RESUMO
Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors' long-term quality of life. However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC patients and identified rs1050851 (within the exon 2 of NFKBIA), a variant with a high deleteriousness score, to be significantly associated with hearing loss risk (HR = 5.46, 95% CI 2.93-10.18, P = 9.51 × 10-08). The risk genotype of rs1050851 was associated with higher NFKBIA expression, which was correlated with lower cellular tolerance to cisplatin. According to permutation-based enrichment analysis, the variants mapping to 149 hereditary deafness genes were significantly enriched among GWAS top signals, which indicated the genetic similarity between hereditary deafness and CRIHL. Pathway analysis suggested that synaptic signaling was involved in the development of CRIHL. Additionally, the risk score integrating genetic and clinical factors can predict the risk of hearing loss with a relatively good performance in the test set. Collectively, this study shed new light on the etiology of chemoradiation-induced hearing loss, which facilitates high-risk individuals' identification for personalized prevention and treatment.
Assuntos
Surdez , Perda Auditiva , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Cisplatino/efeitos adversos , Estudo de Associação Genômica Ampla , Qualidade de Vida , Perda Auditiva/induzido quimicamente , Perda Auditiva/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/induzido quimicamenteRESUMO
Human leukocyte antigen (HLA) molecules are essential for presenting Epstein-Barr virus (EBV) antigens and are closely related to nasopharyngeal carcinoma (NPC). This study aims to systematically investigate the association between HLA-bound EBV peptides and NPC risk through in silico HLA-peptide binding prediction. A total of 455 NPC patients and 463 healthy individuals in NPC endemic areas were recruited, and HLA-target sequencing was performed. HLA-peptide binding prediction for EBV, followed by peptidome-wide logistic regression and motif analysis, was applied. Binding affinity changes for EBV peptides carrying high-risk mutations were analyzed. We found that NPC-associated EBV peptides were significantly enriched in immunogenic proteins and core linkage disequilibrium (LD) proteins related to evolution, especially those binding HLA-A alleles (p = 3.10 × 10-4 for immunogenic proteins and p = 8.10 × 10-5 for core LD proteins related to evolution). These peptides were clustered and showed binding motifs of HLA supertypes, among which supertype A02 presented an NPC-risk effect (padj = 3.77 × 10-4 ) and supertype A03 presented an NPC-protective effect (padj = 4.89 × 10-4 ). Moreover, a decreased binding affinity toward risk HLA supertype A02 was observed for the peptide carrying the NPC-risk mutation BNRF1 V1222I (p = 0.0078), and an increased binding affinity toward protective HLA supertype A03 was observed for the peptide carrying the NPC-risk mutation BALF2 I613V (p = 0.022). This study revealed the distinct preference of EBV peptides for binding HLA supertypes, which may contribute to shaping EBV population structure and be involved in NPC development.
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Epitopos , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Carcinoma Nasofaríngeo/genética , Antígenos de Histocompatibilidade Classe II , Neoplasias Nasofaríngeas/genéticaRESUMO
To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Medicamentos de Ervas Chinesas , Pandemias , Pneumonia Viral , Adolescente , Adulto , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Estudos Prospectivos , SARS-CoV-2 , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
OBJECTIVE: To evaluate the value of blood lactic acid (BLA) as a predictor for the severity and prognosis of neonatal shock. METHODS: A total of 326 neonates with shock were enrolled and divided into three groups based on the severity, namely mild group (n=147), moderate group (n=105), and severe group (n=74). BLA level was measured during and early after (about 6 hours later) fluid resuscitation, and lactate clearance rate (LCR) was calculated. The receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of BLA in neonatal shock. RESULTS: BLA level was high in all subjects prior to treatment, and was highest in the severe group and lowest in the mild group (P<0.01). BLA level was significantly higher among patients with septic shock than among those with hypovolemic, cardiogenic, and asphyxiating shock (P<0.05). BLA level was significantly reduced in patients in recovery after treatment (P<0.05). Mortality was significantly lower in patients with BLA level ≤4 mmol/L or LCR ≥10% than in those with BLA level >4 mmol/L or LCR <10% (P<0.01). BLA at 11.15 mmol/L had 100% sensitivity and 96.8% specificity in predicting severe shock. BLA at 10.65â mmol/L had 88.9% sensitivity and 74.1% specificity in predicting the prognosis (survival or dead) of newborns with shock. CONCLUSIONS: In neonates with shock, arterial BLA level increases as the disease severity increases and is associated with prognosis, so it is a useful predictor of the severity and prognosis of neonatal shock.
Assuntos
Ácido Láctico/sangue , Índice de Gravidade de Doença , Choque/sangue , Choque/mortalidade , Artérias , Feminino , Humanos , Recém-Nascido , Masculino , PrognósticoRESUMO
OBJECTIVES: To compare ocular surface changes after strabismus surgery with different incisions. METHODS: One hundred and twenty eyes with exotropia were randomly assigned to Group A (limbal incision) or Group B (fornix incision). Dry eye questionnaire, corneal sensitivity, tear film breakup time (TFBUT), Schirmer I test (SIT), and corneal fluorescein staining (CFS) were assessed at 1 day preoperatively and at different postoperative times. RESULTS: In the A group, dry eye questionnaire scores increased and TFBUT decreased at postoperative weeks 1, 2, and 4. Corneal sensitivity decreased at postoperative weeks 1 and 2. In the B group, dry eye questionnaire scores increased and TFBUT decreased at postoperative weeks 1 and 2. Corneal sensitivity did not change. Postoperative between-group differences were significant in dry eye questionnaire scores (P = 0.0009, 1 week; P < 0.0001, 2 weeks; P = 0.0001, 4 weeks) and TFBUT (P = 0.004, 1 week; P = 0.0003, 2 weeks; P = 0.0001, 4 weeks). Between-group differences in CFS were significant postoperatively (P = 0.045, 1 week; P = 0.020, 2 weeks). CONCLUSION: Compared to fornix incision, limbal incision results in more serious dry eye symptoms and has a greater impact on corneal sensitivity and tear film stability.
Assuntos
Córnea/fisiopatologia , Síndromes do Olho Seco/fisiopatologia , Exotropia/cirurgia , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/métodos , Lágrimas/fisiologia , Adolescente , Adulto , Criança , Exotropia/fisiopatologia , Feminino , Fluorofotometria , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/fisiopatologia , Estudos Prospectivos , Inquéritos e Questionários , Técnicas de Sutura , Lágrimas/químicaRESUMO
Background: Women undergoing in vitro fertilization and embryo transfer (IVF-ET) often utilize acupuncture to enhance pregnancy outcomes. Yet, the optimal timing for acupuncture sessions and the relationship between dosage and effect remain uncertain. Objectives: To investigate the impact of the timing and dosage of acupuncture on pregnancy outcomes, drawing on existing research. Methods: A comprehensive search of eight databases was conducted from their inception to January 14th, 2023, without restrictions on language. Only randomized controlled trials comparing acupuncture with either sham acupuncture or no adjuvant treatment were selected for inclusion. This meta-analysis assessed the efficacy of acupuncture in IVF-ET, analyzing the influence of varied timing and dosage on pregnancy outcomes. Subgroup analyses were undertaken to address any heterogeneity across the studies. Results: A total of 38 RCTs involving 5,991 participants were analyzed. In infertile women undergoing IVF fresh cycles, acupuncture performed during controlled ovarian hyperstimulation (COH) significantly increased the clinical pregnancy rate (CPR) (relative risk [RR] = 1.33, 95% confidence interval [CI]: 1.07-1.65, p = 0.01), whereas acupuncture administered either before COH or on the day of ET did not demonstrate reproductive benefits. Regarding frozen cycles, acupuncture before freeze-thaw embryo transfer (FET) significantly enhanced the CPR (RR = 1.71, 95% CI: 1.36-2.16, p < 0.00001) and live birth rate (LBR) (RR = 2.40, 95% CI: 1.20-4.79, p = 0.01). Improvements in CPR were observed across all dosage groups, but only the high-dosage group showed a significant increase in LBR (RR = 1.75, 95% CI: 1.05-2.92, p = 0.03). Conclusions: Timing and dosage of acupuncture are crucial factors affecting pregnancy outcomes in IVF-ET. For women undergoing IVF fresh cycles, acupuncture during COH yielded more significant reproductive benefits. In addition, acupuncture before freeze-thaw embryo transfer (FET) was associated with improved pregnancy outcomes in frozen cycles. Furthermore, higher dosages of acupuncture were linked to more favorable outcomes.
RESUMO
Meningioma is a common intracranial tumor in adults. Pediatric cases account for approximately 1.5% of all intracranial meningiomas, and very few cases show malignant histological features. Primary pediatric malignant meningioma in the cerebellopontine angle is extremely uncommon. Herein, we report a 2-year-old girl with malignant meningioma in the cerebellopontine angle. The clinical features, diagnosis, and treatment protocol are discussed.
Assuntos
Neoplasias Cerebelares , Ângulo Cerebelopontino , Neoplasias Meníngeas , Meningioma , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Pré-Escolar , Feminino , Seguimentos , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/metabolismo , Meningioma/patologia , Meningioma/cirurgia , Mucina-1/metabolismo , Radiografia , Proteínas S100/metabolismo , Vimentina/metabolismoRESUMO
BACKGROUND: The human leukocyte antigen (HLA) is a highly polymorphic region, and HLA diversity may play a role in presenting tumour-associated peptides and inducing immune responses. However, the effect of HLA diversity on cancers has not been fully assessed. We aimed to explore the role of HLA diversity on cancer development. METHODS: A pan-cancer analysis was performed to evaluate the effect of HLA diversity, measured by HLA heterozygosity and HLA evolutionary divergence (HED), on the susceptibility of 25 cancers in the UK Biobank. FINDINGS: We observed that the diversity of HLA class II locus was associated with a lower risk of lung cancer (ORhetero = 0.94, 95% CI = 0.90-0.97, P = 1.29 × 10-4) and head and neck cancer (ORhetero = 0.91, 95% CI = 0.86-0.96, P = 1.56 × 10-3). Besides, a lower risk of non-Hodgkin lymphoma was associated with an increased diversity of HLA class I (ORhetero = 0.92, 95% CI = 0.87-0.98, P = 8.38 × 10-3) and class II locus (ORhetero = 0.89, 95% CI = 0.86-0.92, P = 1.65 × 10-10). A lower risk of Hodgkin lymphoma was associated with the HLA class I diversity (ORhetero = 0.85, 95% CI = 0.75-0.96, P = 0.011). The protective effect of HLA diversity was mainly observed in pathological subtypes with higher tumour mutation burden, such as lung squamous cell carcinoma (P = 9.39 × 10-3) and diffuse large B cell lymphoma (Pclass I = 4.12 × 10-4; Pclass â ¡ = 4.71 × 10-5), as well as the smoking subgroups of lung cancer (P = 7.45 × 10-5) and head and neck cancer (P = 4.55 × 10-3). INTERPRETATION: We provided a systematic insight into the effect of HLA diversity on cancers, which might help to understand the etiological role of HLA on cancer development. FUNDING: This study was supported by grants from the National Natural Science Foundation of China (82273705, 82003520); the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515420007); the Science and Technology Planning Project of Guangzhou, China (201804020094); Sino-Sweden Joint Research Programme (81861138006); the National Natural Science Foundation of China (81973131, 81903395, 81803319, 81802708).
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Bancos de Espécimes Biológicos , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Antígenos HLA/genética , Reino Unido/epidemiologiaRESUMO
PURPOSE: Volatile organic compounds (VOCs) have shown great potential as novel biomarkers for cancer detection; however, comprehensive quantitative analysis is lacking. In this study, we performed a bibliometric analysis of non-invasive cancer diagnosis using VOCs to better characterise international trends and to predict future hotspots in this field, and then we focussed on human studies to analyse clinical characteristics for presenting the current controversies and future perspectives of further clinical work. METHODS: Publications, from 2002 to 2022, were retrieved from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to generate network maps and identify the annual publications, top countries, authors, institutions, journals, references, and keywords. Then, we further screened clinical trials, and the key information was extracted into Microsoft Excel for further systematical analysis. RESULTS: Six hundred and forty-one articles were identified to evaluate research trends, of which 301 clinical trials were selected for further systematical analysis. Overall, the annual publications in this area increased, with an overall upward trend, while the quality of clinical research remains remarkably uneven. CONCLUSION: The study of non-invasive cancer diagnosis using VOCs would continue to be an active field. However, without stringent clinical design criteria, most suitable acquisition and analysis devices and statistical approaches, a list of exclusive, specific, reliable and reproducible VOCs to identify a disease and these VOCs appearing in a breath at detectable levels at early stage disease, the clinical utility of VOC tests will be difficult to have any breakthroughs.
Assuntos
Líquidos Corporais , Neoplasias , Compostos Orgânicos Voláteis , Humanos , Neoplasias/diagnóstico , Bases de Dados FactuaisRESUMO
To enhance the therapeutic potential of etoposide (ETO), we devised a targeted drug delivery system (TDDS) of epidermal growth factor-chitosan-carboxyl single-walled carbon nanotubes-ETO (EGF/CHI/SWNT-COOHs/ETO) using modified SWNTs (m-SWNTs) as the carrier, EGF-functionalized SWNTs (f-SWNTs) as the targeted moiety and ETO as the drug. After SWNT-COOHs were conjugated with CHI (CHI/SWNT-COOHs/ETO), they displayed high solubility and stable dispersion in aqueous solution. The drug loading capacity was approximately 25-27%. The m-SWNTs and f-SWNTs had only slight cytotoxicity. ETO was released from EGF/CHI/SWNT-COOHs/ETO at low pH and taken up by tumour cells via adenosine triphosphate (ATP)-dependent endocytosis. The cell death induced by EGF/CHI/SWNT-COOHs/ETO was as much as 2.7 times that due to ETO alone. In summary, these results demonstrated that our TDDS had a greater anticancer effect than free ETO in vitro.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Fator de Crescimento Epidérmico , Etoposídeo , Nanotubos de Carbono/química , Antineoplásicos/farmacologia , Ligação Competitiva/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fator de Crescimento Epidérmico/farmacologia , Etoposídeo/farmacologia , Humanos , Nanotubos de Carbono/ultraestrutura , Espectrofotometria Ultravioleta , Análise Espectral Raman , TermodinâmicaRESUMO
Malignant hyperthermia (MH) is an autosomal dominant genetic condition of the skeletal muscle triggered by inhaled general anesthetic agents or succinylcholine and associated with a hypermetabolic state and skeletal muscle rigidity. Tachycardia, increased carbon dioxide production, hypercarbia, hyperthermia, acidosis, hyperkalemia, cardiac arrhythmias, muscle rigidity, and rhabdomyolysis are common symptoms of MH. As the progression of the syndrome could be rapid or less evident, even experienced physicians have difficulty in diagnosing MH, which can lead to delays in treatment and increased mortality. We report a rare case of a 36-year-old man, who underwent open reduction and internal fixation of the left clavicle after inhaled anesthetics. The patient developed dyspnea, hypotension, unremitting hyperthermia, tachycardia, and elevated serum myoglobin, and finally died of pyemia and disseminated intravascular coagulation. We reviewed the process of disease development, summarized the steps of diagnosis, and improved genetic testing. Exome sequencing revealed a new mutation c.8519G>A (p.arg2840 GLN) in the RYR1 gene that could be associated with MH. The gene mutation was also found in his daughter's genetic test. This case emphasized the importance of the awareness of MH and its atypical clinical symptoms. The presence of dyspnea, hypotension, unremitting hyperthermia, tachycardia, and raised myoglobin in serum might further strengthen the clinical diagnosis of suspected MH.
RESUMO
BACKGROUND: Decreased ovarian reserve function is an ovarian hypofunction disease that occurs in women before 40 years of age, leading to a decline in fertility and perimenopausal symptoms, such as irregular menstruation, amenorrhea, infertility, decreased libido, and autonomic nervous dysfunction. Fenmatong (FMT) is a compound mixture of estradiol tablets and estradiol didroxyprogesterone tablets, which can improve ovarian reserve function by supplementation of exogenous estrogen. However, this treatment has also been shown to cause breast pain, gastrointestinal discomfort, irregular vaginal bleeding, and changes in sexual desire. In severe cases, FMT can promote the development of breast cancer, endometrial cancer, and venous embolic disease. AIM: To observe the effects of Kuntai capsules and FMT on endocrine indexes and uterine artery blood circulation in patients with decreased ovarian reserve function. METHODS: Patients (130) with decreased ovarian reserve function, who were treated in our hospital from May 2018 to May 2020, were divided into two groups: The FMT group, in which patients were treated with FMT, and the observation group, in which patients were treated with Kuntai capsules. Chinese medicine symptom scores, uterine artery blood flow parameters, ovarian ultrasound test indexes, pictorial blood loss assessment chart (PBAC) scores, and hormone levels were recorded, and total effective rates were calculated for both groups. RESULTS: The total effective rate in the observation group was higher than that in the FMT group (P < 0.05).After treatment, primary symptoms, including low menstrual volume, delayed menstruation, red color and thick consistency of menses, dizziness, palpitation, weakness at the waist and knee, insomnia and excessive dreaming, irritability, and dryness and astringency of the pudendal canal in the observation group decreased, and scores for primary and secondary symptoms in the observation group were significantly lower than those in the FMT group (P < 0.05).The systolic peak flow rate (PSV), end-diastolic flow rate (EDV), ovarian diameter, sinus follicle count, and resistance index (RI) of the uterine arteries in the observation group and FMT group increased after treatment. Notably, the PSV, EDV, ovarian diameter, and antral follicle count in the observation group were higher than those in the FMT group, whereas the RI in the observation group was lower than that in the FMT group (P < 0.05).The PBAC scores in the observation and FMT groups increased after treatment, with that in the observation group becoming significantly higher than that in the FMT group (P < 0.05). After treatment, estradiol (E2) and anti-Mullerian hormone (AMH) levels increased, whereas follicle-stimulating hormone (FSH) levels decreased in the observation group and FMT group; E2 and AMH levels became significantly higher and FSH levels became significantly lower in the observation group than in the FMT group (P < 0.05). CONCLUSION: Compared with FMT, Kuntai capsules promoted uterine artery blood circulation, improved menstruation, relieved symptoms, regulated endocrine function, and improved curative effects.
RESUMO
Epidermal growth factor receptor (EGFR) is a classic protein tyrosine kinase receptor, which plays an important role in cell proliferation, survival, adhesion, differentiation and apoptosis. Abnormality of EGFR and its signaling are closely associated with tumor initiation and development. Many environmental physical and chemical agents can interfere with EGFR and its signal transduction pathways via affecting its phosphorylation, conformation and function, or distribution on cell membrane, finally influencing gene expression and cell fate. This review focuses on the recent progress of above aspects for further understanding of epigenetic mechanisms of cellular stress and carcinogenesis related with environmental agents.
Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Receptores ErbB/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Carcinógenos , Receptores ErbB/metabolismo , Humanos , FosforilaçãoRESUMO
OBJECTIVES: To observe whether Graphene oxide (GO) can absorb vitamin B12 (VB12) and Decellularized scaffold - acellular nerve allograft (ANA) modified GO-VB12 promote the repair of ischiadic nervus defects in a rat model. METHODS: The adsorption of GO on vitamin and the optimum adsorption conditions were investigated by single factor experiment. The adsorption properties of the material were observed by scanning electron microscopy (SEM) and energy dispersive spectrometer (EDS) to determine the success of adsorption on VB12. GO-VB12-ANA was prepared by vibration mixing method and bridged to injured ischiadic nervus. The nerve action potential, wet weight ratio of gastrocnemius muscle and the expression of GAP-43 were investigated by contrast test to detect its effect on nerve regeneration. RESULTS: The optimized adsorption conditions for GO on VB12 solution were listed as follows: adsorbent dosage was 6 mg, shaking time was 70 min, the pH value was 6, the optimum concentration of VB12 was 50 mg/L and the theoretical saturated adsorption capacity was 21.51 mg/g. The nerve action potential, wet weight ratio of gastrocnemius muscle and the expression of GAP-43 in nerve fiber of GO-VB12-ANA group were close to the normal values and significantly higher than those of ANA and rotation group. CONCLUSIONS: Based on the adsorption function of GO on VB12, GO-VB12-ANA can promote regeneration of injured ischiadic nervus, providing the experimental basis for the clinical application of nanomaterials.
Assuntos
Grafite , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/fisiopatologia , Alicerces Teciduais , Vitamina B 12 , Adsorção , Animais , Feminino , Grafite/química , Masculino , Teste de Materiais , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Nanoestruturas/química , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/patologia , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , Nervos Periféricos/cirurgia , Distribuição Aleatória , Ratos Sprague-Dawley , Transplante Homólogo , Vitamina B 12/químicaRESUMO
Schwann cells (SCs) combined with acellular nerve allografts (ANAs) effectively promote the regeneration and repair of peripheral nerves, but the exact mechanism has not been fully elucidated. However, the disadvantages of SCs include their limited source and slow rate of expansion in vitro. Previous studies have found that adipose-derived stem cells have the ability to differentiate into Schwann-like cells. Therefore, we speculated that Schwann-like cells combined with ANAs could profoundly facilitate nerve regeneration and repair. The aim of the present study was to investigate the cellular and molecular mechanisms of regeneration and repair. In this study, tissue-engineered nerves were first constructed by adipose-derived Schwann-like cells and ANAs to bridge missing sciatic nerves. Then, the rats were randomly divided into five groups (nâ¯=â¯12 per group): a Control group; a Model group; an ADSC group; an SC-L group; and a DMEM group. Twelve weeks postsurgery, behavioral function tests and molecular biological techniques were used to evaluate the function of regenerated nerves and the relevant molecular mechanisms after sciatic nerve injury (SNI). The results showed that adipose-derived Schwann-like cells combined with ANAs markedly promoted sciatic nerve regeneration and repair. These findings also demonstrated that the expression of neurotrophic factors (NFs) was increased, and the expression of Janus activated kinase2 (JAK2)/P-JAK2, signal transducer and activator of transcription-3 (STAT3)/P-STAT3 was decreased in the spinal cord after SNI. Therefore, these results suggested that highly expressed NFs in the spinal cord could promote nerve regeneration and repair by inhibiting activation of the JAK2/STAT3 signaling pathway.
Assuntos
Aloenxertos/transplante , Janus Quinase 2/fisiologia , Regeneração Nervosa/fisiologia , Fator de Transcrição STAT3/fisiologia , Nervo Isquiático/fisiopatologia , Animais , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Fator Neurotrófico Ciliar/biossíntese , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Fator de Crescimento Neural/biossíntese , Neurônios/transplante , Ratos , Recuperação de Função Fisiológica/fisiologia , Nervo Isquiático/lesões , Nervo Isquiático/cirurgia , Transdução de Sinais/fisiologia , Medula Espinal/metabolismoRESUMO
OBJECTIVE: To clarify the clinical outcomes of cranioplasty with cryopreserved bone flaps and identify risk factors related to bone flap infection and resorption after cranioplasty with cryopreserved bone flaps. METHODS: A total of 946 patients (989 bone flaps) underwent decompressive craniectomy and delayed cranioplasty via the use of cryopreserved autogenous cranial bone flaps. Cranial bone flaps were removed during the initial craniectomy and reserved in liquid nitrogen (-196°C) with dimethyl sulfoxide as a cryoprotectant. Cranioplasty subsequently was performed once the brain injury had healed. Data regarding complications and clinical outcomes were recorded and the potential risk factors were analyzed. RESULTS: Data from 960 flaps were available for analysis. The overall complication rate was 15.83% (152 of 960). Bone resorption occurred in 42 flaps in 37 patients (4.38%). The bone flaps resorption rate was greater in patients ≤18 years than in patients >18 years (9.38% vs. 3.61%, P < 0.05). Cryopreservation for more than 365 days tended to result in a greater bone resorption rate (6.88% vs. 2.92%, P < 0.01). Skull bone grafts infection occurred in 39 flaps in 34 patients (4.06%). The bone graft infection rate was greater in emergency craniectomy cases (8.81% vs. 2.59%, P < 0.01) and in patients with diabetes (10.53% vs. 3.07%, P < 0.01). CONCLUSIONS: Cryopreservation of autologous cranial bone flaps is safe and effective for cranioplasty. Cranioplasty with cryopreserved autologous cranial bone flaps should be performed no more than 1 year after craniectomy. Emergency craniectomy and patients with diabetes require special attention.
Assuntos
Transplante Ósseo/métodos , Criopreservação/métodos , Craniectomia Descompressiva/métodos , Procedimentos de Cirurgia Plástica/métodos , Crânio/cirurgia , Retalhos Cirúrgicos , Infecção da Ferida Cirúrgica/epidemiologia , Transplante Autólogo/métodos , Adolescente , Adulto , Idoso , Reabsorção Óssea , Criança , Crioprotetores , Dimetil Sulfóxido , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Bactrocera dorsalis, the Oriental fruit fly, is one of the world's most destructive agricultural insect pests and a major impediment to international fresh commodity trade. The genetic structuring of the species across its entire geographic range has never been undertaken, because under a former taxonomy B. dorsalis was divided into four distinct taxonomic entities, each with their own, largely non-overlapping, distributions. Based on the extensive sampling of six a priori groups from 63 locations, genetic and geometric morphometric datasets were generated to detect macrogeographic population structure, and to determine prior and current invasion pathways of this species. Weak population structure and high genetic diversity were detected among Asian populations. Invasive populations in Africa and Hawaii are inferred to be the result of separate, single invasions from South Asia, while South Asia is also the likely source of other Asian populations. The current northward invasion of B. dorsalis into Central China is the result of multiple, repeated dispersal events, most likely related to fruit trade. Results are discussed in the context of global quarantine, trade, and management of this pest. The recent expansion of the fly into temperate China, with very few associated genetic changes, clearly demonstrates the threat posed by this pest to ecologically similar areas in Europe and North America.
RESUMO
The current study aimed to identify key genes in glaucoma based on a benchmarked dataset and gene regulatory network (GRN). Local and global noise was added to the gene expression dataset to produce a benchmarked dataset. Differentially-expressed genes (DEGs) between patients with glaucoma and normal controls were identified utilizing the Linear Models for Microarray Data (Limma) package based on benchmarked dataset. A total of 5 GRN inference methods, including Zscore, GeneNet, context likelihood of relatedness (CLR) algorithm, Partial Correlation coefficient with Information Theory (PCIT) and GEne Network Inference with Ensemble of Trees (Genie3) were evaluated using receiver operating characteristic (ROC) and precision and recall (PR) curves. The interference method with the best performance was selected to construct the GRN. Subsequently, topological centrality (degree, closeness and betweenness) was conducted to identify key genes in the GRN of glaucoma. Finally, the key genes were validated by performing reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 176 DEGs were detected from the benchmarked dataset. The ROC and PR curves of the 5 methods were analyzed and it was determined that Genie3 had a clear advantage over the other methods; thus, Genie3 was used to construct the GRN. Following topological centrality analysis, 14 key genes for glaucoma were identified, including IL6, EPHA2 and GSTT1 and 5 of these 14 key genes were validated by RT-qPCR. Therefore, the current study identified 14 key genes in glaucoma, which may be potential biomarkers to use in the diagnosis of glaucoma and aid in identifying the molecular mechanism of this disease.
RESUMO
The objective of the present study is to identify significant genes and pathways associated with hepatocellular carcinoma (HCC) by systematically tracking the dysregulated modules of re-weighted protein-protein interaction (PPI) networks. Firstly, normal and HCC PPI networks were inferred and re-weighted based on Pearson correlation coefficient. Next, modules in the PPI networks were explored by a clique-merging algorithm, and disrupted modules were identified utilizing a maximum weight bipartite matching in non-increasing order. Then, the gene compositions of the disrupted modules were studied and compared with differentially expressed (DE) genes, and pathway enrichment analysis for these genes was performed based on Expression Analysis Systematic Explorer. Finally, validations of significant genes in HCC were conducted using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The present study evaluated 394 disrupted module pairs, which comprised 236 dysregulated genes. When the dysregulated genes were compared with 211 DE genes, a total of 26 common genes [including phospholipase C beta 1, cytochrome P450 (CYP) 2C8 and CYP2B6] were obtained. Furthermore, 6 of these 26 common genes were validated by RT-qPCR. Pathway enrichment analysis of dysregulated genes demonstrated that neuroactive ligand-receptor interaction, purine and drug metabolism, and metabolism of xenobiotics mediated by CYP were significantly disrupted pathways. In conclusion, the present study greatly improved the understanding of HCC in a systematic manner and provided potential biomarkers for early detection and novel therapeutic methods.
RESUMO
Since the first report of a genome-wide association study (GWAS) on human age-related macular degeneration, GWAS has successfully been used to discover genetic variants for a variety of complex human diseases and/or traits, and thousands of associated loci have been identified. However, the underlying mechanisms for these loci remain largely unknown. To make these GWAS findings more useful, it is necessary to perform in-depth data mining. The data analysis in the post-GWAS era will include the following aspects: fine-mapping of susceptibility regions to identify susceptibility genes for elucidating the biological mechanism of action; joint analysis of susceptibility genes in different diseases; integration of GWAS, transcriptome, and epigenetic data to analyze expression and methylation quantitative trait loci at the whole-genome level, and find single-nucleotide polymorphisms that influence gene expression and DNA methylation; genome-wide association analysis of disease-related DNA copy number variations. Applying these strategies and methods will serve to strengthen GWAS data to enhance the utility and significance of GWAS in improving understanding of the genetics of complex diseases or traits and translate these findings for clinical applications.