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Objective To investigate the effect and mechanism of pomalidomide(POM)on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease(COPD).Methods Thirty-six SD rats were randomly divided into control group,model group and POM group,with 12 in each group,half male and half female.The COPD model was established by smoke exposure combined with Klebsiella pneumoniae infection in model group and POM group.The rats in POM group were treated with POM(0.5 mg/kg,once a day for 1 week).The lung function,lung tissue pathology,the proportion of inflammatory cells in bronchoalveolar lavage fluid(BALF)and the levels of serum inflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6 and IL-13 were observed and detected in each group.AB-PAS staining and immunohistochemistry were used to analyze the proliferation of goblet cells and the secretion of mucin(MUC)5AC and MUC5B in airway epithelium of rats.The expression levels of TNF-α receptor 1(TNFR1),IκB kinase(IKK),phosphorylated IKK(p-IKK)and P65 protein in lung tissue were detected by Western blotting.Results Compared with control group,model group showed significant decreased of tidal volume(TV),minute ventilation(MV),forced expiratory vital capacity(FVC),0.1s forced expiratory volume(FEV0.1)and 0.3 s forced expiratory volume(FEV0.3)(P<0.05),increased of the mean linear intercept(MLI)of the alveoli(P<0.01),decreased of the mean alveolar number(MAN)(P<0.01),increased of the proportion of neutrophils and lymphocytes in BALF sediment(P<0.05),and decreased of the proportion of macrophages in BALF sediment(P<0.01);increased of the levels of serum inflammatory factors TNF-α,IL-1β,IL-13 and IL-6(P<0.05),the proportion of goblet cells in airway epithelium(P<0.01),the secretion of MUC5AC and MUC5B in lung tissue(P<0.01),the content of TNFR1 and the ratio of p-IKK/IKK(P<0.01),the content of P65 in nucleus(P<0.01);and decreased of the content of P65 in cytoplasm(P<0.05).Compared with model group,after one week of POM treatment,POM group showed significant improved of the TV,MV,FVC,FEV0.1,FEV0.3,MLI and MAN of rats(P<0.05);decreased of the proportion of neutrophils and lymphocytes in BALF(P<0.05);increased of the proportion of macrophages(P<0.01);decreased of the levels of serum TNF-α,IL-1β,IL-6 and IL-13(P<0.05),the proportion of goblet cells in airway(P<0.01),the secretion of MUC5AC and MUC5B(P<0.01),and the expression of TNFR1,P-IKK and P65(nucleus)(P<0.05);and increased of the level of P65(cytoplasm)(P<0.01).Conclusions POM can improve airway inflammation and mucus hypersecretion in COPD rats,which may be achieved by inhibiting TNF-α/NF-κB signaling pathway.
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Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
الموضوعات
Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Treatment Outcomeالملخص
Objective:To construct a testing system for the effects of plantar surface vibration stimulation on the human postural adjustments, and to explore its practicability. Methods:The mechanical device and control system providing vibration stimulation were designed and built. Twenty-five healthy teachers and students (aged 19~29 years) were recruited from our college to participate in the experimental study from 2nd to 6th, October, 2019. The amplitudes of postural response were compared following non-stimulation and stimulation at left forefoot, left heel, right forefoot, right heel, left foot, right foot, double forefoot, double heels of each subject at the 20 Hz, 40 Hz, 60 Hz and 80 Hz vibrations, respectively. Results:The amplitude of the center of pressure response under foot cutaneous stimulation increased compared with the response amplitude under non-vibration conditions (P < 0.05). Conclusion:The locations of vibration as well as different vibration parameters (such as frequency, amplitude) could be adjusted, and the information of postural response to vibratory stimulation of the plantar surface, especially the excursion of center of pressure could be collected in the system which can be applied in the experimental study on the human posture control.
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Objective:To sort out the assistive device social security policy of Japan. Methods:The assistive devices social security policy for the older adults and the disabled in Japan was summarized in term of four dimensions: who, what, how to deliver and how to fund. Results:Japanese assistive device social security policy covered most of disabled groups according to the legal protections, delivering a variety of assistive devices products and services. Meanwhile, it has tried to avoid over expenditure through ways of lump-sum control, unit price and quantity control, users self-pay and strict evaluation system. For the service delivery system, the evaluators were strictly neutral, while the providers were in market. The funding came from user-payments, public finance and insurances, etc. Conclusion:Japan has established a mature social security policy system and service system for assistive devices, which can be used as a reference for China.
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Objective To explore a training system of high level professionals with international vision and meeting the develop-ment of assistive technology in China. Methods The training system was constructed in the theory framework of International Classification of Functioning, Disability and Health,and work process-oriented. Results and Conclusion A curriculum system with tree-type modes and a practice system with three-level and multi-form of assistive technology specialty were constructed,that was recognized by industry and society in the developing.
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<p><b>BACKGROUND</b>Image-guided radiation therapy (IGRT) is the preferred method for curative treatment of localized prostate cancer, which could improve disease outcome and reduce normal tissue toxicity reaction. IGRT using cone-beam computed tomography (CBCT) in combination with volumetric-modulated arc therapy (VMAT) potentially allows smaller treatment margins and dose escalation to the prostate. The aim of this study was to compare the difference of dosimetric diffusion in conventional IGRT using 7-field, step-and-shoot intensity-modulated radiation therapy (IMRT) and hypofractionated IGRT using VMAT for patients with localized prostate cancer.</p><p><b>METHODS</b>We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT (n = 12) or VMAT (n = 12) for prostate cancer between November 2013 and October 2015. Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator. Offline planning was performed using the daily treatment images registered with simulation computed tomography (CT) images. A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study. Dose distributions were recalculated on CBCT images registered with the planning CT scanner.</p><p><b>RESULTS</b>Compared with 7-field, step-and-shoot IMRT, VMAT plans resulted in improved planning target volume (PTV) D95% (7663.17 ± 69.57 cGy vs. 7789.17 ± 131.76 cGy, P < 0.001). VMAT reduced the rectal D25 (P < 0.001), D35 (P < 0.001), and D50 (P < 0.001), bladder V50 (P < 0.001), D25 (P = 0.002), D35 (P = 0.028), and D50 (P = 0.029). However, VMAT did not statistically significantly reduce the rectal V50, compared with 7-field, step-and-shoot IMRT (25.02 ± 5.54% vs. 27.43 ± 8.79%, P = 0.087).</p><p><b>CONCLUSIONS</b>To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation delivered to adjacent normal tissues comparing to 7-field, step-and-shoot IMRT. Daily online image-guidance and better management of bladder and rectum could make a more precise treatment delivery.</p>
الموضوعات
Aged , Aged, 80 and over , Humans , Male , Prostate , Pathology , Radiation Effects , Prostatic Neoplasms , Pathology , Radiotherapy , Radiotherapy Dosage , Radiotherapy, Image-Guided , Methods , Radiotherapy, Intensity-Modulated , Methods , Retrospective Studiesالملخص
OBJECTIVE@#To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC.@*METHODS@#MTT assay was used to detect proliferation of human non-small cell lung cancer cell line A549. Flow cytometry was used to detect the changes of apoptosis and cycle distribution in each group after 24 h and 48 h. RT-PCR was used to detect the changes of PTEN and 4EBP1 expression levels after 48 h of monotherapy and combination therapy.@*RESULTS@#MTT assay showed that everolimus had dose-dependent inhibition against growth of A549 cells. Flow cytometry showed when everolimus could induce apoptosis and induce G0/G1 phase cell cycle arrest, which was time-dependent (P<0.05). RT-PCR showed everolimus could increase PTEN and 4EBP1 expression.@*CONCLUSIONS@#mTOR inhibitor everolimus has an inhibitory effect on EGFR-TKI resistant NSCLC, which cannot reverse the resistance effect of EGFR-TKI resistant cell line A549. The relationship between EGFR/AKT signaling pathway and the mTOR signaling pathway and the mechanism in non-small cell lung cancer need further study.
الموضوعات
Humans , Adaptor Proteins, Signal Transducing , Genetics , Metabolism , Antineoplastic Agents , Pharmacology , Apoptosis , Carcinoma, Non-Small-Cell Lung , Metabolism , Cell Line, Tumor , Cell Proliferation , ErbB Receptors , Everolimus , Gene Expression Regulation, Neoplastic , Lung Neoplasms , Metabolism , PTEN Phosphohydrolase , Genetics , Metabolism , Phosphoproteins , Genetics , Metabolism , Signal Transduction , Sirolimus , Pharmacology , TOR Serine-Threonine Kinases , Metabolismالملخص
<p><b>OBJECTIVE</b>To investigate the feasibility of construction of tissue-engineered skin in vitro.</p><p><b>METHODS</b>Fibroblasts were seeded on the dermal surface of acellular dermal matrix (ADM). 7 days later, epidermal cells (5 x 10(5)/cm2) were mixed with fibroblasts (0.2 x 10(5)/cm2) and then seeded on epidermal surface of ADM. The culture medium was the mixture liquor containing K-SFM in half and the culture supernatants of fibroblasts in half. In the control group, only epidermal cells (5 x 10(5)/cm2) were seeded and cultured with K-SFM. After composite skin was cultured for 1 week and 3 week, samples were harvested respectively for morphological study and to receive identification by immunohistochemistry.</p><p><b>RESULTS</b>After 3-week culture, there were 3-4 continuous layers of cells in the epidermis in the experiment group. The epidermis was attached tightly to the dermis with trochanterellus. But in the control group, there were just 1-2 layers of cells in the epidermis which was not connected to the dermis. Strong positive dye of Laminin indicated that basement membrane was thoroughly formed in the experiment group. The same result was demonstrated by transmission electron microscope.</p><p><b>CONCLUSIONS</b>The mix-seeding of epidermal cells and few fibroblasts would promote the adhesion and proliferation of epidermal cells on ADM, and the formation of basement membrane.</p>
الموضوعات
Animals , Cells, Cultured , Coculture Techniques , Epidermis , Cell Biology , Fibroblasts , Cell Biology , Skin, Artificial , Swine , Tissue Engineering , Tissue Scaffoldsالملخص
<p><b>OBJECTIVE</b>To study the association of positive expression of nucleotide excision repair cross complementary group 1 (ERCC1) in the tumor tissues with platinum resistance of the tumor cells and the clinical outcomes of neo-adjuvant chemotherapy in elderly patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>ERCC1 expression was detected immunohistochemically in the tumor tissues from 113 elderly patients with NSCLC, of which 58 patients received platinum-containing neo-adjuvant chemotherapy, and the impact of ERCC1 expression on the outcomes of neo-adjuvant chemotherapy was analyzed.</p><p><b>RESULTS</b>The total positivity rate of ERCC1 expression was 35% in these patients. The positivity rates was significantly higher in the patients receiving neo-adjuvant chemotherapy than in the control group (46.7% vs 21.05%, χ² = 3.770, P = 0.048). In the 39 patients positive for ERCC1, the response rate to treatment was 53.85%, as compared to the rate of 51.35% in the 74 ERCC1-negative patients. After neoadjuvant chemotherapy, the median survival time (MST) was 53 months in ERCC1-negative patients, as compared to 37 months in the positive patients. The ERCC1-negative and ERCC1-postivie patients showed similar 3- and 5-year survival rates (48.3% vs 44.4%, χ² = 0.033, P = 0.856; 22.5% vs 18.5%, χ² = 0.096, P = 0.757). Multivariate COX regression analysis showed that ERCC1 expression level in the tumor tissue and TNM stages were independent factors that affected the prognosis of the patients (P < 0.05).</p><p><b>CONCLUSION</b>Neoadjuvant chemotherapy can induce ERCC1 expression in the tumor, and the objective response rate of neoadjuant chemotherapy can be low in NSCLC patients with high ERCC1 expression. ERCC1 expression is an independent factor affecting the prognosis of elderly patients with NSCLC receiving neoadjuant chemotherapy.</p>
الموضوعات
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Metabolism , Chemotherapy, Adjuvant , Methods , DNA-Binding Proteins , Genetics , Metabolism , Endonucleases , Genetics , Metabolism , Lung Neoplasms , Drug Therapy , Metabolism , Treatment Outcomeالملخص
<p><b>OBJECTIVE</b>To explore the mechanism of hypoxic environment lessening in the course of scar maturation.</p><p><b>METHODS</b>The expression of hypoxia inducible factor 1alpha (HIF-1alpha) and p53 in granulation of burn wound, burn scars of different stages, and normal skin was detected with immunohistochemical staining. The expressions were quantified by the weight method. The relationship between HIF-1alpha and p53 was investigated.</p><p><b>RESULTS</b>With the scar maturation, the expression of HIF-1alpha gradually decreased while the expression of p53 gradually increased within one year. There was a negative correlation between HIF-1alpha and p53 (P < 0.01).</p><p><b>CONCLUSION</b>p53 plays an important role in scar maturation. Associated with p53, HIF-1alpha may induce apoptosis, which decreases oxygen consumption and lightens hypoxia in the scar maturation.</p>
الموضوعات
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Apoptosis , Cell Hypoxia , Cicatrix , Metabolism , Pathology , Hypoxia , Metabolism , Pathology , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Tumor Suppressor Protein p53 , Metabolismالملخص
Objective Transpherical technique of CT scanner of beekley spot quality assurance (BBQA) and its effect in CT simulator QA.Methods Vertical column,BB,Jig,Philips PQS-Falcon CT, ACQSIM workstation and the laser system were used.Scanning BB was used in sending image to the AC- QSIM workstation.In this system,after describing the BB,isocenter can be established.Then,tile couch with the lasers were moved to the programmed position.Checking was needed.Results The center of the laser should just be found on the BB.Otherwise the laser system should be regulated again.Conclusions Beekley spot quality assurance,being the very important center of any QA program,influences the accuracy of quality of the treatment.
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Objective To evaluate the short-term therapeutic effect and radiation reaction of stereotactic radiotherapy for early stage non-small cell lung cancer in the elderly patients. Methods Thirty-one patients with stage Ⅰ - Ⅱ non-small cell lung cancer were treated with stereotactic radiotherapy. Patients aged 70-88 years, median age 76; 21 were stage I patients, and 10 stage Ⅱ ; 14 patients had tumor