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Objective:To investigate the value of antioxidant-associated long non-coding RNAs(lncRNAs)risk score model in prognosis and the association with immune microenvironment of the gastric cancer patients.Methods:Gastric cancer transcriptome data and clinical information were downloaded from TCGA database.Antioxidant-associated lncRNAs were obtained by co-ex-pression analysis of lncRNAs and antioxidant genes.Risk score was constructed using univariate cox regression analysis and lasso regression analysis.Log-Rank test was used to compare the survival differences between two groups.Receiver operating characteristic curve(ROC)was used to assess the specificity and sensitivity of the prognostic risk score model.Nomogram was constructed com-bining risk score and clinical parameters.Immune cell infiltration was assessed by TIMER 2.0.Im-munotherapy sensitivity of each sample was analyzed at TIDE website.Results:A risk score in-cluding 12 IncRNAs was constructed by univariate cox regression analysis and lasso regression anal-ysis.The risk score was an independent factor influencing patient prognosis[HR=5.406(3.131~9.335),P<0.001].Risk score was positively correlated with multiple suppressive immune cells infil-tration(M2 macrophage,tumor-associated fibroblast).Meanwhile,multiple aberrant expression of immune checkpoint genes and higher TIDE score were found in high-risk group,suggesting that high-risk groups may be more sensitive to immunotherapy.Conclusion:The antioxidant-associ-ated IncRNAs risk score is a good prognostic predictor and can act as a reference in individualized immunotherapy for gastric cancer patients.
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BACKGROUND:Clinical skin wound healing continues to be a significant concern,and tissue repair research has moved to the forefront with the development of biomaterials with immunomodulatory properties.Therefore,it is crucial to research wound dressings that have immunomodulatory properties. OBJECTIVE:To prepare chitosan hydrogels that have been modified by arginine with different configurations and assess their capacity to speed up wound healing in a rat animal model. METHODS:(1)In vitro trial:Chitosan modified by pure L-arginine,pure D-arginine,and L-arginine and D-arginine was synthesized by EDC/NHS system,which was then crosslinked with aldehyde-modified four-arm polyethylene glycol.Different chitosan-based hydrogels(CS-L,CS-D,and CS-DL)were finally formed via the Schiff base reaction.Three kinds of hydrogel extracts were co-cultured with fibroblasts respectively.Hydrogel cytocompatibility was assessed using the CCK-8 assay and live/dead staining.The effect of hydrogel on the migration capacity of fibroblasts was assessed by using a scratch test.Three kinds of hydrogels were incubated with rat erythrocyte suspension respectively to evaluate the hemocompatibility of the hydrogels.The hydrogel extract was co-cultured with RAW264.7 macrophages to test the hydrogels'capacity to enhance macrophage NO generation and polarize macrophage phenotype.(2)In vivo experiment:A total of 36 adult SD rats were divided into 4 groups with 9 rats in each group by the random number table method.Two full-layer skin defect wounds of 2 cm×2 cm were made on the back of each rat.Normal saline was added to the wounds of the control group,and corresponding hydrogel was added to the wounds of the CS-L,CS-D,and CS-DL groups,respectively,and then bandaged and fixed.The wound healing was observed regularly after operation.Hematoxylin-eosin staining was performed at 3,10,and 21 days after operation.The samples were collected 10 days after operation and M2 macrophage immunofluorescence staining was performed. RESULTS AND CONCLUSION:(1)In vitro experiments:Under scanning electron microscopy,the three kinds of hydrogels exhibited obvious interpenetrating network structures with pore sizes ranging from 70-200 μm.The three kinds of hydrogels have good swelling performance,degradation performance,self-healing performance,and suitable mechanical strength.The three kinds of hydrogels had good cytocompatibility and hemocompatibility and could promote the migration of fibroblasts.All three kinds of hydrogels had the ability to promote the polarization of macrophages,and CS-D hydrogels had the strongest ability to promote the polarization of macrophages.CS-L hydrogel could significantly promote the production of NO in macrophages.(2)In vivo experiment:3 and 10 days after operation,the wound healing rate in the CS-L and CS-D groups was higher than that in the control group(P<0.05).After 21 days,the wound healing rate of the three hydrogel groups was higher than that of the control group.Hematoxylin-eosin staining displayed that a large number of inflammatory cells were infiltrated in the wound tissue of rats in all groups,accompanied by neovessels and fibroblasts 3 days after operation.10 days after operation,there was still more inflammatory cell infiltration in the wound of the control group,and the inflammation of the other three groups was improved,especially the decrease of inflammatory cells in the CS-D group was more obvious.21 days after operation,the wound epithelium of each group was well repaired,and there was basically no inflammatory cell infiltration in the CS-L and CS-D groups,while there was still a small amount of inflammatory cell infiltration in the control group.Immunofluorescence staining revealed that the number of M2-type macrophages in the CS-D group was higher than that in the other three groups(P<0.05).(3)The results conclude that chitosan hydrogels modified by different configurations of arginine can promote wound healing through different mechanisms.
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OBJECTIVES@#To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy.@*METHODS@#Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined;with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm.@*RESULTS@#Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039).@*CONCLUSIONS@#Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.
Subject(s)
Humans , Electroacupuncture , Acupuncture Therapy , Acupuncture Points , Diabetes Mellitus, Type 2/therapy , Glycated Hemoglobin , Cognitive Dysfunction/therapy , Cholesterol , gamma-Aminobutyric Acid摘要
Objective:To explore the quality differences of systemic biopsy specimens from different regions in prostate biopsy.Methods:The data of 806 patients who underwent transperineal prostate biopsy from May 2013 to December 2020 in Northern Jiangsu People’s Hospital were retrospectively reviewed. The median age of the patients was 72 (66, 77) years old, median PSA was 18.4 (10.3, 34.2) ng/ml, and prostate volume was 43 (32, 56) ml. Tissue quality were graded from low to high as follows. One score means multiple fragments with fragmented tissue ≤5 mm. Two scores means at least one fragment >5 mm and ≤10 mm. Three scores means at least one fragment >10 mm. The prostate specimens fragmentation scores and the length of the specimens in different regions of the prostate were collected to analyze.Results:A total of 806 patients were included in our study. The number of tissues was 8 866, and the mean length of tissues was 1.2 (1.0, 1.5) cm. The tissues of different region were scored according to the scoring criteria, of which 618 (7.0%) prostate tissues were scored as 1 score, 2 720 (30.7%) tissues were scored as 2 scores, and 5 528 (62.4%) tissues were scored as 3 scores. In the prostate apex, tissue quality of 1 score accounted for 11.7%(94/806), 2 scores accounted for 34.7%(280/806), and 3 scores accounted for 53.6%(432/806). While in the prostate base, tissue quality of 1 score accounted for 6.5%(524/8 060), 2 scores accounted for 30.3%(2 449/8 060), and 3 scores accounted for 63.2%(5 096/8 060)( H=35.850, P<0.05). The mean length of the prostate apical tissue was 1.0 (0.8, 1.3) cm, which was significantly shorter than prostate basal tissue of 1.2(1.0, 1.5) cm ( Z=-11.353, P<0.05). Conclusions:In transperineal prostate biopsy, the apical tissue was more fragmented and shorter, prostate apex should be concerned.
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Objective To identify the potential prognostic biomarkers of the immune-related genes signature for patients with hepatocellular carcinoma (HCC). Methods Original HCC data were downloaded from TCGA, and the immune activity of each sample was calculated by ssGSEA. HCC samples were divided into high and low immune cell infiltration groups by "GSVA" package and "hclust" package. The ESTIMATE algorithm scored the tumor microenvironment in each HCC sample. The "limma" package and Venn diagram identified effective immune-related genes. Univariate Cox, Lasso regression and multivariate Cox regression analyses were used to explore key genes. The "rms" package was used to create nomograms and draw calibration curves. Results Compared with the high immune cell infiltration group, the tumor purity of the samples in the low immune cell infiltration group was higher, the immune score, ESTIMATE score and stromal score were lower. In the high immune cell infiltration group, the immune components were more abundant, and the expression levels of TIGIT, PD-L1, PD-1, LAG3, TIM-3, CTLA4 and HLA family were higher. Multivariate Cox regression analysis showed that four immune-related genes (S100A9, HMOX1, IL18RAP and FCER1G) were used to construct the prognosis model. Compared with other clinical features, the risk score of this prognostic model was recognized as an independent prognostic factor. Conclusion This study identified the immune-related core genes which may be used in targeted therapy and immunotherapy of HCC.
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The present study retrospectively analyzed the clinical data of 137 patients who underwent prostate in North Jiangsu People's Hospital from June 2020 to May 2021. All patients underwent peripheral prostatic nerve block anesthesia (PPNB). The observation group received 1% ropivacaine 32 ml local, and the control group received the same dose of lidocaine. There was no significant difference in general data before puncture between the two groups ( P>0.05). All 137 cases were performed by the same surgeon. The number of puncture needles in the observation group and the control group was (20.2±2.8) and (20.2±2.9), respectively, and the difference was not statistically significant ( P>0.05). The visual analogue scores (VAS-1) of pain during puncture in the observation group and the control group were (2.62±0.74) and (2.48±0.79) points, respectively. The visual numeric score (VNS-1) was (3.03±0.88) points and (3.15±0.80) points, respectively, and there was no significant difference ( P>0.05). 30 min after puncture, VAS-2 was (0.48±0.53) points and (0.30±0.47) points, VNS-2 was (3.31±0.48) points and (3.55±0.71) points, respectively.The differences were statistically significant ( P<0.05). There was no significant difference in overall complication rate between the two groups ( P=0.661).
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Based on the heat-clearing and detoxifying effects of Gentianae Radix et Rhizoma, the network pharmacology is mainly used to predict the potential targets of Gentianae Radix et Rhizoma for anti-inflammatory activity and to perform the experimental verification. A method for detecting the biological potency of Gentianae Radix et Rhizoma based on verifiable targets has been established to provide a reference for improving the quality evaluation and control standards of Gentianae Radix et Rhizoma. High performance liquid chromatography can be used to construct chemical fingerprints of different batches of Gentianae Radix et Rhizoma. Constructing a component-target-disease network of Gentianae Radix et Rhizoma for its anti-inflammatory activity was applied to screen potential anti-inflammatory components and related targets of Gentianae Radix et Rhizoma, and to verify the target of Gentianae Radix et Rhizoma by using biological evaluation methods. Detecting the biological potency of different batches of Gentianae Radix et Rhizoma extracts was used to inhibit COX-2 enzyme activity based the verifiable target cyclooxygenase-2(COX-2). The results showed that different batches of Gentianae Radix et Rhizoma accorded with the pharmacopoeia testing regulations, and the chemical fingerprints have a high similarity(similarity>0.93), suggesting that there is no significant difference in the characteristics of the chemical components. Based on network pharmacology predictions, 18 candidate targets were found to have potential direct interactions with the ingredients in Gentianae Radix et Rhizoma. Among them, the most important target is COX-2. Based on the experimental verification of recombinant human COX-2 protease activity inhibition, Gentianae Radix et Rhizoma can inhibit the COX-2 enzyme activity in a dose-dependent manner. It can function with a low concentration(0.75 mg·mL~(-1)), which preliminarily confirmed the accuracy of network pharmacology prediction. The biological potency detection method of Gentianae Radix et Rhizoma based on COX-2 inhibitory activity was optimized and established. The qualitative response parallel line method was used to calculate the biological potency of anti-inflammatory activity, which ranged from 23.04 to 46.60 U·mg~(-1). For network pharmacology prediction, it can screen and clarify the possible targets of traditional Chinese medicine rapidly, which can guide the establishment of a biological evaluation method for the quality of medicinal materials with related activities. Compared with chemical fingerprints, the biological potency testing can better detect quality fluctuations of traditional Chinese medicine.
Subject(s)
Humans , Anti-Inflammatory Agents/pharmacology , Biological Assay , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional , Quality Control , Rhizome摘要
Objective: To investigate the expression pattern of tropomyosin 2(TPM2) in aorta of patients with aortic dissection and explore its clinical implication. Methods: Thirteen cases with acute type A aortic dissection(TAAD) diagnosed by transabdominal aortic angiography from 2015 in Tongji Hospital were included. During the operation, the aortic wall tissues of these patients were collected. Ten patients with heart transplantation were selected as control group, and normal aortic wall tissues were taken. The hematoxylin-eosin (HE) and Verhoeff's Van Gieson (EVG) staining were performed to observe the morphological changes of aorta. The mRNA expression level of TPM2 was measured by real-time fluorescent quantitative-PCR, and the protein levels of TPM2 were detected by Western blot and immunohistochemical staining. Image The J software was used to collect the optical density values of each point on the image, obtain the integrated optical density(IOD) value, and calculate the average density(%, IOD/area of the target distribution area). Results: HE and EVG staining revealed medial degeneration and broken elastic fiber in aorta of TAAD patients. The mRNA expression levels of TPM2 were significantly upregulated in aorta of TAAD patients as compared to the control group (P<0.05), so as the TPM2 protein expression levels ((9.73±1.20)% vs. (0.11±0.04)%, P<0.05). And TPM2 was mainly expressed in cytoplasm. Conclusion: The increased expression of TPM2 in TAAD patients hints that TPM2 might be involved in the pathogenesis of aortic dissection.
Subject(s)
Humans , Aortic Dissection/genetics , Aorta , Aortic Aneurysm, Thoracic/genetics , Gene Expression , RNA, Messenger , Tropomyosin/metabolism摘要
Objective To explore the clinical efficacy of vaginal hysterectomy and uterine scar repair in the treatment of type Ⅱ cesare-an scar pregnancy. Methods A total of 157 patients with type Ⅱ cesarean scar pregnancy (CSP) admitted to our obstetrics and gynecology department of our hospital from July 2016 to July 2017 were selected as research subjects. They were divided into ultrasound curettage group (n =87) and vaginal repair group(n =70) according to different surgical methods. The surgical bleeding volume, operative time, hospital stay and human chorionic gonadotropin (β-HCG) level before and after operation,the time of blood β-HCG returning to normal level,hemoglobin (HB) level before and after operation,menstrual recovery time,stress response, inflammatory response and surgical complications were compared between the two groups. Results The intraoperative blood loss volume, operative time and hospital slay in ultrasound curettage group were lower than those in vaginal repair group,the difference was significant(P <0.05). The time of blood β-HCG returning to normal level in vaginal repair group after operation was shorter than that in ultrasound curettage group, the difference was significant (P < 0. 05). There was no significant difference in the HB level between the two groups(P>0.05). The menstrual recovery time in vaginal repair group was shorter than that in ultrasound curettage group,the difference was significant(P <0. 05). The levels of postoperative epinephrine (E) and Cortisol (Cor) in vaginal repair group after operation were lower than those in ultrasound curettage group, while the level of thyroid stimulating hormone (TSH) was higher than that in ultrasound curettage group,the difference was significant(P <0.05). The levels of IL-2, IL-6 and IL-8 in vaginal repair group after operation were lower than those in ultrasound curettage group while the level of C-reactive protein (CRP) was higher than that in ultrasound curettage group,the difference was significant(P <0.05). The incidence rate of postoperative complications in ultrasound curettage group was higher than that in vaginal repair group(P <0. 05). Conclusion Vaginal repair is more beneficial to shortern the time of blood β-HCG returning to normal level and menstrual recovery time, promote the inflammatory factor and hormone recovery to a normal level, and reduce the incidence of complication.
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Xiaojin pills, the first choice for clinical treatment of breast hyperplasia, were selected to explore the suitability of a bioactivity assay with chemical fingerprinting for the development of an overall quality evaluation assay. The liposoluble and water-soluble fraction fingerprints of Xiaojin pills were established. The ability to inhibit platelet aggregation and the rate of inhibition of cyclooxygenase-2 (COX-2) for 16 batches of Xiaojin pills from several manufacturers was analyzed; the chemical fingerprints of these samples were correlated with the bioactivity and chemical analysis. The animal protocol was approved by the Committee on the Ethics of Animal Experiments of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Approval, ID: 2018BL-002. Results showed that the antiplatelet aggregation activity of 16 batches was 0.712-1.278 U∙mg-1, with a relative standard deviation (RSD) of 15.4%. COX-2 inhibition was 52.07%-68.95% and the RSD was 8.91%. The results showed that there was little difference in the biological effects of these samples. However, the chemical fingerprint consistency of these 16 batches of Xiaojin pills was poor, and the similarity of nearly half of the samples was less than 0.9. The total peak area of Xiaojin pills was 32.74%-165.37% across samples, showing very poor chemical consistency. In order to explore the reasons for the poor chemical consistency despite good consistency in the biological assays, the fingerprint chromatogram was analyzed by multivariate statistical analysis. The main chromatographic peaks were identified. The results showed that the similarity of Xiaojin pills was mainly determined by the prominent chromatographic peaks 17, 18, 20, 23 and 27 in the liposoluble fingerprints, which were identified from Liquidambaris resina and Angelica sinensis Radix. However, Liquidambaris resina and Angelicae sinensis Radix had almost no anti-platelet aggregation activity or COX-2 inhibitory effect at the normal prescription ratio. As a result, the ability to utilize chemical fingerprints to evaluate the quality consistency of Xiaojin pills is limited. The selection of biological evaluation methods that reflect clinical efficacy could make up for the shortcomings of chemical evaluation methods for quality assessment, and provide new ideas and methods for the overall quality evaluation of complex Chinese patent medicines.
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To predict the targets of active ingredients of Kuihua Hugan Tablets by network pharmacology, and explore the "multi-component-multi-target-multi-pathway" hepatoprotective mechanism of action. First, through traditional Chinese medicine systems pharmacology(TCMSP) and TCM Database@Taiwan Database, main active ingredients of Kuihua Hugan Tablets were screened out based on oral bioavailability(OB), drug-likeness(DL) and effective half-lives(HL). The targets of active ingredients of Kuihua Hugan Tablets were predicted based on the PharmMapper method. Then, the prediction was conducted by screening the target genes associated with chronic hepatitis and early cirrhosis through CooLGeN and GeneCards databases. Target gene functions and signal pathways were analyzed by bioinformatics annotation database Metascape. Cytoscape software was used to construct the Kuihua Hugan Tablets ingredient-target and ingredient-target-pathway network. String database combined with Cytoscape software was used to construct the networks of component-target and component-target-pathway. STRING database was combined with Cytoscape software to draw protein-protein interaction(PPI) network and conduct network topology analysis. Finally, Systems Dock Web Site software was applied in verifying the molecular docking between active ingredients and potential protein targets. A total of 26 compounds and 509 potential targets were screened out from Kuihua Hugan Tablets in the experiment. The results of PPI network analysis indicated that albumin(ALB), insulin-like growth factor 1(IGF1), matrix metalloproteinase-9(MMP9), matrix metalloproteinase-2(MMP2), non-receptor tyrosine kinase proto-oncogene(SRC), estrogen receptor 1(ESR1) and cancer-signal transduction-inflammation-drugs metabolism-related biological processes and metabolic pathways were closely associated with the active ingredients in Kuihua Hugan Tablets. The effects of Kuihua Hugan Tablets in alleviating chronic hepatitis and early cirrhosis indicated the multi-component, multi-target, and multi-pathway characteristics of traditional Chinese medicines, providing new ideas for further research and development of Kuihua Hugan Tablets.
Subject(s)
Drugs, Chinese Herbal , Pharmacology , Medicine, Chinese Traditional , Metabolic Networks and Pathways , Molecular Docking Simulation , Protein Interaction Mapping , Tablets摘要
Objective To study the overall similarity of composition-activity of different kinds of Paridis Rhizoma, and establish a new method for selecting alternative resources. Methods The HPLC method was used to detect the content of polyphyllin I, II, VI, and VII, and pharmacological model of analgesic and hemostatic were used to detect the efficacy. The data were standardized using standard deviation method. Using polyphyllin I, II, VI, and VII at minimum 0.6%, aspirin and Yunnan Baiyao Group analgesic and hemostatic efficacy data as standard controls, we also established component and activity indexes. SPSS 20.0 Software was used to analyze the principal component analysis (PCA) and hierarchical cluster analysis (HCA) of these seven medicinal plants. Results The total content of the main saponins in seven medicinal plants of Paris genus ranged from 0.125% to 1.649%, and the maximum content (1.649%) was found in the P. forrestii while the minimum content (0.125%) was found in P. daliensis. The study also disclosed that P. polyphylla var. yunnanensis has the most active analgesic activity, and the time of bleeding (BT) in mice and the time of coagulation (CT) in mice were the shortest in P. polyphylla. The shortest mice activated partial thrombin time (APTT) was P. forrestii and the longest was P. thibetica. The shortest prothrombin time (PT) in mice was P. vietnamensis. The longest BT in mice was P. daliensis. The longest CT and PT in mice was P. polyphylla. PCA and HCA results showed that P. polyphylla var. yunnanensis, P. vietnamensis and P. thibetica were in the same class, while P. pubescens, P. daliensis, P. polyphylla, and P. forrestii were in another class. It is indicated that the overall similarity of component-activity of P. vietnamensis, P. thibetica, and P. polyphylla var. yunnanensis was higher, thus they can be considered as alternative sources. Conclusion The quality relations of different kinds of Paris genus were evaluated by the overall similarity of the component and activity index, which provides ideas and methods for the search of the replacement resources of the endangered plants.
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BACKGROUND: Antagonism of bone sclerosis protein can stimulate osteogenesis and increase bone synthesis and metabolism through the Wnt/β-catenin signaling pathway. OBJECTIVE: To investigate the effects of sclerostin-single chain antibody fragment (Scl-scFv) on the proliferation and osteogenic differentiation of C57BL/6 mouse bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated from C57BL/6 mice using whole bone marrow adherence method. Alizarin red staining was performed at the 14thday of osteogenic induction, and oil red O staining performed at the 7thday of adipogenic induction. Passage 3 BMSCs were cultured with α-MEM complete medium with (experimental) or without (control) 50 μg/L Scl-scFv aScl-scFv. Real-time PCR was used to detect type 1 collagen, alkaline phosphatase, RUNX2, osteopontin, osteocalcin at the 7thday of culture and meanwhile, alkaline phosphatase staining was done; western blot assay was used to detect expression of type 1 collagen and osteopontin proteins, and ELISA was used to detect the level of osteocalcin in the cell supernatant at 4, 7, 10 days of culture. RESULTS AND CONCLUSION: Formation of calcium nodules and orangered oil droplets was obviously visible in the BMSCs after osteogenic and adipogenic induction, respectively. Over time, the absorbance value showed no difference between the experimental and control group. Compared with the control group, the experimental group showed significant increases in mRNA and protein expression of type 1 collagen and osteopontin as well as in protein expression of alkaline phosphatase, RUNX2 and osteocalcin (P < 0.05). Moreover, stronger alkaline phosphatase staining was found in the experimental group relative to the control group. These findings indicate that Scl-scFv has no effect on BMSCs proliferation,but can promote the osteogenic capacity of BMSCs in vitro.
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Objective:To investigate the expression and clinical significance of B7-H3 and IL-21 in serum of patients with HBV-related primary liver cancer.Methods: Gathering 121 cases of HBV-related patients,50 cases of primary hepatic carcinoma of them were considered as hepatic carcinoma group,71 cases of benign group including 12 cases with acute hepatitis,21 cases of chronic moderate to severe hepatitis,20 cases of compensatory phase cirrhosis,18 cases of decompensated cirrhosis and 20 cases of healthy persons in the same period as normal control.The content of serum B7-H3 and IL-21 were detected by ELISA.HBV DNA quantitative results were analyzed by Quantitative Real-time PCR.Results: The levels of B7-H3 and IL-21 in patients with primary hepatic carcinoma were (207.60±57.16)ng/ml and(2 357.28±805.01)pg/ml,respectively,which were significantly higher than those of the normal control subjects(P<0.001).Comparison with the normal control subjects,the content of B7-H3 and IL-21 in serum of patients with different clinical types in the benign group increased significantly(P<0.001).B7-H3 and IL-21 were positively associated with each other in serum of patients with HBV-related primary liver cancer.The expression of sB7-H3 was not significantly correlated with the degree of HBV DNA replication.The expression of IL-21 was correlated with HBV DNA replication in patients with HBV associated hepatocellular carcinoma,but was not significantly correlated with the degree of HBV DNA replication.Conclusion: HBV-related primary hepatic carcinoma express sB7-H3 and IL-21 with high level.The continuous high expression of sB7-H3 and IL-21 in the body may be related to the development and prognosis of the patients.
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Objective:To explore the effect of nano-carbon in lymph node dissection for thyroid cancer.Methods:46 patients with thyriod cancer were randomly divided into treatment group and control group.The identification rate of lymph nodes,lymph node positivity and parathyroid function were compared after surgery.Results:Compare to the control group,the identification rate of lymph nodes in treatment group was higher (P<0.05),but there was no significant difference on lymph node positivity (P>0.05).what's more,patients with low blood calcium and parathyroid hormone in treatment group were less than that in control group after surgery (P<0.05).The difference of severity of clinical symptoms was not statistically significant (P>0.05).Conclusion:Nano-carbon increases the lymph node identification rate and reduces the risk of parathyriod injury in patients with thyroidectomy.
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By using Zinc nitrate as precursor and hydraZine hydrate as reducing agent, polydiallyl dimethyl ammonium chloride modified reduced graphene oxide/Zinc oxide composite materials ( PDDA-rGO/ZnO) were prepared by simultaneous reduction of graphene oxide ( GO) and Zinc nitrate.The composite materials were characteriZed by Fourier transform infrared ( FTIR ) spectroscopy, X-ray diffractometer ( XRD ) and transmission electron microscopy ( TEM) , and their electrochemical catalytic activity for uric acid was studied by cyclic voltammetry ( CV ) and linear sweep voltammetry ( LSV ) measurements.The result showed that PDDA-rGO/ZnO modified glassy carbon electrode prepared here was sensitive, reproducible and stable, and had significant electrocatalytic activity for UA.When using linear sweep voltammetry for detection of UA, the responses of modified electrode were linear with UA concentration in the ranges of 0.02-0.1 mmol/L and 0.1-1.0 mmol/L respectively, with detection limit of 15.9 nmol/L (S/N=3).
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<p><b>Background</b>Facioscapulohumeral muscular dystrophy (FSHD) is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a "complex disease plus" patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy.</p><p><b>Methods</b>Standard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification (MLPA), whole exome sequencing (WES), and targeted methylation sequencing.</p><p><b>Results</b>The patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient's mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES.</p><p><b>Conclusions</b>The present study described a "tripe trouble" with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.</p>
Subject(s)
Adult , Child , Humans , Male , Epilepsies, Myoclonic , Evoked Potentials, Visual , Muscle, Skeletal , Muscular Dystrophy, Facioscapulohumeral , Peripheral Nervous System Diseases摘要
Objective To explore the effect of L-ascorbic acid(AA) for reducing the fibroblast cells induced by cobalt(co)cytotoxicity.Methods The experiment was divided into the blank control group,Co2+ group,Co2++AA group,cobalt nanoparticles(CoNPs) group,CoNPs+AA group and AA group.The AA pretreated for 1 h was performed in advance.The CCK8 assay was used to detect the CoNPs and Co2+ induced and AA-treated cytotoxicity.The fluorescence staining was used to measure the production of ROS in mitochondria.The real-time polymerase chain reaction(PCR) and Western blot were used to measure the expression of related protein and related molecular mRNA respectively.Moreover the cytochrome-C level in cytoplasml was detected.Results After treating the cells by CoNPs and Co2+,the cells appeared apoptosis.CoNPs could significantly induce ROS generation;the proapoptotic factors(caspases-3,and Bax) were significantly increased,while the anti-apoptotic factor Bcl-2 expression was decreased;cytochrome C and AIF expressions were up-regulated and released from mitochondria into the cytoplasm,after AA pretreatment,these changes caused by CoNPs were decreased.Conclusion AA can reduce the CoNPs caused cytotoxicity by reducing ROS generation and release,but can not weaken the Co2+ toxic effect.
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BACKGROUND:Sclerostin has been shown to promote bone formation and decrease bone resorption,which provides a new idea for the treatment of osteoporosis.OBJECTIVE:To review the literatures related to sclerostin and osteoporosis,thereby providing theoretical basis for sclerostin applied in the treatment and prevention of osteoporosis,so as to improve the diagnosis and curative efficacy of osteoporosis.METHODS:PubMed database was searched using the keywords of "osteoporosis,sclerostin,sclerosteosis,Wnt/β-catenin,LRP5/6,sclerostin antibody,sclerostin and expertise,romosozumab,blosozumab".Finally,58 pertinent articles were enrolled for analysis.RESULTS AND CONCLUSION:Sclerostin inhibits bone formation,so anti-sclerostin antibody is utilized,and animal experiments and clinical trials have shown that it can promote bone formation and inhibit bone reaorption.Phase Ⅲ trial results potentially signify a significant step in achieving market approval,which support the preclinical and clinical emergence of sclerostin antibody therapies for both osteoporosis and alternative applications.The serum level of sclerostin is found to be closely related to lifestyle,but still need to be studied in depth.Increasing trial results show that sclerostin is the promising therapeutic candidate,which provides a new direction in the prevention and treatment of osteoporosis.
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Objective To investigate the clinical distribution and antimicrobial resistance of carbapenem-resistant Enterobacteriaceae (CRE) in Dongguan.Methods CRE isolated from hospitalized patients in 22 secondary and above medical institutions which participated in bacterial monitoring in Dongguan between January 2015 and June 2016 were retrospectively analyzed,antimicrobial resistance was analyzed by WHONET 5.6 software.Results A total of 71 CRE isolates were detected,with a isolation rate of 0.34% (71/20 713).53 strains(74.65%) of CRE were isolated from patients aged 15-60 years old;46 (64.79 %) were from male patients;CRE were mainly isolated from patients in intensive care unit(36 strains,50.70 %);the main specimen was sputum(34 strains,47.89 %),followed by urine (11 strians,15.49 %) and wound secretion(6 strains,8.45 %);the main infection type was healthcare associated infection (64 strains,90.14 %);CRE were mainly distributed in tertiary hospitals(56 strains,78.87 %),the isolation rate of CRE in tertiary and secondary hospitals were 0.41 %(56/13 677)and 0.21%(15/7 036) respectively.71 strains of CRE were all resistant to imipenem,resistance rate to meropenem was 81.12%,only amikacin and tobramycin had drug resistance rates of <40% (21.38% and 38.79% respectively),resistance rate to trime thoprim/sulfamethoxazole was 48.23 %,while resistance rates to fluoroquinolones,third-generation cephalosporins,and enzyme inhibitors were all>60.Conclusion The isolation rate of CRE in Dongguan is lower than that of the whole nation and the other provinces,effective prevention and control measures should be taken according to the key population and departments that isolated CRE,antimicrobial use should be rational.