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Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory clinical syndrome of uncontrolled immune response which results in hypercytokinemia due to underlying primary or secondary immune defect. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only cure therapy for primary HLH and recurrent/refractory hemophagocytic lymphohistiocytosis. Compared with children HLH, adult HLH is a much more heterogeneous syndrome requiring a more individualized protocol depending on the underlying trigger, disease severity and genetic background. At present, there remain controversies in various aspects including indications of haematopoietic cell transplantation (HCT), conditioning regimen, efficacy and prognosis. This article will review the recent advances of allo-HSCT in the treatment of adult HLH based on the above issues.
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Criança , Humanos , Adulto , Linfo-Histiocitose Hemofagocítica/terapia , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante/métodosRESUMO
OBJECTIVE@#To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed.@*RESULTS@#APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34+ cells was 6.82 (1.27-22.57)×106/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34+ cells≥2×106 cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34+ cells≥5×106 cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively.@*CONCLUSION@#The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.
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Humanos , Mieloma Múltiplo/terapia , Etoposídeo/uso terapêutico , Células-Tronco de Sangue Periférico , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Fator Estimulador de Colônias de Granulócitos , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Autólogo/efeitos adversosRESUMO
The paper introduces professor ZHUANG Li-xing's clinical experience in treatment of dyskinesia of Parkinson's disease with acupuncture at triple-acupoint prescription. In pathogenesis, dyskinesia of Parkinson's disease refers to yang deficiency and disturbing wind. In treatment, acupuncture focuses on warming yang, promoting the circulation of the governor vessel, regulating the spirit and stopping trembling; and Baihui (GV 20), Suliao (GV 25) and Dingchanxue (Extra) are selected to be "trembling relief needling". In combination with Jin's three needling, named "three-trembling needling" "three-governor-vessel needling" and "three-spasm needling", the triple-acupoint prescription is composed. To ensure the favorable therapeutic effect, this prescription is modified according to the symptoms and the specific techniques of acupuncture are combined such as conducting qi, harmonizing yin and yang, and manipulating gently for reinforcing and reducing.
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Humanos , Pontos de Acupuntura , Doença de Parkinson/terapia , Terapia por Acupuntura/métodos , Acupuntura , DiscinesiasRESUMO
Objective: To explore the predictive value of the impedance measured during leadless pacemaker Micra implantation on the trend of changes of pacing threshold post implantation. Methods: This is a retrospective cross-sectional study. Patients who received implantation of leadless pacemaker Micra at the Second Xiangya Hospital of Central South University from December 2019 to August 2020 were enrolled. The clinical data and the intraoperative electrical parameters during leadless pacemaker implantation were collected. The impedance and pacing threshold data were analyzed at three time points: immediate release, 5-10 min after release, and after traction test. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to analyze the value of the impedance at immediate release on predicting the trend of changes of pacing threshold post implantation. Results: A total of 21 patients (mean age: (72.2±12.5) years, 12 males) were included. The impedance of 21 patients was (798.1±35.3) Ω immediately after implantation, (800.9±35.6) Ω after 5-10 minutes of release, and (883.6±31.7) Ω after traction test. Impedance was similar between the three time points (P>0.05). The threshold was (0.97±0.11) V/0.24 ms immediately after implantation, (0.95±0.12) V/0.24 ms at 5-10 min after the release, and (0.59±0.06) V/0.24 ms after the traction test. The threshold was significantly lower after the traction test than that immediately after release (P=0.003) and than that at 5-10 minutes after release (P=0.008), suggesting a decreased tendency of the threshold over time. According to the analysis of the ROC curve, the immediate impedance after the release ≥680 Ω could predict the ideal pacing threshold after the traction test (AUC=0.989, 95%CI 0.702-0.964, P<0.001), the prediction sensitivity was 87%, and the specificity was 100%. The pacing threshold would be not ideal with the immediate impedance ≤ 520 Ω (95%CI 0.893-1.000, P<0.001), the sensitivity was 100%, and the specificity was 80%. Conclusions: The impedance immediately after the release has predictive value for the changing trend of threshold post leadless pacemaker Micra implantation. Impedance ≥680 Ω immediately after release is often related with ideal pacing threshold after the traction test. In contrast, the impedance ≤ 520 Ω pacing is often related with unsatisfactory threshold after the traction test, therefore, it is recommended to find a new pacing site to achieve the impedance ≥680 Ω immediately after release during leadless pacemaker Micra implantation.
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Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Cardíaca Artificial , Estudos Transversais , Impedância Elétrica , Marca-Passo Artificial , Estudos Retrospectivos , Resultado do TratamentoRESUMO
ObjectiveTo observe the clinical effect of Jianpi Yangyin Guse decoction on patients with diabetic nephropathy (DN),and to explore its protection against podocyte injury. MethodThe enrolled 120 DN patients at stages Ⅲ and Ⅳ and diagnosed with Qi and Yin deficiency from January 2017 to January 2020 were randomly divided into observation group and control group. During the same period,20 healthy volunteers were recruited as the normal group. In addition to the basic treatment in control group,patients in the observation group were given Jianpi Yangyin Guse decoction,and the course of treatment lasted for 3 months. The traditional Chinese medicine (TCM)syndrome score,24 h urine protein (24 h UP),urine albumin-to-creatinine ratio(UACR),liver and renal functions,D-dimer, hemoglobin A1c (HbA1c), urine podocin and nephrin and α-smooth muscle actin (α-SMA) excretion of the two groups were observed before and after treatment,and the changes were statistically analyzed and compared with those in the normal group. ResultAfter treatment,the reduction of TCM syndrome score in the observation group was more significant than that in the control group(P<0.01). The 24 h UP level,UACR and renal function in the observation group in the 2nd and 3rd months after treatment were lower than the conditions before treatment(P<0.05), and those in the 3rd month after treatment were decreased compared with the conditions in the control group during the same period. The levels of podocin and nephrin in each month and the α-SMA excretion in the 3rd month after treatment in the observation group were down-regulated compared with the conditions before treatment and in the control group (P<0.05), and the observation group had reduced α-SMA excretion in the 2nd month after treatment compared with before treatment. There were no marked changes in D-dimer and liver function of the two groups before and after treatment. The level of HbA1c in the observation group was higher than that in the control group after treatment(P<0.05). ConclusionJianpi Yangyin Guse decoction has desirable clinical efficacy in DN patients,and its mechanism may be related to reducing podocin and nephrin and α-SMA excretion levels.
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OBJECTIVE: To observe the effect of Mongolian medicine three-acupoints balance needling on the expression of p11/tPA/BDNF pathway and miRNA-16 in the hippocampus and middle raphe nucleus (MRN) in chronic stress depression model rats, so as to explore its mechanisms underlying improvement of depression. METHODS: Male SD rats were randomly divided into blank control, model, medication and Mongolian medicine acupuncture (acupuncture) groups, with 12 rats in each group. The depression model was established by using chronic unpredictable mild stress method. The rats in the medication group received gavage of prozac (2 mg/kg, diluted with normal saline, 1 mg/mL) 1 h after stress stimulation, once per day for 28 days, and those in the acupuncture group received three-acupoints (Heyi, Badagan and Xin) needling, once a day for 28 days. The behavioral changes were detected by using open field test and sugar consumption test before modeling and after the intervention. The immunoactivity of p11 and tPA proteins in the MRN, and their expression levels in both the MRN and hippocampus were detected by using immunofluorescence histochemistry and Western blot, separately, and the expression levels of miRNA-16 and BDNF mRNA in the hippocampus and MRN detected by using real-time quantitative PCR. RESULTS: After modeling, the crossing and rearing scores of open field tests and the relative consumption of sucrose in the model group were apparently lower than those of the blank control group (P<0.05), the expression levels of p11 and tPA in the MRN, and those of p11 and tPA proteins and BDNF mRNA in the MRN and hippocampus were significantly down-regulated (P<0.05), while those of miRNA-16 in the hippocampus and MRN were significantly up-regulated (P<0.05). Compared with the model group, the crossing and rearing scores of open field tests and glucose consumption, as well as the expression levels of p11 and tPA proteins and BDNF mRNA in the hippocampus and MRN were obviously increased in both the medication and acupuncture groups (P<0.05), while the expression of miRNA-16 in hippocampus was markedly down-regulated in both the medication and acupuncture groups (P<0.05). No significant differences were found between the acupuncture and medication groups in all the indexes mentioned above (P>0.05). CONCLUSION: Mongolian medicine three-acupoints balance needling can improve the depressive state in depression rats, which may be associated with its effects in up-regulating the expression of p11 and tPA proteins and BDNF mRNA in the hippocampus and MRN and in down-regulating miRNA-16 in the hippocampus, suggesting an involvement of miRNA-16 controlled p11/tPA/BDNF signaling pathway in the antidepressant effect of acupuncture.
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Pontos de Acupuntura , MicroRNAs , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Depressão/genética , Depressão/terapia , Núcleo Dorsal da Rafe , Hipocampo , Masculino , Medicina Tradicional da Mongólia , MicroRNAs/genética , Ratos , Ratos Sprague-DawleyRESUMO
BackgroundInformation regarding the impact of cardiovascular disease (CVD) on disease progression among patients with mild coronavirus disease 2019 (COVID-19) is limited. MethodsThis study evaluated the association of underlying CVD with disease progression in patients with mild COVID-19. The primary outcome was the need to be transferred to intensive care due to disease progression. The patients were divided with and without CVD as well as stable and intensive care groups. ResultsOf 332 patients with mild COVID-19, median age was 51 years (IQR, 40-59 years), and 200 (61.2%) were female. Of 48 (14.5%) patients with CVD, 23 (47.9%) progressed to severe disease status and required intensive care. Compared with patients without CVD, patients with CVD were older, and more likely to have fatigue, chest tightness, and myalgia. The rate of requiring intensive care was significantly higher among patients with CVD than in patients without CVD (47.92% vs. 12.4%; P<0.001). In subgroup analysis, rate of requiring intensive care was also higher among patients with either hypertension or coronary heart disease than in patients without hypertension or coronary heart disease. The multivariable regression model showed CVD served as an independent risk factor for intensive care (Odd ratio [OR], 2.652 [95% CI, 1.019-6.899]) after adjustment for various cofounders. ConclusionsPatients with mild COVID-19 complicating CVD in are susceptible to develop severe disease status and requirement for intensive care. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the impact of coexisting cardiovascular diseases (CVD) on disease progression in patients with mild COVID-19? FindingsAlthough most patients with mild COVID-19 were discharged alive from hospital, approximately 47.9% patients with coexisting CVD developed severe disease status and required intensive care. CVD is an independent risk factor of intensive care among patients with mild COVID-19. MeaningCoexisting CVD is associated with unfavorable outcomes among patients with mild COVID-19. Special monitoring is required for these patients to improve their outcome.
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Pectin methylesterase (PME) is an important pectinase that hydrolyzes methyl esters in pectin to release methanol and reduce the degree of methylation of pectin. At present, it has broad application prospects in food processing, tea beverage, paper making and other production processes. With the in-depth study of PME, the crystal structures with different sources have been reported. Analysis of these resolved crystal structures reveals that PME belongs to the right-hand parallel β-helix structure, and its catalytic residues are two aspartic acids and a glutamine, which play the role of general acid-base, nucleophile and stable intermediate, in the catalytic process. At the same time, the substrate specificity is analyzed to understand the recognition mechanism of the substrate and active sites. This paper systematically reviews these related aspects.
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Hidrolases de Éster Carboxílico , Química , Metabolismo , Domínio Catalítico , Cristalografia , Pectinas , Metabolismo , Estrutura Terciária de Proteína , Especificidade por SubstratoRESUMO
Glucoamylase is a critical ingredient for saccharification in the starch decomposition, and widely used in food, pharmaceutical and fermentation industries. Glucoamylases are usually thermostable and have peak activities at high temperature, as required for the industrial process of glucose production. In this study, a glucoamylase gene belonging to the glycoside hydrolase (GH) family 15, Tlga15A, was cloned from Talaromyces leycettanus JCM12802, and successfully expressed in Pichia pastoris GS115. Recombinant glucoamylase TlGA showed optimal activities at pH 4.5 and 75 °C. The result of thermostability analysis showed that TlGA retained above 70% activity after incubating for 1 h at 65 °C, and 43% residual activity after 30 min at 70 °C. Moreover, TlGA had high resistance to most metal ions and chemical reagents tested. Various starch substrates could be hydrolyzed by TlGA, including soluble starch (255.6±15.3) U/mg, amylopectin (342.3±24.7) U/mg, glycogen (185.4±12.5) U/mg, dextrin (423.3±29.3) U/mg and pullulan (65.7±8.1) U/mg. The primary, secondary and tertiary structures of glucoamylase were further analyzed. The low ratio of Gly in the primary structure and low exposed nonpolarity solvent accessible surface in the tertiary structure may be the main reasons for TlGA's thermostability. These results show that TlGA is great promising for potential use in the commercial production of glucose syrups. Moreover, this research will provide knowledge and innovating ideas for the improvement of glucoamylase thermostability.
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Clonagem Molecular , Estabilidade Enzimática , Glucana 1,4-alfa-Glucosidase , Concentração de Íons de Hidrogênio , Pichia , Talaromyces , TemperaturaRESUMO
Objective To explore the expression of mitochondrial ubiquitin ligase(MITOL)in the cere-brospinal fluid from patients with postherpetic neuralgia(PHN). Methods A total of 45 patients who were diag-nosed with PHN in our hospital from August 2015 to December 2016 were enrolled in this study,and 38 gender-and age-matched patients with lumbar disc herniation were recruited as IDH group.The MITOL was measured by the ELISA and Western blot methods.The correlation between the expression of MITOL in cerebrospinal fluids and clinical characteristics of patients with PHN was evaluated.Results The expression of MITOL was significantly in-creased in cerebrospinal fluids of patients with PHN compared with IDH,and it was associated with age and the pain intensity(P<0.05).Logistic regression analysis showed age(OR,2.717)and the pain intensity(OR,3.042) were risk factors for PHN. Conclusions The expression of MITOL is significantly increased in the cerebrospinal fluid of PHN,which may be associated with age and pain intensity.
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Efficient utilization of cellulose and xylan is of importance in the bioethanol industry. In this study, a novel bifunctional xylanase/cellulase gene, Tcxyn10a, was cloned from Thermoascus crustaceus JCM12803, and the gene product was successfully overexpressed in Pichia pastoris GS115. The recombinant protein was then purified and characterized. The pH and temperature optima of TcXyn10A were determined to be 5.0 and 65-70 °C, respectively. The enzyme retained stable under acid to alkaline conditions (pH 3.0-11.0) or after 1-h treatment at 60 °C. The specific activities of TcXyn10A towards beechwood xylan, wheat arabinoxylan, sodium carboxymethyl cellulose and lichenan were (1 480±26) U/mg, (2 055±28) U/mg, (7.4±0.2) U/mg and (10.9±0.4) U/mg, respectively. Homologous modeling and molecular docking analyses indicated that the bifunctional TcXyn10A has a single catalytic domain, in which the substrate xylan and cellulose shared the same binding cleft. This study provides a valuable material for the study of structure and function relationship of bifunctional enzymes.
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Celulase , Endo-1,4-beta-Xilanases , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Simulação de Acoplamento Molecular , Pichia , Especificidade por Substrato , ThermoascusRESUMO
<p><b>OBJECTIVE</b>To compare shear bond strength (SBS) between two types of silicone soft liner and polymethyl methacrylate (PMMA) under the condition of heat curing and room temperature curing.</p><p><b>METHODS</b>A total of 48 PMMA specimens (50 mm x 10 mm x 3 mm) were made by water-bath heating method, and randomly divided into four groups. By using Ufi Gel P (UGP) as soft liner material, group A1 was prepared under heat curing, and group A2 was prepared under room temperature curing. To form the other two groups, Silagum-Comfort (SLC) as soft-liner material was used. Group B1 was prepared under heat curing, and group B2 was prepared under room temperature curing. Shear bond strength (SBS) was tested by using the electronic universal testing machine. The adhesives layer and surface of silastic and PMMA were observed by optical microscope and scanning electron microscopy (SEM).</p><p><b>RESULTS</b>The SBS of groups A1, A2, B1, B2 were (2.39 +/- 0.24), (1.74 +/- 0.27), (3.09 +/- 0.26), and (2.21 +/- 0.29) MPa, respectively. Significant differences were found between A1 and A2, B1 and B2, A1 and B1, and A2 and B2 (P < 0.05). Optical microscope showed numerous bubbles in the cured UGP, and no air bubbles in the SLC. The surface of PMMA was rough. SEM images showed that each group had continual consistent adhesive interface and a whisker hump on the adhesive layer of A2 and B2.</p><p><b>CONCLUSION</b>The SBS ofUGP, SLC, and PMMA achieved minimum clinical standard of 0.44 MPa. The SBS of UGP and PMMA were higher than that of SLC and PMMA. The polymerization method of heat curing was higher than room temperature curing.</p>
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Colagem Dentária , Reembasadores de Dentadura , Dimetilpolisiloxanos , Teste de Materiais , Polimerização , Polimetil Metacrilato , Elastômeros de Silicone , Silicones , Resistência à TraçãoRESUMO
CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Though in vitro angiogenic function of CD146 has been extensively reported, in vivo evidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout (CD146(EC-KO)) mice using the Tg(Tek-cre) system. Surprisingly, these mice did not exhibit any apparent morphological defects in the development of normal retinal vasculature. To evaluate the role of CD146 in pathological angiogenesis, a xenograft tumor model was used. We found that both tumor volume and vascular density were significantly lower in CD146(EC-KO) mice when compared to WT littermates. Additionally, the ability for sprouting, migration and tube formation in response to VEGF treatment was impaired in endothelial cells (ECs) of CD146(EC-KO) mice. Mechanistic studies further confirmed that VEGF-induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/NF-κB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146(EC-KO) mice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.
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Animais , Feminino , Masculino , Camundongos , Antígeno CD146 , Genética , Metabolismo , Células Cultivadas , Células Endoteliais , Biologia Celular , Metabolismo , Fibrossarcoma , Metabolismo , Patologia , Melanoma Experimental , Metabolismo , Patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B , Metabolismo , Neovascularização Fisiológica , Fosforilação , Proteínas Proto-Oncogênicas c-akt , Metabolismo , Veia Retiniana , Patologia , Transdução de Sinais , Transplante Homólogo , Fator A de Crescimento do Endotélio Vascular , Farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To assess the effect and safety of Jinhua Qinggan Granule (JHG) in treating influenza patients of wind-heat affecting Fei syndrome (WHAFS).</p><p><b>METHODS</b>Totally 136 influenza patients of WHAFS were randomized by stratification into 3 groups, the high dose JHG group (44 cases, 10 g each time), the low dose JHG group (45 cases, 5 g JHG + 5 g placebo each time), and the placebo control group (47 cases, 10 g placebo each time). All medication was administered three times daily for 5 days. The fever disappearance time, the fever disappearance rate, efficacy of TCM syndrome, the disappearance rate of main symptoms and physical signs of flu, the negative rate of virus nucleic acid in the pharyngeal secretion, and safety indicators were assessed.</p><p><b>RESULTS</b>The median fever disappearance time was 32.8 h (95% CI: 22.5-41.0 h) in the high dose JHG group, 26.0 h (95% CI: 14.5-36.5 h) in the low dose JHG group, 39.5 h (95% CI: 29.0-46.0 h) in the placebo control group. There was statistical difference in the median fever disappearance time between the low dose JHG group and the placebo control group (P = 0.011). Three days after treatment, the markedly effective rate of TCM symptoms in the low dose JHG group was 66.7%, higher than that of the placebo control group (38.3%), and its effective rate was superior to that of the high dose JHG group (P = 0.043). Five days after treatment, the recovery rate of the low dose JHG group (42.2%) was higher than that of the high dose JHG group (25.0%, P = 0.026) and that of the placebo control group (14.9%, P = 0.002). The markedly effective rate of the low dose JHG group (86.7%) was higher than that of the placebo control group (55.3%, P = 0.001). Similar effects were obtained in the low dose JHG group and the high dose JHG group, but slightly poor in partial indicators of the high dose JHG group. There was no statistical difference in adverse reaction among these three groups (P > 0.05).</p><p><b>CONCLUSIONS</b>JHG was effective and safe in treating influenza patients of WHAFS. Routinely low dose was the optimal dosage of JHG.</p>
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Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Método Duplo-Cego , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Influenza Humana , Diagnóstico , Tratamento Farmacológico , Medicina Tradicional Chinesa , FitoterapiaRESUMO
AimTo compare the protective immunity against challenge infection in mice immunized by crude antigen preparations derived from adult worms, newborn larvae and musele larvae of T richinella spiralis. MethodIntestinal adult worms, muscle larvae and blood absolute eosinophil level were counted; the level of serum IgG to antigens of T. spiralis muscle larvae was detected by ELISA. ResultsAdults reduimg rate was 82.19 %, 72.31% and 42.88 % in the adult, newborn larvae and muscle larvae antigen groups respectively. Muscle larvae were reduced 68.83%. 78.19% and 51.96% respectively. The serum IgG titer in all immunized groups increased significantly, the GMRT values of adult, newborn larvae and mudscle larval antigen groups were 7.46, 5.28and 4.92times higher than that in control group respectively. Periphery blood absolute eosinophil level enhanced significantly. ConclusionThe data demonstrate that all of the adult, newborn larvae and muscle larvae antigens of T. spiralis can activate specific humoral and cellular immunity which induce protection to challenge infection in mice. Among these antigens, adult and newborn larvae antigens show better immunogenicity and it may be possible that adult antigen will provide a potential vaccine for trichinosis.