75), the difference was significant ( χ2=11.05, P<0.01). Conclusions:Visual preconditioning can effectively improve recovery quality after general anesthesia and decrease the incidence rate of emergence agitation in ophthalmic surgery among preschool pediatric patients. It′s well worthy of application and dissemination of visual preconditioning clinically.
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Objective:To investigate the diagnostic efficiency of the 2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) and the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) in the diagnosis of benign and malignant thyroid nodules.Methods:A retrospective analysis of the two-dimensional ultrasound image results of 324 thyroid nodules in 289 patients with thyroid nodules and thyroid nodules were performed in the physical examination of the Health Management Department of the Guangdong Second Provincial General Hospital from January 2018 to January 2019. A superficial professional doctor with a senior professional title simultaneously uses the C-TIRADS and ACR-TIRADS methods to evaluate the above nodules. The results are all pathologically referenced for the χ2 test and the receiver operating characteristic curve is drawn. Results:The sensitivity of C-TIRADS in diagnosing benign and malignant thyroid nodules was 81.90%, specificity was 97.72%, accuracy was 92.59%, negative predictive value was 91.85%, positive predictive value was 84.51%; ACR-TIRADS diagnosis The sensitivity of benign and malignant thyroid nodules was 59.05%, specificity was 99.54%, accuracy was 86.42%, negative predictive value was 83.52%, and positive predictive value was 98.41%. The area under the ROC curve was 0.958 and 0.935( Z=2.31 P=0.021). Conclusion:C-TIRADS classification based on counting method is better than ACR-TIRADS classification based on sub-method in the diagnosis of thyroid nodules. It has better efficacy and is more suitable for the current status of diagnosis and treatment of thyroid nodules in China.
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Cardiac magnetic resonance imaging (MRI) serves as a clinical gold-standard noninvasive imaging technique for the assessment of global and regional cardiac function. Conventional cardiac MRI is limited by the long acquisition time, the need for ECG gating and/or long breathhold, and insufficient spatiotemporal resolution. Real-time cardiac cine MRI refers to high spatiotemporal cardiac imaging using data acquired continuously without synchronization or binning, and therefore of potential interest in overcoming the limitations of conventional cardiac MRI. Novel acquisition and reconstruction techniques must be employed to facilitate real-time cardiac MRI. The goal of this study is to discuss methods that have been developed for realtime cardiac MRI. In particular, we classified existing techniques into two categories based on the use of non-iterative and iterative reconstruction. In addition, we present several research trends in this direction, including deep learning-based image reconstruction and other advanced real-time cardiac MRI strategies that reconstruct images acquired from real-time free-breathing techniques.
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AIM: To explore whether Agkistrodon Halys venom antitumor component-I (AHVAC-I) affects the migration of gastric cancer cells by human primary gastric cancer-associated fibroblast (GCAFs). METHODS: Tissue block culture and trypsin digestion were used to separate and culture human primary gastric cancer-associated fibroblasts (GCAFs); the GCAFs-CM
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Follicular thyroid carcinoma(FTC) is a differentiated thyroid carcinoma originated from thyroid follicular cells. The sensitivity and specificity of ultrasound classification and scoring systems in diagnosis of follicular carcinoma are insufficient. Ultrasound guided fine needle aspiration(US-FNA) can screen but cannot diagnose FTC. Core needle biology(CNB) can reduce repeated FNA and unnecessary operations, and improve the diagnostic accuracy of FN patients, but CNB still has many controversies. Ultrasound guided FNA combined with gene detection (such as RAS) can significantly improve the diagnostic accuracy of follicular neoplasm. In recent years, artificial intelligence assisted diagnosis has shown high specificity in distinguishing FTC from follicular thyroid adenoma (FTA), which is conducive to the standardized treatment of thyroid follicular neoplasm. In this paper, the research progress of ultrasound based in diagnosis of FTC was reviewed.
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Nail unit tumors are a group of rare tumors only occurring in the nail unit, including onychopapilloma, onychomatricoma, onychocytic matricoma, onycholemmal carcinoma, and so on. These tumors have specific clinical manifestations and pathological features due to their special anatomical locations. This review focuses on clinical manifestations, histopathological characteristics and treatment of the above tumors.
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With the further understanding and the accumulation of experiences in diagnosis and treatment for chronic cough, a growing number of evaluation scales about chronic cough are used in clinical practice.Medical workers try to quantitatively evaluate chronic cough and accurately guide clinical practices with evaluation scales.At present, the evaluation scales of chronic cough mostly focus on health-related quality of life, because chronic cough will seriously affect the quality of life for patients, and further affect the psychology, daily life and family members of patients.
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Objective:To investigate the characteristics and significance of insulin-like growth factor 1(IGF- 1) and insulin-like growth factor binding protein 2 (IGFBP2) expressions in ankle cartilage of patients with Kashin-Beck disease (KBD).Methods:In this case-control study, 10 KBD patients who were hospitalized in the Department of Orthopedics of Shaanxi Provincial People's Hospital from January 2010 to December 2016 were selected as KBD group, and 10 patients with ankle fracture caused by trauma but without talus injury during the same period were selected as control group, the cartilage tissues of the two groups were collected. IGF-1, IGFBP2 positive cells, the mRNA and protein expressions of IGF-1, IGFBP2 in the cartilage tissues were detected by immunohistochemistry, real-time fluorescent quantitative PCR and Western blotting, respectively. According to the expressions of IGF-1 and IGFBP2 in ankle cartilage of KBD patients, a patient with amputation caused by trauma was selected in Shaanxi Provincial People's Hospital, and ankle joint cartilage was taken to prepare chondrocytes for in vitro cell verification experiments. The chondrocyte were divided into control group (0 ng/ml T-2 toxin), T-2 treatment group (20 ng/ml T-2 toxin) and T-2+ IGFBP2 silenced group (20 ng/ml T-2 toxin+ 50 nmol/L IGFBP2 siRNA), the MTT method and dimethyl methylene blue staining were used to detect the activity of chondrocyte and the secretion of sulfated glycosaminoglycan (sGAG). Results:In the control group and the KBD group, the number of IGF-1[(47.26 ± 8.97), (68.15 ± 7.42) cells] and IGFBP2 positive cells [(27.56 ± 5.40), (71.85 ± 7.62) cells] in the cartilage tissues were significantly different ( t = 4.487, 9.402, P < 0.01). Compared with the control group, the IGF-1, IGFBP2 mRNA and protein expression levels in KBD group were significantly higher, the differences were significantly different ( t = 3.340, 20.700, 4.684, 8.699, P < 0.05 or < 0.01). In cell experiment, the chondrocyte activitives and sGAG contents of the control group, T-2 treatment group, and T-2+ IGFBP2 silenced group were significantly different ( F = 226.70, 80.66, P < 0.01); among them, the cell activitives and sGAG contents of the T-2 treatment group and T-2+ IGFBP2 silenced group were lower than those of control group ( P < 0.05), and the T-2+ IGFBP2 silenced group were higher than those of the T-2 treatment group ( P < 0.05). Conclusions:The expressions of IGF-1 and IGFBP2 in the ankle cartilage of KBD patients are significantly higher. Silencing IGFBP2 gene can reduce the inhibitory effect of T-2 toxin on chondrocyte activity and the secretion of sGAG.
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Background: Endoscopy combined with biopsy-based histology is most commonly used in the surveillance of ulcerative colitis (UC). However, the endoscopic and histological results for assessing disease activity are often inconsistent. Aims: To investigate the consistency and correlation of endoscopic and histological scoring systems in assessing the disease activity in UC patients. Methods: A retrospective study was conducted in UC patients admitted from January 2014 to January 2020 at Renji Hospital, School of Medicine, Shanghai Jiao Tong University. The clinical manifestations, endoscopic and histological findings were collected and analyzed, and the disease activity was examined endoscopically and histologically by Mayo Endoscopic Subscore and Simplified Geboes Score, respectively. Results: One hundred and forty-three UC patients were enrolled. Basal plasmacytosis is frequently seen in endoscopically active UC (OR=11.19, 95% CI: 4.80-26.09, P<0.001). Approximately half of the patients (53.7%) who achieved endoscopic remission still had inflammatory activity histologically. Kappa consistency test showed that the agreement between Mayo Endoscopic Subscore and Simplified Geboes Score for assessing disease activity was moderate (κ=0.4, P<0.001). By Spearman correlation coefficient analysis, a moderate correlation between the two scoring systems was identified (r
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BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.
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OBJECTIVE：To study the composition and contents of flavonoids chemical components in waste material during industrialization of Pueraria thomsonii resources，and to provide reference for comprehensive development and reasonable utilization of the variety. METHODS ：Using“No. 2 Gange”of P. thomsonii from Jiangxi as objects ，UPLC-Q-TOF-MS and HPLC method were adopted to detect the components and contents of flavonoids in the root （with or without cortex ），cortex，flower， fibrous root ，stem，head and dregs （with or without cortex ）of P. thomsonii as well as dry matter of industrial wastewater （with or without cortex ）after precipitation of pueraria powder. RESULTS ：The linearity ，precision，repeatability，stability and recovery of the established method for content determination of 7 flavonoids（puerarin，daidzin，iridoxine-7-O-xylose glucoside ，genistin， iridin，daidzein and kakkalide ）were all in line with the requirements. Totally 12 kinds of flavonoids were identified ，among which the flavonoids in the root ，cortex，stem，fibrous root ，head and dregs of P. thomsonii as well as dry matter of industrial wastewater were the same ，mainly were puerarin ，daidzin，genistein，daidzein and malonyl-daidzein. The flower of P. thomsonii mainly included iridoxine- 7-O-xylose glucoside ，genistin，iridin，kakkalide，6″-O-xylosyldaidzein，but the components as puerarin ， daidzin and its aglycone were not be detected. The content of puerarin in the head of P. thomsonii was the highest （5.765％）. The contents of puerarin in root and dregs of P. thomsonii as well as dry matter of industrial waste-water in samples with cortex were all higher than in corresponding peeled sample. CONCLUSIONS ：The waste material from the industrialization of P. thomsonii resources contains a lot of flavonoids with rich species and high content ，and can be used as an important raw material for obtaining flavonoids such as puerarin.
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Objective:To detect the expression levels of interleukin (IL)-1β, insulin-like growth factors (IGF)-1 in serum and synovial fluid of patients with Kaschin-Beck disease (KBD) and osteoarthritis (OA) and analyze the relationship between IL-1β, IGF-1 levels and visual analogue scale (VAS) score.Methods:From January 2010 to December 2016, 60 patients visited the department of orthopedics of Shaanxi Provincial People's Hospital were selected, included 20 patients with KBD (arthroscopic debridement of ankle), 20 patients with OA (arthroscopic debridement of ankle), and 20 patients with ankle fracture (no talus injury) as control group. The peripheral blood and synovial fluid samples from the patients were collected. Enzyme-linked immunosorbent assay was used to detect the expression levels of IL-1β, IGF-1 in serum and synovial fluid. In each group, VAS score was calculated pre-operative and post-operative at 3, 7, 14 and 28 d. The relationship between IL-1β, IGF-1 levels and VAS score was evaluated by correlation analysis.Results:Synovial fluid IL-1β and IGF-1 levels in the KBD and OA groups were (67.32 ± 6.22), (56.46 ± 5.43) and (24.36 ± 6.22), (21.45 ± 4.35) pg/ml, respectively, which were higher than those in the control group [(27.01 ± 3.15), (10.21 ± 2.50) pg/ml, P < 0.05]. Meanwhile, serum IL-1β and IGF-1 levels in the KBD and OA groups were higher than those in the control group ( P < 0.05). Pearson correlation analysis showed that the expression levels of IL-1β and IGF-1 in serum pre-operative and post-operative at 3, 7, 14 and 28 d were positively correlated with VAS score in KBD and OA groups, respectively ( r = 0.427, 0.502, 0.562, 0.628, P < 0.05). Conclusion:The levels of IL-1β and IGF-1 in synovial fluid from ankle joints and serum are significantly increased in KBD group and OA group, and the levels of IL-1β and IGF-1 in serum are positively correlated with VAS score, respectively.