RESUMO
Objective: To understand the prevalence, blood pressure control, and influencing factors of hypertension in residents aged 35-75 years in Jiangsu Province, and provide data support and basis for hypertension prevention and treatment. Methods: A stratified cluster sampling method was adopted to conduct community population surveys in 22 districts and counties in 12 prefectures in Jiangsu from 2021 to 2022. A total of 123 531 permanent residents aged 35-75 years were included in the study. The questionnaire survey collected the information about the demographic characteristics, disease history, lifestyle, and control of hypertension of study subjects. Statistical software SPSS 23.0 was used for χ2 test and multivariate logistic regression analysis, and Joinpoint 4.9.1.0 software was used to evaluate the trend of age change. Results: The standardized prevalence of hypertension in study subjects was 46.60%, the prevalence was higher in men than in women, and in rural residents than in urban residents, and the standardized blood pressure control rate was 11.24%, and it was lower in men than in women and in rural residents than in urban residents. The hypertension prevalence and control rates showed increasing trends with age (both P<0.001). The multivariate analysis results showed that being man, older age, being rural resident, higher frequency of alcohol consumption, marital status of being separated and widowed, overweight and obese, abdominal obesity and stroke, diabetes mellitus and dyslipidaemic diseases histories, and family history of hypertension were risk factors for hypertension, and being man, being rural resident, living north area, higher frequency of alcohol consumption, and obesity were risk factors for blood pressure control. Conclusions: The prevalence of hypertension in residents aged 35-75 years in Jiangsu was high, and the rate of blood pressure control was low. It is suggested to take integrated intervention measures, especially in in rural residents and people with low levels of education to reduce the disease burden of the patients.
Assuntos
Hipertensão , População Rural , Humanos , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Prevalência , Masculino , Feminino , Idoso , Adulto , China/epidemiologia , População Rural/estatística & dados numéricos , Fatores de Risco , Inquéritos e Questionários , Pressão Sanguínea , População Urbana/estatística & dados numéricos , Estilo de VidaAssuntos
Infecções por Papillomavirus , Neoplasias dos Seios Paranasais , Humanos , Feminino , Infecções por Papillomavirus/virologia , Neoplasias dos Seios Paranasais/virologia , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/genética , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/virologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Papillomaviridae/genética , Fatores de Transcrição SOXERESUMO
Objective: To investigate the influence of corneal e-value on the effectiveness of orthokeratology in controlling myopia in children and adolescents. Methods: A retrospective cohort study was conducted, involving the data from 1 563 myopic patients (1 563 eyes) who underwent orthokeratology at the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine from June 2015 to August 2021 and adhered to lens wear for at least 2 years. The cohort consisted of 737 males and 826 females with an average age of (10.84±2.13) years. Based on corneal e-value parameters obtained from corneal topography, patients were categorized into a low e-value group (n=425) and a high e-value group (n=1 138). Data on gender, age, parental myopia history, and baseline measures such as spherical equivalent (SE), axial length, and corneal e-value were collected. Differences in axial length change and corneal fluorescein staining rates were compared between the two groups at 1 and 2 years after the start of lens wear. A generalized linear mixed model was established with axial length change as the dependent variable to analyze the correlation between axial length change and baseline corneal e-value. Results: The initial age of the 1 563 myopic patients was (10.84±2.13) years, with a baseline SE of (-3.05±1.30) D. After 1 year of lens wear, the axial length change was (0.20±0.19) mm in the low e-value group and (0.24±0.20) mm in the high e-value group. After 2 years, the changes were (0.38±0.25) mm and (0.43±0.27) mm, respectively, with statistically significant differences (all P<0.05). The incidence of corneal staining after 1 year of lens wear was 9.2% (39/425) in the low e-value group and 14.1% (160/1 138) in the high e-value group. After 2 years, the rates were 15.8% (67/425) and 21.8% (248/1 138), respectively, with statistically significant differences (all P<0.05). After adjusting for parental myopia history, age, SE, and baseline axial length, the baseline corneal e-value was positively correlated with axial length change at 1 and 2 years after lens wear (all P<0.05). Conclusions: Corneal e-value is an independent factor influencing the effectiveness of orthokeratology in controlling myopia. A smaller corneal e-value is associated with slower axial length growth after orthokeratology, indicating better control of myopia in treated eyes.
Assuntos
Lentes de Contato , Miopia , Procedimentos Ortoceratológicos , Masculino , Feminino , Criança , Humanos , Adolescente , Estudos Retrospectivos , Comprimento Axial do Olho , Miopia/terapia , Topografia da Córnea , Refração OcularRESUMO
OBJECTIVE: Tislelizumab, a monoclonal antibody against programed death protein-1 (PD-1), has shown encouraging antitumor activity in urothelial cancer. This study was designed to assess the efficacy and safety of tislelizumab in urotelial cancer in a real-world setting. METHODS: The study was a real-world retrospective study undertaken at Liaoning Cancer Hospital & Institute, China. Eligible patients were ≥18 years. Patients received 200-mg tislelizumab monotherapy intravenously every 3 weeks until the disease progressed to intolerable toxicity. Outcomes included an objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Between March 2020 and December 2022, 33 patients were enrolled. The median follow-up was 10.17 (IQR 5.73-12.47) months. Of all 33 patients, ORR and DCR were 30.30% (95% CI 15.6%-48.7%) and 42.42% (95% CI 25.48%-60.78%), respectively. The median PFS was 5.73 (95% CI 3.27-13.00) months, with a 12-month PFS rate of 31.90% (95% CI 19.20%-53.00%). The median OS was 17.7 (95% CI 12.80-not reach) months, with a 12-month OS rate of 67.50% (95% CI 52.70%-86.40%). Eleven (33.33%) and 8 (24.24%) experienced ≥grade 3 treatment-related adverse events (TRAEs) and immune-related Aes, respectively. No treatment-related deaths occurred. CONCLUSION: The excellent efficacy and controllable safety of tislelizumab in locally advanced or metastatic urothelial cancer suggest that it may be a promising therapeutic option for this population.
Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento , Neoplasias Urológicas/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso de 80 Anos ou maisRESUMO
Objective: To analyze the mortality trend of hypertension in Xinjiang Uygur Autonomous Region, Qinghai Province, Shaanxi Province, Gansu Province, Ningxia Hui Autonomous Region and Inner Mongolia Autonomous Region (6 provinces) in northwestern China, from 2013 to 2021, and evaluate the influence of hypertension on people's life expectancy. Methods: Based on national death surveillance data and demographic data in the 6 provinces from 2013 to 2021, the mortality rate, standardized mortality rate, life expectancy, cause eliminated life expectancy (CELE), potential gains in life expectancy (PGLEs) and life loss rate of hypertension were calculated. Software Joinpoint was used to analyze the mortality trends and calculate average annual percentage change (AAPC) and annual percentage change (APC) in hypertension deaths. Results: From 2013 to 2021, the overall standardized mortality rate of hypertension in the 6 provinces showed a downward trend (AAPC=-1.82%, P=0.050). The mortality rate in rural area was always higher than that in urban area, and showed an increasing trend after 2016 (APC=4.74%, P=0.003), and the mortality rate in men was always higher than that in women. The incidence trend of deaths of different types of hypertension were different, and the deaths caused by hypertensive heart disease accounted for the highest proportion (72.69%). In 2021, the life expectancy of the population in the 6 provinces increased by 1.01 years, the CELE increased by 0.93 years, the PGLEs decreased by 0.08 years, and the life loss rate decreased by 0.11% compared with 2013. Conclusions: The overall standardized mortality rate of hypertension showed a decreasing trend in the 6 northwestern provinces from 2013 to 2021, but it showed an increasing trend in rural area after 2016. Prevention of hypertension should be further strengthened in rural area, men and elderly population.
Assuntos
Cardiopatias , Hipertensão , Masculino , Humanos , Idoso , Feminino , China/epidemiologia , Hipertensão/epidemiologia , Expectativa de Vida , SoftwareRESUMO
Monocular elevation deficiency (MED) is a functional defect in upward eye movement caused by paralysis, restriction, or a combination of factors. The affected eye experiences limited movement in the upward, nasal, and temporal directions, often accompanied by downward deviation and ptosis. Previously known as double elevator palsy (DEP), MED can result from muscle paralysis responsible for upward movement, restriction of the inferior rectus muscle, or lesions in the supranuclear pathway. The Knapp procedure was once the most commonly used surgical approach for MED. However, in cases involving restriction of the inferior rectus muscle, a staged approach combining inferior rectus muscle weakening and subsequent Knapp procedure is necessary to avoid anterior segment ischemia. This has led to the development of alternative surgical techniques, such as single-rectus muscle transposition, partial tendon transposition, and muscle belly transposition. Differentiating MED subtypes based on the underlying paralysis or restriction etiology is crucial for determining the appropriate surgical plan. This review article summarizes the clinical features, classification, and available surgical options for MED, aiming to provide valuable insights for clinical research and treatment.
Assuntos
Blefaroptose , Humanos , Movimentos Oculares , Nariz , ParalisiaAssuntos
Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Humanos , Rituximab/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Sulfonamidas/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
Cataracts often develop early and rapidly in patients with high myopia, which is one of the common causes of vision loss in these patients. Cataract surgery is usually required to treat this condition. However, patients with high myopia have specific anatomies and pathological changes, and eye balance needs to be considered. Based on the domestic and international research literature, this article discusses related hot issues, including the use of a monofocal or multifocal intraocular lens, the design of the postoperative refractive state for both eyes, and the lens size and material selection.
Assuntos
Extração de Catarata , Catarata , Lentes Intraoculares , Miopia , Humanos , Acuidade Visual , Catarata/terapia , Miopia/cirurgiaRESUMO
An age-related cataract patient who underwent femtosecond laser intrastromal keratotomy in the right eye for presbyopia correction 8 years ago was subjected to femtosecond laser-assisted phacoemulsification, with implantation of a monofocal intraocular lens (IOL) and a trifocal IOL in the right and left eyes, respectively. The corneal stromal ring was complementary to the monofocal IOL, which recovered the distance and near visual acuity, in the right eye postoperatively. The trifocal IOL provided good intermediate visual acuity for the left eye. The vision of the patient reached an ideal level for all visual distances. The binocular fusion was within the normal range, and the stereoscopic vision was restored. We hope that this case report can act as a reference for the treatment of cataract after presbyopia corrective surgery.
Assuntos
Ceratotomia Radial , Implante de Lente Intraocular , Facoemulsificação , Presbiopia , Extração de Catarata/métodos , Humanos , Ceratotomia Radial/métodos , Terapia a Laser/métodos , Implante de Lente Intraocular/métodos , Lentes Intraoculares , Facoemulsificação/métodos , Presbiopia/cirurgia , Reoperação , Resultado do TratamentoRESUMO
Objective: To investigate the clinical efficacy and safety of compound wild chrysanthemum eye masks for mild and moderate dry eye. Methods: In this double-masked, multicenter, placebo-controlled, randomized trial, middle-aged and elderly patients with mild and moderate dry eye were enrolled from six hospitals (Xiamen Eye Center of Xiamen University, China-Japan Friendship Hospital, Peking Union Medical College Hospital, Wangjing Hospital of China Academy of Chinese Medical Sciences, Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine and Hebei Eye Hospital). The patients were assigned to the compound wild chrysanthemum eye mask group and the eye mask simulator group based on the random number table. Subjective symptoms of dry eye, visual acuity, break-up time (BUT), Schirmer â test, and corneal fluorescent staining were evaluated in all patients before treatment and at 1 and 2 weeks after treatment. All adverse reactions during the treatment and follow-up were recorded. Results: A total of 120 patients were enrolled. Among them, 112 subjects were included for statistical analyses after the exclusion of 8 subjects who were lost for follow-up or had an adverse event, with an age of (54.26±7.44) years. All the indicators were equally comparable between the two groups. Before treatment and at 1 and 2 weeks after treatment, the median (lower quartile, upper quartile) of total score of questionnaires in the eye mask group was 14.50 (10.00, 19.00), 9.00 (5.00, 14.00) and 7.00 (4.00, 10.00), respectively, and that in the control group was 14.00 (9.00, 22.50), 12.00 (6.00, 20.00) and 10.00 (3.50, 17.00), respectively. The score decreased significantly in both groups after 1 week (t=9.1604, S=398.00; P<0.01) and 2 weeks (S=681.00, 575.50; P<0.05) of treatment. The total score of questionnaires in the eye mask group was significantly lower than that in the control group (Z=3.27, 2.81; P<0.05) after treatment. After 1 week of treatment, the average BUT of the eye mask group was (5.71±2.31) s, which was significantly longer than that before treatment (5.06±2.00) s (S =208.50, P<0.05). But there was no significant difference in the control group (S=150.00, P>0.05). After 2 weeks of treatment, there was statistically significant difference in BUT between the two groups (S=407.00, t=3.07; P<0.01). After 1 week of the treatment, the amount of tear secretion in the eye mask group [(6.88±4.78) mm] was significantly larger than that before treatment (S=196.50, P<0.05), while the control group [(6.80±5.85) mm] showed no significant difference (S=55.00, P<0.05). After 2 weeks of the treatment, the amount increased significantly to (7.43±4.86) mm and (7.29±4.56) mm, respectively, in both groups (t=-3.29, -2.26; P<0.05). The difference in the average BUT, Schirmer â test result and corneal fluorescent staining between both groups was not statistically significant at each time point. Five mild adverse events occurred, including 2 adverse events (2 times, 3.51%) in the eye mask group and 3 adverse events (4 times, 5.36%) in the control group. Conclusions: Compound wild chrysanthemum eye masks can effectively improve the symptoms and physical signs of mild and moderate dry eye and can be used as an auxiliary treatment. (Chin J Ophthalmol, 2021, 57: 601-607).
Assuntos
Chrysanthemum , Síndromes do Olho Seco , Idoso , China , Córnea , Método Duplo-Cego , Síndromes do Olho Seco/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Soluções Oftálmicas , Lágrimas , Resultado do TratamentoRESUMO
PURPOSE: To study the relationship between surface membrane-bound APRIL and ITP. METHODS: The peripheral blood of all subjects, 50 patients diagnosed with ITP and 25 healthy controls, was collected. Flow cytometry was used to detect the expression of membrane-bound APRIL on immune cells and platelets. ELISA was used to detect the content of soluble APRIL in plasma. RESULTS: Membrane-bound APRIL was only expressed on the surface of platelets in both ITP patients and controls. APRIL expression on the platelet surface was significantly lower in newly diagnosed (P < 0.001) and chronic (P < 0.001) ITP patients than in controls. Platelet surface APRIL level was significantly enhanced in patients with complete remission after treatment (P = 0.02) but not in those with no response after treatment. Platelet surface APRIL level in ITP patients was negatively correlated with serum APRIL level (r = -0.09765, P = 0.0424). CONCLUSIONS: Platelet surface APRIL may play a key immunoregulative role. Platelet surface APRIL is likely to be one source of the excessive serum APRIL in ITP patients. The effectiveness of treatment may be measured by determining the platelet surface APRIL levels in ITP patients.
Assuntos
Autoimunidade , Plaquetas/imunologia , Plaquetas/metabolismo , Suscetibilidade a Doenças , Expressão Gênica , Púrpura Trombocitopênica Idiopática/etiologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Adulto , Idoso , Doenças Autoimunes , Biomarcadores , Gerenciamento Clínico , Suscetibilidade a Doenças/imunologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Resultado do Tratamento , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Adulto JovemRESUMO
The effects of remifentanil were studied on cerebral ischemia-reperfusion injury (IRI) in rats, and its regulatory effect was explored on the N-methyl D-aspartate receptor subtype 2B (NR2B)/calcium/calmodulin-dependent protein kinase type II subunit alpha (CaMKII) signaling pathway in cerebral tissues. A total of 40 Sprague-Dawley rats were randomly assigned into sham group, model group, low-dose group (remifentanil injected into the caudal veins at 2 µg/kg) and high-dose group (remifentanil injected into the caudal veins at 10 µg/kg). Then, in the model, low-dose and high-dose groups, the rat model of cerebral IRI was established through middle cerebral artery occlusion (namely, ischemia for 1 h and reperfusion for 2 h), while no thread was inserted into the rats in the sham group. Neurological function of rats in each group was evaluated, and the cerebral infarct size was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Moreover, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to determine the neuronal apoptosis level, and mitochondrial membrane potential was measured via JC-1 assay. Moreover, the reactive oxygen species (ROS) level in neurons and the malondialdehyde (MDA) content in cerebral tissues were determined using 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay and enzyme-linked immunosorbent assay (ELISA), respectively. Finally, the expression levels of apoptosis-associated proteins and the NR2B/CaMKIIα signaling pathway-associated proteins in cerebral tissues were measured by Western blotting. Remifentanil preconditioning substantially decreased the neurological score of rats (p<0.01), cerebral infarct size (p<0.01), neuronal apoptosis level (p<0.01), ROS level in neurons (p<0.01), MDA content (p<0.01) and expression levels of cysteinyl aspartate specific proteinase-3 (Caspase-3), NR2B, phosphorylated CaMKIIα (p-CaMKIIα) and p-cAMP responsive element binding protein (p-CREB) (p<0.01), but it increased the mitochondrial membrane potential (p<0.01) and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio (p<0.01). Remifentanil can repress the NR2B/ CaMKIIα signaling pathway in the neurons of rats with cerebral IRI to decrease the p-CREB expression, ROS level and MDA content in neurons, neuronal apoptosis level and cerebral infarct size, and increase the mitochondrial membrane potential, thereby protecting the neurological function.
Assuntos
Traumatismo por Reperfusão , Animais , Apoptose , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato , Remifentanil/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Transdução de SinaisRESUMO
OBJECTIVE: This study aims to clarify potential diagnostic and prognostic values of KLK11 in nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: KLK11 levels in 81 primary NPC tissues, 24 recurrent NPC tissues, and 60 nasopharyngeal tissues with chronic mucosal inflammation were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, receiver operating characteristic (ROC) curves were depicted for assessing the diagnostic value of KLK11 in primary and recurrent NPC. Next, correlation between KLK11 level and pathological indexes of NPC patients was analyzed by Chi-square test. Enrolled NPC patients were followed up for 5 years, and the follow-up data were recorded to determine the potential influence of KLK11 on overall survival by Kaplan-Meier method. In addition, Cox regression model was applied for assessing factors that could affect prognosis of NPC patients. RESULTS: It was found that KLK11 level was higher in primary NPC tissues than that in nasopharyngeal tissues with chronic mucosal inflammation. In recurrent NPC tissues, KLK11 was upregulated relative to primary ones. In addition, ROC curves revealed a certain diagnostic value of KLK11 in NPC. Overall survival was worse in primary and recurrent NPC patients expressing a high level of KLK11. By analyzing the pathological indexes of NPC patients, KLK11 level was found to be correlated with age, T stage, and clinical stage of NPC patients. Furthermore, KLK11 level was found to be the risk factor influencing the survival of NPC patients. CONCLUSIONS: KLK11 is upregulated in NPC tissues, and unfavorable to the prognosis of NPC. Besides, it can be utilized as a potential hallmark for diagnosing NPC.
Assuntos
Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Serina Endopeptidases/análise , Idoso , Feminino , Humanos , Masculino , Análise Multivariada , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Curva ROC , Serina Endopeptidases/metabolismoAssuntos
Trombose Coronária , Anticoagulantes/uso terapêutico , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/tratamento farmacológico , Trombose Coronária/etiologia , Vasos Coronários/diagnóstico por imagem , Quimioterapia Combinada , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , VarfarinaRESUMO
OBJECTIVE: The aim of this study was to uncover the expression characteristic and biological function of STYK1 in the progression of laryngeal squamous cell carcinoma (LSCC), and to explore the underlying mechanism. PATIENTS AND METHODS: Expression level of STYK1 in 44 paired LSCC and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between STYK1 level and clinical parameters of LSCC patients was analyzed. Subsequently, the regulatory effect of STYK1 on the proliferative ability of AMC-HN-8 and Hep-2 cells was evaluated by cell counting kit-8 (CCK-8) assay and colony formation assay. Dual-Luciferase reporter gene assay and rescue experiments were conducted to uncover the role of STYK1/TGF-ß1 axis in regulating the progression of LSCC. RESULTS: STYK1 was significantly up-regulated in LSCC tissues than that of adjacent normal tissues (p<0.05). LSCC patients with high expression level of STYK1 exhibited significantly higher clinical stage and lower survival rate (p<0.05). Knockdown of STYK1 remarkably attenuated viability and clonality in Hep-2 cells, while overexpression of STYK1 achieved the opposite trends in AMC-HN-8 cells (p<0.05). TGF-ß1 was confirmed to be the direct target binding STYK1, whose expression level was negatively regulated by STYK1. TGF-ß1 was significantly down-regulated in LSCC tissues (p<0.05). Meanwhile, its low expression predicted significantly poor prognosis of LSCC patients. In addition, TGF-ß1 was responsible for STYK1-regulated malignant progression of LSCC. CONCLUSIONS: STYK1 is upregulated in LSCC and is closely associated with T stage and poor prognosis. Furthermore, STYK1 promotes the proliferative ability of LSCC cells through targeting TGF-ß1, thus aggravating the malignant progression of LSCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Progressão da Doença , Neoplasias Laríngeas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Receptores Proteína Tirosina Quinases/genética , Fator de Crescimento Transformador beta1/genéticaRESUMO
Uveitis is a serious intra-ocular inflammatory disease that can lead to visual impairment even blindness worldwide. Notch signaling can regulate the differentiation of naive CD4+ T cells, influencing the development of uveitis. DNA methylation is closely related to the autoimmune diseases. In this study, we measured the Notch1 DNA methylation level, determined the Notch1 and related DNA methylases mRNA expression and evaluated the ratio of T helper type 17 regulatory T cell (Th17/Treg ) in peripheral blood mononuclear cells (PBMCs) from uveitis patients and normal control subjects; we also tested the levels of relevant inflammatory cytokines in serum from the participants. Results indicated that compared with those in normal control individuals, the expression of ten-eleven translocation 2 (TET2) and Notch1 mRNA is elevated in uveitis patients, whereas the methylation level in Notch1 DNA promotor region [-842 ~ -646 base pairs (bp)] is down-regulated, and is unrelated to anatomical location. Moreover, the Th17/Treg ratio is up-regulated in PBMCs from uveitis patients, accompanied by the elevated levels of proinflammatory cytokines [e.g. interleukin (IL)-2, IL-6, IL-17 and interferon (IFN)-γ] in serum from uveitis patients. These findings suggest that the over-expression of TET2 DNA demethylase may lead to hypomethylation of Notch1, activate the Notch1 signaling, induce naive CD4+ T cells to differentiate theTh17 subset and thus disturb the balance of the Th17/Treg ratio in uveitis patients. Overall, hypomethylation of Notch1 DNA is closely associated with the occurrence of uveitis. Our study preliminarily reveals the underlying mechanism for the occurrence of uveitis related to the hypomethylation of Notch1 DNA, providing a novel therapeutic strategy against uveitis in clinical practice.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas Proto-Oncogênicas/genética , Receptor Notch1/genética , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Uveíte/genética , Adolescente , Adulto , Células Cultivadas , Citocinas/metabolismo , DNA/análise , Metilação de DNA , Dioxigenases , Feminino , Humanos , Masculino , Uveíte/imunologia , Adulto JovemRESUMO
The osteogenic differentiation of mesenchymal stem cells (MSCs) has potential clinical values in the treatment of bone-related diseases. Long non-coding RNA H19 and microRNA-140-5p (miR-140-5p) have attracted much attention of researchers by virtue of their biological importance in cell differentiation and bone formation. Moreover, bioinformatics analyses suggest that miR-140-5p have the potential to bind with H19 and SATB homeobox 2 (SATB2). In this study, we further explored whether H19 could regulate osteogenic differentiation of human bone marrow-derived MSCs (BM-MSCs) by miR-140-5p/SATB2 axis. RT-qPCR assay was conducted to examine the expression of H19, miR-140-5p and SATB2. The osteogenic differentiation capacity of BM-MSCs was assessed through alkaline phosphatase (ALP) activity and osteogenic marker expression. The relationships among H19, miR-140-5p and SATB2 were examined through bioinformatics analyses, luciferase reporter assay, RIP assay and RNA pull-down assay. H19 expression was remarkably increased and miR-140-5p expression was dramatically reduced during osteogenic differentiation of BMMSCs. Functional analyses revealed that H19 overexpression or miR-140-5p depletion accelerated osteogenic differentiation of BM-MSCs. Conversely, H19 loss or miR-140-5p increase suppressed osteogenic differentiation of BM-MSCs. MiR-140-5p was confirmed as a target of H19, and miR-140-5p could bind to SATB2 as well. Moreover, H19 knockdown reduced SATB2 expression by upregulating miR-140-5p. Additionally, miR140-5p depletion antagonized the inhibitory effect of H19 knockdown on osteogenic differentiation of BMMSCs. And, miR-140-5p inhibited osteogenic differentiation of BM-MSCs by targeting SATB2. In conclusion, H19 promoted osteogenic differentiation of BM-MSCs through regulating miR-140-5p/SATB2 axis, deepening our understanding on the molecular mechanisms of H19 in coordinating osteogenesis.
Assuntos
Diferenciação Celular/genética , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteogênese/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Fosfatase Alcalina/metabolismo , Células da Medula Óssea/metabolismo , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Proteínas de Ligação à Região de Interação com a Matriz/genética , Osteoblastos/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: To evaluate the safety and efficacy of the seven-step two-lobe holmium laser enucleation of the prostate (HoLEP) technique with low power laser device, and to introduce the detailed operating procedures, key points, short-term outcomes of this modified HoLEP technique. METHODS: From March 2016 to November 2017, 90 patients underwent HoLEP in Peking University Third Hospital. The patients were divided into two groups: high-power group (32 patients) were performed with traditional Gilling's three-lobe enucleation using high power (90 W) laser; Low-power group (58 patients) were performed with seven-step two-lobe enucleation using low power (40 W) laser. The main steps of the low power seven-step two-lobe HoLEP phase included: (1) The identification of the correct plane between adenoma and capsule at 5 and 7 o'clock laterally to the veru montanum; (2) The connection of the bilateral plane by making a adenoma incision at the proximal point of veru montanum; (3) The extension of the dorsal plane under the whole three lobes between adenoma and capsule towards the bladder neck; (4) The separation of the middle lobe from two lateral lobes by making two retrograde incisions separately from apex 5 and 7 o'clock towards the bladder neck; (5) The enucleation of the middle lobe adenoma by extending the dorsal plane through into the bladder; (6) The prevention of the apex mucosa by making a circle incision at the apex of the prostate; (7) The en-bloc enucleation of the two lateral lobe adenomas by extending the lateral and ventral plane between adenoma and capsule from 5 and 7 o'clock to 12 o'clock conjunction and through into the bladder. RESULTS: The mean patient age was (66.25±5.37) years vs. (68.00±5.18) years; The mean body mass indexes were (24.13±4.06) kg/m2 vs. (24.57±3.50) kg/m2; The mean prostate specific antigen values were (3.23±2.47) µg/L vs. (6.00±6.09) µg/L; The average prostatic volumes evaluated by ultrasound was (49.03±20.63) mL vs. (67.55±36.97) mL. There was no significant difference between the two groups. Furthermore, there were no significant differences in terms of perioperative and follow up data, including operative time; enucleation efficiencies; hemoglobin decrease; blood sodium and potassiumthe change postoperatively; catheterization duration and hospital stay; the international prostate symptom scores and quality of life scores pre- and post-operatively. There was 1 transurethral resection of the prostate (TURP) conversion in high-power group and 1 transfusion in low-power group during the operations. The follow-up one month after operation showed no severe stress incontinence in both the groups, whereas 3 cases ejaculatory dysfunctions in high-power group versus 1 case in low-power group were observed; Other surgeryîrelated complications included: 2 cases postoperative hemorrhage (Clavien II and Clavien IIIb) in high-power group, 2 cases postoperative temperature more than 38 °C (Clavien I) and 1 case dysuria following catheter removal (Clavien I) in low-power group. CONCLUSION: Low power laser device can be applied safe and effectively for HoLEP procedure using the seven-step two-lobe HoLEP technique. The outcomes comparable with high power laser HoLEP can be achieved.