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1.
Hum Brain Mapp ; 44(6): 2407-2417, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36799621

RESUMO

Moyamoya disease (MMD) patients were now classified according to their cerebrovascular manifestations, with cognition and emotion ignored, which attenuated the therapy. The present study tried to classify them based on their cognitive and emotional performance and explored the neural basis underlying this classification using resting-state fMRI (rs-fMRI). Thirty-nine MMD patients were recruited, assessed mental function and MRI scanned. We adopted hierarchical analysis of their mental performance for new subtypes. Next, a three-step analysis, with each step consisting of 10 random cross validation, was conducted for robust brain regions in classifying the three subtypes of patients in a support vector machine (SVM) model with hypergraph of rs-fMRI. We found three new subtypes including high depression-high anxiety-low cognition (HE-LC, 50%), low depression-low anxiety-high cognition (LE-HC, 14%), and low depression-low anxiety-low cognition (LE-LC, 36%), and no hemorrhagic MMD patients fell into the LE-HC group. The temporal and the bilateral superior frontal cortex, and so forth were included in all 10 randomized SVM modeling. The classification accuracy of the final three-way classification model was 67.5% in average of 10 random cross validation. In addition, the S value between the frontal cortex and the angular cortex was positively correlated with the anxiety score and backward digit span (p < .05). Our results might provide a new perspective for MMD classification concerning patients' mental status, guide timely surgery and suggest angular cortex, and so forth should be protected in surgery for cognitive consideration.


Assuntos
Doença de Moyamoya , Humanos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/psicologia , Máquina de Vetores de Suporte , Encéfalo/diagnóstico por imagem , Cognição , Imageamento por Ressonância Magnética/métodos
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(7): 1017-1025, 2023 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37724404

RESUMO

OBJECTIVES: Immunoglobulin A nephropathy (IgAN) is one of the most common types of kidney disease, and kidney transplantation is the most effective treatment for end-stage renal disease. This study aims to analyze the clinical curative effect of renal transplantation for adults with IgAN and to discuss the efficacy and safety of kidney transplantation for IgAN at the perioperative period and medium- and long-term follow-up. METHODS: This retrospective study included the clinical and follow-up data of 81 adult patients with IgAN who underwent kidney transplantation at the Second Xiangya Hospital, Central South University from January 2018 to January 2022. Of the 81 patients whose age at (34.1±9.9) years old, 47 (58.0%) were male. The body mass index was (20.8±3.2) kg/m2, and the human leukocyte antigen (HLA) mismatch number was 3.5±1.2. The estimated glomerular filtration rate (eGFR) and daily 24-hour urine output for the recipients on the 1st, 5th, and 7th day after kidney transplantation and when they were discharged were analyzed. The recovery of the transplanted kidney and occurrence of complications were comprehensively evaluated. The eGFR, urinary protein, and occult blood were evaluated at the 6th, 12th, 24th, 36th, and 48th month and at the last follow-up. RESULTS: The follow-up time was (25.7±15.8) months. No primary non-function occurred in any patient during the perioperative period time. Fifty-one (63.0%) patients had immediate graft function recovery, and 16 (19.8%) patients had slow graft function recovery. Delayed recovery of graft function was observed in 14 (17.3%) patients. A total of 19 perioperative complications occurred, including 9 patients with acute rejection, 5 patients with urinary fistula, 1 thrombosis in both lower limbs, and 4 lymphatic fistula. The eGFR at 6th, 12th, 24th, 36th, and 48th month of follow-up were (65.3±22.9), (67.6±23.0), (64.3±21.8), (65.9±24.7), and (68.7±31.2) mL/(min·1.73 m2), respectively. The eGFR remained high during the medium- and long-term follow-ups. At the longest follow-up of 56 months, eGFR fluctuation was still mild, and the positive rate of urine protein and occult blood was low. IgAN recurred in 4 transplanted kidneys, accounting for 4.94% of the total patients, without severe renal insufficiency. Three patients had kidney dysfunction due to severe pneumonia, rejection, and stone in the transplanted kidney. The overall survival rate of the transplanted kidney was higher than 95%, and the survival rate of all patients was 100% till Januray 2022. CONCLUSIONS: Renal transplantation for adults with IgAN had a remarkable short-term effect. The recipients can be beneficial significantly to favorable midium- and long-term outcomes. IgAN recurrence is infrequent and rarely causes severe renal function damage.


Assuntos
Glomerulonefrite por IGA , Falência Renal Crônica , Transplante de Rim , Adulto , Humanos , Masculino , Adulto Jovem , Feminino , Glomerulonefrite por IGA/cirurgia , Estudos Retrospectivos , Rim , Falência Renal Crônica/cirurgia
3.
Neurosurg Rev ; 45(2): 1709-1720, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34859335

RESUMO

Whether surgical revascularization can prevent recurrent hemorrhage in hemorrhagic moyamoya disease (HMD) patients remains a matter of debate. This study mainly aims at the comparison of treatment effect between surgical revascularization and conservative treatment of adult HMD patients. We retrospectively enrolled 322 adult HMD patients, including 133 in revascularization group and 189 in conservative group. The revascularization group included patients who underwent combined (n = 97) or indirect revascularization alone (n = 36). Ninety-two and forty-one patients underwent unilateral and bilateral revascularization respectively. The modified Rankin scale (mRS) was used to assess the functional status. The comparison was made based on initial treatment paradigm among two categories: (1) revascularization vs. conservative, (2) unilateral vs. bilateral revascularization. The rebleeding rate was significantly lower in revascularization group than that in conservative group (14.3% vs. 27.0%, P = 0.007). As for the functional outcomes, the average mRS was significantly better in revascularization group (1.7 ± 1.5) than that in conservative group (2.8 ± 1.9) (P < 0.001). The death rate in revascularization group was 8.3% (11/133), comparing to 20.1% (38/189) in conservative group (P = 0.004). While comparing between unilateral and bilateral revascularization within the revascularization group, the result demonstrated lower annual rebleeding rate in bilateral group (0.5%/side-year) than that in unilateral group (3.3%/side-year) (P = 0.001). This study proved the better treatment efficacy of surgical revascularization than that of conservative treatment in HMD patients, regarding both in rebleeding rate and mortality rate. Furthermore, bilateral revascularization seems more effective in preventing rebleeding than unilateral revascularization.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Adulto , Hemorragia Cerebral/cirurgia , Tratamento Conservador , Humanos , Doença de Moyamoya/complicações , Doença de Moyamoya/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
4.
J Stroke Cerebrovasc Dis ; 30(1): 105413, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33160127

RESUMO

BACKGROUND: In adult patients with moyamoya disease (MMD) underwent combined revascularization, cerebral infarction during the acute postoperative phase is common and can lead to neurological dysfunction after revascularization in MMD patients. The aim of this study was to share the experience of individualized perioperative blood pressure (BP) management for adult MMD patients in one single center. METHODS: We retrospectively reviewed 144 adult patients with MMD who underwent 186 procedures of combined revascularization at our institution from March 2013 to July 2019. Clinical features and outcomes were analyzed, in particular regarding cerebral infarction and hyperperfusion syndrome (HPS). All of the patients received individualized management perioperatively, especially about the blood pressure management according to the characteristics of moyamoya disease. RESULTS: Postoperative cerebral infarction and HPS within 14 days after revascularization were recorded. Cerebral infarction occurred in four (2.1%) procedures among four patients. No patients suffered from a malignant cerebral infarction and only one patient had permanent neurological deficits. The incidence of HPS was 10.8% and no one presented with intracranial hemorrhage. All of the symptoms were reversible without any brain parenchymal injury. CONCLUSIONS: Our findings suggest that we can decrease the incidence and extent of cerebral infarction in adult MMD patients following combined revascularization by individualized perioperative BP management.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Infarto Cerebral/prevenção & controle , Revascularização Cerebral , Hidratação , Doença de Moyamoya/cirurgia , Assistência Perioperatória , Adulto , Anti-Hipertensivos/efeitos adversos , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Infarto Cerebral/fisiopatologia , Revascularização Cerebral/efeitos adversos , Circulação Cerebrovascular , Feminino , Hidratação/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
5.
Pediatr Transplant ; 23(6): e13386, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30884087

RESUMO

No studies have reported making use of kidneys from pediatric donors with severe HFMD. Here, we retrospectively analyzed the feasibility and clinical effect of six cases of kidney transplantation from four pediatric donors with severe HFMD in our center between January 2014 and December 2016. The donors' age ranged from 6 months to 3 years and 11 months. The recipients' age ranged from 18 to 41 years. Single kidney transplantation was performed in four recipients, and dual splitting kidney transplantation and en bloc kidney transplantation were performed in two recipients, respectively. During the 1.5-4 years follow-up, all recipients maintained normal kidney allograft function except for one recipient whose allograft was removed due to the allograft artery thrombosis. The survival rates of recipient and allograft were 100% and 83.3%, respectively. None of the six recipients showed any symptoms associated with HFMD. In conclusion, it is feasible to perform kidney transplantation from pediatric donors with severe HFMD to adult recipients with immunity to the pathogens. The clinical effect is satisfactory.


Assuntos
Doença de Mão, Pé e Boca/fisiopatologia , Transplante de Rim , Doadores de Tecidos , Adulto , Aloenxertos , Pré-Escolar , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Lactente , Rim/cirurgia , Masculino , Estudos Retrospectivos , Trombose
6.
Am J Transplant ; 18(9): 2200-2207, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29446251

RESUMO

Pediatric kidney donors remain underutilized due to the high risk of postoperative thrombosis. To address this problem, we developed a novel en bloc kidney transplantation technique using donor thoracic aorta and the distal abdominal aorta as inflow and outflow tracts, respectively. Briefly, eight kidneys from deceased infant donors under five months old and with low body weight (1.9-4.9 kg) were transplanted en bloc into four pediatric and four adult patients. The donor's common iliac artery or external iliac artery was anastomosed to the recipient's distal external iliac artery or inferior epigastric artery, respectively, as an outflow tract. Recipients received basiliximab or antithymocyte globulin as induction therapy followed by tacrolimus, mycophenolate mofetil, and prednisone but without prophylactic anticoagulation. Delayed graft function was observed in one patient but was reversed at 90 days posttransplant. Two patients had urine leakage, which was cured by conservative treatment. Two recipients developed lung infections that eventually cleared. No patients experienced posttransplant vascular thrombosis. After 1-1.5 years of follow-up, all patients are well and have normal serum creatinine levels. In conclusion, this novel en bloc kidney transplantation technique using a modified arterial inflow and outflow tract can prevent vascular thrombosis and provide adequate graft function.


Assuntos
Aorta Abdominal/cirurgia , Peso Corporal , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Trombose/prevenção & controle , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Adulto , Criança , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico
7.
Br J Clin Pharmacol ; 84(7): 1587-1597, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29607533

RESUMO

AIMS: The aims of the present study were to characterize the pharmacokinetics of voriconazole in renal transplant recipients and to identify factors significantly affecting pharmacokinetic parameters. We also aimed to explore the optimal dosing regimens for patients who developed invasive fungal infections. METHODS: A total of 105 patients (342 concentrations) were included prospectively in a population pharmacokinetic analysis. Nonlinear mixed-effects models were developed using Phoenix NLME software. Dosing simulations were performed based on the final model. RESULTS: A one-compartment model with first-order absorption and elimination was used to characterize voriconazole pharmacokinetics. Population estimates of clearance, volume of distribution and oral bioavailability were 2.88 l·h-1 , 169.3 l and 58%, respectively. The allele frequencies of cytochrome P450 gene (CYP) 2C19*2, *3 and *17 variants were 29.2%, 5.2% and 0.5%, respectively. CYP2C19 genotype had a significant effect on the clearance. Voriconazole trough concentrations in poor metabolizers were significantly higher than in intermediate metabolizers and extensive metabolizers alike. The volume of distribution increased with increased body weight. The oral bioavailability was substantially lower within 1 month after transplantation but increased with postoperative time. Dosing simulations indicated that during the early postoperative period, poor metabolizers could be treated with 150 mg intravenously or 250 mg orally twice daily; intermediate metabolizers with 200 mg intravenously or 350 mg orally twice daily; and extensive metabolizers with 300 mg intravenously twice daily. CONCLUSIONS: Using a combination of CYP2C19 genotype and postoperative time to determine the initial voriconazole dosing regimens followed by therapeutic drug monitoring could help to advance individualized treatment in renal transplantation patients with invasive fungal infections.


Assuntos
Antifúngicos/farmacocinética , Citocromo P-450 CYP2C19/genética , Modelos Biológicos , Voriconazol/farmacocinética , Administração Oral , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Disponibilidade Biológica , Variação Biológica da População/fisiologia , Peso Corporal , Citocromo P-450 CYP2C19/metabolismo , Relação Dose-Resposta a Droga , Feminino , Genótipo , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Absorção Intestinal , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/imunologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Período Pós-Operatório , Estudos Prospectivos , Fatores de Tempo , Transplantados , Voriconazol/administração & dosagem , Voriconazol/efeitos adversos , Adulto Jovem
8.
Ren Fail ; 38(8): 1199-205, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27453328

RESUMO

BACKGROUND: NDUFA4L2 is overexpressed in VHL-deficient cell lines and neuroblastoma. The clinical significance of NDUFA4L2 in clear cell renal cell carcinoma (ccRCC) has not been well studied. Therefore, we evaluated the prognostic value of NDUFA4L2 in ccRCC patients. METHODS: In our study, NDUFA4L2 expression in 86 cases of ccRCC and adjacent normal tissues was monitored by immunohistochemistry, semi-quantitative RT-PCR, and Western blot analyses. The relationship between NDUFA4L2 expression and the clinical features of ccRCC was assessed. RESULTS: The results showed that NDUFA4L2 protein expression was found to be higher in ccRCC tissues 81.4% (70/86) than in normal tissues 26.7% (23/86) (p = 0.021). The average level of NDUFA4L2 mRNA expression was found to be 122.23 ± 6.018 and 21.34 ± 1.036 in ccRCC tissue and adjacent normal tissue (p < 0.001). NDUFA4L2 expression levels were correlated with some clinical features of ccRCC. Multivariate analysis showed NDUFA4L2 expression was an independent prognostic factor for ccRCC patients. CONCLUSIONS: Our study has provided the significant clinical relevance of NDUFA4L2 in ccRCC and suggested that ccRCC patients with NDUFA4L2 overexpression may be suitable as a potential therapeutic target for ccRCC patients.


Assuntos
Carcinoma de Células Renais/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Neoplasias Renais/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , China , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , RNA Mensageiro/genética
9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 39(2): 204-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24608394

RESUMO

OBJECTIVE: To gain an insight into the transplantation with donor kidneys from extended criterion donation after cardiac death (DCD) and to improve the management during and after renal transplantation METHODS: Renal transplantation in 2 patients who used organs from small pediatric donors (<3 years) was performed. The graft kidneys were procured from 1 donor aged 11 months and the other 1 year and 7 months. The 2 donors were diagnosed as brain death caused by serious infantile hepatitis syndrome and severe craniocerebral injury, respectively. After the cardiac death, en bloc organ resection was performed. En bloc kidneys were transplanted to 2 adult recipients who were 37 and 41 years old, respectively. RESULTS: The recipients were followed-up for 6 months. Both of them developed large volume of bloody drainage in the early post-operational period and relieved after relevant treatment. The kidney grafts functioned well and no other surgical complications or acute rejections happened during the follow-up. CONCLUSION: Based on modified peri-operative techniques, it is safe to perform renal transplantation with kidneys procured from cardiac death donors who are younger than 3 years old, an important source to increase the number of organs available for transplantation, yet the vascular complications require attention.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim , Doadores de Tecidos , Adulto , Humanos , Lactente , Rim , Período Pós-Operatório
10.
Int J Infect Dis ; 141: 106962, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38360204

RESUMO

OBJECTIVES: SARS-CoV-2 pneumonia poses significant challenges to health systems worldwide, particularly, in severe and critical cases. Immunosuppressed renal transplant recipients appear to be at a particularly high risk for severe or critical COVID-19 illness. However, few studies elucidated the risk factors of SARS-CoV-2 pneumonia in renal transplant recipients with COVID-19. METHODS: A postinfection cross-sectional survey was conducted in 312 renal transplant recipients and 503 age- and sex-matched controls to explore risk factors for SARS-CoV-2 pneumonia in immunosuppressed renal transplant recipients. RESULTS: The results showed that renal transplant recipients had a much higher incidence of SARS-CoV-2 pneumonia (48.1%) after infection with the SARS-CoV-2 Omicron variant than controls (5.6%). The multivariate binary logistic regression analysis identified older age, lower creatinine clearance before infection, and higher dose of prednisone before infection as risk factors for SARS-CoV-2 pneumonia in renal transplant recipients. Preexisting renal dysfunction was a major risk factor for SARS-CoV-2 pneumonia, with an odds ratio of 3.27 (1.01-10.61). CONCLUSIONS: Preexisting renal graft dysfunction was a major risk factor for SARS-CoV-2 Omicron variant pneumonia. It is suggested that high-risk renal transplant recipients should undergo computed tomography scanning within 14 days after infection with SARS-CoV-2.


Assuntos
COVID-19 , Transplante de Rim , Pneumonia , Humanos , Transplante de Rim/efeitos adversos , SARS-CoV-2 , Estudos Transversais , COVID-19/complicações , COVID-19/epidemiologia , Fatores de Risco , Transplantados
11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 38(1): 90-4, 2013 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-23406862

RESUMO

OBJECTIVE: To better understand the pre-operation evaluation of donor kidneys from extended criteria donation after cardiac death and to improve the management during and after renal transplantation. METHODS: Both of the donor kidneys were from the donor who underwent liver transplantation 5 years ago in the Center of Organ Transplantation of Central South University. The donor was admitted because of liver function deterioration which led to hepatic coma, brain death, hepatorenal syndrome and cardiac death sequentially. Deceased donor score (DDS) and "zero point" kidney biopsy were applied to evaluate the donor kidney. After thorough examination of the donor and the renal function, renal transplantation was performed on 2 recipients. RESULTS: The recipients were followed up by 6 months, both of whom developed pulmonary infection and relieved after treatments. The kidney grafts functioned well and no surgical complication and no acute rejection occurred during the follow-up. CONCLUSION: Proper evaluation of the donor organs ensures the safety of renal transplantation with kidneys from cardiac death donors who underwent liver transplantation, which is an important way to increase the number of organs for transplantation, yet the long-term effects need further observation.


Assuntos
Parada Cardíaca , Transplante de Rim , Transplante de Fígado , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Adulto , Morte , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
12.
Medicine (Baltimore) ; 102(23): e33997, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37335666

RESUMO

Work stress and anxiety are major problems faced by graduate nursing students. Research on the relationships between these factors has the potential to improve the psychological state of graduate nursing students. This study gathered a valid sample of 321 graduate nursing students and performed structural equation modeling and multiple regression to test the proposed research model. The study used the Clinician Work Stress Scale, Psychological Capital Scale, Social Support Rating Scale, and State-Trait Anxiety Scale to survey the sample. Correlation analysis showed that job stress was significantly correlated with psychological capital (r = -0.46, P < .01), social support (r = -0.21, P < .01), and anxiety (r = 0.47, P < .01). Psychological capital (r = -0.56, P < .01) and social support (r = -0.43, P < .01) were significantly correlated with anxiety. The results of the path analysis showed that psychological capital (0.21, 95% confidence interval: 0.19-0.39) and social support (0.07, 95% CI: 0.02-0.15) played a mediating role in the relationship between job stress and anxiety, and the mediating effect accounted for a percentage of the total effect (51.85%). There is a direct relationship between clinical social work stress and anxiety among nursing postgraduates. Anxiety is significantly reduced through the intermediary effects of psychological capital and social support.


Assuntos
Estresse Ocupacional , Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Estresse Ocupacional/epidemiologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Transtornos de Ansiedade , Apoio Social
13.
Medicine (Baltimore) ; 102(37): e35207, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37713842

RESUMO

This study examines the current status of and relationship between learning burnout, professional commitment, and psychological capital in undergraduate clinical medical students. A total of 249 undergraduate students were randomly selected from a 5-year clinical medical program at a medical university in Shandong, China. The study employed the Learning Burnout Scale, Professional Commitment Scale, Psychological Capital Scale to survey the sample, and performed structural equation modeling and multiple regression to test the proposed research model using SPSS 19.0. Significant differences in learning burnout were found among students in terms of their gender, years in the medical program, and student leadership (t = 1.811, F = 22.091, t = -2.295; P < .01). There were also significant differences in their professional commitment according to their gender, years in the program, and student leadership (t = -2.711, F = 4.275, t = 3.389; P < .01). Psychological capital differed significantly based on gender, years in the program, and student leadership (t = 8.709, F = 6.182, P < .01, t = 2.086, P < .05). Learning burnout showed significant negative correlations with professional commitment and psychological capital (r = -0.311, r = -0.291; P < .01). The psychological capital and professional commitment of undergraduate students of clinical medicine serve as predictors of learning burnout. Psychological capital partially mediates the relationship between professional commitment and learning burnout.


Assuntos
Esgotamento Profissional , Estudantes de Medicina , Humanos , Esgotamento Profissional/epidemiologia , Aprendizagem , Esgotamento Psicológico , China/epidemiologia
14.
J Genet Genomics ; 49(3): 208-216, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861413

RESUMO

Decreased functional ß-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10 (GRB10), a negative regulator of insulin and mTORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. ß-cell-specific knockout of Grb10 in mice increased ß-cell mass and improved ß-cell function. Grb10-deficient ß-cells exhibit enhanced mTORC1 signaling and reduced ß-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced ß-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of ß-cell dedifferentiation and ß-cell mass, which exerts its effect by inhibiting mTORC1 signaling.


Assuntos
Diabetes Mellitus Experimental , Proteína Adaptadora GRB10 , Animais , Desdiferenciação Celular/genética , Proliferação de Células/genética , Proteína Adaptadora GRB10/genética , Proteína Adaptadora GRB10/metabolismo , Insulina/metabolismo , Camundongos
15.
Front Immunol ; 13: 979983, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059468

RESUMO

Background: Patients after kidney transplantation need to take long-term immunosuppressive and other drugs. Some of these drug side effects are easily confused with the symptoms of Fanconi syndrome, resulting in misdiagnosis and missed diagnosis, and causing serious consequences to patients. Therefore, improving awareness, early diagnosis and treatment of Fanconi syndrome after kidney transplantation is critical. Methods: This retrospective study analyzed 1728 cases of allogeneic kidney transplant patients admitted to the Second Xiangya Hospital of Central South University from July 2016 to January 2021. Two patients with Fanconi syndrome secondary to drugs, adefovir dipivoxil (ADV) and tacrolimus, were screened. We summarized the diagnostic process, clinical data, and prognosis. Results: The onset of Fanconi syndrome secondary to ADV after renal transplantation was insidious, and the condition developed after long-term medication (>10 years). It mainly manifested as bone pain, osteomalacia, and scoliosis in the late stage and was accompanied by obvious proximal renal tubular damage (severe hypophosphatemia, hypokalemia, hypocalcemia, hypouricemia, glycosuria, protein urine, acidosis, etc.) and renal function damage (increased creatinine and azotemia). The pathological findings included mitochondrial swelling and deformity in renal tubular epithelial cells. The above symptoms and signs were relieved after drug withdrawal, but the scoliosis was difficult to rectify. Fanconi syndrome secondary to tacrolimus has a single manifestation, increased creatinine, which can be easily confused with tacrolimus nephrotoxicity. However, it is often ineffective to reduce the dose of tacrolomus, and proximal renal failure can be found in the later stage of disease development. There was no abnormality in the bone metabolism index and imageological examination findings. The creatinine level decreased rapidly, the proximal renal tubule function returned to normal, and no severe electrolyte imbalance or urinary component loss occurred when the immunosuppression was changed from tacrolimus to cyclosporine A. Conclusions: For the first time, drug-induced Fanconi syndrome after kidney transplantation was reported. These results confirmed that the long-term use of ADV or tacrolimus after kidney transplantation may have serious consequences, some of which are irreversible. Greater understanding of Fanconi syndrome after kidney transplantation is necessary in order to avoid incorrect and missed diagnosis.


Assuntos
Anemia de Fanconi , Síndrome de Fanconi , Transplante de Rim , Insuficiência Renal , Escoliose , Aloenxertos , Antivirais/efeitos adversos , Creatinina , Anemia de Fanconi/patologia , Síndrome de Fanconi/induzido quimicamente , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/terapia , Humanos , Transplante de Rim/efeitos adversos , Túbulos Renais Proximais/patologia , Estudos Retrospectivos , Escoliose/induzido quimicamente , Escoliose/patologia , Tacrolimo/efeitos adversos
16.
Sci Adv ; 8(38): eabq1799, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36129988

RESUMO

Pancreatic ß cell failure is a hallmark of diabetes. However, the causes of ß cell failure remain incomplete. Here, we report the identification of tetranectin (TN), an adipose tissue-enriched secretory molecule, as a negative regulator of insulin secretion in ß cells in diabetes. TN expression is stimulated by high glucose in adipocytes via the p38 MAPK/TXNIP/thioredoxin/OCT4 signaling pathway, and elevated serum TN levels are associated with diabetes. TN treatment greatly exacerbates hyperglycemia in mice and suppresses glucose-stimulated insulin secretion in islets. Conversely, knockout of TN or neutralization of TN function notably improves insulin secretion and glucose tolerance in high-fat diet-fed mice. Mechanistically, TN binds with high selectivity to ß cells and inhibits insulin secretion by blocking L-type Ca2+ channels. Our study uncovers an adipocyte-ß cell cross-talk that contributes to ß cell dysfunction in diabetes and suggests that neutralization of TN levels may provide a new treatment strategy for type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Adipócitos/metabolismo , Animais , Glucose/metabolismo , Insulina/metabolismo , Secreção de Insulina , Lectinas Tipo C , Camundongos , Tiorredoxinas , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 36(9): 881-8, 2011 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-21946207

RESUMO

OBJECTIVE: To determine the expression and mechanism of osteoactivin (OA) in the kidney by establishing SD rat model of acute cyclosporine A (CsA) toxicity. METHODS: SD rats were fed with normal diet for a week, which they were then randomly divided into 3 groups: an experimental group (gavage with cycloporin A and olive oil), a vector group (gavage with olive oil), and a control group (gavage with normal saline). SD rats were killed 2 days, 1 week, or 2 weeks after the gavage to examine the serum creatinine (SCr) and body weight. HE staining was used to detect the kidney histopathological change. Immunohistochemistry was used to observe the staining degree and area of OA. Western blot was used to detect the OA protein.The mRNA expressions of the OA, matrix metalloproteinase-13(MMP-13), and collagen type III(Col III) were examined by RT-PCR. RESULTS: The body weight and SCr of the rats in the experimental group 1 week and 2 days after the gavage had no significant difference compared with the vector group or the control group (P>0.05).On the end of 2nd week, the rats' body weight was significantly reduced, and SCr significantly increased compared with the vector group or the control group (P<0.001).The main histopathological changes in the experimental group were inflammatory cell infiltration, vacuolar degeneration of interstitial cells, or tubular epithelial cell necrosis. Intense OA expression located in the tubular epithelium and interstitial fibroblasts in the kidney of the experimental group was observed by immunohistochemistry. After CsA gavage, the relative mRNA expressions of OA, MMP-13, and Col III significantly increased with time. Western blot did not find the expression of OA protein in the control and the vector group, which increased with time in the experimental group. CONCLUSION: OA expresses in the kidney of SD rats after acute CsA toxicity and mainly expresses in the tubular epithelial cells and renal interstitium. OA is more sensitive to the damage of kidney tissue caused by CsA than by SCr. The early-phase up-regulation of OA expression in the tubular epithelium in response to renal injury caused by acute CsA toxicity might play a key role in triggering the renal interstitial fibrosis via activating expression of MMPs and collagen remodeling in SD rats.


Assuntos
Ciclosporina/toxicidade , Imunossupressores/toxicidade , Nefropatias/induzido quimicamente , Túbulos Renais/metabolismo , Glicoproteínas de Membrana/metabolismo , Animais , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Túbulos Renais/patologia , Masculino , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Glicoproteínas de Membrana/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
18.
Transpl Immunol ; 69: 101459, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34461243

RESUMO

Humoral rejection plays a crucial role in the chronic deterioration of kidney allografts, but there is no effective therapeutic strategy to prevent or treat it. T follicular helper (Tfh) cells provide help to B cells, subsequently contributing to humoral rejection. Investigation of Tfh cells may be a useful strategy for assessing the risk and level of humoral rejection. However, it is difficult to investigate Tfh cells from patient-derived lymphoid tissue. Recent studies have shown that circulating Tfh (cTfh) cells, working in parallel to Tfh cells, have the capacity to promote antibody-secreting B cell differentiation and antibody secretion. Here, we review recent studies of cTfh cells in kidney transplantation and discuss the characteristics and functions of cTfh cells in kidney transplant recipients.


Assuntos
Transplante de Rim , Células T Auxiliares Foliculares , Linfócitos B , Rejeição de Enxerto , Humanos , Linfócitos T Auxiliares-Indutores , Transplantados
19.
Neurol Res ; 43(4): 259-266, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33176620

RESUMO

Background: Surgery of parasagittal meningiomas (PSMs) is still technically challenging, for the balance between radical resection and preservation of venous circulation. In this article, we'd systemically introduce the technical nuances of a simplified strategy for radical resection of all types of PSMs. All the cases were operated by one single neurosurgeon from a single institution.Methods: Clinical charts of patients with PSMs between 2014 and 2020were retrospectively reviewed. A simplified classification method was adopted, which was based on the relationship between the tumor and superior sagittal sinus (SSS). Surgery aiming at radical resection and venous flow preservation was performed. Only in case of total occlusion of SSS, we performed tumor resection without reconstruction of the venous sinus.Results: Clinical data obtained in 55 consecutive patients (47 primary and 8 recurrent cases) were analyzed, among which 20 were with patent sinus, 27 were with partially occluded sinus and 8 were with completely occluded sinus. Forty-two (76.4%) and 13 patients (23.6%) had the same and improved functional status as compared to that of pre-operation, respectively. Four patients (7.3%) experienced transient neurological deterioration but improved to the normal level in the long-term follow-up. All patients achieved Simpson I/II radical resection. No patients suffered from post-operative recurrence in the follow-up duration of 27.05 ± 19.55 (2-91) months.Conclusion: Radical and safe resection of all types of PSMs is achievable and not difficult if the simplified surgical strategy mentioned in the article is adopted, no matter to which extent the sinus is invaded.


Assuntos
Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Seio Sagital Superior/diagnóstico por imagem , Seio Sagital Superior/cirurgia , Resultado do Tratamento
20.
Metabolism ; 123: 154863, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34375645

RESUMO

Reduced ß-cell mass and impaired ß-cell function are primary causes of all types of diabetes. However, the intrinsic molecular mechanism that regulates ß-cell growth and function remains elusive. Here, we demonstrate that the small GTPase Rheb1 is a critical regulator of glucose-stimulated insulin secretion (GSIS) in ß-cells. Rheb1 was highly expressed in mouse and human islets. In addition, ß-cell-specific knockout of Rheb1 reduced the ß-cell size and mass by suppressing ß-cell proliferation and increasing ß-cell apoptosis. However, tamoxifen-induced deletion of Rheb1 in ß-cells had no significant effect on ß-cell mass and size but significantly impaired GSIS. Rheb1 facilitates GSIS in human or mouse islets by upregulating GLUT1 or GLUT2 expression, respectively, in a mTORC1 signaling pathway-dependent manner. Our findings reveal a critical role of Rheb1 in regulating GSIS in ß-cells and identified a new target for the therapeutic treatment of diabetes mellitus.


Assuntos
Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Regulação para Cima , Proteínas ras/fisiologia , Animais , Proliferação de Células , Humanos , Camundongos , Transdução de Sinais , Proteínas ras/metabolismo
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