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BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.
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Adulte , Humains , Eczéma atopique/traitement médicamenteux , Résultat thérapeutique , Indice de gravité de la maladie , Anticorps monoclonaux humanisés/usage thérapeutique , Injections sous-cutanées , Méthode en double aveugleRésumé
AIM: To observe the multimodal imaging characteristics of Best vitelliform macular dystrophy(BVMD).METHODS:The clinical data of 30 patients(60 eyes)diagnosed as BVMD at stage Ⅰ to Ⅳ in Nanjing Medical University Affiliated Eye Hospital from June 2016 to October 2022 were collected for a retrospective analysis, and all patients are binocular involved. All patients underwent best corrected visual acuity(BCVA), slit lamp microscopy, indirect ophthalmoscopy, intraocular pressure, fundus photography, spectral-domain optical coherence tomography(SD-OCT), fundus autofluorescence(FAF), fundus fluorescein angiography(FFA), electro-oculogram(EOG)and optical coherence tomography angiography(OCTA).RESULTS: A total of 30 patients(60 eyes)were included, with 8 eyes at stage Ⅰ, 24 eyes at stage Ⅱ, 22 eyes at stage Ⅲ and 6 eyes at stage Ⅵ. The imaging characteristics of fundus photography, FAF, FFA and SD-OCT were basically consistent with previous literature reports. EOG showed Arden ratio <1.55. OCTA could detect early lesions, observe the location of vitelliform substance, external segment of photoreceptor, fluid and choroidal neovascularization(CNV).CONCLUSION: Multimodal imaging assisted in diagnosing BVMD, reducing missed diagnosis and misdiagnosis, among which OCTA had significant advantages over other examinations, and fast and non-invasive were its biggest advantages.
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【Objective】 To explore the effect of inspection sheet on improving the quality of apheresis platelet, the satisfaction of blood donors and the cooperation ability of phlebotomists in the process of apheresis platelet collection. 【Methods】 Apheresis platelet donors from May to August 2021 in our center were selected as control group(without inspection sheet) and those from September to December 2021 were included in the observation group (with inspection sheet). The incidence of abnormal collection and the causes during collection process were compared between the two groups.And 100 first-time blood donors in each group were randomly selected for satisfaction survey. The questionnaire was made to investigate the phlebotomists’ recognition on the implementation of inspection sheet. 【Results】 The number of blood donors in the two groups were 6 673 and 6 559, with 111 and 49 abnormal cases, respectively. The total incidence of abnormal cases during blood collection before and after the implementation of inspection sheet was 1.66% and 0.75%, respectively, with the latter significantly lower than the former(P<0.001). The most common causes of abnormal conditions were repetitive puncture, followed by adverse reaction of blood donation, red blood cells contamination in platelet and fatty blood. The satisfaction of first-time blood donors was higher than before the implementation, and the recognition of phlebotomists on the inspection sheet was more than 90%. 【Conclusion】 The implementation of inspection sheet helps to regulate the collection process, strengthen the responsibility and service consciousness of phlebotomists, improve the satisfaction of blood donors, reduce the incidence of adverse events, and improve the quality of platelet products, which is worth popularizing in blood collection and supply institutions.
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We have analyzed the current status of recognization and qualification of orphan drugs in China and abroad, looking at the aspects of the authority institutions, identification and qualification process, and the number of orphan drugs identified and available in the market. By comparing and analyzing horizontally the differences in orphan drugs identification between representative developed countries vs. some developing countries, we discuss the inadequacy of orphan drugs supervision in China. We introduce the advanced experience from the developed countries and some developing countries to provide suggestions for the identification and management of orphan drugs, hoping to speed up the process of development and market availability of orphan drugs and to maximize patient's accessibility to treatment in China.
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OBJECTIVE To evaluate the cost -effectiveness of tislelizumab in the second -line treatment of advanced or metastatic esophageal squamous cell carcinoma (ESCC)in China .METHODS A three -state Markov model was constructed to assess the cost -effectiveness of tislelizumab versus chemotherapy in the second -line treatment of advanced or metastatic ESCC and programmed death receptor 1(PD-L1)positive patients . The cycle length of the model was 1 month,and the time horizon of the model was set as 10 years. The discount rate of cost and utility was 5%. One-way sensitivity analysis ,probability sensitivity analysis and scenario analysis were used to verify the robustness of the base -case analysis results . RESULTS The results of the base-case analysis showed that compared with chemotherapy ,the incremental cost -effectiveness ratio (ICER)of tislelizumab in the second-line treatment of advanced or metastatic ESCC and PD -L1-positive patients were 26 864.01 yuan/QALY and 37 510.07 yuan/QALY,respectively,which was much lower than 1 time per capita gross domestic product (GDP)in 2021(80 976 yuan). Results of scenario analysis showed that the ICER was less than 1 times per capita GDP ,regardless of the chemotherapy regimens(paclitaxel,docetaxel or irinotecan )used. With the extension of the simulation time limit ,the ICER of tirelizumab regimen gradually decreased ,and the reduction rate gradually E-mail:lishunping@sdu.edu.cn decreased,but they were all less than 1 time China ’s per capita GDP in 2021. The results of the one -way sensitivity analysis showed that the 3 parameters with the most significant impact on the ICER were progression -free survival of tislelizumab group ,price of tislelizumab ,and the proportion of patients receiving follow-up treatment in the tislelizumab group . The results of the probability sensitivity analysis showed that the probability of tislelizumab with cost -effectiveness in the treatment of advanced or metastatic ESCC patients and PD -L1-positive patients were 99.09% and 99.94%,respectively,when using 3 times per capita GDP as the willingness -to-pay threshold . CONCLUSIONS Tislelizumab has economic advantages over chemotherapy alone in the second -line treatment of advanced or metastatic ESCC patients.
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In canonical Wnt/β-catenin signaling pathway, β-catenin/TCF4 (T-cell factor 4) interaction plays an important role in the pathogenesis and development of non-small cell lung cancer (NSCLC), and it is tightly associated with the proliferation, chemoresistance, recurrence and metastasis of NSCLC. Therefore, suppressing β-catenin/TCF4 interaction in Wnt/β-catenin signaling pathway would be a new therapeutic avenue against NSCLC metastasis. In this study, considering the principle of enzyme-linked immunosorbent assay (ELISA), an optimized high-throughput screening (HTS) assay was developed for the discovery of β-catenin/TCF4 interaction antagonists. Subsequently, this ELISA-like screening assay was performed using 2 μg/mL GST-TCF4 βBD and 0.5 μg/mL β-catenin, then a high Z' factor of 0.83 was achieved. A pilot screening of a natural product library using this ELISA-like screening assay identified plumbagin as a potential β-catenin/TCF4 interaction antagonist. Plumbagin remarkably inhibited the proliferation of A549, H1299, MCF7 and SW480 cell lines. More importantly, plumbagin significantly suppressed the β-catenin-responsive transcription in TOPFlash assay. In short, this newly developed ELISA-like screening assay will be vital for the rapid screening of novel Wnt inhibitors targeting β-catenin/TCF4 interaction, and this interaction is a potential anticancer target of plumbagin in vitro.
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Humains , Carcinome pulmonaire non à petites cellules , Lignée cellulaire tumorale , Test ELISA , Tests de criblage à haut débit , Tumeurs du poumon , Facteur-4 de transcription/génétique , bêta-Caténine/génétiqueRésumé
In Gram-negative bacteria, lipopolysaccharide transport (Lpt) protein LptA and LptC form a complex to transport LPS from the inner membrane (IM) to the outer membrane (OM). Blocking the interaction between LptA and LptC will lead to the defect of OM and cell death. Therefore, Lpt protein interaction could be used as a target to screen new drugs for killing Gram-negative bacteria. Here we used biolayer interferometry (BLI) assay to detect the interaction between LptA and LptC, with the aim to develop a method for screening the LptA/LptC interaction blockers in vitro. Firstly, LptC and LptA with or without signal peptide (LptAfull or LptAno signal) were expressed in E. coli BL21(DE3). The purified proteins were then labeled with biotin and the super streptavidin (SSA) biosensor was blocked with diluent. The biotin labeled protein sample was mixed with the sensor, and then the binding of the protein with a series of diluted non biotinylated protein was detected. At the same time, non-biotinylated protein was used as a control. The binding of biotinylated protein to a small molecule IMB-881 and the blocking of interaction were also detected by the same method. In the blank control, the biosensor without biotinylated protein was used to detect the serially diluted samples. The signal response constant was calculated by using steady analysis. The results showed that biotinylated LptC had a good binding activity with LptAfull and LptAno signal with KD value 2.9e⁻⁷±7.9e⁻⁸ and 6.0e⁻⁷±2.8e⁻⁸, respectively; biotinylated LptAno signal had a good binding activity with LptC, with a KD value of 9.6e⁻⁷±7.2e⁻⁸. All binding curves showed obvious fast binding and fast dissociation morphology. The small molecule compound IMB-881 can bind to LptA to block the interaction between LptA and LptC, but has no binding activity with LptC. In summary, we developed a method for detecting the LptA/LptC interaction based on the BLI technology, and confirmed that this method can be used to evaluate the blocking activity of small molecule blockers, providing a new approach for the screening of LptA/LptC interaction blockers.
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Protéines de transport , Escherichia coli/métabolisme , Protéines Escherichia coli/métabolisme , Interférométrie , Protéines membranaires/métabolismeRésumé
【Objective】 To verify the results of HBV DNA and HCV RNA screening under different brands of vacuum collection tubes for blood samples, storage temperature and storage time. 【Methods】 Experiment 1 was conducted as follows: blood samples were collected simultaneously from 52 voluntary blood donors using two brands(divided into group A and group B) of vacuum collection tubes for blood samples. The plasma separation of group A and group B were compared, and the effects of storage time on the NAT yield of HBV DNA and HCV RNA were statistically analyzed. Experiment 2 was conducted as follows: the effects of different storage temperature, time and tubes on the NAT yield of HBV DNA and HCV RNA samples with low viral load in group A and B were verified and compared in the simulated phlebotomy condition. 【Results】 In Experiment 1: After centrifugation, blood plasma layer and cells layer were separated completely in group A(100%, 52/52), but one sample was not well separated in group B(1/52, 1.92%). After 4 to 10 h after collection, blood samples of two groups were centrifuged and screened for HBV DNA, HCV RNA within 24 h. No positive samples were yielded and the Ct values of internal control(IC-DNA and IC-RNA) were uniform. In Experiment 2: Whole blood samples, stored for either 4 h or 6~10 h at 4 ℃ or 25℃ before centrifugation, showed no difference on the NAT-yield of HBV DNA nor HCV RNA samples with low viral load(P>0.05). Ct values of HBV DNA and HCV RNA of group A was similar to those of group B as centrifuged samples were stored for 24 h or 72~104 h at 4℃(P>0.05), but all increased as the storage time prolonged. Ct values of HBV DNA in group A increased from 33.45±0.29(24 h) to 33.82±0.08(72~104 h) and HCV RNA from 35.21±0.20 to 36.12±0.43; HBV DNA from 33.46±0.25 to 34.30±0.60 and HCV RNA from 35.47±0.24 to 36.49±0.51 in group B. 【Conclusion】 Under certain laboratory condition, different storage time, storage temperature and tubes shed few effect on the NAT-yield of HBV DNA and HCV RNA samples with low virus loads. However, it is suggested that the blood sample be detected within 72 h after centrifugation at 4 ℃ storage.
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Objective To evaluate the clinical efficacy and safety of adalimumab for the treatment of severe psoriasis.Methods Between December 2015 and August 2017,14 patients with severe psoriasis who showed no response to traditional therapy were enrolled into this study.All the patients received subcutaneous injection of adalimumab at an initial dose of 80 mg,which decreased to a dose of 40 mg once every 2 weeks after l-week treatment.At week 4,8 and 12,the psoriasis area severity index (PASI)and physician's global assessment (PGA) scores were recorded,and clinical efficacy and adverse drug reactions were observed.In patients with psoriatic arthritis,the improvement of arthritis was evaluated according to the American College of Rheumatology 20% response criteria (ACR20).Results All the 14 patients received the drug treatment for at least 12 weeks.At week 4,8 patients achieved 50% reduction in PASI (PASI 50).At week 8,8 patients achieved PASI 75,and 2 of the 8 patients achieved PASI 90.At week 12,14 patients achieved PASI 75,7 of them achieved PASI 90,and 3 of them achieved PASI 100.Before the treatment,the average PGA score of the 14 patients were 4.92 ± 0.02,and decreased to 1.21 ± 0.02 at week 12.The arthritis symptom was markedly improved in the 3 patients with psoriatic arthritis.At week 8,2 patients achieved ACR20,and 3 achieved ACR20 at week 12.There were no serious adverse drug reactions such as serious infections and malignant tumors in any of the patients.Urticaria occurred in 3 patients,and was relieved after antihistamine treatment.Conclusion Subcutaneous injection of adalimumab every other week is markedly effective and safe for the treatment of severe psoriasis with few adverse drug reactions,and it provides a new treatment choice for patients with severe psoriasis who show no response to traditional therapy.
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Objective To study the application value of G-lipopolysaccharides(G-LPS) detection in patients with traumatic brain injury(TBI).Methods From Jan.2013 to Jun.2014,plasma G-LPS of TBI-patients and non-patients in this hospital were detected by using MB-80 microbiology analyzer and compared.Results of pathogenic microbiological detection of G-LPS positive TBI patients were analyzed,and G-LPS levels,detected before and after treatment,were also analyzed.Results G-LPS positive rate of TBI patients(33.33%) was higher than the 13.34% of non-TBI patients(P<0.05).After treatment,G-LPS level in G-LPS positive TBI patients significantly decreased(P<0.05).The common pathogenic bacteria,causing infection in TBI patients,included Acinetobacter bauman,Klebsiella pneumoniae and Escherichia coli,and the most common infection diseases included respiratory tract infections and urinary tract infections.Conclusion G-LPS detection could be used for the early detection of secondary infection in TIB patients,with significance for guiding clinical treatment.
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Objective To determine the expression of miRNA211 (miR-211) in the development of malignant melanoma,and to investigate the correlation between miR-211 and its target molecule,matrix metalloproteinase 16 (MMP-16).Methods Cultured A375 melanoma cells were divided into 3 groups:miR-211 overexpression group and mock-vehicle group transfected with miR-211 mimics and empty vehicle respectively,and negative control group receiving no treatment.TaqMan fluorescence-based quantitative PCR was performed to determine the expression of miR-211 in HER1 primary melanocytes,A375,C32 and G361malignant melanoma cell lines,as well as in nevus tissues (n =18) and melanoma tissues (n =41),and to evaluate changes of MMP-16 mRNA expression in A375 cells before and after the overexpression of miR-211.Sulforhodamine B (SRB) assay and flow cytometry were conducted to evaluate cellular proliferative activity and determine cell cycle distribution respectively,and methylcellulose assay and Transwell assay to evaluate colony formation and cell migration abilities respectively.The size of selected colonies was used to represent colony formation ability,while the ratio of the number of migrating cells to that of non-migrating cells to represent cell migration ability.Results There were significant differences in the expression level of miR-211 among the G361,C32 and A375 cells (0.09 ± 0.02 vs.0.000 52 ± 0.000 20 vs.0.000 03 ± 0.000 01,F =10 410,P < 0.01).The expression of miR-21 1 was significantly decreased in melanoma tissues compared with nevus tissues (0.17 ± 0.03 vs.0.87 ± 0.08,t =9.118,P < 0.01).No significant differences were observed in cellular proliferative activity or cell cycle distribution among the miR-211 overexpression group,mock-vehicle group and negative control group.Compared with the mock-vehicle group,the miR-211 overexpression group showed significantly suppressed colony formation (0.49 ± 0.05 vs.0.85 ± 0.09,t =2.19,P < 0.05) and cell migration (0.49 ± 0.06 vs.0.82 ± 0.09,t =3.15,P < 0.05) abilities,while no significant difference was observed between the mock-vehicle group and negative control group.Additionally,the mRNA expression of MMP-16 significantly decreased in the miR-211 overexpression group compared with the mock-vehicle group after transfeetion (24 hours:0.33 ± 0.02 vs.0.91 ± 0.03,t =11.30,P < 0.01;48 hours:0.52 ± 0.01 vs.0.96 ± 0.02,t =5.02,P < 0.05;72 hours:0.71 ± 0.01 vs.0.97 ± 0.03,t =3.85,P < 0.05),with no significant difference between the mock-vehicle group and negative control group at the above time points.Conclusions miR-211 was lowly expressed in both malignant melanoma cells and tissues,and it could inhibit both anchorage-independent growth and migration of melanoma cells.After up-regulation of miR-211 expression,the mRNA expression of MMP-16 decreased in A375 cells,suggesting that MMP-16 may be a downstream target of miR-211,and can influence melanoma metastasis.
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Objective: To investigate the effect of sevolfurane (SEVO) post-conditioning on protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway for protecting ischemia/reperfusion (I/R) injury in isolated rat’s heart. Methods: A total of 84 isolated rat’s heart prepared by Langendorff method were randomly divided into 7 groups andn=12 in each group.①Sham group,②I/R group,③SEVO post- conditioning (SPC) group,④NVP-BEZ235 solvent dimenthyl sulfoxide (DMSO) group,⑤Phosphatidyl inositol 3-kinase (PI3K)/mTOR dual inhibitor NVP-BEZ235 (BEZ) group,⑥BEZ+SPC group and⑦SEVO alone group. The hearts received 30 min ischemia followed by 120 min reperfusion with relevant treatment except for Sham group and SEVO group in which the hearts were without ischemia process. Myocardial infarct (MI) size and tissue pathological changes were observed, protein expressions of phosphor-AKT (P-AKT)/total-AKT, P-mTOR/total-mTOR, Beclin1, Bax/Bcl-2 and cleaved Caspase-3 were examined at the end of reperfusion respectively. Results: Compared with I/R group, SPC group presented decreased MI size (26.28±4.00) % vs (49.22±3.66) % and reduced tissue pathological changes; up-regulated protein expressions of P-AKT/total-AKT and P-mTOR/total-mTOR by 79.85% and 67.02%, while down-regulated protein expressions of Beclin1, Bax/Bcl-2 and cleaved Caspase-3 by 33.77%, 69.26% and 48.84%respectively, allP<0.05. Compared with SPC group, BEZ+SPC group sowed increased MI size (53.85±4.06) % vs (26.28±4.00) %and elevated tissue pathological changes; down-regulated proteins expressions of P-AKT/total-AKT and P-mTOR/total-mTOR by 46.06% and 42.95%, while up-regulated protein expressions of Beclin1, Bax/Bcl-2 and cleaved Caspase-3 by 29.90%, 206.85% and 114.65% respectively, allP<0.05. Conclusion: SPC may activate AKT/mTOR pathway and inhibit cardiomyocyte autophagy and apoptosis, thereby attenuate I/R injury in isolated rats’ heart.
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Objective To evaluate the effect of the intervention of involving clinical pharmacists in perioperative total parenteral nutrition (TPN) prescription,including rationality of prescriptions,the length of hospital stay and economic evaluation.Methods We respectively selected TPN prescriptions in September to November 2015 (pre-intervention) and December 2015 to February 2016 (post-intervention) from a surgery department of Harbin Medical University Cancer Hospital.The data regarding rationality of prescription,length of hospital stay,and economic benefit were analyzed in order to evaluate the effect of involvement of clinical pharmacists in TPN prescriptions.Results A total of 81 patients with 115 TPN prescriptions before the intervention and 92 patients with 124 TPN prescriptions after the intervention were recruited.Through comparative analysis,the rationality of TPN prescriptions increased significantly after the participation of clinical pharmacists in terms of the rational glucose:fat ratio,energy:nitrogen ratio,electrolyte concentration,and the choice of vitamin preparations;and the utilization of controversial treatments such as invert sugar and other drugs into readyto-use TPN solution was decreased significantly;average daily cost of TPN was decreased from (1 021 ± 218) yuan to (860 ± 176) yuan (P <0.001);average duration of hospital stays was decreased but the difference was not statistically significant (P > 0.05).Compared with the data before the intervention,serum albumin levels after the intervention showed no statistically significant difference but pre-albumin levels were significantly higher after the participation of clinical pharmacists [(175.0 ± 77.9) g/L vs.(153.2 ± 64.8) g/L,P < 0.05].The liver and kidney function indicators showed no statistically significant differences between pre-and post-intervention (P > 0.05).Conclusion Engaging clinical pharmacists in TPN prescription can improve prescription rationality,ensure clinical drug safety,reduce the daily cost of nutrition treatment and thus reduce the economic burden of patients.
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Objective To study the clinical features and spirometry of children with chronic cough and positive findings by bronchial provocation test.Methods Four hundred and fifty children with chronic cough from 3 hospitals of Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong Medical University School of Medicine,Gong Li Hospital of Pudong New Area,Pudong Hospital,were enrolled in this study from December 2012 to December 2014,and among them,373 cases completed the questionnaires,spirometry and bronchial provocation test.The differences in clinical features and spirometry between the bronchial provocation test positive group and negative group were compared.And the further evaluation of their clinical value was performed.Results Two hundred and thirty-six cases of children with bronchial provocation tests positive showed much higher rate of dry [72.03% (170/236 cases)] and night cough[58.90% (139/236 cases)] than those in the negative group[27.00% (37/137 cases),22.63% (31/137cases)],and the differences were significant (x2 =71.154,45.973,all P <0.01).Children in positive group also had higher morbidity of eczema[52.12% (123/236 cases)],allergic conjunctivitis [24.15% (57/236 cases)] and inhaled allergy history[40.25% (95/236 cases)] than those in negative group[32.85% (45/137 cases),10.95% (15/137cases),18.98% (26/137 cases)],and there existed significant differences (x2 =13.006,9.701,17.904,all P <0.01).And they also had higher asthma heredity [18.22% (43/236 cases)] than that in negative group [9.49%(13/137 cases)],and the difference was significant (x2 =5.179,P =0.023);with worse small airway function [50.85% (120/137 cases) vs 36.50% (50/137 cases)] (x2 =7.197,P =0.007).For further study,the sensitivity and specificity for dry cough were both high(72.03% and 72.99%).For specificity,family history was the most highest one (90.51%),and night cough and allergic conjunctivitis were also high.Conclusions Pulmonary function tests to reflect small airway function abnormalities,combined with a family history of asthma and chronic cough in children related to eczema,allergic conjunctivitis,and inhalation allergy history clinical features,can better predict airway hyperresponsiveness.
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ObjectiveTo investigate bronchial provocation test (BPT) and small airway function in children with cough variant asthma (CVA).MethodsA total of 353 children with chronic cough whose mean age was (7.45±2.58) years from three hospitals of Pudong district were enrolled during May 2012 and February 2014. Conventional pulmonary function tests, BPT and questionnaire survey were performed and the difference in pulmonary function was analyzed between children with positive BPT and negative BPT.ResultsIn 353 children with chronic cough, there were 200 children (56.66%) diagnosed as CVA with posi-tive BPT. Compared with BPT negative group, the percentages of nighttime cough and severe dry cough in BPT positive group were signiifcantly higher while the percentages of morning/daytime cough and wet cough were signiifcantly lower (P<0.01). Fur-thermore, the rates of history of atopic dermatitis and rhinitis in BPT positive group were signiifcantly higher than those in BPT negative group (P<0.01). Forced expiratory lfow at 75% relfecting the small airway function was signiifcantly lower in BPT posi-tive group than that in BPT negative group (P=0.032).ConclusionsBronchial hyperresponsiveness and decreased small airway function are the important pathological features of CVA. BPT and spirometry have clinical signiifcances in the CVA diagnosis and the analysis of cause of chronic cough.
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Objective To develop an immunohistochemical assay for the diagnosis of cutaneous malignant melanoma (CMM) micrometastasis via blood and lymphatic vessels,and to evaluate its clinical significance.Methods Fifty-three patients (32 males and 21 females) histopathologically diagnosed as CMM were enrolled in this study.The patients were aged (61.2 ± 8.4) years (range,52-72 years).Tissue specimens were obtained from the central area of tumor in each case,and also from removed lymph nodes in some cases.The average duration of follow-up was (65.00 ± 5.68) months.During the follow-up,17 patients died of the recurrence or metastasis of CMM,and 6 patients were lost to follow-up.The expressions of D2-40,S100 and CD34 antigens in 53 tissue specimens were examined by immunohistochemical staining with three individual monoclonal antibodies,or by an immunohistochemical method using 2 two-antibody cocktails (D2-40/S 100 and CD34/S100) and double-color chromogens in single tissue sections.Results Of the 53 patients,30.19% (16/53) were positive for hematoxylin-eosin (HE) staining combined with immunohistochemical staining with individual monoclonal antibodies,and 49.06% (26/53) for the immunohistochemical method using two-antibody cocktails and double-color chromogens.Statistical differences were found in the positive rate between the two methods (x2 =3.94,P< 0.05).Compared with patients without blood/lymph vessel tumor emboli,those with blood/lymph vessel tumor emboli showed higher lymph node metastasis rate (80.77% (21/26) vs.37.04% (10/27),x2 =10.43,P < 0.001),but lower five-year survival rate (42.31% (11/26) vs.70.37% (19/27),x2 =4.25,P < 0.05).Conclusions The immunohistochemical method with two-antibody cocktails is superior to HE staining combined with immunohistochemical staining with individual monoclonal antibodies in the detection of blood/lymph vessel tumor emboli.And blood/lymph vessel tumor emboli may be an important prognostic factor in patients with CMM.
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Objective] To observe the diagnosis value of noninvasive diagnosis model S index used to evaluate the fibrosis degree of slight chronic hepatitis B(CHB). [Method] Trace back and investigate the routine serological indicators GGT, PLT, ALB and liver aspiration biopsy results of 63 cases of CHB;use noninvasive diagnosis formula to calculate:S index=1000×GGT/(PLT×ALB2),use ROC curve to analyze and evaluate the clinical diagnosis value of S index. [Result] S index is in positive relation with liver fibrosis degree. S index can forecast the fibrosis having or not with best truncation point 0.04h, the sensitivity 87.0%, specificity 47.5%and area under the curve(AUC) 0.690,close to 0. 7; in forecasting obvious fibrosis, with best truncation point 0.04h, sensitivity 100%,specificity 36.8%,AUC 0.664. [Conclusion] S index used for forecasting slight CHB having or not fibrosis has high value of diagnosis, but it has low correctness for diagnosing having or not obvious liver fibrosis.
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A 69-year-old male patient presented with a gradually enlarging mass in the left inner upper thigh for more than 2 months,and pigmented patches in the left medial leg for more than 20 years.Physical examination revealed a painless mass measuring 3 cm × 2 cm × 2 cm in size in the left inner upper thigh.Several pigmented patches were observed in the left medial leg,and the largest pigmented patch measured 2 cm× 2 cm in size with an irregular border and uneven pigmentation.The mass in the left inner upper thigh was resected and subjected to histopathological examination,which showed proliferative epithelioid neoplastic cells with mucous matrix,round and spindle cells of varying sizes separated by mucous matrix.The immunohistochemical study of tumor cells showed positive staining for vimentin,S100 and Melan-A,but negative staining for actin,desmin,CD56,epithelial membrane antigen,cytokeratin,leukocyte common antigen,CD99,chromogranin A and synaptophysin.Hematoxylin-eosin staining of pigmented patches on the left medial leg revealed squamous epithelium covering the surface of lesions with no superficial ulceration or atypia in epithelial cells,unevenly distributed melanophages,fibroplasia accompanied by collagen formation,obviously decreased skin appendages,infiltration of a few inflammatory cells in the dermis.AB-PAS staining was negative.The immunohistochemical study of pigmented patches showed positive staining for vimentin and Melan-A.The patient was pathologically diagnosed with metastatic myxoid melanoma with partial regression of the primary lesion.
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Objective To describe the clinicopathologic features of two cases of mucoepidermoid carcinoma of the skin.Methods Two cases of mucoepidermoid carcinoma of the skin were analyzed histopathologically using hematoxylin and eosin (HE) staining,alcian blue-periodic acid Schiff (AB-PAS) staining and immunohistochemical staining.Relavant literature was reviewed.Results Histopathological examination showed that the tumor was subcutaneously located in both cases,with epidermoid cells and intermediate cells arranged in sheets or nests,as well as different sizes of glandular structures lined by mucinous columnar epithelium in some areas.Both tumors had a relatively clear boundary with peripheral invasive growth and no obvious capsules.Immunohistochemical examination showed positive staining for carcinoembryonic antigen (CEA),high and low molecular weight cytokeratin (CK(H) and CK(L)).The cytoplasm of mucous cells was stained blue with,and mucus was visualized after,AB-PAS staining.Conclusions Primary mucoepidermoid carcinoma of the skin is a kind of malignant tumor arising from skin appendages,whose diagnosis depends on histological and immunohistochemical examination.
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<p><b>OBJECTIVE</b>To construct an double-layered tube-shaped poly (lactic-co-glycolic acid) (PLGA) scaffold composited with vascular endothelial growth factor (VEGF)/ platelet-derived growth factor (PDGF), and to evaluate in vivo the axial vascularization from femoral arteriovenous bundle encapsulated.</p><p><b>METHODS</b>Eighteen male adult New Zealand rabbits were assigned randomly into 3 groups: Experimental group (n = 8), experimental control group (n = 8), empty control group (n=2). The femoral arteriovenous bundle were separated and encapsulated in double-layered tubeshaped PLGA scaffold prepared by solution casting and particle leaching. According to the way of cell factors being composited to the prepared double-layered scaffold: 1) experimental group: VEGF in inner layer and PDGF in outer layer; 2) experimental control group: VEGF in inner layer with blank outer layer; 3) empty control group: Pure blank. Specimens were retrieved at 7, 10, 14, 21 days postoperatively (7, 10 days in empty control group). The histological evaluation was performed.</p><p><b>RESULTS</b>At 7 days postoperatively, blood vessel sprouts were observed in experimental group and experimental control group, radially from the central femoral arteriovenous bundle. At 10 days postoperatively, completely penetrations of the double-layered scaffold by abundant new generated blood vessel sprouts were observed, and density descended gradiently from inside to outside. At 14 days postoperatively, new blood vessels in experimental group showed more thickness and layered structure of the wall, while monolayer endothelial cells in experimental control group. At 21 days postoperatively, new blood vessels in experimental group showed more mature characteristics, while less density of blood vessels in experimental control group. There was no obvious blood vessel structure in empty control group.</p><p><b>CONCLUSION</b>The double-layered tube-shaped PLGA scaffold composited with VEGF/PDGF could induce early angiogenesis.</p>