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Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.
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OBJECTIVE@#To compare the clinical efficacy on cervical spondylosis of nerve root type with qi stagnation and blood stasis treated with warming needle with different lengths of moxa stick.@*METHODS@#Six hundred patients with cervical spondylosis of nerve root type with qi stagnation and blood stasis were randomly divided into 4 groups: a 4 cm length group (150 cases, 5 cases dropped off, 2 cases suspended), a 3 cm length group (150 cases, 6 cases dropped off, 2 cases suspended), a 2 cm length group (150 cases, 6 cases dropped off), and a routine acupuncture group (150 cases, 6 cases dropped off). Warming needle with moxa stick in the length of 4 cm, 3 cm and 2 cm was delivered in the 4 cm length group, the 3 cm length group and the 2 cm length group, respectively. In the routine acupuncture group, simple acupuncture was applied. The acupoints selected in the above groups included Dazhui (GV 14) and bilateral Jiaji (EX-B 2) of C5 and C7, Fengchi (GB 20), Jianzhen (SI 9), Quchi (LI 11), Zhongzhu (TE 3), etc. In each group, the intervention was delivered once daily and 5 times a week. One course of intervention was composed of 2 weeks and 2 courses were required. The TCM syndrome score, the score of clinical assessment scale for cervical spondylosis (CASCS), the score of the brachial plexus traction test of the affected upper limb, F wave occurrence rate and conduction velocity of the ulnar nerve, the median nerve and the radial nerve of the affected upper limb were compared before and after treatment in the patients of each group. The levels of serum inflammatory factors, i.e. interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and hypersensitive C-reactive protein (hs-CRP), were measured before and after treatment in the patients of each group. The clinical cfficacy was evaluated in the 4 groups.@*RESULTS@#After treatment, the results of TCM syndrome evaluation, i.e. the scores of neck pain, activity limitation and upper limb numbness and pain, as well as the total scores; and the scores of brachial plexus traction test were reduced when compared with those before treatment in each group (P<0.01, P<0.05). The scores of subjective symptoms and adaptability, and the total scores of CASCS were elevated in comparison with those before treatment in each group (P<0.01, P<0.05). In the 4 cm length group, compared with the other 3 groups, the scores of neck pain and activity limitation for TCM syndrome evaluation, and its total score were lower (P<0.05, P<0.01); and the scores of subjective symptoms and adaptability, and the total score of CASCS were higher (P<0.05, P<0.01). The score of the brachial plexus traction test in the 4 cm length group was lower than that of the routine acupuncture group (P<0.05). After treatment, F wave occurrence rates and conduction velocity of median nerve and radial nerve were increased when compared with those before treatment in each group (P<0.05, P<0.01). F wave occurrence rate and conduction velocity of the radial nerve in the 4 cm length group were higher than those of the other 3 groups (P<0.05), and those of the median nerve were higher when compared with the routine acupuncture group (P<0.05). After treatment, the levels of serum IL-1β, IL-6 and TNF-α were all reduced when compared with those before treatment in each group (P<0.01, P<0.05); the level of serum IL-6 in the 4 cm length group was lower than those of the other 3 groups and serum level of TNF-α was lower compared with that in the routine acupuncture group (P<0.05). The total effective rate of the 4 cm length group was 78.3% (112/143), which was higher when compared with the 3 cm length group (67.6%, 96/142), the 2 cm length group (65.3%, 94/144) and the routine acupuncture group (53.5%, 77/144), respectively (P<0.05).@*CONCLUSION@#Warming needle with moxa stick of 4 cm in length effectively relieves the clinical symptoms of cervical spondylosis of nerve root type with qi stagnation and blood stasis, improves the nerve function of the upper limbs, and reduces the inflammatory responses caused by nerve compression. The clinical efficacy of this therapy with moxa stick of 4 cm in length is superior to the warming needle with moxa sticks of 3 cm and 2 cm, as well as the routine acupuncture.
الموضوعات
Humans , Interleukin-6 , Neck Pain , Qi , Tumor Necrosis Factor-alpha , Spondylosis/therapyالملخص
Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.
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Objective@#To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). @*Materials and Methods@#Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CTguided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. @*Results@#All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. @*Conclusion@#CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.
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Objective@#To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). @*Materials and Methods@#Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CTguided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. @*Results@#All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. @*Conclusion@#CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.
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OBJECTIVE@#To analyze the gene defect types and distribution characteristics of α- and β-thalassemia in Lingui District of Guilin City, Guangxi, so as to provide scientific basis for genetic consultation and prevention measures.@*METHODS@#A total of 6 496 suspected cases for screening the thalassemia during physical examination, premarital examination, pregnancy examination and hospitalization in the Second Affiliated Hospital of Guilin Medical University from May 2016 to October 2019 were analyzed. Gap-PCR, PCR-RDB and DNA sequencing techniques were used to detect the types and constituent ratios of gene defects in α- and β-thalassemia positive cases.@*RESULTS@#Among 6 496 suspected patients, 1 363 were thalassemia carriers, the total positive rate was 20.98%. There were 677 cases of single-gene deletion and 26 cases of double-gene detetion on the deletional α-thalassemia, 115 cases of non-deletion α-thalassemia mutation and 4 cases of deletion plus mutation. The positive rate of α-thalassemia was 12.66%. There were 11 gene abnormalities for α-thalassemia, of which --@*CONCLUSION@#Lingui district of Guilin city is a high incidence area of thalassemia. The mutation rate of α-thalassemia --
الموضوعات
Female , Humans , Pregnancy , China/epidemiology , Genotype , Heterozygote , Mutation , alpha-Thalassemia/genetics , beta-Thalassemia/geneticsالملخص
Objective:To explore the clinical efficacy of Modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease and its effect on inflammatory reaction, airway remodeling and thrombokinesis. Method:A total of 80 patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were randomly divided into control group (40 cases) and therapy group (40 cases) by random number table. The control group was treated with conventional therapy. In addition to the therapy for the control group, the patients in therapy group also received modified Qingqi Huatan Wan. The treatment course was 14 days for both groups. Scores of traditional Chinese medicine(TCM) syndrome, chronic obstructive pulmonary disease and asthma physiology Score (CAPS), and chronic obstructive pulmonary disease patients self-assessment test questionnaire (CAT) were compared. The secondary indicators were pulmonary function, arterial blood gas analysis, and blood rheology indexes. In addition, the levels of serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), transforming growth factor-beta1 (TGF-β1) and plasma tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-willebrand factor (v-WF), clinical efficacy and safety were evaluated. Result:The total clinical effective rate was 94.74% in therapy group,which was higher than 78.38% in control group (χ2=4.341,P2, serum NF-κB, IL-6, IL-8, MMP-2, TIMP-2, TGF-β1 and plasma PAI-1, v-WF in therapy group were lower than those in control group(P2, PaO2, FEV1, FEV1%, FEV1/FVC in therapy group were higher than those in control group(PPConclusion:Modified Qingqi Huatan Wan can control the symptoms safely, alleviate CAPS and lung function, effectively reduce the inflammatory response and inhibit the formation of airway remodeling and thrombosis, and its mechanism may be protect the lung tissue by reducing the level of inflammatory cytokines, regulating the balance of MMP-2/TIMP-2 and t-PA/PAI-1 and improving extracellular matrix and vascular endothelial function.
الملخص
Objective: To explore the clinical efficacy of modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease (syndrome of phlegm-heat obstructing lung) and investigate its effects on serum tumor necrosis factor-alpha (TNF-α),interleukin-8(IL-8) and matrix metalloproteinase-9(MMP-9).Method: Sixty-four patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were randomly divided into control group (32 cases) and treatment group (32 cases) by random number table.The control group was treated with routine western medicine therapy according to the guidance and disease conditions.Based on treatment in control group,patients in treatment group also received modified Qingqi Huatan Wan.The treatment course was 14 days for both groups.The scores of traditional Chinese medicine (TCM) syndrome,chronic obstructive pulmonary disease (COPD) assessment test (CAT),and modified version of the British Medical Research Council's Respiratory Questionnaire (mMRC),pulmonary function,blood gas analysis indicators,levels of serum TNF-α,IL-8 and MMP-9,clinical efficacy and safety were evaluated and compared once before treatment and 14 d after treatment.Result: The total clinical effective rate was 96.67% in treatment group,higher than 76.67% in control group (χ2=5.192,PPP1),percent of FEV1 in predicted value (FEV1%),and ratio of FEV1 to forced vital capacity (FEV1/FVC) were increased in both groups after treatment (PP2) and partial pressure of oxygen (PaO2) were increased in both groups,while partial pressure of carbon dioxide (PaCO2) was decreased (P2 and PaO2 in treatment group were higher than those in control group,while PaCO2 was lower than that in control group (Pα,IL-8 and MMP-9 were decreased in both groups (PPConclusion: Modified Qingqi Huatan Wan can control the symptoms safely and ameliorate pulmonary function,reduce the levels of serum TNF-α,IL-8,MMP-9 and inflammation in treatment of AECOPD.
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Objective To evaluate the status of rehabilitation resource configuration and rehabilitation service of health system in Guangdong province,and to provide basis for the development of rehabilitation institutions. Methods From November to December in 2015, an online survey was conducted among rehabilitation hospitals in Health and Family Planning Commission of 21 cities in Guangdong province by using self-administered ques-tionnaire.The deadline was December 30th,2015. Results There were 38 rehabilitation hospitals in Guangdong province including 18 non-profit and 20 for-profit ones. Only one was tertiary rehabilitation hospital.There were totally 4524 open beds,hospitals with 50 to199 beds ac-counted for 68.4%. There were 37,262 rehabilitation equipments worth more than 10,000 Yuan, in which less than 500,000 Yuan was the most.There were 776 rehabilitation doctors,1051 nurses,749 therapists,and 248 oth-er staff members. The annual hospital admissions were more than 55,000, hospital bed utilization rate was 74.6%,bed turnover rates was 12.75,the working time of bed was 272.3 days,and the average length of stay in hospital was 19.5 days. Conclusion These rehabilitation institutions cannot meet the need of people in Guangdong province.Many problems ex-isted,such as low hospital scales,unbalanced geographical distribution,low rates of hospital beds utilization and turnover,inadequate hospital management and imperfect health system.The service and management capabilities of rehabilitation institutions should be strengthened.
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The computer-aided design was used to simulate the docking of PDGF receptor with known active compounds, and the active groups that can bind to key sites were identified by analyzing the key amino acid residue fragments that exerted active effects on the target proteins. The natural product oleanolic acid was used as the parent, and the active group was introduced into the 2-position, and the C-28 carboxyl group was esterified and amidated. A series of oleanolic acid analogues targeting PDGF receptor inhibitors were designed and synthesized. Their structures were confirmed by MS and NMR. Through MTT assay, SGC-7901 and A549 cells were selected for preliminary in vitro anti-tumor activity screening. PDGF receptor protein inhibition test was performed on I3 and Ⅱ5 by FPIA. The activity tests showed that I3 and Ⅱ5, compared with the positive control drug, had stronger inhibition. FPIA test showed that Ⅱ5 and PDGF receptor protein had good binding ability. The newly synthesized oleanolic acid analogues have significantly higher antitumor activity than the parent compound and deserve further study.
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PURPOSE: Although the polymorphisms of erythrocyte complement receptor type 1 (CR1) in patients with malaria have been extensively studied, a question of whether the polymorphisms of CR1 are associated with severe malaria remains controversial. Furthermore, no study has examined the association of CR1 polymorphisms with malaria in Chinese population. Therefore, we investigated the relationship of CR1 gene polymorphism and malaria in Chinese population. MATERIALS AND METHODS: We analyzed polymorphisms of CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T in 509 patients with malaria and 503 controls, using the Taqman genotyping assay and PCR-direct sequencing. RESULTS: There were no significant differences in the genotype, allele and haplotype frequencies of CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T polymorphisms between patients with malaria and controls. Furthermore, there was no association of polymorphisms in the CR1 gene with the severity of malaria in Chinese population. CONCLUSION: These findings suggest that CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T polymorphisms may not be involved in susceptibility to malaria in Chinese population.
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Adult , Female , Humans , Male , Middle Aged , Alleles , Asian People , Case-Control Studies , China , Erythrocytes/parasitology , Genetic Predisposition to Disease , Genotype , Haplotypes , Malaria/ethnology , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/genetics , Receptors, Complement/blood , Taq Polymeraseالملخص
Objective To study the efficacy of chitosan on rehabilitation treatment after sinuses open surgery .Methods Fifty-six cases patients after sinuses open surgery were collected during June 2013 to October 2014 and divided into experimental group and control group by random sampling method, 28 cases in each group.The experimental group were smeared with chitosan on surface after cleaning by normal saline, while control group cleaned by normal saline alone.The efficacy, adhesion of nasal mucosa and time of mucosa complete epithelialization in two groups at three and six months were analysed while out-patient review.ResuIts After three and six months, the total effective rate of experimental group was significantly higher than that of control group[85.71% vs.60.71%(χ2 =4.46,P<0.05);92.86% vs.67.86%(χ2 =5.54,P<0.05)].The time of mucosa complete epithelialization in experimental group was (50.4 ±6.5)d, which was shorter than (62.3 ±7.5)d of control group (t=6.34,P<0.05).After three and six months, the nasal mucosa without adhesion in experimental group was better than that in control group (χ2 =5.60, χ2 =5.49;P<0.05). ConcIusion Chitosan can promote nasal mucosa epithelialization, reduce adhesion of nasal mucosa, improve the postoperative curative effect of chronic nasal-sinusitis.
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The effect of thymic stromal lymphopoietin (TSLP) on macrophage-derived foam cell formation and the underlying mechanism were studied. Macrophages isolated from C57BL/6 mice were co-cultured in vitro with different concentrations of TSLP or TSLPR-antibody in the presence of oxidized low density lipoprotein (ox-LDL). The effects of TSLP on macrophage-derived foam cell formation were observed by using oil red O staining and intracellular lipid determination. The expression levels of foam cell scavenger receptors (CD36 and SRA) as well as ABCA1 and TSLPR were detected by using RT-PCR and Western blotting. As compared with the control group, TSLP treatment significantly promoted lipid accumulation in macrophages, significantly increased protein expression of CD36 and TSLPR in a dose-dependent manner, and significantly reduced the expression of ABCA1 protein in a dose-dependent manner. No significant differences were noted between the TSLPR-antibody group and the control group. TSLP may down-regulate the expression of cholesterol efflux receptor ABCA1 and up-regulate scavenger receptor expression via the TSLPR signaling pathway, thereby promoting macrophage-derived foam cell formation.
الموضوعات
Animals , Mice , ATP Binding Cassette Transporter 1 , Genetics , Metabolism , Antibodies , Allergy and Immunology , Pharmacology , Blotting, Western , CD36 Antigens , Genetics , Metabolism , Cells, Cultured , Cholesterol , Metabolism , Cholesterol Esters , Metabolism , Cytokines , Pharmacology , Dose-Response Relationship, Drug , Foam Cells , Cell Biology , Metabolism , Gene Expression , Immunoglobulins , Allergy and Immunology , Metabolism , Lipoproteins, LDL , Pharmacology , Macrophages , Cell Biology , Metabolism , Mice, Inbred C57BL , Receptors, Cytokine , Allergy and Immunology , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Scavenger Receptors, Class A , Genetics , Metabolismالملخص
PURPOSE: To analyze the correlation of polymorphisms of toll-like receptor 7 (TLR7) (rs179009) and toll-like receptor 9 (TLR9) (rs187084) in hepatitis C virus (HCV) infections in the Han population. MATERIALS AND METHODS: The genotypes of TLR7IVS2-151 in HCV infection were detected by Sanger sequencing using polymerase chain reaction-restriction fragment length polymorphism to determine the TLR9 T-1486C single nucleotide polymorphisms (SNP) for all enrolled patients. RESULTS: We found no significant difference between males with spontaneous clearance of HCV versus those chronically infected [chi2=2.71, p=0.10, odd ratios (OR)=0.58, 95% confidence interval (CI) 0.31-1.11]. However, significant differences were found for the distribution of TLR7 (rs179009) in females (chi2=9.46, p=0.01). In females, a significant difference was also found between chronic hepatitis C and those with spontaneous clearance of HCV in terms of TLR7 IVS2-151G/A allele frequencies (chi2=9.50, p=0.00, OR=0.46, 95% CI 0.28-0.75). In HCV-infected patients, no significant association was found between the frequency of TLR9 genotypes and alleles. CONCLUSION: The site of TLR7 IVS2-151 (rs179009) G/A may be a factor for susceptibility of chronic HCV in the female Han population. TLR9T-1486C (rs18084) SNP may not play a major role in HCV infection. However, individual risk profiles for HCV infection did vary by sex and this relationship should be further investigated.
الموضوعات
Female , Humans , Male , Alleles , China , Confidence Intervals , Gene Frequency , Genotype , Hepacivirus , Hepatitis C , Hepatitis C, Chronic , Hepatitis , Methods , Polymorphism, Single Nucleotide , Toll-Like Receptor 7 , Toll-Like Receptor 9 , Toll-Like Receptorsالملخص
The effect of thymic stromal lymphopoietin (TSLP) on macrophage-derived foam cell formation and the underlying mechanism were studied. Macrophages isolated from C57BL/6 mice were co-cultured in vitro with different concentrations of TSLP or TSLPR-antibody in the presence of oxidized low density lipoprotein (ox-LDL). The effects of TSLP on macrophage-derived foam cell formation were observed by using oil red O staining and intracellular lipid determination. The expression levels of foam cell scavenger receptors (CD36 and SRA) as well as ABCA1 and TSLPR were detected by using RT-PCR and Western blotting. As compared with the control group, TSLP treatment significantly promoted lipid accumulation in macrophages, significantly increased protein expression of CD36 and TSLPR in a dose-dependent manner, and significantly reduced the expression of ABCA1 protein in a dose-dependent manner. No significant differences were noted between the TSLPR-antibody group and the control group. TSLP may down-regulate the expression of cholesterol efflux receptor ABCA1 and up-regulate scavenger receptor expression via the TSLPR signaling pathway, thereby promoting macrophage-derived foam cell formation.
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Objective:This study aimed to construct a lentiviral expression vector for microRNA-194 and investigate its effect on the metastasis of human osteosarcoma cell line U2-OS. Methods:Pri-and mature miR-194 amplified by PCR were inserted into the plenty-GFP vector and identified by restriction endonuclease digestion and nucleotide sequencing. The osteosarcoma cell line U2-OS was transfected with the lentivirus. Then, the stable transfected cells were used in Transwell and wound healing assay. Results:Restric-tion analysis and sequencing showed that the recombinant lentiviral expression vector was constructed correctly. The titers of obtained overexpression and suppression expression recombinant lentivirus were 1.5*108 and 4*108 TU/ml. Cell metastasis ability was signifi-cantly different in different experimental groups (P<0.01). Conclusion:The lentiviral expression vector for microRNA-194 was suc-cessfully constructed. MicroRNA-194 could influence the metastasis of the osteosarcoma cell line U2-OS;thus, it could be further ex-plored as a potential target in osteosarcoma therapy.
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Objective To study the subcellular location of HAUSP and NANOG in glioma cells and their expressions in glioma tissues,and explore their significance in the pathogenesis of gliomas.Methods Seventy-two glioma samples (19 with WHO graded Ⅱ,25 with WHO graded Ⅲ and 28 with WHO graded Ⅳ),collected in our hospital from January 2010 to November 2010,were chosen in our study; protein expressions of HAUSP and NANOG in the glioma tissues were detected by immunohistochemical staining; the subcellular location of HAUSP and NANOG in human glioma cell line U87 was detected by double immunofluorescence staining.Results The positive rate of HAUSP protein in gliomas with different grades was significantly different (F=15.926,P=0.000); the higher the malignancy grade,the higher the positive rate of HAUSP protein (P＜0.05); the malignancy grade of gliomas was positively correlated with the protein expression of HAUSP (r=0.726,P=0.000).The positive rate of NANOG protein in gliomas with different grades was significantly different (F=14.768,P=0.000);the higher the malignancy grade,the higher the positive rate of NANOG protein (P＜0.05); the malignancy grade ofgliomas was positively correlated with the protein expression of NANOG (r=0.685,P=0.000).Both NANOG and HAUSP expressed in U87,and co-located in the nucleus.Conclusion HAUSP and NANOG play important roles in the pathogenesis of human gliomas and are related to the malignancy; NANOG,as the marker of glioma stem cells in undifferentiated state,plays a vital role in maintaining the cancer stem cells in undifferentiated state through deubiquitinylation of HAUSP.
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Objective To investigate the effect ofhistone deacetylase inhibitor apicidin induced Nanog repression on proliferation,migration and invasion of glioma stem cells (GSCs).Methods GSCs were isolated from glioma cell line U87 and cultured in simplified serum-free neural stem cell medium by nanosphere suspension culture method,and purified continuously through the monoclonal formation experiment.The immunofluorescence staining of cells was employed to detect the CD133 and Nestin expressions to identify GSCs.Apicidin treatment group (GSCs treated with 0.5 μmol/L apicidin for 48 h) and blank control group were employed.Nanog mRNA and protein expressions were detected by real time-PCR and Western blotting,respectively.Double immunofluorescence staining was used to detect the co-expressions ofNanog/CD133.MTT assay was used to detect the proliferation modification of GSCs,while migration and invasion of GSCs were detected by Transwell migration and invasion assay after 0.2,0.5,1.0 and 2.0 μg/mL apicidin of treatment.Results GSCs were isolated,cultured and purified from glioblastoma cell line U87; as compared with those in the blank control group,the mRNA and protein expressions of Nanog were significantly repressed and Nanog+,CD133+ and Nanog+/CD133+ cells were obviously reduced in the apicidin treatment group (P＜0.05).The migration and invasion in the apicidin treatment group were inhibited dramatically as compared with those in the blank control group (cell number of migration:[87.50±4.65]/field vs.[128.50±6.14]/field; cell number of transmembrane:[55.75±4.79]/field vs.[81.50±5.45]/field,P＜0.05).MTT assay indicated that the absorbance value of the apicidin treatment group was significantly lower as compared with that in the blank control group (P＜0.05); the higher the apicidin concentration,the lower the absorbance value and the more obvious the proliferation inhibition.Conclusion Histone deacetylase inhibitor apicidin could inhibit the mRNA and protein expressions of Nanog,and sequentially repress the proliferation,migration and invasion of GSCs.
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The aim of this study was to explore the regulatory function of interleukin-6(IL-6) on human Th17 cells. Human peripheral blood CD4(+) T cells were purified from healthy donors by anti-CD4 monoclonal antibody (mAb) conjugated microbeads. The experiment was divided into 2 groups. Test group in which CD4(+) T cells (1 × 10(6)/ml) were stimulated by human recombined IL-6 (20 ng/ml) for 4 days; control group in which CD4(+) T cells did not stimulated by IL-6. The concentrations of IL-17 protein in the supernatants were assayed by enzyme-linked immunosorbent assay (ELISA), and quantity of Th17 cells were detected by flow cytometry. The results showed that as compared to control group, IL-17 protein level in the supernatants of CD4(+) T cells significantly increased in IL-6 stimulated group: (337.05 ± 189.09 pg/ml; vs 15.07 ± 12.70 pg/ml) (p < 0.05). Furthermore, the percentage of Th17 cells in cultures of CD4(+) T cells stimulated by IL-6 was significantly higher than that in control group (4.05% ± 0.30% vs. 2.81% ± 0.44%)(p < 0.01). It is concluded that IL-6 promotes the expansion of Th17 cells in vitro.
الموضوعات
Humans , CD4-Positive T-Lymphocytes , Cell Biology , Allergy and Immunology , Cells, Cultured , Interleukin-6 , Pharmacology , Lymphocyte Activation , Allergy and Immunology , Th17 Cells , Allergy and Immunologyالملخص
<p><b>OBJECTIVE</b>To identify the IgE-binding epitopes in the allergen Der p 1 of main house dust mites, which can be recognized by the specific IgE in the sera from allergic individuals, and obtain a hypoallergen derived from the T-B epitope fused peptide for potential use in specific immunotherapy (SIT).</p><p><b>METHODS</b>Thirty-one peptides containing 15 amino acids each, which covered the full 222 amino acids of Der p 1 protein sequence, were synthesized on the cellulous membrane by solid-phase peptide (SPOTs) synthesis, with 8 overlapping amino acids between every two neighboring peptides. The membrane bearing the spots of the synthesized peptides were incubated with the allergic serum pools consisting of the sera from 5 allergic individuals. The membrane was then probed with HRP-conjugated anti-human IgE, followed by enhanced chemiluminescence (ECL) for visualization and gray scale analysis of the positive peptide spots.</p><p><b>RESULTS</b>Three strong IgE-binding epitopes were identified in the amino acid sequence of Der p 1 molecule, namely Ep1 (amino acids 85-99), Ep2 (amino acids 106-120) and Ep3 (amino acids 190-204).</p><p><b>CONCLUSION</b>The 3 IgE-binding epitopes (B cell epitopes) identified in Der p 1 confirm the presence of linear epitopes in Der p 1, suggesting the possibility of constructing T/B epitope-fused hypoallergens.</p>