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Network pharmacological approaches were used to predict the components, targets and pathways of Erhuang decoction (EhD) in the treatment of acute lung injury (ALI). The SwissTargetPrediction platform, DisGeNET, Therapeutic Target Database (TTD), GeneCards and Online Mendelian Inheritance in Man (OMIM) databases were used to predict potential targets of EhD and were integrated with the predicted targets for the treatment of ALI. A protein-protein interaction network model was constructed by using String database and Cytoscape software; the DAVID platform was used for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of drug components-targets-pathways was constructed by Cytoscape software and the SwissDock platform was used to dock the molecules of EhD found in blood with the key disease targets. An ALI model was established in mice and inflammatory factor detection and Western blot protein expression experiments with lung tissue sections were carried out to verify the effect of EhD in the treatment of ALI. Animal experiment ethical requirements were approved by the Ethical Committee Experimental Animal Center of Shandong University (Grant Number: 2016020). We identified 148 potential targets including signal transducer and activator of transcription 3 (STAT3), vascular endothelial cell growth factor A (VEGFA), RAC-alpha serine/threonine-protein kinase (AKT1), and nuclear factor-kappa B/p65 (RELA). The potential targets are largely associated with the biological processes of inflammation, oxidative stress, and apoptosis. Additional pathways relate to cancer, VEGF signaling, mitogen-activated protein kinase (MAPK) signaling, and Toll-like receptors (TLRs) signaling, along with other signaling pathways. Pharmacodynamic experiments showed that EhD could significantly reduce the content of inflammatory factors and the degree of lung injury of ALI mice. Western blot revealed that EhD could significantly decrease the expression of NF-κB/p65 and upregulate the expression of NF-kappa-B inhibitor alpha (IκBα). From the perspective of network pharmacology, the mechanisms of EhD in the treatment of ALI is consistent with the characteristics of multiple ingredients, multiple targets and multiple pathways. This research provides a reference for further study of the mechanism of this traditional Chinese medicine.
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Due to its own internal laws of development, Chinese medicine (CM) seems more inclined to empirical medicine in a relatively long historical period. It is considered to be lacking objective and unified clinical practice guidelines (CPGs), and the difficulties in diagnosis and therapeutic effect evaluation comes with it, have restricted its further inheritance, development and international communication. Over the years, our research group has been committed to improving the standardization theory and methodology of CM, also perfecting relative techniques for further application, which are all based on the stratified evidence scoring method. We have already applied this method to 45 issued guidelines, including 5 national guidelines, 3 industrial guidelines, and 37 formulation/revision social organization guidelines. The stratified evidence scoring method has been recognized and used widely. It helps scholars and applicators to study, formulate, publish and popularize the acupuncture therapy clinical practice guidelines better, thus further promotes the development of acupuncture therapy.
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The indication of bloodletting therapy was determined based on the multi-dimensional evidence assessment, which could provide guidance for the clinical application of bloodletting therapy. The literature of bloodletting therapy was comprehensively collected by retrieval in CNKI, Wanfang and VIP databases (until February 23, 2019), modern books in Library of Tianjing University of TCM and the (Fifth Edition). The disease spectrum of bloodletting therapy was determined by self-designed questionnaire survey e-mailed to relevant experts. The indication of bloodletting therapy was determined by Delphi expert meeting. As a result, 746 pieces of ancient literature and 32 775 modern literature were included. The indications of bloodletting therapy based on the multi-dimensional evidence assessment include herpes zoster, acne, acute tonsillitis, vascular headache, varicose veins of lower extremities, acute lumbar sprain, early erysipelas, wheat swelling, exogenous fever of children, stroke, which are mainly the syndromes of blood stasis, toxin, excess and heat.
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Humans , Bloodletting , Medicine, Chinese TraditionalABSTRACT
Objective To observe the efficacy and safety of DAAs in treating HCV patients with HIV/HCV co-infection.Method 53 patients were divided into groups based on HCV genotype. Sofosbuvir + Ledipasvir regime were used for 1b and 6a subtypes; sofosbuvir+Daclatasvir regime were used for 3a, 3b and those cannot be typed; all the patients diagnosed with cirrhosis were also administrated with ribavirin. The course of treatment for all patients is 12 weeks.Results All 53 patients completed HCV treatment, the overall SVR rate of DAAs treatment rate was 98.1%(52/53), failure rate 1.9%(1/53) ; SVR rate of DAAs treatment among non-cirrhosis patients was 100%(41/41) ; SVR rate of DAAs treatment among cirrhosis patients was 91.7%(11/12), failure rate 8.3%(1/11) . After treatment, ALT and AST levels of DAAs treatment patients were decreased (P＜0.05), while CD4 level increased (P＜0.05) . Main adverse effects are: 12 patients had gastrointestinal symptoms (22.6%) ; 6 had nausea, vomiting (11.3%), 4 had diarrhea (7.6%), 1 had mild rash (1.9%), and 5 had elevated serum total bilirubin (9.4%) . Conclusion The overall SVR rate among DAA treatment for HIV/HCV co-infected patients is high (98.1%) with broad indications. Even patients with cirrhosis are eligible. It yielded optimistic outcomes among different gene subtypes, and effectively improved liver function and CD4 level. With oral administration, short regime course, and mild adverse effects, patients can tolerate well, indicating its effectiveness and safety.
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BACKGROUND: Previous studies have found that polygonatum sibiricum polysaccharide (PSP) exhibits anti-osteoporosis effect, but its therapeutic effect in ovariectomized osteoporotic rats and the molecular mechanisms are poorly understood. OBJECTIVE: To investigate the effect of administration of PSP on the bone microstructure, bone mineral density as well as osteoblast- and osteoclast-related gene expression in rats. METHODS: Twenty-five infertile female Sprague-Dawley rats aged 3 months were randomly allotted into five groups (n=5 per group): sham operation (same volume normal saline), model, zoledronate (0.2 mg/kg?d), high-dose PSP (800 mg/kg?d) and medium-dose PSP (400 mg/kg?d) groups. All rats were subjected to ovariectomy except sham operation group. The administration was intragastrically given every 2 days beginning at 7 days after modeling and lasted 12 weeks. Then, the rats were sacrificed, and the uterus was weighed. The bilateral tibias were removed, one side for histomorphometric analysis by micro-CT, and the other one for RNA detection by qualified PCR. RESULTS AND CONCLUSION: Compared with the sham operation group, the rat body mass in the model group was significantly increased and the weight of uterus was significantly decreased (P < 0.05). Compared with the model group, zoledronate and high-dose PSP could significantly alleviate the excessive increase in body mass (P < 0.05). The bone mineral density in the model group was decreased by 63% compared with the sham operation group (P < 0.01), Compared with the model group, after 12-week high-dose PSP and zoledronate administration, the bone mineral density was increased by 44% and 38%, respectively (P < 0.01); the trabecular bone volume fraction and trabecular number rose significantly(P<0.05),while the trabecular separation decreased significantly(P<0.05).In vivo,PSP could significantly promote the expression levels of osteoblast-related genes (alkaline phosphatase, RUNX2, Col1a1 and osteocalcin), and significantly inhibit the expression levels of osteoblast-related genes (ACP5 and CTSK) (P < 0.05). These results imply that high-dose PSP can reduce bone loss and decrease of bone mineral density, improve the destruction of bone microstructure, as well as promote osteoblast-related genes but inhibit osteoclast-related gene mRNA expression in the ovariectomized rats.
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BACKGROUND: As a special source of stem cells, dental pulp stem cells (DPSCs) make much progress in the development of tissue engineering field due to their high proliferation and self-renewal ability. In the certain conditions DPSCs can be induced to differentiate into a variety of specialized tissue cells, providing a new way for tissue engineering development. OBJECTIVE: To review the main progress in the DPSCs biological characteristics, original source, isolation method, and its related application in tissue engineering research. METHODS: "Dental pulp stem cell, differentiation, regenerative medicine, tissue engineering" in English and Chinese were termed as the keywords to search relevant articles about DPSCs and tissue engineering published from 2005 to 2017 in PubMed, Medline, WanFang, and CNKI databases. After removal of repetitive or irrelevant articles, 66 articles were finally reviewed. RESULTS AND CONCLUSION: With the development of tissue engineering and regenerative medicine, the effective combination of DPSCs and tissue engineering scaffolds have be further achieved. Recent studies on DPSCs focus on the properties of DPSCs differentiating into odontoblasts and osteocytes/osteoblasts and on the potential of nerve repair, vascular remodeling, corneal reconstruction and chondrogenic differentiation.
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BACKGROUND: Particulated juvenile cartilage allograft is simple and easy to obtain, and chondrocytes can migrate and proliferate as confirmed by in vitro culture.In the Unite States,this technique has been used in the repair of cartilage defects in the hip, knee, ankle, and elbow joints. OBJECTIVE: To review the present situation, application, and value of particulated juvenile cartilage allograft transplantation for articular cartilage repair. METHODS: A computer-based search of CNKI, PubMed, and Elsevier was performed for retrieving articles concerning particulated juvenile cartilage allograft transplantation for articular cartilage repair published from October 1983 to June 2017. The keywords were "allogeneic juvenile cartilage particles; cartilage tissue engineering; articular cartilage defects;repair" in Chinese and English, respectively. After initial screening of titles and abstracts and exclusion of irrelevant articles, 48 eligible articles were included in final analysis. RESULTS AND CONCLUSION: (1) Although a variety of treatments for cartilage repair have achieved good clinical outcomes in short-term follow-up, improving the motor function of patients and relieving pain, patients eventually develop progressive degeneration of the articular cartilage and suffer from osteoarthritis. (2) Chondrocytes from allogeneic juvenile cartilage particles have stronger ability of proliferating and repairing cartilage defects in vitro than mature chondrocytes,and have low antigenicity,which cannot cause a strong rejection after in vivo transplantation.What's more, particulated juvenile cartilage allograft transplantation can be performed as one-stage surgery if cartilage defects are confirmed under arthroscopy. (3) Particulated juvenile cartilage allograft transplantation has achieved good outcomes in basic and clinical studies in the United States. Its potential superiority has gradually been accepted by doctors and patients. (4) There are also risks for being contaminated and spreading diseases during the preparation of particulated juvenile cartilage allograft. This technology has been widely used in the United States, but there are rare data concerning its follow-up studies. Therefore, an investigation on its long-term follow-up is indispensable for the objective assessment of its long-term efficacy, with a view to the extensive promotion of this technology in the clinical practice.
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BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) are adult stem cells with multipotential differentiation, which can be induced to differentiate into bone, cartilage and other connective tissues. Meanwhile, as a highly specific marker of tenocytes, Scleraxis is involved in aggregation and differentiation of tendon progenitor cells as well as the formation of tendon extracellular matrix. OBJECTIVE: To investigate whether hAMSCs have the ability of differentiation into tenocytes by ectopic expression of Scleraxis. METHODS: Agreed by puerpera, the amniotic membrane from the full-term placenta was separated, and hAMSCs were isolated by a two-step enzyme digestion, observed under inverted phase contrast microscope, and identified by flow cytometry. Passage 3 cells were induced via plasmid-mediated Scleraxis overexpression in overexpression group. Untransfected cells cultured in normal medium served as blank control group, and those with empty plasmid transfection were defined as empty plasmid group. Cell proliferation was tested in each group using cell counting kit-8 within 7 days of culture. Real-time quantitative PCR and western blot were used to assess the tenogenic differentiation of hAMSCs in each group at 3 and 7 days of culture. RESULTS AND CONCLUSION: Findings from the cell counting kit-8 indicated that the cell viability had no significant differences among the groups within 7 days of culture (P > 0.05). Western blot results showed the protein expression of Scleraxis in the treatment group was significantly higher than that in the other two groups (P < 0.05). Real-time PCR results showed, at 3 days of culture, the expression of collagen type I, collagen type III, Fibronectin and Tenascin-C in the overexpression group was significantly higher than that in the empty plasmid group (P < 0.05), but the expression of Tenomodulin had no difference (P > 0.05); at 7 days of culture, the expressions of collagen type I, collagen type III, Fibronectin, Tenascin-C and Tenomodulin in the overexpression group were significantly higher than those in the empty plasmid group (P < 0.05). In summary, hAMSCs can be differentiated into tenocytes by ectopic expression of Scleraxis.
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It has always been controversial whether a single allergen performs better than multiple allergens in polysensitized patients during the allergen-specific immunotherapy.This study aimed to examine the clinical efficacy of single-allergen sublingual immunotherapy (SLIT) versus multi-allergen subcutaneous immunotherapy (SCIT) and to discover the change of the biomarker IL-4 after 1-year immunotherapy in polysensitized children aged 6-13 years with allergic rhinitis (AR) induced by house dust mites (HDMs).The AR polysensitized children (n=78) were randomly divided into two groups:SLIT group and SCIT group.Patients in the SLIT group sublingually received a single HDM extract and those in the SCIT group were subcutaneously given multiple-allergen extracts (HDM in combination with other clinically relevant allergen extracts).Before and 1 year after the allergen-specific immunotherapy (ASIT),the total nasal symptom scores (TNSS),total medication scores (TMS) and IL-4 levels in peripheral blood mononuclear cells (PBMCs) were compared respectively between the two groups.The results showed that the TNSS were greatly improved,and the TMS and IL-4 levels were significantly decreased after 1-year ASIT in both groups (SLIT group:P＜0.001;SCIT group:P＜0.001).There were no significant differences in any outcome measures between the two groups (for TNSS:P＞0.05;for TMS:P＞0.05;for IL-4 levels:P＞0.05).It was concluded that the clinical efficacy of single-allergen SLIT is comparable with that of multi-allergen SCIT in 6-13-year-old children with HDM-induced AR.
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<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of posterior mediastinal route (PR) as compared with anterior mediastinal route (AR) after esophagectomy.</p><p><b>METHODS</b>A systematic literature retrieval was carried out to obtain studies of randomized controlled trials (RCT) comparing PR with AR after esophagectomy before June 2012. Study selection, data collections and methodological quality assessments of retrieved studies were independently performed by two individual reviewers and meta-analysis was conducted using the RevMan 5.0 software.</p><p><b>RESULTS</b>Six RCTs involving 376 patients (PR:197 cases, AR:179 cases) met the selection criteria. Meta-analysis showed that operative mortality (RR=0.49, 95%CI:0.18-1.36), anastomotic leaks (RR=0.95, 95%CI:0.44-2.07), cardiac morbidity (RR=0.51, 95%CI:0.25-1.04), pulmonary morbidity (RR=0.69, 95%CI:0.41-1.15), anastomotic strictures (RR=0.88, 95%CI:0.62-1.25), dysphagia (RR=1.26, 95%CI:0.75-2.11), 6-month body weight after esophagectomy were not significantly different between these two routes of reconstruction (all P>0.05).</p><p><b>CONCLUSION</b>AR should be the choice of reconstruction in view of its potential advantages in the prevention of tumor recurrence within the gastric conduit and avoidance of conduit irradiation when undergoing postoperative radiotherapy. However, further studies are needed to confirm the difference of long-term efficacy between the two routes.</p>
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Humans , Esophageal Neoplasms , General Surgery , Esophagectomy , Gastroenterostomy , Methods , Randomized Controlled Trials as Topic , Stomach , General SurgeryABSTRACT
<p><b>OBJECTIVE</b>To explore the common dysregulated genes and pathways shared by two sets of nasopharyngeal carcinoma (NPC) biopsy samples collected from different regions.</p><p><b>METHODS</b>Using bioinformatics analysis, the dysregulated genes and pathways in the two sets of samples were compared, and the relationship between the common dysregulated functions and genes was explored.</p><p><b>RESULTS</b>The common up-regulated genes in the two sets of samples were involved with such cell functions as cell cycle regulation, cell proliferation, DNA damage and repair, cell adhesion and migration, cell metabolism, and protein binding, but their common down-regulated genes did not show functional clustering. Those common dysregulated gene functions shown by differential gene expression profiling were not completely dictated by identical genes. The top 4 of the 10 common dysregulated pathways included leukocyte transendothelial migration, cell adhesion molecules, adherens junction, and phosphatidylinositol signaling system.</p><p><b>CONCLUSIONS</b>The differentially expressed genes in NPC are mainly related to cell cycle regulation, DNA damage and repair, cell adhesion and migration, a finding supporting the primary choice of chemotherapy in clinical treatment. The 4 most distinct common dysregulated pathways in the NPC samples are associated with tumor adhesion and migration, and by interventions of these pathways, especially the phosphatidylinositol signaling system in tumorigenesis, adhesion and migration, improvements in the therapeutic effect and prognosis of NPC can be expected.</p>
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Humans , Biopsy , Carcinoma , Genetics , Metabolism , Pathology , Cell Adhesion , Genetics , Cell Movement , Genetics , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Nasopharyngeal Neoplasms , Genetics , Metabolism , Pathology , Oligonucleotide Array Sequence Analysis , Signal TransductionABSTRACT
<p><b>UNLABELLED</b>To screen and analyze the apoptosis- and proliferation-related genes in human nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>According to gene ontology classification, the abnormal expressions of the genes related to cell apoptosis and proliferation were identified in the NPC gene chip data. The cell apoptosis- and proliferation-related genes expressed in each of the 3 stages, as defined by the tree model for the pathogenesis and progression of NPC, were screened, and with literature review, their distribution in the tree model were analyzed.</p><p><b>RESULTS</b>Nineteen genes related to cell apoptosis were found in NPC, among which 9 were down-regulated (such as DNASE1L3) and located in the chromosome deletion regions, and 10 were up-regulated (such as DEDD) in the chromosome amplification regions. Twenty-one cell proliferation-related genes were identified, including 8 down-regulated genes (such as TUSC2) in the chromosome deletion regions and 13 up-regulated ones (such as EMP1) in the chromosome amplification regions. In the chromosome deletion regions, the down-regulated cell apoptosis-related genes participated mostly in inducing and regulating cell apoptosis, and the up-regulated cell proliferation-related genes in the chromosome amplification regions were mostly associated with the positive regulation of cell proliferation.</p><p><b>CONCLUSION</b>NPC occurs possibly through two pathways by inhibiting cell apoptosis or by promoting excessive cell proliferation.</p>
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Humans , Apoptosis , Genetics , Cell Proliferation , Chromosome Deletion , Down-Regulation , Gene Expression Profiling , Nasopharyngeal Neoplasms , Genetics , Pathology , Oligonucleotide Array Sequence Analysis , Up-RegulationABSTRACT
The hypothesis that tumor comes from stem cells has been demonstrated in various human tumors.Cancer is not only a genetic disease but also a stem cell disease. It is a key to regeneration, mutations and recurrence of tumors that gene mutations affect stem cells, and then stem cells mutate to cancer stem cells. In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas(HCC)arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells?More recently, there is a hypothesis that HCC arise from maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties(ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.
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<p><b>OBJECTIVE</b>To study the genera and seasonal distribution of airborne pollen in Hubei province of China, and its relationship with pollinosis.</p><p><b>METHODS</b>From November 2003 to October 2004, an airborne pollen investigation was performed in 16 chosen areas in 12 cities of Hubei province using gravity sedimentation technique. Meanwhile, univalent skin prick tests of pollens were performed and the invasion season was studied on 2,300 patients with pollinosis. Among them, 352 cases underwent the airway responsiveness measurements, and the correlation between airway responsiveness and results of pollen count was analyzed.</p><p><b>RESULTS</b>A total of 61 pollen genera were observed and 257,520 pollens were collected. The peak of airborne pollen distribution occurred in two seasons each year: spring (March and April) and autumn (from August to October). The attack of pollinosis corresponded to the peak of pollen distribution. There was a significantly negative relationship between the provocation dose causing a 20% decrease of forced expiratory volume in one second (FEV1) from baseline and airborne pollen concentration (r= -0.6829, P < 0.05).</p><p><b>CONCLUSION</b>This study provides useful information for airborne pollen epidemiology of Hubei province, and it provides important insights to clinical prevention, diagnosis, and treatment of pollen-related allergic diseases.</p>
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Humans , Air Pollutants , Allergy and Immunology , Allergens , Allergy and Immunology , China , Environmental Monitoring , Pollen , Allergy and Immunology , Rhinitis, Allergic, Seasonal , Allergy and Immunology , Seasons , Skin TestsABSTRACT
<p><b>OBJECTIVE</b>To establish a nude mouse model of nasopharyngeal carcinoma (NPC) lymph node metastasis and screen the signature genes associated with the metastasis.</p><p><b>METHODS</b>The NPC 5-8F-EGFP cells were inoculated into nude mice, from which a 5-8F-LN cell line with lymph node metastasis potential was obtained. The lymphatic metastasis-related signature genes of breast cancer and head and neck squamous cell carcinoma were screened by data mining method.</p><p><b>RESULTS</b>The NPC cell lines 5-8F and 6-10B showed 307 differentially expressed genes by microarray analysis, from which 20 overlapping genes were identified, and 3 overexpressed genes were found with probable metastasis potential, namely the ADM, IRF1, and CAV1 genes. Quantitative RT-PCR validated the data mining results in the 5-8F-EGFP, 6-10B-EGFP, NP69, and 5-8F-LN cell lines. The 3 NPC cell lines 5-8F-EGFP, 6-10B-EGFP and 5-8F-LN showed significantly higher expressions of IRF1 than NP69 cells (P=0.008, 0.022, and 0.006, respectively. The expression level of CAV1 in 5-8F-EGFP cells was significantly higher than that in 6-10B-EGFP cells (P=0.014), but ADM expression showed no significant difference between the 4 cell lines.</p><p><b>CONCLUSIONS</b>IRF1 may play an important role in the progression of NPC. The overexpression of CAV1 in 5-8F-EGFP cells can be associated with the high metastatic potential of the cells.</p>
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Animals , Humans , Mice , Adrenomedullin , Genetics , Caveolin 1 , Genetics , Cell Line, Tumor , Disease Models, Animal , Gene Expression Profiling , Interferon Regulatory Factor-1 , Genetics , Lymphatic Metastasis , Mice, Inbred BALB C , Mice, Nude , Nasopharyngeal Neoplasms , Genetics , Pathology , Neoplasm Transplantation , Reverse Transcriptase Polymerase Chain Reaction , Transplantation, HeterologousABSTRACT
<p><b>OBJECTIVE</b>To construct tree models for nasopharyngeal carcinoma (NPC)and explore the oncogenesis process of NPC.</p><p><b>METHODS</b>Based on the software which Desper et al developed, tree models were constructed for colorectal carcinoma (CC) from the comparative genomic hybridization (CGH) data of 118 CC patients and for NPC from the CGH data of 140 southern Chinese patients, respectively.</p><p><b>RESULTS</b>Tree models for CC suggested that changes in -18q and +20q were important early events in colorectal carcinogenesis. As changes in -18q occurred prior to those in -17p, there might be some cause-effect relationship. Tree models for NPC suggested that change in -3p was an important early event in nasopharyngeal carcinogenesis, and those in -11q, -14q, -16q, -9p were also non-random genetic events in carcinogenesis, suggesting that there might be tumor-associated genes existing on these chromosome arms. The tree model also suggested the existence of oncogene on the short arm of chromosome 12.</p><p><b>CONCLUSION</b>Constructing tree models based on the CGH data to demonstrate the initiation and progression of NPC might help elucidate its multigene, multistep and multipathway development. It may provide valuable clues to explore the mechanism of tumorigenesis.</p>