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1.
Front Pediatr ; 12: 1409046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774298

RESUMO

Purpose: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis. Patients & methods: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model. Results: A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908). Conclusion: We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis.

2.
Proc Biol Sci ; 290(1990): 20221658, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629113

RESUMO

Human-induced biodiversity loss negatively affects ecosystem function, but the interactive effects of biodiversity change across trophic levels remain insufficiently understood. We sampled arboreal spiders and lepidopteran larvae across seasons in 2 years in a subtropical tree diversity experiment, and then disentangled the links between tree diversity and arthropod predator diversity by deconstructing the pathways among multiple components of diversity (taxonomic, phylogenetic and functional) with structural equation models. We found that herbivores were major mediators of plant species richness effects on abundance, species richness, functional and phylogenetic diversity of predators, while phylogenetic, functional and structural diversity of trees were also important mediators of this process. However, the strength and direction differed between functional, structural and phylogenetic diversity effects, indicating different underlying mechanisms for predator community assembly. Abundance and multiple diversity components of predators were consistently affected by tree functional diversity, indicating that the variation in structure and environment caused by plant functional composition might play key roles in predator community assembly. Our study highlights the importance of an integrated approach based on multiple biodiversity components in understanding the consequences of biodiversity loss in multitrophic communities.


Assuntos
Artrópodes , Aranhas , Animais , Humanos , Ecossistema , Filogenia , Biodiversidade , Plantas
3.
J Anim Ecol ; 92(2): 442-453, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36507573

RESUMO

Global biodiversity decline and its cascading effects through trophic interactions pose a severe threat to human society. Establishing the impacts of biodiversity decline requires a more thorough understanding of multi-trophic interactions and, more specifically, the effects that loss of diversity in primary producers has on multi-trophic community assembly. Within a synthetic conceptual framework for multi-trophic beta-diversity, we tested a series of hypotheses on neutral and niche-based bottom-up processes in assembling herbivore and carnivore communities in a subtropical forest using linear models, hieratical variance partitioning based on linear mixed-effects models (LMMs) and simulation. We found that the observed taxonomic, phylogenetic and functional beta-diversity of both herbivorous caterpillars and carnivorous spiders were significantly and positively related to tree dissimilarity. Linear models and variance partitioning for LMMs jointly suggested that as a result of bottom-up effects, producer dissimilarities were predominant in structuring consumer dissimilarity, the strength of which highly depended on the trophic dependencies on producers, the diversity facet examined, and data quality. Importantly, linear models for standardized beta-diversities against producer dissimilarities implied a transition between niche-based processes such as environmental filtering and competitive exclusion, which supports the role of bottom-up effect in determining consumer community assembly. These findings enrich our mechanistic understanding of the 'Diversity Begets Diversity' hypothesis and the complexity of higher-trophic community assembly, which is fundamental for sustainable biodiversity conservation and ecosystem management.


Assuntos
Ecossistema , Herbivoria , Humanos , Animais , Filogenia , Biodiversidade , Florestas
4.
BMC Cancer ; 22(1): 919, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008784

RESUMO

OBJECTIVES: There are increasing numbers of studies of pleural tags (PTs). The purpose of this case series was to classify the PTs in patients with peripheral pulmonary adenocarcinoma based on radiologic-pathologic comparison and to study the prognosis. METHODS: The clinical, imaging, pathological and prognostic data of 161 patients with peripheral pulmonary adenocarcinoma in three hospitals were analyzed retrospectively. We classified PTs using computed tomography (CT) for pathologic comparison. RESULTS: According to the relationship between tumors and pleural on CT images, PTs were classified into four types: type 1, one or more linear pleural tag; type 2, one or more linear pleural tag with soft tissue component at the pleural end; type 3, one soft tissue cord-like pleural tag; type 4, directly abutting the visceral pleura, pulling or pushing the visceral pleura. In these PTs, the incidence of visceral pleural invasion (VPI) was high in type 2 (46.88%) and type 3 (56.41%) of PTs. Our prognostic analysis showed that micropapillary or solid histological subtype (HR = 5.766, 95% CI: 1.435-23.159, P = 0.014) and type 3 of PTs (HR = 11.058, 95% CI: 1.349-90.623, P = 0.025) were two independent risk factors for tumor progression. CONCLUSIONS: PT is a risk factor for poor prognosis in patients with peripheral pulmonary adenocarcinoma, the presence of which on CT images can remind us to provide patients with a more reasonable treatment.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Pleura/diagnóstico por imagem , Pleura/patologia , Prognóstico , Estudos Retrospectivos
5.
ANZ J Surg ; 91(7-8): 1485-1490, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33908173

RESUMO

BACKGROUND: To determine risk factors for intestinal necrosis in intussusception cases among children with failed non-surgical reduction for intussusception. METHODS: Totally, 540 hospitalized individuals with unsuccessful air-enema reduction in our hospital between November 2010 and November 2020 were assessed in this retrospective study. The 540 intussusception cases were divided into the intestinal necrosis and non-intestinal necrosis groups. Haemostatic parameters, demographic and clinical features were assessed. Predictors of intestinal necrosis were examined by univariable and multivariable logistic regression analyses. RESULTS: Of the 540 patients included, 113 showed intestinal necrosis. This intestinal necrosis group had a longer duration of symptom or length of illness, younger ages, higher platelet counts, fibrinogen amounts and d-dimer levels (all P = 0.000) compared with the non-intestinal necrosis group. Multivariable analysis revealed that duration of symptom (odds ratio (OR) 1.12; 95% confidence interval (CI) 1.16-1.23, P = 0.000), fibrinogen (OR 1.26; 95% CI 1.10-1.31, P = 0.010) and d-dimer (OR 2.07; 95% CI 1.91-2.28, P = 0.000) independently predicted intestinal necrosis in individuals undergoing surgical reduction for intussusception. Receiver operating characteristic curve analysis showed that d-dimer amounts had the largest area under the curve for predicting intestinal necrosis. CONCLUSION: On admission, long duration of symptom, high fibrinogen and d-dimer levels are critical risk factors for intestinal necrosis development in children with unsuccessful non-surgical reduction. d-Dimer levels have the best predictive value for intestinal necrosis.


Assuntos
Hemostáticos , Intussuscepção , Criança , Enema , Humanos , Lactente , Intussuscepção/diagnóstico , Intussuscepção/cirurgia , Necrose , Estudos Retrospectivos
6.
J Cell Physiol ; 235(9): 6307-6320, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037568

RESUMO

Long noncoding RNA colon cancer-associated transcript 2 (CCAT2) has been recently found to function as an oncogene in hepatocellular carcinoma (HCC). However, the mechanisms of CCAT2 in HCC development remain to be further explored. In the present study, we found that CCAT2 was abnormally upregulated in HCC cells and tissue specimens, exhibiting an inverse correlation with microRNA (miR)-145 expression. Mechanistic investigation showed that CCAT2 selectively blocked miR-145 processing, leading to decreased mature miR-145 presence. Both the in vitro and in vivo effects of CCAT2 knockdown on the proliferation and metastasis of HCC cells were reversed by miR-145 inhibitor, indicating that miR-145 modulation accounts for CCAT2-meditated HCC progression. Furthermore, miR-145 mimic dramatically suppressed HCC cells' proliferation and metastasis, revealing a tumor suppressor role of miR-145 in HCC. Mechanistically, MDM2 was predicted to be a potential target of miR-145. The luciferase and western blot assay demonstrated that miR-145 mimic largely inhibited MDM2 3'-untranslated region luciferase activity and MDM2 expression, followed by the upregulation of p53/p21 expression. Finally, the coexpression of MDM2 in miR-145 mimic-transfected HCC cells was able to largely compromise the inhibitory effects of miR-145 mimic on HCC cells' proliferation and metastasis in vitro and tumor formation in a xenograft model, confirming MDM2 is the critical mediator of miR-145 in HCC. In summary, our findings indicated that CCAT2 selectively blocks the miR-145 maturation process and plays an oncogene in HCC. Furthermore, a novel CCAT2/miR-145/MDM2 axis was revealed in HCC development and might provide a new target in the molecular treatment of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , RNA Longo não Codificante/genética , Animais , Apoptose/genética , Carcinoma Hepatocelular/patologia , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Xenoenxertos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos
7.
J Gastrointest Surg ; 23(11): 2255-2262, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30859429

RESUMO

BACKGROUND: Intussusception is among the most common acute abdominal emergencies in infancy, but only some cases need surgical reduction. This study assessed the clinical characteristics of patients undergoing surgical reduction of intussusception. METHODS: This retrospective study reviewed 568 pediatric patients who failed air-enema reduction and underwent surgical reduction for intussusception in our department between 2008 and 2017. RESULTS: The series comprised 376 boys and 192 girls (2.0:1, male:female ratio) and most of the intussusceptions were primary, which is typical before the age of 1 year. The success rate of air-enema reduction in our hospital was 94.2%. Patients over 3 years old had the highest rate of surgical reduction (ca. 11.8%). The probabilities of primary and secondary intussusception were equal above 2 years old. Intussusception caused by intestinal malignant lymphoma was diagnosed above 2 years of age with atypical symptoms. Gender was irrelevant regarding the presence of bloody stools (P = 0.594), but the younger patients and children with complex/compound intussusception had a higher proportion of bloody stools (n = 148, 40.0%, P = 0.000) and intestinal necrosis (n = 44, 42.3%, P = 0.024). The occurrence time of bloody stools (OTBS) in complex/compound intussusception was shorter than for other types. CONCLUSIONS: This retrospective study analyzed the clinical features of patients undergoing surgical reduction for intussusception and summarized the characteristics and management of complex/compound intussusception.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Emergências , Intestino Delgado/cirurgia , Intussuscepção/cirurgia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do Tratamento
8.
Cell Physiol Biochem ; 49(3): 1097-1109, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30196284

RESUMO

BACKGROUND/AIMS: Transforming growth factor beta-induced protein (TGFBI) is an extracellular matrix protein induced by TGF-ß. Previous studies have reported that the abnormal expression of TGFBI is related to the occurrence and development of some types of cancers, while the role of TGFBI in glioma is uncertain. METHODS: The association between TGFBI expression and the prognosis of patients with glioma was analyzed based on data obtained from The Cancer Genome Atlas database. TGFBI expression was analyzed in 3 normal human brains and 57 cases of human gliomas by immunohistochemistry followed by an evaluation of the relationships between TGFBI expression and clinic-pathological features. Furthermore, the RNA interference plasmid pSUPER-shTGFBI was constructed and transfected into U87 and U251 cells to explore the effect of short hairpin RNA against TGFBI (shTGFBI) on cell proliferation, migration, invasion and apoptosis. Western blot analysis was performed to examine the expression of proteins related to apoptosis and proteins in the PI3K/Akt signaling pathway. RESULTS: High TGFBI expression was found to be associated with poor prognosis in patients with glioblastoma multiforme. Immunohistochemistry showed that TGFBI expression was significantly higher in glioma tissue than in normal human brain tissues. The expression level of TGFBI showed no significant correlation with age, sex, lymph-node metastasis, or pathological grade. sh-TGFBI could inhibit proliferation, invasion and migration and induce apoptosis in U87 and U251 cells in vitro. Furthermore, the phosphorylation levels of AKT and mTOR declined significantly in sh-TGFBI transfected U81 and U251 cells when compared with control. CONCLUSION: TGFBI was up-regulated in glioma cells and played a promoting role in the growth and motility of U87 and U251 cells. These results suggested that TGFBI has the potential to be a diagnostic marker and to serve as a target for the treatment of gliomas.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Fator de Crescimento Transformador beta1/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Linhagem Celular , Movimento Celular , Proliferação de Células , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Glioma/metabolismo , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/genética , Proteína X Associada a bcl-2/metabolismo
9.
Biomed Pharmacother ; 97: 886-894, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29136765

RESUMO

Treatments for osteoarthritis (OA) seek to restore chondrocyte function and inhibit cell apoptosis. Panax quinquefolium saponin (PQS) is the major active ingredient of Radix panacis quinquefolii (American ginseng), and has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in various diseases. However, any potential effect of PQS on the pathological process of OA remains unclear. This work aimed to explore the role of PQS in chondrocytes and to clarify its potential mechanisms. We showed that PQS treatment could protect chondrocytes against endoplasmic reticulum (ER) stress and associated apoptosis induced by interleukin (IL)-1ß. Also, PQS further attenuated triglyceride (TG)-induced ER stress and associated apoptosis. Moreover, PQS may inhibit the ER stress-activated NF-κB pathway and associated inflammatory response in chondrocytes. Finally, PQS abolished rat cartilage degeneration in an in-vivo OA model of the knee joint. Our results indicate that PQS may be a potential novel treatment for OA.


Assuntos
Artrite Experimental/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Saponinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Artrite Experimental/fisiopatologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Progressão da Doença , Inflamação/tratamento farmacológico , Inflamação/patologia , Interleucina-1beta/metabolismo , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Osteoartrite/fisiopatologia , Ratos , Ratos Sprague-Dawley
10.
Med Sci Monit ; 23: 2284-2291, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28502974

RESUMO

BACKGROUND This study aimed to compare the efficacy and prognostic value of partial sensory rhizotomy (PSR) and microvascular decompression (MVD) for primary trigeminal neuralgia (PTN). MATERIAL AND METHODS From June 2010 to June 2012, 117 patients with PTN were recruited for the study, of which 52 cases were treated with MVD (the MVD group) and 65 cases were treated with PSR (the PSR group). Visual Analog Scoring (VAS) was performed at 1 and 2 weeks, and at 1, 3, and 6 month after surgery. The overall response rate (ORR) was determined 1 month after surgery. Barrow Neurological Institute score was adopted to value the reoccurrence at 6, 12, 24, and 36 months after surgery. A 3-year follow-up was conducted and the complications were recorded. RESULTS The ORR 2 weeks after surgery in the MVD and PSR groups was 98.08% and 84.62%, respectively. One and 2 weeks after surgery, the VAS was lower in the MVD group than in the PSR group, but there was no significant difference in VAS between the 2 groups at 1, 3, and 6 months after surgery. Three years after surgery, the recurrence rate was significantly lower in the MVD group than in the PSR group. The recurrence-free survival time was longer in the MVD group than in the PSR group. The occurrence rates of herpes and total postoperative complications were significantly higher in the PSR group than in the MVD group. CONCLUSIONS Compared with PSR, MVD is more suitable for PTN treatment, with less disturbance, lower recurrence rate, and better efficacy.


Assuntos
Cirurgia de Descompressão Microvascular/efeitos adversos , Rizotomia/efeitos adversos , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Feminino , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Prognóstico , Recidiva , Resultado do Tratamento , Escala Visual Analógica
11.
Lipids Health Dis ; 16(1): 62, 2017 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-28335773

RESUMO

BACKGROUND: Propionic acid is a three-carbon short chain fatty acid (SCFA) that has various effects on colonic functions. Although several studies have shown the effects of propionic acid on intestinal mucosal barrier function, studies of the promotion effect during pre-weaning are rare in the literature as far as we know. METHODS: Pre-weaning male Sprague-Dawley rats 7 days after birth were given an oral 0.2 mL/10 g of 200 mM propionic acid solution in the propionic acid group or normal saline solution in the control group by gavage twice a day for ten days. The proximal colonic contents were used for extraction and determination of propionic acid by gas chromatographic analysis; the transepithelial electrical resistance (TER) of colonic tissue was detected by an Ussing chamber; the alterations of ZO-1, Claudin-1, Claudin-8 and Occludin proteins were analyzed by Western blot and immunohistochemistry; and The activity of ERK and p38 MAPK was determined by the phosphorylation status of ERK1/2 and p38 with Western blot. RESULTS: Our results suggested a higher concentration (23.5 ± 1.9 mmol/kg) of propionic acid compared to the physiological concentration (18.1 ± 0.9 mmol/kg) in colonic contents after oral administration increased the value of TER and the expression of ZO-1, Claudin-1, Claudin-8 and Occludin compared to the control group. Furthermore, the expression levels of phosphorylated ERK1/2 and p38 MAPK were increased in propionic acid group. CONCLUSIONS: We concluded that continuous oral administration of propionic acid during lactation may increase its concentration in the proximal colon and promote epithelial barrier function of proximal colon by enhancing the expression of ZO-1, Claudin-8, Claudin-1 and Occludin via increases in the expression of ERK1/2 and p38 MAPK.


Assuntos
Colo/metabolismo , Propionatos/administração & dosagem , Administração Oral , Animais , Claudina-1/metabolismo , Claudinas/metabolismo , Colo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Ocludina/metabolismo , Permeabilidade , Fosforilação , Propionatos/farmacocinética , Processamento de Proteína Pós-Traducional , Ratos Sprague-Dawley , Junções Íntimas/metabolismo , Distribuição Tecidual , Proteína da Zônula de Oclusão-1/metabolismo
12.
PLoS One ; 12(1): e0170421, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28099464

RESUMO

OBJECTIVE: Anorectal malformations (ARMs) are one of the commonest anomalies in neonates. Both laparoscopically assisted anorectal pull-through (LAARP) and posterior sagittal anorectoplasty (PSARP) can be used for the treatment of ARMs. The aim of this systematic review and meta-analysis is to compare these two approaches in terms of intraoperative and postoperative outcomes. METHODS: MEDLINE, Embase, Web of Science and the Cochrane Library were searched from 2000 to August 2016. Both randomized and non-randomized studies, assessing LAARP and PSARP in pediatric patients with high/intermediate ARMs, were included. The primary outcome measures were operative time, length of hospital stay and total postoperative complications. The second outcome measures were rectal prolapse, anal stenosis, wound infection/dehiscence, anorectal manometry, Kelly's clinical score, and Krickenbeck classification. The quality of the randomized and non-randomized studies was assessed using the Cochrane Collaboration's Risk of Bias tool and Newcastle-Ottawa scale (NOS) respectively. The quality of evidence was assessed by GRADEpro. RESULTS: From 332 retrieved articles, 1, 1, and 8 of randomized control, prospective and retrospective studies, respectively, met the inclusion criteria. The randomized clinical trial was judged to be of low risk of bias, and the nine cohort studies were of moderate to high quality. 191 and 169 pediatric participants had undergone LAARP and PSARP, respectively. Shorter hospital stays, less wound infection/dehiscence, higher anal canal resting pressure, and a lower incidence of grade 2 or 3 constipation were obtained after LAARP compared with PSARP group values. Besides, the LAARP group had marginally less total postoperative complications. However, the result of operative time was inconclusive; meanwhile, there was no significant difference in rectal prolapse, anal stenosis, anorectal manometry, Kelly's clinical score and Krickenbeck classification. CONCLUSION: For pediatric patients with high/intermediate anorectal malformations, LAARP is a better option compared with PSARP. However, the quality of evidence was very low to moderate.


Assuntos
Canal Anal/cirurgia , Malformações Anorretais/cirurgia , Laparoscopia/métodos , Reto/cirurgia , Canal Anal/anormalidades , Humanos , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias , Reto/anormalidades , Resultado do Tratamento
13.
Viruses ; 6(2): 371-90, 2014 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-24469503

RESUMO

Herpes simplex virus type 2 (HSV-2), a globally sexually transmitted virus, and also one of the main causes of genital ulcer diseases, increases susceptibility to HIV-1. Effective vaccines to prevent HSV-2 infection are not yet available, but are currently being developed. To facilitate this process, the latest progress in development of these vaccines is reviewed in this paper. A summary of the most promising HSV-2 vaccines tested in animals in the last five years is presented, including the main factors, and new ideas for developing an effective vaccine from animal experiments and human clinical trials. Experimental results indicate that future HSV-2 vaccines may depend on a strategy that targets mucosal immunity. Furthermore, estradiol, which increases the effectiveness of vaccines, may be considered as an adjuvant. Therefore, this review is expected to provide possible strategies for development of future HSV-2 vaccines.


Assuntos
Descoberta de Drogas , Vacinas contra o Vírus do Herpes Simples/imunologia , Vacinas contra o Vírus do Herpes Simples/isolamento & purificação , Herpesvirus Humano 2/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Descoberta de Drogas/tendências , Avaliação Pré-Clínica de Medicamentos , Estradiol/administração & dosagem , Humanos , Imunidade nas Mucosas , Fatores Imunológicos/administração & dosagem , Vacinação/métodos
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