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1.
Front Public Health ; 12: 1295975, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550327

RESUMEN

Objectives: Workplace violence (WPV) against healthcare workers (HCWs) has reached significant levels globally, impeding the quality and accessibility of healthcare systems. However, there is limited available knowledge regarding the determinants linked with WPV among HCWs and the discrepancies observed across various levels of hospitals in China. The objective of the present research was to investigate the factors linked to WPV and job satisfaction among HCWs in China. Methods: A self-developed questionnaire based on WeChat was employed to collect data. The questionnaire consisted of demographic information as well as occupational factors. To measure WPV, the Chinese version of the Workplace Violence Scale was utilized. Career satisfaction was assessed through two questions regarding career choices. The collected data was analyzed using descriptive analyses, chi-square tests, and multivariate logistic regressions. Results: A total of 3,781 valid questionnaires (1,029 doctors and 2,752 nurses) were collected. Among all participants, 2,201 (58.2%) reported experiencing at least one form of WPV in the past year, with emotional abuse being the most frequent occurrence (49.7%), followed by threats (27.9%). The multivariate logistic regression analysis revealed several risk factors associated with WPV, including male gender, shift work, senior professional title, bachelor's degree education, employment in secondary-level hospitals, and working over 50 h per week (p < 0.05). Career satisfaction among HCWs who experienced high levels of WPV was low, with only 11.2% remaining confident in their profession, and a mere 2.0% supporting their children pursuing careers in healthcare. Conclusion: WPV poses a significant challenge within the Chinese healthcare system. Efforts should be made to address the identified risk factors and promote a safe and satisfying working environment for HCWs.


Asunto(s)
Médicos , Violencia Laboral , Niño , Humanos , Masculino , Violencia Laboral/psicología , Estudios Transversales , China/epidemiología , Médicos/psicología , Hospitales
2.
J Inorg Biochem ; 246: 112293, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37354605

RESUMEN

A series of O-phenanthroline silver(I) complexes were synthesized and characterized by infrared (IR) spectroscopy, mass spectrometry (MS), 1H nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray crystallography. The cytotoxicity of the silver(I) complex (P-131) was evaluated in the cancer cell lines HCT-116, HeLa, and MDA-MB-231 and the normal cell line LO2 via MTT assays. The 50% inhibition concentration (IC50) of P-131 on HCT116 cell line is 0.86 ± 0.03 µM. It is far lower than the IC50 value of cisplatin (9.08 ± 1.10 µM), the IC50 value of normal cell LO2 (76.20 ± 0.48 µM) is much higher than that of cisplatin (3.99 ± 0.74 µM), indicating that its anticancer effect is stronger than that of cisplatin, and its biological safety is greater than that of cisplatin. Furthermore, anticancer mechanistic studies showed that P-131 inhibited cell proliferation by blocking DNA synthesis and acted temporally on the nucleus in dividing HCT-116 cells. Moreover, P-131 increased intracellular reactive oxygen species (ROS) levels in a dose-dependent manner. Notably, 10 mg/kg P-131 showed better antitumor effects than oxaliplatin in an HCT116 human colorectal xenograft mouse model without inducing toxicity. Moreover, the microdilution broth method was used to evaluate the antimicrobial properties of P-131 against Pseudomonas aeruginosa and Candida albicans. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy.


Asunto(s)
Adenocarcinoma , Antiinfecciosos , Antineoplásicos , Neoplasias Colorrectales , Complejos de Coordinación , Humanos , Animales , Ratones , Cisplatino/farmacología , Plata/farmacología , Plata/química , Antiinfecciosos/farmacología , Células HeLa , Neoplasias Colorrectales/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Proliferación Celular , Línea Celular Tumoral
3.
Front Genet ; 14: 1120827, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37124619

RESUMEN

Background: Esophageal carcinoma (ESCA) is one of the most prevalent malignant tumors in the world. The prognosis of patients has significantly improved with the development of surgery, targeted therapy and immunotherapy. But the 5-year survival rate of ESCA patients is still incredibly low. Cuproptosis is a type of mitochondrial cell death induced by copper. It is unclear how cuproptosis-related lncRNAs (CRLs) affect ESCA prognosis. Methods: In this study, we obtained the clinical data of ESCA patients, the transcriptome data from TCGA and identified CRLs by co-expression analysis, lasso regression, and cox regression analysis, to build a prognostic model. Then we validated the prognostic model using the Kaplan-Meier curve, cox regression analysis, and ROC, to create a nomogram based on risk score to forecast the prognosis of ESCA. Next, the immune escape of the CRLs was examined using the TIDE algorithm to assess its sensitivity to possible ESCA medications. Results: To predict the prognosis of ESCA patients, we created a predictive model using 6 CRLs (AC034199.1, AC125437.1, AC107032.2, CTBP1-DT, AL024508.1, and AC008610.1), validated by the Kaplan-Meier and ROC curves. The model has a higher diagnostic value compared to other clinical features. The 6 CRLs expressed high in TCGA and ESCA specimens. Enrichment analysis revealed CRLs largely contributed to the interaction between cytokines and their receptors as well as complement coagulation cascades. The immunity escape analysis demonstrated that immunotherapy had a worse effect in the low-risk group than in the high-risk group. Additionally, we screened out potential antineoplastic drugs according to the results of the immunoassay and obtained 5 drugs, including CP-466722, crizotinib, MS-275, KIN001-135, and CP-466722. Conclusion: The prognosis of patients with ESCA can be correctly predicted by the 6 CRLs chosen from this investigation. It lays the groundwork for more investigation into the ESCA mechanism and the identification of novel therapeutic targets.

5.
Int J Nanomedicine ; 18: 225-241, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36660337

RESUMEN

Background: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach. Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex. Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models. Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.


Asunto(s)
Antineoplásicos , Portadores de Fármacos , Galio , Grafito , Nanopartículas del Metal , Oxiquinolina , Animales , Humanos , Ratones , Materiales Biocompatibles , Línea Celular Tumoral , Portadores de Fármacos/síntesis química , Galio/química , Grafito/química , Células HCT116 , Nanopartículas del Metal/análisis , Nanopartículas/análisis , Oxiquinolina/química , Tamaño de la Partícula , Albúmina Sérica Bovina/farmacología , Agua , Antineoplásicos/síntesis química , Antineoplásicos/química
6.
Curr Stem Cell Res Ther ; 18(8): 1113-1119, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36165522

RESUMEN

AIM: The study aims to investigate the immunomodulatory effect of Amniotic fluid stem (AFS) cells to Th2-skewed allergic rhinitis (AR) on T-lymphocyte proliferation, viability, activation and cytokine production. BACKGROUND: AFS cells can suppress peripheral blood mononuclear cells (PBMCs) proliferation and display immunomodulatory properties, but AFS cells' immunoregulation on AR has not been defined. METHODS: Human AFS cells were derived from magnetic cell sorting and co-cultured with PBMCs from AR patients stimulated by phytohemagglutinin (PHA). The AFS cells-associated suppressive proliferation was analyzed using CellTrace™ Violet assay; the T lymphocytes proliferation, viability, activation and the Foxp3+ Treg cells were determined by flow cytometry; cytokine levels were measured using an enzyme- linked immunosorbent assay. RESULTS: We determined that AFS cells significantly inhibited PHA-induced CD3+ T lymphocyte proliferation at the ratio higher than 1:50 (AFS cells: PBMCs) (P<0.05); AFS cells obviously increased the T lymphocytes viability (P<0.01), inhibited the apoptosis of T lymphocytes (P<0.001), compared to PBMCs alone; AFS cells suppressed CD3+CD25+ T lymphocytes activated by PHA (P<0.05); AFS cells significantly promote Treg cells expansion in house dust mite (HDM)-stimulated PBMCs from AR patients (P<0.05). Compared with HDM-stimulated PBMCs, AFS cell co-culture predominantly decreased IL-4 level (P<0.05), but increased IFN-γ and IL-10 levels (P<0.01). CONCLUSION: AFS cells modulate the T-cells' immune imbalance towards Th2 suppression in AR, which can be used as a new cell banking for allergic airway diseases.


Asunto(s)
Leucocitos Mononucleares , Rinitis Alérgica , Humanos , Líquido Amniótico , Citocinas , Células Madre
7.
Front Public Health ; 10: 1030035, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36339236

RESUMEN

Objectives: Patient-initiated hospital violence is a global problem which threatens the safety of health professionals and is indicative of doctor-patient tensions, impeding health system quality and access. The current study aimed to improve the understanding of medical workplace violence (WPV) in China, using authoritative and nationally representative judgment records, and to approach violence prevention strategies. Methods: All litigation records relating to violence against health professionals between 2013 and 2021 were extracted from the China Judgment Online System. Basic case information, victim characteristics, perpetrator characteristics and the nature of the violence were collated. The relationship between different treatment outcomes and violence was also explored. Results: Numbers of cases of hospital violence gradually increased from 2013 to a peak in 2016 before gradually decreasing in the following years. The most common perpetrators were patients' relatives (58.2%), followed by patients themselves (38.2%). Only 9 perpetrators had a confirmed history of mental illness and only two were intoxicated with alcohol. More than half of the cases (52.5%) occurred in rural areas and this percentage is even greater for primary health care institutions (71.4%) and secondary hospitals (73.5%). On a departmental level, the highest incidence of medical WPV was found in the emergency (18.9%), pediatrics (13.2%) and obstetrics (11.5%) departments. Violent behaviors, such as stalking, mass occupation of the ward and sharp instrument injury were significantly related to cases not involving patient death (p < 0.05). Disruptive behavior, such as hanging banners, blocking hospital passages, placing flower wreaths and burning paper money were significantly correlated with cases involving patient death (p < 0.01). The interval between a patient's death and the ensuing violence was short, happening on the same day in 54.8% of cases. Conclusions: A comprehensive overview of medical WPV in China is presented and may have utility for the formulation of prevention strategies.


Asunto(s)
Criminales , Violencia Laboral , Humanos , Niño , Violencia Laboral/prevención & control , Juicio , Personal de Salud , China/epidemiología
8.
Front Vet Sci ; 9: 1079916, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36619964

RESUMEN

Rabies is a fatal encephalitis caused by the rabies virus. The diagnosis of the disease depends in large part on the exposure history of the victim and clinical manifestations of the disease. Rapid rabies diagnosis is an important step in its prevention and control. Therefore, for accurate and timely diagnosis and prevention of rabies, we developed nanomaterials for a novel photoelectrochemical biosensing approach (PBA) for the rapid and reliable diagnosis of rabies virus. This approach uses high-efficiency exciton energy transfer between cadmium telluride quantum dots and Au nanoparticles and is low cost, and easy to miniaturize. By constructing PBA, rabies virus can be detected quickly and with a high degree of sensitivity and specificity; the minimum detection concentration limit for rabies virus is approximately 2.16 ffu/mL of rabies virus particles, or 2.53 × 101 fg/mL of rabies virus RNA. PBA could also detect rabies virus in the brain and lung tissue from rabid dogs and mice with better sensitivity than RT-PCR.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 263: 120220, 2021 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-34329848

RESUMEN

It is well-known that As2O3 has significant anticancer effects, however, little is known regarding its mechanism for treating gastric cancer. Thus, we investigated biomacromolecular (DNA, proteins and lipids) changes of human gastric cancer cell line MGC803 to further understand As2O3-induced apoptosis. Conventional methods showed the increase of the apoptosis rate, the decrease of mitochondrial membrane potential (MMP), the accumulation of reactive oxygen species (ROS) and the changes of apoptotic proteins, etc. Fourier transform infrared (FTIR) microspectroscopy sensitively recognized overall biomacromolecular changes caused by the above: Peak-area ratios indicated the content/structure changes in DNA, proteins and lipids. Principle component analysis (PCA) revealed significant changes in intracellular DNA concentration and structure. This study suggests that As2O3 may exert anti-gastric cancer effect by altering intracellular biomacromolecules especially DNA.


Asunto(s)
Antineoplásicos , Arsenicales , Antineoplásicos/farmacología , Apoptosis , Trióxido de Arsénico/farmacología , Línea Celular Tumoral , Análisis de Fourier , Humanos , Potencial de la Membrana Mitocondrial , Óxidos/farmacología , Especies Reactivas de Oxígeno , Espectroscopía Infrarroja por Transformada de Fourier
10.
Fam Pract ; 38(6): 848-849, 2021 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-34173653
11.
Huan Jing Ke Xue ; 42(2): 819-830, 2021 Feb 08.
Artículo en Chino | MEDLINE | ID: mdl-33742876

RESUMEN

Periphytic algae are often used as an indicator to evaluate water quality. Here, the community structure of periphytic algae and its relationship with environment factors were analyzed in the main stream of the Songhua River during the summers of 2014 to 2019. The status and trends in ecological water quality were also evaluated based on bioassessments. Phytoplankton species belonging to 4 phyla and 58 genera were recorded, including 28 Bacillariophyta genera, 17 Chlorophyta genera, 10 Cyanophyta genera, and 3 Euglenophyta genera; Bacillariophyta, Chlorophyta, and Cyanophyta accounted for 48.28%, 29.31%, and 17.24% of the community, respectively. Cell densities varied between 1.29×104 and 8.42×104 ind·cm-3, with an average of 4.35×104 ind·cm-3. The dominant genera were Cyclotella, Melosira, Asterionella, Cymbella, Synedra, Pinnularia, Navicula, and Scenedesmus. The physicochemical water quality showed notable changes during the past six-year monitoring period. Specifically, the dissolved oxygen content increased year on year; ammonia nitrogen, total phosphorus, and total nitrogen first increased and then decreased; and, overall, water quality significantly improved in 2019. Relationship between periphytic algae and environmental factors was further examined using redundancy analysis (RDA), which showed that time was the main factor driving the succession of algal community structure. Dissolved oxygen (DO), ammonia nitrogen (NH4+-N), total nitrogen (TN), total phosphorus (TP), five-day biochemical oxygen demand (BOD), and chemical oxygen demand (COD) were also important environmental variables affecting algal community structure.


Asunto(s)
Diatomeas , Ríos , China , Monitoreo del Ambiente , Nitrógeno/análisis , Fósforo/análisis , Fitoplancton , Estaciones del Año , Calidad del Agua
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 252: 119542, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33581574

RESUMEN

Recent studies have shown that bacteria can also undergo apoptosis, which has gradually attracted researchers' attention. Cisplatin is a first-line drug to treat several cancers, but it can damage beneficial bacteria. Hence it is very important to explore the damage mechanism of cisplatin on beneficial bacteria. In this study, Lactobacillus paracasei, one kind of beneficial bacteria, was used as the model to investigate cisplatin damage. Conventional detection showed that cisplatin induced the apoptosis of Lactobacillus paracasei. Then Fourier transform infrared (FTIR) microspectroscopy was used to detect biomacromolecular changes in Lactobacillus paracasei apoptosis, and the following results were obtained: ① Second derivative IR spectra showed the changes of DNA, proteins, polysaccharides and lipids; ② Peak-area ratios suggested the changes of the protein and lipid structure and the decrease of DNA content; ③ Principal component analysis (PCA) further revealed significant changes in the DNA and protein content/structure. This study may have a new insight into the adverse reaction mechanism of cisplatin on Lactobacillus, moreover, it suggests that FTIR microspectroscopy may be a useful supplementary tool for investigating bacterial apoptosis.


Asunto(s)
Lacticaseibacillus paracasei , Apoptosis , Cisplatino/farmacología , Análisis de Fourier , Espectroscopía Infrarroja por Transformada de Fourier
13.
Cancer Manag Res ; 12: 2265-2278, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32273764

RESUMEN

PURPOSE: Previous studies have identified the important roles of a long noncoding RNA called FGD5 antisense RNA 1 (FGD5-AS1) in several types of human cancer. Nonetheless, to our knowledge, the expression and functions of FGD5-AS1 in esophageal squamous cell carcinoma (ESCC) have not been clarified. In this study, we aimed to determine the expression status of long noncoding RNA FGD5-AS1 in ESCC, determine its participation in ESCC progression, and uncover the underlying mechanisms. METHODS: ESCC tissue samples and paired normal adjacent tissues were collected to quantify FGD5-AS1 expression by reverse-transcription quantitative PCR. The effects of FGD5-AS1 on ESCC cell proliferation, apoptosis, migration, and invasion in vitro as well as tumor growth in vivo were studied using a Cell Counting Kit-8 assay, flow cytometry, Transwell migration and invasion assays, and an in vivo tumor xenograft experiment. RESULTS: FGD5-AS1 was found to be aberrantly upregulated in both ESCC tumors and cell lines compared to the control groups. Increased FGD5-AS1 expression manifested a close association with tumor size, TNM stage, and lymph node metastasis in patients with ESCC. Overall survival of patients with ESCC was shorter in the FGD5-AS1 high-expression group than in the FGD5-AS1 low-expression group. An FGD5-AS1 knockdown markedly attenuated ESCC cell proliferation, migration, and invasion and promoted apoptosis in vitro as well as slowed tumor growth in vivo. Mechanism investigation revealed that FGD5-AS1 can increase SP1 expression by sponging microRNA-383 (miR-383), thus functioning as a competing endogenous RNA. An miR-383 knockdown and recovery of SP1 expression attenuated the inhibition of the malignant characteristics of ESCC cells by the FGD5-AS1 knockdown. CONCLUSION: Thus, FGD5-AS1 enhances the aggressive phenotype of ESCC cells in vitro and in vivo via the miR-383-SP1 axis, which may represent a novel target for ESCC therapy.

14.
Biomater Sci ; 7(5): 2134-2143, 2019 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-30869660

RESUMEN

Smart micelles which undergo dramatic property changes in response to temperature have aroused extensive interest in specific cancer therapy. To date, studies on thermosensitive polymers have mainly focused on lower critical solution temperature (LCST) polymers. Materials with upper critical solution temperature (UCST) which can swell and disassemble at elevated temperatures have much less been documented, although they have been reported to be ideal carriers for quick and complete drug release upon applying a stimulus. Here, magnetic micelles with UCST are developed for doxorubicin (DOX) delivery. Hydrophobic Fe3O4 magnetic nanoparticles with a particle size of 8 nm are fabricated and enveloped in an amphiphilic polymer, poly(AAm-co-AN)-g-PEG (PAAP), to form UCST micelles (Fe3O4@PAAP). The resulting micelles exhibit excellent photothermal effects and burst drug release in response to near infrared (NIR) laser irradiation. The in vitro and in vivo antitumor experiments indicate that DOX-Fe3O4@PAAP micelles can significantly enhance the therapeutic effect upon NIR light irradiation. A novel thermosensitive platform is thus offered for in situ drug release and combined photothermal-chemotherapy, holding a favorable prospect for cancer therapy.


Asunto(s)
Portadores de Fármacos/química , Liberación de Fármacos , Rayos Infrarrojos , Fenómenos Magnéticos , Micelas , Temperatura , Animales , Compuestos Azo/química , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidad , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Células MCF-7 , Nanopartículas de Magnetita/química , Ratones , Piridinas/química , Soluciones , Distribución Tisular
15.
Am J Otolaryngol ; 40(2): 274-278, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30473168

RESUMEN

OBJECTIVE: To explore the hearing outcomes and prognostic factors in patients with sudden sensorineural hearing loss resulting from inner ear hemorrhage. METHODS: 42 patients (22 male and 20 female) were recruited from January 2016 to December 2017. Intravenous methylprednisolone and/or intratympanic corticosteroid were used as salvage therapy. The main measures included systemic risk factors and audiometric outcomes as proposed by American Academy of Otolaryngology-Head and Neck Surgery Hearing Loss Scale. All individuals were assessed at baseline, discharge (2 weeks post-treatment) and at 1, 3 and 6 months. RESULTS: The mean ages of patients were 39.3 ±â€¯14.8 yrs. Cardiovascular disorders were seen in 19.0-33.3% of cases. Restoration of hearing and speech discrimination abilities were assessed at the first month post-treatment versus initial levels (95.5 ±â€¯15.5 vs. 109.2 ±â€¯9.6 dB, p = 0.000; and 17.6 ±â€¯24.4 vs. 1.3 ±â€¯4.0%, p = 0.003, respectively). Word recognition scores continued to recover at month 6 (38.7 ±â€¯35.4%, p = 0.000), whereas puretone ceased to change (90.8 ±â€¯16.2 dB, p = 0.139). The final percentages of complete, partial and no recovery were 0%, 57.1% and 42.9% respectively. The prognosis was independent of accompanying systemic risk factors as analyzed in this study. Intratympanic intervention was associated with improved word recognition scores, although intravenous corticosteroid was not. CONCLUSIONS: Profound sudden sensorineural hearing loss caused by inner ear hemorrhage often has an unsatisfactory prognosis. However, this cohort did experience partial audiological recovery with delayed onset. Immediate and effective intratympanic corticosteroid may have therapeutic potential for this intractable disease.


Asunto(s)
Corticoesteroides/administración & dosificación , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Súbita/tratamiento farmacológico , Pérdida Auditiva Súbita/etiología , Audición , Hemorragia/complicaciones , Enfermedades del Laberinto/complicaciones , Adulto , Percepción Auditiva , Estudios de Cohortes , Femenino , Pérdida Auditiva Sensorineural/fisiopatología , Pérdida Auditiva Sensorineural/rehabilitación , Pérdida Auditiva Súbita/fisiopatología , Pérdida Auditiva Súbita/rehabilitación , Humanos , Infusiones Intravenosas , Inyección Intratimpánica , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Terapia Recuperativa , Resultado del Tratamiento
16.
Int J Pediatr Otorhinolaryngol ; 115: 19-23, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30368385

RESUMEN

OBJECTIVE: To study the genetic etiology of auditory neuropathy spectrum disorder (ANSD) in a Chinese family and perform a literature review of OTOF mutations and cochlear implantation (CI). METHODS: Sequential targeted next generation sequencing (NGS) and CI was performed for the proband. Further, 50 DNA samples from unrelated families with nonsyndromic deafness were examined for frequency determination. The impact of OTOF mutations on hearing recovery after CI was assessed through the literature survey. RESULTS: In the proband, the targeted NGS panel revealed five suspected variants in four genes (OTOF, EYA4, PCDH15, and GIPC3), of which two mutations-c.5098G > C (p.Glu1700Gln) and c.1702C > T (p.Arg568Trp)-in the OTOF gene were found to be correlated with ANSD. The c.5098G > C allele was identified in only one child from the 50 unrelated participants. The proband's hearing and speech abilities were restored 2 years after the surgery. Most ANSD patients (90.9%; 30/33) with OTOF mutations have acceptable surgical outcomes, as indicated by existing reports. CONCLUSIONS: Our results support the feasibility of CI for patients with ANSD and OTOF mutations, and this hypothesis was supported by the review of existing data. A larger number of cases studies is required to determine possible modifies on the prognosis of surgery.


Asunto(s)
Pérdida Auditiva Central/genética , Pérdida Auditiva Central/cirugía , Proteínas de la Membrana/genética , Alelos , Estudios de Casos y Controles , Preescolar , Implantación Coclear , Sordera/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Mutación , Resultado del Tratamiento
17.
Int J Pediatr Otorhinolaryngol ; 114: 5-8, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30262366

RESUMEN

OBJECTIVE: Most studies on sudden sensorineural hearing loss (SSNHL) do not differentiate the outcomes within varied affected ears in children. The present study was designed to determine the clinical differences between unilateral and bilateral SSNHL in children. METHODS: The clinical data, from a total of 101 pediatric patients with SSNHL, was retrospectively analyzed from January 2003 to December 2016. The main outcome measures included basic characteristics, etiology, clinical symptoms and treatment courses. RESULTS: When the bilateral group (n = 28) was compared to the unilateral group (n = 73), neither gender nor onset of SSNHL was significantly different (p > 0.05 each); However, bilateral SSNHL tended to occur in younger ages (8.1 ±â€¯4.0 yrs), with higher percentages of suspected etiologies (50%) and proportion of profound deafness (55.4%, p < 0.05 each). The short-term recovery rate was superior in the unilateral cases over the bilateral cases (37.0% vs. 12.5%, p < 0.05). Milder initial hearing threshold, early onset of treatment (5.6 ±â€¯4.8 days) with unilateral involvement and an older age (11.3 ±â€¯3.0 yrs) in bilaterally affected cases were associated with a better prognosis in this cohort. In addition, the unilateral group showed comparable outcomes, when sub-analyzed by comparison to that in either left- (n = 42) or right-sided (n = 31) SSNHL. CONCLUSION: Although bilateral and unilateral pediatric SSNHL could cause partial to complete cochlear lesion, they may be relevant to distinct backgrounds. Our data also provides valuable information about demographics and outcomes of SSNHL in children.


Asunto(s)
Pérdida Auditiva Bilateral/diagnóstico , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Súbita/diagnóstico , Pérdida Auditiva Unilateral/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Audición , Pérdida Auditiva Bilateral/etiología , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Súbita/etiología , Pérdida Auditiva Unilateral/etiología , Pruebas Auditivas/métodos , Humanos , Masculino , Pronóstico , Estudios Retrospectivos
18.
Mol Med Rep ; 18(2): 1253-1262, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29901127

RESUMEN

Auditory hair cell regeneration following injury is critical to hearing restoration. The Notch signaling pathway participates in the regulation of inner ear development and cell differentiation. Recent evidence suggests that microRNA (miR)­183 has a similar role in the inner ear. However, it is unclear how Notch signaling functions in hair cell regeneration in mammals and if there is cross­talk between Notch signaling and miR­183. The present study used a gentamicin­induced cochlear injury mouse model. Gentamicin­induced damage of the hair cells activated the Notch signaling pathway and downregulated miR­183 expression. Notch signaling inhibition by the γ­secretase inhibitor, 24­diamino­5­phenylthiazole (DAPT), attenuated gentamicin­induced hair cell loss and reversed the downregulation of miR­183 expression. Further investigation revealed that the novel hair cells produced, induced by DAPT, were derived from transdifferentiated supporting cells. Additionally, myosin VI­positive hair cell numbers were increased by Notch signaling inhibition in in vitro experiments with cultured neonatal mouse inner ear precursor cells. This effect was reversed by miR­183 inhibition. These findings indicate that the Notch signaling pathway served a repressing role during the regeneration of hair cells. Inhibiting this signal improved hair cell regeneration in the gentamicin­damaged cochlear model. miR­183 was demonstrated to be involved in hair cell differentiation and regeneration, and was required for the differentiation of the Notch­inhibited hair cells.


Asunto(s)
Diferenciación Celular , Células Ciliadas Auditivas/metabolismo , MicroARNs/biosíntesis , Receptores Notch/metabolismo , Regeneración , Transducción de Señal , Animales , Diaminas/farmacología , Células Ciliadas Auditivas/patología , Ratones , MicroARNs/genética , Receptores Notch/antagonistas & inhibidores , Receptores Notch/genética , Tiazoles/farmacología
19.
J Clin Lab Anal ; 32(9): e22592, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29926981

RESUMEN

BACKGROUND: Genetic analysis detected excessive mono-allelic recessive GJB2 mutations in individuals with idiopathic deafness; the remaining alleles in trans/cis are underdetermined. The aim of this study was to assess the contributions of variants in GJB3 or GJB6 to non-syndromic sensorineural hearing impairment (NSHI) in Chinese patients with mono-allelic GJB2 mutations. METHODS: The entire coding sequences of GJB3/GJB6, as well as deletions in GJB6, in a cohort of NSHI patients (n = 100) carrying likely pathogenic heterozygous GJB2 mutations, were tested. Targeted next generation sequencing was further performed in a multiplex family GDHY with moderate to profound NSHI. RESULTS: Putatively causative GJB3 variant underlied 1% (1/100) in this cohort. In family GDHY, we identified a rare GJB3 c.250G>A mutation, as double heterozygotes with GJB2 c.109G>A and/or a novel GJB2 mutation c.638T>C predicted to be damaging in a digenic inheritance after precluding other attributable mutations from 127 deafness genes. No GJB6 mutation was found. CONCLUSIONS: GJB3/GJB6 variants account for a low proportion in autosomal recessive GJB2 mutation carriers in our cohort. Environmental causes, or other NSHI relevant genes, revealed by targeted next generation sequencing or whole exome sequencing, may play major roles in triggering deafness in these patients.


Asunto(s)
Conexina 30/genética , Conexinas/genética , Pruebas Genéticas/métodos , Pérdida Auditiva/genética , Mutación/genética , Adolescente , Niño , Preescolar , Estudios de Cohortes , Simulación por Computador , Conexina 26 , Salud de la Familia , Femenino , Heterocigoto , Humanos , Masculino , Modelos Moleculares , Adulto Joven
20.
Drug Deliv Transl Res ; 8(5): 985-993, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29717473

RESUMEN

Systematic chemotherapy has required high time span for recovery in cancer patients, serious toxic effects, and increased the time of cancer-free survival of patient but decreased the overall survival time of patients irrespective of diseased condition(s). To compare the quick recovery of inhalable doxorubicin and cisplatin in the lung cancer patients. A total of 240 patients with non-small cell lung cancer (NSCLC) patients were randomly divided into two groups of 120 each. Patients had inhaled 25 mg/m2 doxorubicin (DON group) or 10 mg/m2 cisplatin (CPN group) once in a day for 21 days. Volume, diameter, type, and a number of lung nodes, pulmonary function, and 21-day lung cancer risk assessment were evaluated. One-way ANOVA following Bonferroni multiple comparison tests was performed at 95% of confidence level. DON and CPN both groups had shrunken the lung cancer nodule, decreased solid nodules and non-solid nodules, and increased partially solid nodules. The DON group (5.88 ± 3.98%) had strongly decreased nodule size than the CPN group (4.15 ± 2.92%; p < 0.0001, q = 3.721). The incidence of nodular size reduction was 9.47 ± 1.13% higher for doxorubicin than cisplatin. The CPN group had 36.53 ± 0.66% and the DON group had 34.65 ± 0.7% lung cancer risk assessment after 21 days (p < 0.0001, q = 3.785). Inhalable doxorubicin might be an effective therapy in NSCLC patients with acceptable hematologic and non-hematologic toxic effects. TRIAL REGISTRY: researchregistry3382, dated 28 December 2014 ( www.researchregistry.com ).


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Administración por Inhalación , Adulto , Anciano , Cisplatino/uso terapéutico , Método Doble Ciego , Doxorrubicina/uso terapéutico , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
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