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This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.
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Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Masculino , Ratones , Animales , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Glucógeno Hepático , Deficiencia Yang/tratamiento farmacológico , Deficiencia Yin/tratamiento farmacológico , Riñón , Peso CorporalRESUMEN
BACKGROUND: Germline variants in PTPN11 are the primary cause of Noonan syndrome with multiple lentigines (NSML) and Noonan syndrome (NS), which share common skin and facial symptoms, cardiac anomalies and retardation of growth. Hearing loss is considered an infrequent feature in patients with NSML/NS. However, in our cohort, we identified a group of patients with PTPN11 pathogenic variants that were primarily manifested in congenital sensorineural hearing loss (SNHL). This study evaluated the incidence of PTPN11-related NSML or NS in patients with congenital SNHL and explored the expression of PTPN11 and the underlying mechanisms in the auditory system. METHODS: A total of 1502 patients with congenital SNHL were enrolled. Detailed phenotype-genotype correlations were analysed in patients with PTPN11 variants. Immunolabelling of Ptpn11 was performed in P35 mice. Zebrafish with Ptpn11 knockdown/mutant overexpression were constructed to further explore mechanism underlying the phenotypes. RESULTS: Ten NSML/NS probands were diagnosed via the identification of pathogenic variants of PTPN11, which accounted for ~0.67% of the congenital SNHL cases. In mice cochlea, Shp2, which is encoded by Ptpn11, is distributed in the spiral ganglion neurons, hair cells and supporting cells of the inner ear. In zebrafish, knockdown of ptpn11a and overexpression of mutant PTPN11 were associated with a significant decrease in hair cells and supporting cells. We concluded that congenital SNHL could be a major symptom in PTPN11-associated NSML or NS. Other features may be mild, especially in children. CONCLUSION: Screening for PTPN11 in patients with congenital hearing loss and variant-based diagnoses are recommended.
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Pérdida Auditiva Sensorineural/congénito , Síndrome de Noonan/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Adolescente , Animales , Pueblo Asiatico/genética , Niño , Preescolar , Estudios de Cohortes , Femenino , Técnicas de Silenciamiento del Gen , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/epidemiología , Humanos , Incidencia , Lactante , Masculino , Ratones , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Transducción de Señal , Proteínas Wnt/metabolismo , Pez Cebra , beta Catenina/metabolismoRESUMEN
Despite a comprehensive national program of free HIV services, men living with HIV in Botswana participate at lower rates and have worse outcomes than women. Directed content analysis of five focus groups (n = 38) and 50 in-depth interviews with men and women with known and unknown HIV status in Gaborone, Botswana in 2017 used the "what matters most" (WMM) and "structural vulnerability" frameworks to examine how the most valued cultural aspects of manhood interact with HIV-related stigma. WMM for manhood in Botswana included fulfilling male responsibilities by being a capable provider and maintaining social status. Being identified with HIV threatened WMM, which fear of employment discrimination could further exacerbate. Our findings indicate how cultural and structural forces interact to worsen or mitigate HIV-related stigma for urban men in Botswana. These threats to manhood deter HIV testing and treatment, but interventions could capitalize on cultural capabilities for manhood to promote stigma resistance.
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Infecciones por VIH , Botswana , Femenino , Grupos Focales , Infecciones por VIH/epidemiología , Humanos , Masculino , Estigma SocialRESUMEN
Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) - a protein that functions in the Jak/ STAT pathway- are associated with ADNSHL Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. ConclusionIFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.
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Predisposición Genética a la Enfermedad , Pérdida Auditiva Sensorineural/genética , Receptores de Citocinas/genética , Receptores de Interferón/genética , Animales , Técnicas de Silenciamiento del Gen , Ligamiento Genético , Pérdida Auditiva Sensorineural/fisiopatología , Heterocigoto , Humanos , Janus Quinasa 1/genética , Ratones , Morfolinas , Mutación Missense/genética , Factor de Transcripción STAT3/genética , Transducción de Señal , Secuenciación del Exoma , Pez Cebra/genéticaRESUMEN
BACKGROUND: Myhre syndrome is a rare multisystem genetic disorder that is caused by de novo heterozygous gain-of-function variants in SMAD4. Patients with Myhre syndrome exhibit several phenotypes at different ages such as small size, autism, developmental delay, left-sided heart defects, and hearing loss and often have a characteristic facial appearance. The early clinical diagnosis of Myhre syndrome remains a major challenge, particularly in the first year of life. METHODS: A Chinese male infant with syndactyly of fingers, hypertelorism, short palpebral fissures, and short philtrum was enrolled into the ENT department of the Chinese PLA General Hospital. Whole exome sequencing analysis was used to detect the disease-causing variant. A literature review of Myhre syndrome was also performed. RESULTS: A recurrent de novo missense variant c.1498A > G p.I500V(p. Ile500Val) in SMAD4 was detected confirming the clinical diagnosis of Myhre syndrome at the age of 38 days. The infant appears to be the youngest reported case of Myhre syndrome. At 23-month follow-up, the affected infant has dysmorphic facial features, growth retardation, and previously undescribed complete syndactyly. Review the literatures noted several common features in Myhre syndrome patients including hearing loss (72.7%), characteristic facial features (26.0%-54.5%), finger and toe abnormalities (3.9%-48.1%), short stature (45.5%), and respiratory (30.0%) and cardiovascular problems (65.0%). CONCLUSIONS: Clinicians should have a low threshold to perform genetic testing on patients with features suggesting Myhre syndrome even in the first year of life. Although some individuals with Myhre syndrome have normal hearing, early onset or progressive hearing loss usually occur in one or both ears in most patients, with remarkable phenotypic heterogeneity. Syndactyly may be minor such as typical 2-3 toe involvement, or more complicated as was observed in our patient.
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Sordera , Pérdida Auditiva , Discapacidad Intelectual , Sindactilia , Humanos , Masculino , Trastornos del Crecimiento/genética , Discapacidad Intelectual/genética , Recién NacidoRESUMEN
Uridine diphosphate glucuronosyltransferase (UGT)1A4 is responsible for N-glucuronidation of tertiary amines but is a pseudogene in commonly used rodent models in toxicity and safety assessment. As a continuation of our investigation into the toxicity and safety assessment of pyrrolizidine alkaloid (PA)-containing herbs, we generated a UGT1A4-humanized (hUGT1A4) transgenic mouse model to systematically study the toxicity, metabolism network, and toxicokinetic characteristics of senecionine (a representative toxic PA) and compared with that in the wide-type controls in parallel. As results, senecionine-induced toxicity was significantly decreased as approved by mortality, pathology, and biochemistry assays in hUGT1A4 mice and cultured primary hepatocytes. More importantly N-glucuronidation adduct was exclusively identified in all the hUGT1A4 mice, liver microsomes, and cultured primary hepatocytes, yet absent in the wide-type controls. The variation in toxicokinetic characters was also observed between hUGT1A4 mice and the wide-type controls with a notably inhibition of the toxification metabolites, i.e., pyrrole-protein adducts, in hUGT1A4 mice. Conclusively, UGT1A4 plays an important role in detoxification of senecionine and the hUGT1A4 mouse model is promising for the pre-clinical evaluation of the efficacy and toxicity of tertiary amine agents in drug development and safety assessment.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Glucuronosiltransferasa , Alcaloides de Pirrolicidina , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Glucurónidos , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Ratones , Ratones Transgénicos , Microsomas Hepáticos/metabolismo , Alcaloides de Pirrolicidina/metabolismo , Alcaloides de Pirrolicidina/toxicidadRESUMEN
BACKGROUND: IFNLR1 has been recently identified to be related to autosomal dominant nonsyndromic sensorineural hearing loss (ADNSHL). It is reported to be expressed in the inner ear of mice and the lateral line of zebrafish. However, it remains unclear how defects in this gene lead to hearing loss. OBJECTIVES: To elucidate the global gene expression changes in zebrafish when the expression of ifnlr1 is downregulated. METHODS: Transcriptome analysis was performed on ifnlr1 morpholino knockdown zebrafish and the control zebrafish using RNA-seq technology. RESULTS: The results show that 262 differentially expressed genes (DEGs) were up-regulated while 146 DEGs were down-regulated in the E4I4-Mo zebrafish larvae compared to the control-Mo. Six pathways were significantly enriched, including steroid biosynthesis pathway, adipocytokine signaling pathway, cytokine-cytokine receptor interaction pathway, p53 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and terpenoid backbone biosynthesis pathway. Among them, three pathways (steroid biosynthesis pathway, cytokine-cytokine receptor interaction pathway and p53 signaling pathway) are immune-associated. CONCLUSIONS: The transcriptome analysis results contribute to the groundwork for future research on the pathogenesis of IFNLR1-associated hearing loss.
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Transcriptoma , Pez Cebra , Animales , Citocinas , Perfilación de la Expresión Génica , Inmunidad , Receptores de Citocinas/genética , Esteroides , Proteína p53 Supresora de Tumor/genética , Pez Cebra/genéticaRESUMEN
Non-syndromic hearing loss (NSHL) is a common neurosensory disease with an extreme genetic heterogeneity which has been linked to variants in over 120 genes. The LOXHD1 gene (DFNB77), encoding lipoxygenase homology domain 1, is a rare hearing loss gene found in several populations. To evaluate the importance of LOXHD1 variants in Chinese patients with NSHL, we performed genetic analysis on LOXHD1 in 2,901 sporadic Chinese patients to identify the aspect and frequency of LOXHD1 causative variants. Next-generation sequencing using a custom gene panel of HL was conducted on 2,641 unrelated patients and whole-exome sequencing on the remaining 260 patients. A total of 33 likely causative variants were identified in 21 patients, including 20 novel variants and 13 previously reported pathogenic variants. Each of the 20 novel variants was evaluated according to ACMG criteria. These findings showed that causative variants in LOXHD1 were found in about 0.72% (21/2,901) of Chinese NSHL patients. This study is by far the largest number of novel variants identified in this gene expanding the range of pathogenic variants in LOXHD1, and suggests that variants in this gene occur relatively commonly in Chinese NSHL patients. This extensive investigation of LOXHD1 in Chinese NSHL patients proposed six recurrent LOXHD1 variants. These findings may assist in both molecular diagnosis and genetic counseling.
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OBJECTIVE: To observe expression of CD38, a key modulator of nicotinamide dinucleotide (NAD+) metabolism in mice with knee osteoarthritis, and protective effect of CD38 inhibition during the osteoarthritis (OA) development. METHOD: The destabilization of the medial meniscus (DMM) model was performed in mice to mimic the process of OA. Immunofluorescence of CD38 was performed to evaluate its response during the OA process. Limb bud-derived mesenchymal cells were isolated for micromass culture. 100 nM or 1 µM CD38 inhibitor (78c) treatment for 14 days and CD38 sgRNA infection were then used to explore the effects of chondrogenic differentiation via Alcian blue staining. The expressions of chondrogenic markers were detected using RT-PCR and Western blot. To explore the protective effect of CD38 inhibitor on cartilage degradation during OA in vivo, a CD38 inhibitor was injected into the knee joint after DMM operations. Micro-CT analysis and Safranin O-fast green staining were used to evaluate subchondral bone micro-architecture changes and cartilage degeneration. RESULTS: Compared to the control group, the CD38 expression in superficial cartilage was obviously increased in DMM group (P < 0.05). During the normal chondrogenic differentiation, the extracellular matrix formed and expression of Sox9, Col2, aggrecan increased apparently while CD38 expression decreased, which could be reversed with ablation of CD38 in limb bud-derived mesenchymal cells. Consistent with findings in vitro, CD38 blockage via CD38 inhibitor injection protected against osteosclerosis in medial subchondral bone and cartilage degeneration in DMM-induced experimental mice. Compared to the Sham group, DMM mice showed significantly increased values of BV and BV/TV in subchondral bone (P < 0.05) and Mankin score, which could be rescued by 78c treatment (P < 0.05). Also the CD38 inhibitor contributed to homeostasis of anabolism and catabolism by upregulating Sox9, Col2, aggrecan and downregulating Runx2, Col10 and Mmp13. CONCLUSION: This study primarily implicates CD38 as an important regulator of chondrogenic differentiation. Inhibition of CD38 demonstrated protection against cartilage degeneration, which suggests that CD38 could be a potential therapeutic target for OA.
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ADP-Ribosil Ciclasa 1 , Cartílago Articular , Glicoproteínas de Membrana , Osteoartritis de la Rodilla , ADP-Ribosil Ciclasa 1/metabolismo , Agrecanos , Animales , Cartílago Articular/fisiopatología , Condrocitos , Modelos Animales de Enfermedad , Homeostasis , Glicoproteínas de Membrana/metabolismo , Meniscos Tibiales/cirugía , Ratones , Osteoartritis de la Rodilla/metabolismoRESUMEN
Pathogenic variants in MYO15A are known to cause autosomal recessive nonsyndromic hearing loss (ARNSHL), DFNB3. We have previously reported on one ARNSHL family including two affected siblings and identified MYO15A c.5964+3G > A and c.8375 T > C (p.Val2792Ala) as the possible deafness-causing variants. Eight year follow up identified one new affected individual in this family, who also showed congenital, severe to profound sensorineural hearing loss. By whole exome sequencing, we identified a new splice-site variant c.5531+1G > C (maternal allele), in a compound heterozygote with previously identified missense variant c.8375 T > C (p.Val2792Ala) (paternal allele) in MYO15A as the disease-causing variants. The new affected individual underwent unilateral cochlear implantation at the age of 1 year, and 5 year follow-up showed satisfactory speech and language outcomes. Our results further indicate that MYO15A-associated hearing loss is good candidates for cochlear implantation, which is in accordance with previous report. In light of our findings and review of the literatures, 58 splice-site variants in MYO15A are correlated with a severe deafness phenotype, composed of 46 canonical splice-site variants and 12 non-canonical splice-site variants.
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Sordera , Pérdida Auditiva , Humanos , Linaje , Miosinas/genética , Sordera/genética , Pérdida Auditiva/genética , Fenotipo , Familia , GenotipoRESUMEN
Dominant deafness-onychodystrophy (DDOD) syndrome is a rare autosomal dominant disorder caused by mutations in ATP6V1B2 gene. We previously generated an induced pluripotent stem cell (iPSC) line (CPGHi002-A) from a DDOD patient with a heterozygous c.1516 C>T mutation in the ATP6V1B2 gene. Here we genetically corrected the c.1516 C>T mutation in the ATP6V1B2 gene using CRISPR/Cas9 technology to generate an isogenic control, CPGHi002-A-1. The characterization of CPGHi002-A-1 demonstrates normal karyotype, pluripotent state, and potential to differentiate in vitro towards endoderm, mesoderm, and ectoderm.
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Células Madre Pluripotentes Inducidas , ATPasas de Translocación de Protón Vacuolares , Sistemas CRISPR-Cas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Heterocigoto , Humanos , Mutación , ATPasas de Translocación de Protón Vacuolares/genéticaRESUMEN
Mutations in the Forkhead Box C1 (FOXC1) are known to cause autosomal dominant hereditary Axenfeld-Rieger syndrome, which is a genetic disorder characterized by ocular and systemic features including glaucoma, variable dental defects, craniofacial dysmorphism and hearing loss. Due to late-onset of ocular disorders and lack of typical presentation, clinical diagnosis presents a huge challenge. In this study, we described a pathogenic in-frame variant in FOXC1 in one 5-year-old boy who is presented with hypertelorism, pupil deformation in both eyes, conductive hearing loss, and dental defects. By whole exome sequencing, we identified a 3 bp deletion in FOXC1, c.516_518delGCG (p.Arg173del) as the disease-causing variant, which was de novo and not detected in the parents, and could be classified as a "pathogenic variant" according to the American College of Medical Genetics and Genomics guidelines. After confirmation of this FOXC1 variant, clinical data on Axenfeld-Rieger syndrome-associated clinical features were collected and analyzed. Furthermore, Although the affected individual present hearing loss, however, the hearing loss is conductive and is reversible during the follow-up, which might not linke to the FOXC1 variant and is coincidental. Routine examination of FOXC1 is necessary for the genetic diagnosis of hypertelorism-associated syndrome. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling.
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Anomalías del Ojo , Enfermedades Hereditarias del Ojo , Segmento Anterior del Ojo/anomalías , Preescolar , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Enfermedades Hereditarias del Ojo/genética , Factores de Transcripción Forkhead/genética , Humanos , MasculinoRESUMEN
OBJECTIVE: To study the stress distribution under dynamic loading in the presence or absence of an abutment buffer layer by using three-dimensional finite element analysis. METHODS: A three-dimensional solid geometric model of an implant in a human mandible was established on the basis of CT scan data. A buffer-free abutment prosthesis and a buffer-abutment abutment prosthesis were installed above the implant. The buffer layer was made of high-density polyethylene. A vertical load of 200 N and a horizontal load of 100 N (45°) were concentrated on the centers of the implant restorations of the two groups. Stresses on the implant neck and body, abutment neck and body, central bolt neck and body, and bone interface were compared via three-dimensional finite element analysis. RESULTS: Stresses on the implant neck and body, abutment neck and body, central bolt neck and body, and bone interface on the abutment with a buffer layer were significantly lower than those on the abutment without a buffer layer. CONCLUSIONS: The increase in the buffer layer of the abutment neck significantly reduced stress on the implant neck, abutment, central bolt neck, and bone interface.
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Pilares Dentales , Implantes Dentales , Análisis del Estrés Dental , Análisis de Elementos Finitos , Humanos , Estrés MecánicoRESUMEN
Background: Home care workers (HCWs)-including home health aides, personal care aides, and other direct care workers-provide functional and other essential support that allows older, disabled, and seriously ill people to live at home. As a growing number of patients are aging and dying at home, HCWs are increasingly providing care at the end of life (EOL). Although prior qualitative studies have shown that patient death is an impactful and challenging experience for HCWs, the majority of HCWs receive almost no training on EOL issues. Objective: The goal of this scoping review is to identify intervention studies describing training of HCWs in EOL issues to map types of training and to assess the degree to which existing efforts address HCW health and well-being. Design: Our scoping review covered three databases and focused on articles published in English since 2000. Results: Of the 393 articles screened, 26 underwent full-text review and 6 met inclusion criteria. Only one article discussed training designed for and implemented with HCWs exclusively. Other trainings simultaneously targeted multiple kinds of workers. Supporting HCWs in reducing their stress and improving their coping skills was substantially addressed in only one article, although HCWs' emotional needs were addressed less centrally in several others. Conclusion: Our findings suggest that there is a paucity of EOL training interventions tailored specifically to the experiences and positioning of HCWs. We recommend that future intervention studies address the multiple facets of HCWs' stress related to patient death to improve EOL care in the home.
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Auxiliares de Salud a Domicilio , Cuidados Paliativos al Final de la Vida , Cuidado Terminal , Humanos , Investigación CualitativaRESUMEN
PURPOSE: To evaluate preoperative anxiety and postoperative quality of life in patients with periodontal mucogingival surgery, and provide a theoretical basis for preventing preoperative anxiety and improving postoperative quality of life in mucogingival surgery. METHODS: According to the inclusion and exclusion criteria, 26 patients with mucogingival surgery were randomly selected, including 13 cases undergoing free gingival graft and 13 cases undergoing subepithelial connective tissue graft. All patients were asked to answer the following questionnaires which included self-rating anxiety scale (SAS), modified dental anxiety scale (MDAS), pain evaluation using visual pain scale (VAS), clinical performance evaluation (swelling, bleeding, nausea, oral odor), and oral function evaluation (chewing, speaking, sleeping, working). Data analysis was performed using SPSS 18.0 software package. RESULTS: The preoperative SAS score was 44.33±11.99, 4 patients had anxiety, accounting for 15.38%. The preoperative MDSA score was 9.85±2.41, 4 patients had anxiety, accounting for 15.38%. The VAS values at 1 day, 3 days, 5 days, 7 days, and 10 days after surgery were moderate pain (4.54±1.32), mild pain (3.31±1.31), mild pain (2.00±1.14), and painless( 0.70±0.72), painless (0.08±0.27). The VAS values at 1 day, 3 days, and 5 days after FGG were greater than those after CTG (P<0.05).The most common discomforts after mucogingival surgery were swelling, bleeding, disturbance in chewing and speech. Swelling, disturbance in chewing and speech persisted until 7 days after surgery, and bleeding continued until 5 days after surgery. The postoperative discomfort of FGG was significantly higher than that of CTG. CONCLUSIONS: Four had preoperative anxiety prior to mucogingival surgery. The main clinical symptoms after surgery were moderate to mild pain, swelling, bleeding, disturbance in chewing and speech within 1-7 days after surgery. The effect of CTG on the quality of life of patients was significantly less than that of FGG.
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Ansiedad , Procedimientos Quirúrgicos Orales , Calidad de Vida , Humanos , Procedimientos Quirúrgicos Orales/psicología , Dimensión del Dolor , Dolor Postoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y CuestionariosRESUMEN
Michael reaction acceptors (MRAs) are a class of active compounds. There is a great prospect to screen STAT3 inhibitors from Eupatorium lindleyanum, furthermore, to discover lead compounds for anti-triple-negative breast cancer (TNBC). In this study, glutathione (GSH) was employed, and a UPLC-MS screening method was developed to discover MRAs. We screened MRAs which can inhibit STAT3 using a STAT3-dependent reporter system. Six sesquiterpene lactones, including a new compound Eupalinolide O (1), together with five known compounds, Eupalinolide I (2), Eupalinolide K (3), Eupalinolide H (4), Eupalinolide J (5) and Eupalinolide G (6) were isolated. Eupalinolide J was identified as MRA that decreased luciferase activity of STAT3. Preliminary activity assessment showed that Eupalinolide J could inhibit the viability of TNBC cell lines. We demonstrated that Eupalinolide J, which is a natural typical MRA, has a notable inhibition of STAT3 activity and a potential cytotoxic activity against TNBC cell lines.
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Antineoplásicos Fitogénicos/farmacología , Eupatorium/química , Lactonas/farmacología , Factor de Transcripción STAT3/antagonistas & inhibidores , Sesquiterpenos de Germacrano/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Cromatografía Liquida/métodos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Glutatión/metabolismo , Humanos , Lactonas/uso terapéutico , Extractos Vegetales/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos de Germacrano/uso terapéutico , Espectrometría de Masas en Tándem/métodos , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the POU class 4 transcription factor 3 (POU4F3) are known to cause autosomal dominant nonsyndromic hearing loss linked to the loci of DFNA15. In this study, we describe a pathogenic missense mutation in POU4F3 in a four-generation Chinese family (6126) with midfrequency, progressive, and postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 129 known deafness genes, next-generation sequencing, and bioinformatic analysis, we identified POU4F3 c.602T>C (p.Leu201Pro) as the disease-causing variant. This variant cosegregated with hearing loss in other family members but was not detected in 580 normal controls or the ExAC database and could be classified as a "pathogenic variant" according to the American College of Medical Genetics and Genomics guidelines. We conclude that POU4F3 c.602T>C (p.Leu201Pro) is related to midfrequency hearing loss in this family. Routine examination of POU4F3 is necessary for the genetic diagnosis of midfrequency hearing loss.
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Pueblo Asiatico/genética , Pérdida Auditiva Sensorineural/genética , Proteínas de Homeodominio/genética , Mutación Missense/genética , Factor de Transcripción Brn-3C/genética , Adulto , Anciano , Secuencia de Aminoácidos , Secuencia de Bases , Preescolar , Análisis Mutacional de ADN , Familia , Femenino , Proteínas de Homeodominio/química , Humanos , Persona de Mediana Edad , Linaje , Factor de Transcripción Brn-3C/químicaRESUMEN
PURPOSE: To evaluate the clinical effects of selective laser melting (SLM) deposition basal crowns and cobalt chromium alloy casting base crowns. METHODS: One hundred and sixty eight patients treated with either SLM deposition basal crowns (110 teeth) or cobalt chromium alloy casting basal crowns (110 teeth) were followed-up for 1 month, 6 months, 12 months and 24 months. The revised standard of American Public Health Association was used to evaluate the clinical effect of restoration, including the color of porcelain crowns, gingival inflammation, gingival margin discoloration, and crack or fracture. Data analysis was conducted with SPSS 20 software package for Student's t test and Chi-square test. RESULTS: Six cases were lost to follow-up. The patients who were treated with SLM deposition basal crowns (104 teeth) and cobalt chromium alloy casting base crowns (101 teeth) completed the study. Patients were more satisfied with SLM deposition cobalt chromium alloy porcelain crowns. There was 1 prosthesis with poor marginal fit after 24 months of restoration in SLM crowns. There were 6 prostheses with edge coloring and 8 with poor marginal fit in cobalt chromium alloy casting base crowns, which was significantly different between the 2 groups(P<0.05). CONCLUSIONS: The SLM deposition copings results in smaller edge coloring and better marginal fit than those of cobalt-chrome copings. Patients are pleased with short-term clinical results.
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Aleaciones de Cromo , Coronas , Rayos Láser , Porcelana Dental , HumanosRESUMEN
PURPOSE: The aim of this short-term study was to compare the clinical efficacy of 2 different methods to treat acute periodontal abscesses. METHODS: After patient selection, 100 cases of acute periodontal abscess were randomly divided into two groups. The experimental group was treated by supra- and subgingival scaling, while the control group was treated by incision and drainage. A clinical examination was carried out to record the following variables: subjective clinical variables including pain, edema, redness and swelling; objective clinical variables including gingival index(GI), bleeding index(BI), probing depth(PD),suppuration, lymphadenopathy and tooth mobility. The data was analyzed with SPSS 19.0 software package. RESULES: Subjective clinical variables demonstrated statistically significant improvements with both methods from the first day after treatment and lasted for at least 30 days(P<0.05), but the results of experimental group showed much better than the control group 1 day and 7 days after treatment. 30 days after treatment, there was no significant difference between the two groups in pain and swelling improvement(P>0.05), but the experimental group showed more improvement in edema and redness than the control group(P<0.05).On improving objective variables, the experimental group showed significant improvement in GI,BI,PD and suppuration 1 day after treatment(P<0.05).After 7 days, all objective clinical variables in the experimental group improved significantly(P<0.05) in the control group, there were significant improvements in GI,suppuration,lymphadenopathy and tooth mobility(P<0.05) but the four variables of the experimental group showed more improvement than the control group(P<0.05).After 30 days, all objective clinical variables improved significantly in both groups as compared to baseline, but in the experimental group, improvements were more significant regarding to GI,BI,PD,suppuration and tooth mobility(P<0.05). CONCLUSION: The method of supra- and subgingival scaling was rapid and effective in treatment of acute periodontal abscesses.
Asunto(s)
Absceso Periodontal , Pérdida de la Inserción Periodontal , Raspado Dental , Humanos , Índice Periodontal , Resultado del TratamientoRESUMEN
PURPOSE: To compare the clinical effect of Clearfil AP-X(TM) and 3M Filte k(TM) Z350 in filling Class IV cavity. METHODS: 200 teeth were divided into two groups after class-IV cavity preparation according to composite resin filling technique. These teeth were then filled by Clearfil AP-X(TM) (with Clearfil SE Bond) and 3M Filtek(TM) Z350 (with 3M Adper Prompt Bond) step by step according to the instruction manual. The clinical effect was evaluated and compared after 3 months, 6 months, 1 year and 2 years respectively. The data were collected and analyzed with USPH&Ryge evaluation standard and SPSS13.0 software package. RESULTS: The result indicated that there was no significant difference between the two group at half a year and 1 year. At 2-year there was significant difference in secondary caries occurrence,attrition, marginal discrepancy, marginal color and color matching between them, 3M group was better than clearfil group, but there was no significant difference in other indexes between them. CONCLUSIONS: When filling Class IV cavity, compared to Clearfil AP-X(TM), 3M Filtek(TM) Z350 has more advantages, and worthy of wider clinical application.