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2.
Artigo em Chinês | MEDLINE | ID: mdl-37150993

RESUMO

Objective: To summarize clinical features and our experience of the diagnosis and treatment of laryngocele. Methods: Clinical data of 11 laryngocele patients in department of Otorhinolaryngology Head and Neck Surgery of the Second Affiliated Hospital of Shanxi Medical University from January 2012 to December 2021 were retrospectively reviewed, including 9 men and 2 women, aged from 12 to 75 years, with median age of 56 years. Electronic laryngoscope was performed in 10 of all patients, laryngeal CT in 10 and cervical color ultrasound in 5 before operation.All the operations were performed under general anesthesia, and the external cervical approach was used for external and combined laryngocele. The internal laryngocele was resected by low temperature plasma through transoral endoscopy. Patients were followed up regularly after operation to evaluate the effect. Clinical feature, types of lesions, imaging findings, surgical approaches and follow-up results were analyzed through descriptive statistical method. Results: Eleven laryngocele patients were divided into mixed type (n=6), internal type (n=4) and external type (n=1).Nine patients presented with hoarseness or dysphonia, 7 with cervical mass and 1 with airway obstruction. Surgical resections were done through external cervical approach (n=7)or transoral endoscopic approach (n=4). All the operations were successful and no complication occurred. All cases were followed up from 17 to 110 months. No recurrence was encountered. Conclusions: Laryngocele is a rare lesion with atypical clinical presentation. Preoperative imaging including CT scan and electronic laryngoscope is essential to evaluate the location, and extent of the lesion, and to make the surgical plan.Complete surgical excision is required. Surgical resection is the only effective method for the treatment of laryngocele.


Assuntos
Laringocele , Laringe , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Criança , Adolescente , Adulto Jovem , Adulto , Idoso , Laringocele/cirurgia , Laringocele/complicações , Laringocele/patologia , Estudos Retrospectivos , Laringe/cirurgia , Laringe/patologia , Laringoscopia/métodos , Rouquidão
3.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 57(11): 1334-1338, 2022 Nov 07.
Artigo em Chinês | MEDLINE | ID: mdl-36404660

RESUMO

Objective: To investigate the clinical and pathological features, treatments and prognosis of laryngeal neuroendocrine carcinoma (LNEC). Methods: We conducted the retrospective analysis of the clinical data of 12 patients with LNEC admitted to the Department of Otorhinolaryngology Head and Neck Surgery, Second Hospital of Shanxi Medical University from May 2014 to December 2021, including 9 males and 3 females, aged 50-77 years. There were 4 cases of typical carcinoid tumour (highly differentiated), 5 cases of atypical carcinoid tumour (moderately differentiated) and 3 cases of neuroendocrine small cell carcinoma (hypofractionated). The clinical features, diagnosis, treatment and prognosis of LNEC were analysed. Results: The clinical manifestations of LNEC varied according to the tumour type but did not correlate with the pathological types. The supraglottic type was characterized by sore throat, foreign body sensation in the pharynx, coughing, obstructive sensation when eating and choking on water. The treatments were determined according to the pathological types, lesion location and invasion scope. Of 12 patients 4 underwent horizontal partial laryngectomy plus elective lymphatic dissection plus postoperative radiotherapy/chemotherapy, 4 underwent vertical partial laryngectomy (3 of them with cervical lymphatic dissection), 3 underwent supported laryngoscopic plasma laryngectomy for laryngeal cancer, and 1 abandoned for treatment. With the follow-up of 8 -78 months, 5 patients were alive, 1 died from chemotherapy reactions, 3 died from other diseases, 1 died from lung metastasis, 1 died from lung infection and 1 was lost to follow-up. Conclusion: LNEC is clinically rare, the clinical manifestations are less specificity, diagnosis relies on pathological and immunohistochemical examinations, and treatment modalities and prognoses are closely related to the pathological subtypes of LNEC.


Assuntos
Tumor Carcinoide , Carcinoma Neuroendócrino , Neoplasias Laríngeas , Humanos , Masculino , Feminino , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/patologia , Estudos Retrospectivos , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Carcinoma Neuroendócrino/patologia , Laringectomia , Tumor Carcinoide/patologia
6.
Artigo em Chinês | MEDLINE | ID: mdl-30970404

RESUMO

Objective:The study aimed to investigate the efficacy of sublingual immunotherapy(SLIT) in treatment of adult allergic rhinitis, and to explore the predictive role of baseline serum cytokine levels in its therapeutic effect.Method:Sixty patients with moderatesevere perennial AR sensitized with house dust mites were treated for 2 years. The SLIT group(n=30) were treated with standardized dust mite vaccine SLIT and conventional drugs, and the control group(n=30) were treated with placebo and conventional drugs. The combined symptom and medication score(CSMS) were compared between the two groups to evaluate the efficacy at baseline and 2 year endpoint. According to therapeutic effect, the SLIT group and the control group were divided into subgroups respectively, and the baseline IFN-γ and IL4, IL10, IL17 levels were compared between the effective group and the ineffective group in each group. The ROC curve was drawn to find the best predictive index and the best cut-off value was calculated. Result:①There was no significant difference between the SLIT group and the control group at baseline CSMS(P>0.05). There was significant difference between the two groups at 2year endpoint CSMS(P<0.05). ②In the SLIT group, there was no significant difference between the effective group and the ineffective group with the IFN-γ and IL17(P>0.05). The IL4 level in the effective group was significantly higher than the ineffective group while the IL10 level was significantly lower(P<0.05). In the control group, there were no significant differences in the levels of IFN-γ, IL4, IL10 and IL17 between the two subgroups(P>0.05). ③Baseline IL4/IL10 has higher predictive value than IL4 and IL10 alone. The best cut-off value is 2.04, and the sensitivity and specificity of predictive value were 72.7% and 73.7% respectively. Conclusion: SLIT combined with conventional drug therapy is more effective than conventional drug therapy alone. IL4/IL10 has a better predictive role in SLIT effect than IL4 or IL10 alone. The higher the ratio, the better therapeutic effect is.


Assuntos
Antígenos de Dermatophagoides , Rinite Alérgica , Imunoterapia Sublingual , Administração Sublingual , Adulto , Animais , Citocinas , Humanos , Pyroglyphidae , Rinite Alérgica/terapia , Resultado do Tratamento
7.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 32(19): 1455-1458, 2018 Oct 05.
Artigo em Chinês | MEDLINE | ID: mdl-30550186

RESUMO

Objective: To explore the clinical efficacy of unilateral vidian neurectomy following endoscopic trans-sphenoethmoidal recess approach in treating allergic rhinitis.Method: The clinical data of 80 patients with moderate-severe allergic rhinitis who underwent unilateral vidian neurectomy following endoscopic trans-sphenoethmoidal recess approach were reviewed retrospectively. Visual analogue scale(VAS) was used to assess total symptom scores and nasal symptoms including nasal itching, nasal sneezing, rhinorrhea and nasal congestion. The paired T test was used to compare the scores between surgical side and control side. Twenty-four patients with 3 years of follow-up were assessed by analysis of variance with comparison of means between multiple groups. Further comparison between any two means was performed by LSD-t test. Result: A total of 80 patients were followed up for one year, with 51 patients for two years and 24 patients for three years. Among 24 patients, total symptom scores and nasal symptoms (nasal itching, nasal sneezing, rhinorrhea and nasal congestion) at pre-operation, 1 year,2 year and 3 year after operation were compared between surgical side and control side. There was no significant difference by the paired T test(P>0.05),but there was statically significant by analysis of variance(P<0.05) .The analysis of LSD-t test showed significant differences between pre-operative time point and each of the three time points after operation (P<0.05). Conclusion:The unilateral vidian neurectomy following endoscopic trans-sphenoethmoidal recess approach is an safe and effective technique in the management of moderate severe allergic rhinitis,and unilateral surgery could relieve bilateral nasal symptoms.

8.
Artigo em Chinês | MEDLINE | ID: mdl-30400703

RESUMO

Objective:The aim of this study is to explore an improved trans-nasal endoscopic surgical approach for vidian neurectomy. Method:Ninety-one patients with nasal hyperreactive disease were collected, including 49 cases of allergic rhinitis and 42 cases of non allergic rhinitis. All sufferers enrolled in the study have treated with medicine, but the symptoms were not effectively controlled. Preoperative CT localization of the vidian canal was performed in each candidate. During the surgery a"Three-step" surgical approach were followed under endoscopic guidance in accordance with the operation procedures. Briefly, such a three-step procedure consists of the following, that is, a transnasal endoscopic sphenoidectomy through sphenoethmoidal recess as step one, with enlargement of the sinus ostium along the junction of the anterior wall and the floor of the sinus until the exposure of the vidian nerve canal toward the lateral wall of the sinus as step two. The last step was further exposure of the vidian nerve going through the canal and electric cautery preventing bleeding from the neurovascular bundle in the canal. Result:All patients were completed successfully with 100% preoperative CT location of the vidian canal in the CT scan and 100% intraoperative accurate exposure of the canal and therefore the cut of the vidian nerve. Conclusion:"Three-step" endoscopic resection of the vidian neurectomy is easy to master and repetitive with less injury.

9.
Nanoscale ; 10(12): 5642-5649, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29528344

RESUMO

For obtaining high-resolution macroscopical anatomical information and high sensitivity microscopical optical signals, it is highly desirable to develop dual-modality magnetic resonance imaging (MRI) and fluorescent probes in medical imaging simultaneously. In this study, Gd2O3 nanoparticles were modified with two-photon graphene quantum dots (GQD), integrating a magnetic resonance imaging (MRI) contrast agent with two-photon imaging functionality into one nanoprobe. A photoluminescence study indicated that the GQD modification process integrated MRI properties with both one-photon and two-photon imaging properties. Gd2O3/GQD nanocomposites showed a significantly improved longitudinal relaxivity (r1 = 15.995 mM-1 s-1) in comparison with commercial Magnevist (Gd-DTPA, r1 = 4.5 mM-1 s-1) and some reported papers. Excellent water solubility and good biocompatibility make Gd2O3/GQD nanocomposites an ideal dual-modal imaging agent, suggesting their potential and significant biological and clinical applications in the future.


Assuntos
Meios de Contraste , Gadolínio , Grafite , Imageamento por Ressonância Magnética , Nanocompostos , Pontos Quânticos , Humanos , Células MCF-7 , Fótons
10.
Allergy ; 72(11): 1704-1712, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28426164

RESUMO

BACKGROUND AND AIMS: The function of interleukin (IL)-10-producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immunoregulatory functions. This study aimed to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells. METHODS: Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2-like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed. RESULTS: We observed that the expression of IL-10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10 expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12-shRNA-carrying liposomes reversed the capability of IL-10 expression and the immunosuppressive function. Administration of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice. CONCLUSIONS: Activation of PAR2 inhibits the expression of IL-10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment for AR.


Assuntos
Linfócitos B/metabolismo , Interleucina-10/metabolismo , Proteínas Musculares/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptor PAR-2/fisiologia , Rinite Alérgica/metabolismo , Regulação para Cima , Animais , Linfócitos B/enzimologia , Humanos , Camundongos , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Rinite Alérgica/genética
12.
Artigo em Chinês | MEDLINE | ID: mdl-29871274

RESUMO

Recently, the role of staphylococcus aureus (s. aureus) in the pathogenesis of refractory rhinosinusitis (RRS) has gradually been elucidated. Studies have shown that intracellular s. aureus, s. aureus biofilm and s. aureus superantigens are the key factors in the mechanisms of staphylococcus aureus induced RRS. Therefore, in this article, we emphatically reviewed these three aspects of s. aureus, hoping to provide a clue in the clinical treatments of RRS and the future research in the field.


Assuntos
Biofilmes/crescimento & desenvolvimento , Rinite/imunologia , Sinusite/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/patogenicidade , Doença Crônica , Humanos , Staphylococcus aureus/imunologia , Superantígenos/imunologia
13.
Proc Math Phys Eng Sci ; 471(2177): 20140832, 2015 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-27547091

RESUMO

In this paper, a self-consistent plasticity theory is proposed to model the mechanical behaviours of irradiated face-centred cubic nanocrystalline metals. At the grain level, a tensorial crystal model with both irradiation and grain size effects is applied for the grain interior (GI), whereas both grain boundary (GB) sliding with irradiation effect and GB diffusion are considered in modelling the behaviours of GBs. The elastic-viscoplastic self-consistent method with considering grain size distribution is developed to transit the microscopic behaviour of individual grains to the macroscopic properties of nanocrystals (NCs). The proposed theory is applied to model the mechanical properties of irradiated NC copper, and the feasibility and efficiency have been validated by comparing with experimental data. Numerical results show that: (i) irradiation-induced defects can lead to irradiation hardening in the GIs, but the hardening effect decreases with the grain size due to the increasing absorption of defects by GBs. Meanwhile, the absorbed defects would make the GBs softer than the unirradiated case. (ii) There exists a critical grain size for irradiated NC metals, which separates the grain size into the irradiation hardening dominant region (above the critical size) and irradiation softening dominant region (below the critical size). (iii) The distribution of grain size has a significant influence on the mechanical behaviours of both irradiated and unirradiated NCs. The proposed model can offer a valid theoretical foundation to study the irradiation effect on NC materials.

14.
Mutat Res ; 751-752: 24-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24064032

RESUMO

Screening and nurturing algae with high productivity, high lipid content and strong stress resistance are very important in algae industry. In order to increase the lipid content, the Nitzschia sp. was irradiated with a 3MeV C(2+) beam. The sample pretreatment method was optimized to obtain the best mutagenic condition and the survival ratio curve. The positive mutants with a significant improvement in lipid content were screened and their C(2+) mutagenic effects were analyzed by comparing the greasiness and growth characteristics with the wild type algae. Results showed that when the Nitzschia sp. was cultivated in nutritious medium containing 10% glycerol solution, and dried on the filter for 5 min after centrifugation, the realization of the microalgae heavy ion mutagenesis could be done. The survival ratio curve caused by C(2+) irradiation was proved to be "saddle-shaped". A positive mutant was screened among 20 survivals after irradiation, the average lipid content of the mutation increased by 9.8% than the wild type after 4 generations. But the growth rate of the screened mutation didn't change after the heavy ion implantation compared to the wild type algae.


Assuntos
Carbono , Microalgas/genética , Microalgas/efeitos da radiação , Mutação , Diatomáceas/genética , Diatomáceas/efeitos da radiação , Íons , Metabolismo dos Lipídeos/efeitos da radiação , Microalgas/crescimento & desenvolvimento
15.
Nat Commun ; 3: 727, 2012 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-22395618

RESUMO

The ferromagnetism in many carbon nanostructures is attributed to carbon dangling bonds or vacancies. This provides opportunities to develop new functional materials, such as molecular and polymeric ferromagnets and organic spintronic materials, without magnetic elements (for example, 3d and 4f metals). Here we report the observation of room temperature ferromagnetism in Teflon tape (polytetrafluoroethylene) subjected to simple mechanical stretching, cutting or heating. First-principles calculations indicate that the room temperature ferromagnetism originates from carbon dangling bonds and strong ferromagnetic coupling between them. Room temperature ferromagnetism has also been successfully realized in another polymer, polyethylene, through cutting and stretching. Our findings suggest that ferromagnetism due to networks of carbon dangling bonds can arise in polymers and carbon-based molecular materials.


Assuntos
Fenômenos Magnéticos , Nanotubos de Carbono , Politetrafluoretileno/química , Estresse Mecânico , Carbono/química , Ferro , Magnetismo , Imãs , Nanoestruturas/química , Nanotecnologia , Polietileno/química , Polímeros , Propriedades de Superfície , Temperatura
16.
Int J Radiat Biol ; 83(5): 301-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17457755

RESUMO

PURPOSE: To investigate the biological effects of radiation damage induced at different depths of a plant seed and to investigate the difference in radiation response between dry seeds and water-imbibed seeds to the same type of radiation. MATERIALS AND METHODS: Arabidopsis seeds of the wild-type Columbia ecotype were used in our experiments. Dry or water-imbibed Arabidopsis seeds were irradiated with 1.1 MeV, 2.6 MeV or 6.5 MeV protons (H+). For comparison, 30 keV nitrogen ions (N+) were also used to irradiate dry Arabidopsis seeds. The germination and survival rates of the seeds were measured after each irradiation. RESULTS: After irradiation with 2.6 MeV H+ and 6.5 MeV H+, the fluence-response curves for germination and survival had distinct shoulders and then survival was reduced rapidly with increasing fluence. 2.6 MeV H+ was more effective than 6.5 MeV H+ in inhibiting germination and survival and water-imbibed seeds were more sensitive to the 6.5 MeV H+ irradiation than dry seeds. For 1.1 MeV H+ the germination and survival rates were reduced gradually and an intermediate plateau emerged for germination, which was similar to that observed for survival following 30 keV N+ irradiation. One of the key morphologic malformations, the multi-SAM (shoot apical meristem), was observed both for dry and water-imbibed seeds after all proton irradiations and for the dry seeds after 30 keV N+ irradiation. CONCLUSIONS: Radiation-induced damage produced at different ranges in Arabidopsis seeds results in different fluence-response curves with water-imbibed seeds being more sensitive to proton irradiation than dry seeds. As well as the shoot apical meristem (SAM) being the primary target for irradiation, there exists a secondary target around the SAM that also contributes to the radiation response.


Assuntos
Arabidopsis/efeitos da radiação , Prótons , Sementes/efeitos da radiação , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Relação Dose-Resposta à Radiação , Germinação/efeitos da radiação , Íons Pesados , Transferência Linear de Energia , Nitrogênio , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Análise de Sobrevida , Água/metabolismo
17.
J Biomed Mater Res B Appl Biomater ; 78(2): 417-22, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16470829

RESUMO

Single and double layered composite microspheres were prepared by encapsulating gentamicin-loaded silica xerogels with biodegradable PLGA polymers (poly(DL-lactide-co-glycolide)). The in vitro drug release properties of both the composite microspheres were investigated. The single layered composite microspheres showed a high initial burst, followed by two sustained release stages lasting for approximately 6 weeks. The two sustained release stages of the single layered composite microspheres could be attributed to the swelling and bulk erosion of the polymer encapsulations, respectively. In comparison with the single layered composite microspheres, the double layered composite microspheres realized a much reduced initial burst together with three sustained release stages. The whole release period of the double layered composite microspheres could last more than 9 weeks. These distinct behaviors make the double layered composite microspheres promising as a new drug release material for localized drug delivery applications.


Assuntos
Materiais Biocompatíveis/química , Gentamicinas/química , Microesferas , Dióxido de Silício/química , Biodegradação Ambiental , Preparações de Ação Retardada/química , Estabilidade de Medicamentos , Géis/química , Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros
18.
Med Mycol ; 42(3): 189-216, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15283234

RESUMO

Coccidioides is a fungal pathogen of humans which can cause a life-threatening respiratory disease in immunocompetent individuals. Recurrent epidemics of coccidioidal infections in Southwestern United States has raised the specter of awareness of this soil-borne microbe, particularly among residents of Arizona and Southern California, and has galvanized research efforts to develop a human vaccine against coccidioidomycosis. In this review, we discuss the rationale for such a vaccine, examine the features of host innate and acquired immune response to Coccidioides infection, describe strategies used to identify and evaluate vaccine candidates, and provide an update on progress toward development of a vaccine against this endemic pathogen.


Assuntos
Coccidioides/imunologia , Coccidioidomicose/imunologia , Coccidioidomicose/prevenção & controle , Vacinas Fúngicas , Animais , Coccidioides/genética , Coccidioides/patogenicidade , Coccidioidomicose/epidemiologia , Coccidioidomicose/microbiologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Vacinas Fúngicas/imunologia , Humanos , Camundongos , Vacinação , Vacinas Atenuadas/imunologia
19.
J Control Release ; 98(2): 209-17, 2004 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-15262413

RESUMO

In this paper, we report a poly(D,L-lactide-co-glycolide) (PLGA)/mesoporous silica hybrid structure (PS hybrid structure), which was synthesized via a novel sol-gel route assisted by single emulsion solvent evaporation. The in intro drug release properties of both the mesoporous silica and the PS hybrid structure were investigated. It was observed that gentamicin-loaded mesoporous silica showed a sharp initial burst during the first day followed by a rather constant and low release over the subsequent period of 3 weeks. In comparison with the mesoporous silica without biodegradable polymer encapsulation, the PS hybrid structure could realize a reduced initial burst, with a plateau stage for nearly 3 weeks of slow release, followed by a sustained release stage lasting for nearly 2 weeks. The whole release period could last as long as 5 weeks. These distinct behaviors make the hybrid structure material promising as a new drug release material for bone filling applications.


Assuntos
Preparações de Ação Retardada/química , Ácido Láctico/química , Ácido Poliglicólico/química , Polímeros/química , Dióxido de Silício/química , Disponibilidade Biológica , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Gentamicinas/administração & dosagem , Gentamicinas/farmacocinética , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Microscopia de Polarização , Microesferas , Peso Molecular , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Silanos/química
20.
Theor Appl Genet ; 92(8): 1099-102, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24166642

RESUMO

Nine cytoplasmic male-sterile lines and five restorer lines were used in an incomplete diallel cross to analyze seed effects, cytoplasmic effects, and maternal gene effects on nutrient quality traits of indica rice (Oryza sauva L.). The results indicated that nutrient quality traits were controlled by cytoplasmic and maternal effects as well as by seed direct effects. Maternal effects for lysine content (LC), lysine index (LI), and the ratio of lysine content to protein content (RLP) were more important than seed direct effects, while protein content (PC) and protein index (PI) were mainly affected by seed direct effects. Cytoplasmic effects accounted for 2.41-20.80% of the total genetic variation and were significant for all nutrient quality traits. Additive genetic effects were much more important than dominance effects for all of the traits studied, so that selection could be applied for these traits in early generations.

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