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AIMS: This study describes the incidence of fatigue in kidney transplant recipients and analyses the relationship between physiological factors, psychological factors, situational factors and fatigue in kidney transplant recipients. BACKGROUND: Fatigue, as a common symptom after kidney transplantation, is affected by many factors, but the influence of some factors on the fatigue of kidney transplant recipients is still controversial. DESIGN: This cross-sectional study was designed based on the theory of unpleasant symptoms. METHODS: Our survey involved 307 participants attending the kidney transplant outpatient clinic of a tertiary Class A hospital (Changsha, Hunan, China). Data were collected between February and April 2021 using a structured questionnaire and electronic medical records. Data were analysed using IBM SPSS 25.0 (SPSS Inc.) RESULTS: It was found that the incidence of fatigue in kidney transplant recipients was 53.1%. According to the binary logistic regression analysis, sleep quality, hypokalemia, anxiety, depression and education level were independent risk factors for fatigue in kidney transplant recipients. CONCLUSION: The incidence of fatigue in kidney transplant recipients was high and was influenced by physical, psychological and situational factors. Clinical nurses should assess fatigue levels in a timely and multidimensional manner in clinical practice and provide effective and scientific guidance about fatigue self-coping and symptom management for kidney transplant recipients.
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When a pulsed laser cleans a glass insulator, the laser power, scanning speed, and repetition frequency affect the laser-cleaning effect. Herein, we considered glass insulators and their surface contaminations as objects, established a finite element model, analyzed the influence of these parameters on the temperature and stress fields, and explored the optimal cleaning parameters for glass insulator surface contamination. In addition, a laser test platform was constructed to verify the cleaning effect. The results indicated that the difference in the cleaning effect was negligible for lasers at repetition frequencies of 10-75 kHz. When the power increased, the scanning speed decreased and the temperature of the fouled layer increased. When the power was 60-70 W and the scanning speed was 240 mm/s, the equivalent tensile stress did not exceed the tensile strength of the insulator. The ablation reaction can remove the fouling part, and the tensile stress can overcome the adhesion force generated between the dirt and glass insulator to achieve effective cleaning. Experiments confirmed that the surface dirt removal rate of glass insulators can be approximately 99% at 60-70 W (laser power) and 240 mm/s (scanning speed).
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Background: Studies have reported that empathy had a positive effect on professional identity (PI) in nursing students. However, little was known about the mechanism underlying this relationship between empathy and professional identity in nursing students. Objective: The purpose of this study was to analyze in depth the mediating effect of workplace violence (WVP) between empathy and professional identity in nursing students. Methods: A total of 405 nursing students participated and were investigated using the Chinese version of the Jefferson Scale of Empathy-Health Professional (JSE-HP), the scale of professional identity about nursing students, and the workplace violence Incident Survey in this study. Hierarchical regression was used to analyze the mediating effect of workplace violence on the relationship between empathy and professional identity among nursing students. Results: The score of nursing students' professional identity was 103.69 ± 17.79. Workplace violence had a significant negative correlation with empathy (r = -0.449, P < 0.001) and professional identity (r = -0.330, P < 0.001). Workplace violence accounted for 14.59% of the total mediating effect on the relationship between empathy and professional identity for nursing students. Conclusions: In this study, the level of professional identity of nursing students was low. Workplace violence had a partially significantly mediating effect on the relationship between empathy and professional identity. Maybe, it was suggested that nursing students' professional identity might be improved and driven by a decrease in workplace violence. Targeted interventions at reducing nursing students' workplace violence should be developed and implemented. In addition, nursing managers and educators should be aware of the importance of empathy and improve professional identity in nursing students.
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Tacrolimus is an immunosuppressant with a narrow therapeutic window. Tacrolimus exposure increased significantly during voriconazole co-therapy. The magnitude of this interaction is highly variable, but it is hard to predict quantitatively. We conducted a study on 91 kidney transplantation recipients with voriconazole co-therapy. Furthermore, 1701 tacrolimus concentration data were collected. Standard concentration adjusted by tacrolimus daily dose (C/D) and weight-adjusted standard concentration (CDW) increased to 6 times higher during voriconazole co-therapy. C/D and CDW increased with voriconazole concentration. Patients with the genotype of CYP3A5 *3/*3 and CYP2C19 *2/*2 or *2/*3 were more variable at the same voriconazole concentration level. The final prediction model could explain 54.27% of the variation in C/D and 51.11% of the variation in CDW. In conclusion, voriconazole was the main factor causing C/D and CDW variation, and the effect intensity should be quantitative by its concentration. Kidney transplant recipients with CYP3A5 genotype of *3/*3 and CYP2C19 genotype of *2/*2 and *2/*3 should be given more attention during voriconazole co-therapy. The prediction model established in this study may help to reduce the occurrence of rejection.
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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.
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Anemia de Fanconi , Síndrome de Fanconi , Trasplante de Riñón , Insuficiencia Renal , Escoliosis , Aloinjertos , Antivirales/efectos adversos , Creatinina , Anemia de Fanconi/patología , Síndrome de Fanconi/inducido químicamente , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/terapia , Humanos , Trasplante de Riñón/efectos adversos , Túbulos Renales Proximales/patología , Estudios Retrospectivos , Escoliosis/inducido químicamente , Escoliosis/patología , Tacrolimus/efectos adversosRESUMEN
Background: Owing to the advent of pangenotypic direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) treatment, utilization of HCV-infected deceased donor kidneys with simplified genotyping/subtyping-free sofosbuvir/velpatasvir (SOF/VEL) treatment strategy is now becoming a promising strategy for expanding the organ donor pool. Methods: This retrospective, comparative, single-center study included HCV viremic donor kidneys that were transplanted to 9 HCV-positive (HCV Ab-positive) recipients (D+/R+ group) and 14 HCV-negative recipients (D+/R- group) from May 2018 to January 2021. Both groups received prophylaxis with SOF/VEL treatment within 1-week posttransplant devoid of HCV genotyping/subtyping. The primary outcomes were sustained virologic response 12 weeks after completion of therapy (SVR12) and graft survival at 1-year posttransplant. Results: Baseline characteristics were similar between the HCV D+/R- and D+/R+ groups. The mean age of all recipients was 39.09 ± 9.65 (SD) years, and 73.9% were male. A total of 92.9% (13 out of 14) recipients had pretreatment HCV viremia in the D+/R- group. The pretreatment HCV viral load in the D+/R+ group (5.98, log 10 IU/mL; IQR, 5.28-6.53) was significantly higher than that in the D+/R- group (3.61, log 10 IU/mL; IQR, 2.57-4.57). After SOF/VEL treatment, SVR12 was achieved in all recipients, with a 100% 1-year patient and graft survival rates. The D+/R+ group had a higher incidence of abnormal liver function (44.4% vs. 7.1%). No significant difference was observed between the two groups in terms of DGF, acute rejection, ALT, serum creatinine, and eGFR within 1-year posttransplant. No severe adverse events associated with either HCV viremia or SOF/VEL were observed. Conclusions: Using a simplified genotyping/subtyping-free SOF/VEL treatment strategy, kidneys from hepatitis C viremic donors for both infected and uninfected recipients presented with safe, excellent, and comparable 1-year outcomes, which can safely expand the donor pool. HCV-positive donor kidneys should be utilized regularly, regardless of the recipient's HCV status.
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Hepatitis C Crónica , Hepatitis C , Adulto , Antivirales , Carbamatos , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos , Humanos , Riñón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sofosbuvir/uso terapéutico , Viremia/tratamiento farmacológicoRESUMEN
Background: Kidney transplantation from donors who weigh ≤5 kg is performed at only a few transplant centers owing to the high complication and low graft survival rates associated with this approach. Methods: We retrospectively compared the results of kidney transplantation at our center between January 2015 and December 2019 based on the following pediatric donor criteria: donor body weight ≤5 kg (n=32), 5 kg< donor weight ≤20 kg (n=143), and donor weight >20 kg (n=110). We also perform subgroup analysis of kidney transplantation outcomes from ≤5 kg donors, using conventional (dual separate and classic en-bloc KTx)/novel (en-bloc KTx with outflow tract) surgical methods and allocating to adult/pediatric recipients. Results: The death-censored graft survival rates from extremely low body weight ≤5kg at 1 month, and 1, 3, and 5 years were 90.6%, 80.9%, 77.5%, and 73.9%, respectively, which were significantly lower than that from larger body weight pediatric donors. However, the 3-, and 5-year post-transplantation eGFRs were not significantly different between the pediatric and adult recipient group. The thrombosis (18.8%) and urinary leakage (18.8%) rates were significantly higher in the donor weight ≤5 kg group. Compared with 5 kg< donor weight ≤20 kg group, donor weight ≤5kg group was at elevated risk of graft loss due to thrombosis (OR: 13.4) and acute rejection (OR: 6.7). No significant difference on the outcomes of extremely low body weight donor kidney transplantation was observed between adults and pediatric recipients. Urinary leakage rate is significantly lower in the novel operation (8.7%) than in the conventional operation group (44.4%). Conclusions: Although the outcomes of donor body weight ≤5kg kidney transplantation is inferior to that from donors with large body weight, it can be improved through technical improvement. Donors with body weight ≤5 kg can be considered as an useful source to expand the donor pool.
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Peso Corporal , Selección de Donante , Rechazo de Injerto/etiología , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/etiología , Donantes de Tejidos , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Myosin (Ms) is abundant in fish meat, but it has limited application in the food industry because of its low solubility and thermal stability. Our previous reports found that these functional properties of Ms can be significantly improved after glycation with konjac oligo-glucomannan (KOG). However, the effects of phosphorylated KOG (PKOG) on physicochemical, structural and functional properties of silver carp Ms are still unknown. RESULTS: This study characterized the silver carp Ms protein glycated with PKOG at 50 °C and 75% relative humidity for 48 h. As degree of phosphorylation increased, free amino content increased, whereas degree of grafting decreased. Meanwhile, isoelectric point (pI) reduced, however, PKOGs showed no differences in pI. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis suggested the formation of glycoconjugates, and scanning electron microscopy revealed thinner flakes and uneven appearance of glycoconjugates. Fourier transform infrared spectroscopy indicated that the amide I, II and III bands of Ms were changed by the glycation. Ms became highly soluble in 0.5 mol L-1 NaCl with increased phosphate addition in PKOGs. Thermal stability of Ms was effectively improved when heated at 80 °C for 60 min. CONCLUSION: Glycation with appropriate PKOG might be a promising method for Ms modification because of the resulting improvement in solubility and thermal stability. © 2021 Society of Chemical Industry.
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Proteínas de Peces/química , Manipulación de Alimentos/métodos , Mananos/química , Miosinas/química , Amorphophallus/química , Animales , Carpas , Electroforesis en Gel de Poliacrilamida , Glicosilación , Punto Isoeléctrico , Carne/análisis , Fosforilación , SolubilidadRESUMEN
The purpose of this meta-analysis was to assess the health-related quality of life (HRQoL) of living kidney donors using the 36-item Medical Outcomes Short-Form-36 questionnaire (SF-36). A systematic search of the Web of Science, PubMed, Embase, Elsevier/ScienceDirect, Wanfang, Weipu, and China National Knowledge Infrastructure databases for studies that used the SF-36 to evaluate the HRQoL of living kidney donors up to April 2020 was performed. Stata version 12.0 (StataCorp LLC, College Station, TX, USA) was used for meta-analysis. In all, nine studies comprising 802 living kidney donors were included in this meta-analysis. The research revealed that living kidney donors were inferior in physical health to the general population with regard to bodily pain (BP), superior to the general population in terms of general health (GH), and exhibited no significant difference from the general population in physical function (PF) and role-physical (RP). In the case of psychological health, living kidney donation had a positive impact on well-screened living kidney donors. Based on our results, clinicians can inform potential kidney donors that there is a low risk in donating a kidney, which contributes to provide guidance to design counseling interventions for both kidney recipients and donors.
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Trasplante de Riñón , Donadores Vivos , Calidad de Vida , Humanos , Encuestas y CuestionariosRESUMEN
Laparoscopic surgery is widely used for living donor nephrectomy and has demonstrated superiority over open surgery by improving several outcomes, such as length of hospital stay and morphine requirements. The purpose of the present study was to compare the long-term outcomes of open donor nephrectomy (ODN) versus laparoscopic donor nephrectomy (LDN) using meta-analytical techniques. The Web of Science, PubMed and Cochrane Library databases were searched, for relevant articles published between 1980 and January 20, 2020. Lists of reference articles retrieved in primary searches were manually screened for potentially eligible studies. Outcome parameters were explored using Review Manager version 5.3. The evaluated outcomes included donor serum creatinine levels, incidence of hypertension or proteinuria at 1 year postoperative, donor health-related quality of life, donation attitude, and graft survival. Thirteen of the 111 articles fulfilled the inclusion criteria. The LDN group demonstrated similar 1 year outcomes compared with ODN with respect to serum creatinine levels (weighted mean difference [WMD] -0.02 mg/dL [95% confidence interval (CI) -0.18-0.13]; P=0.77); hypertension (odds ratio [OR] 1.21 [95% CI 0.48-3.08]; P=0.68); proteinuria (OR 0.28 [95% CI 0.02-3.11]; P=0.30); and donation attitude (OR 4.26 [95% CI 0.06-298.27]; P=0.50). Donor health-related quality of life and recipient graft survival were also not significantly different between the groups analyzed. Thus, the long-term outcomes between LDN and ODN for living donor kidney transplantation are similar.
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OBJECTIVES: To summarize the emergency management of the kidney transplantation for a large tertiary first-class hospital in response to the epidemic of coronavirus disease 2019 (COVID-19). METHODS: The clinical data of inpatients in the Department of Kidney Transplantation from January 24, 2020 to February 29, 2020 were retrospectively analyzed. Since the outbreak of COVID-19, we conducted telephone, Wechat follow-up, and online education for kidney transplant recipients and patients on waiting-list for kidney transplantation one by one. We also strictly screened for COVID-19 in outpatients. To guarantee the security of medical staff and recipients and to reduce the transmission risk of COVID-19, we have made detailed approaches to prevent COVID-19, which mainly included 6 aspects of preventive approaches, such as kidney transplant clinic, kidney transplant ward, patients on waiting-list for kidney transplantation, kidney transplant operation, medical staff self-protection, and postoperative follow-up of kidney transplant recipients. RESULTS: There were altogether 47 inpatients which included 20 recipients who had just received kidney transplantation in the meantime, 2 577 kidney transplant recipients, 1 689 patients on waiting-list for kidney transplantation, and 794 outpatients in our hospital. No case of COVID-19 occurred in this period. CONCLUSIONS: Through strictly implementing proactive and preventive approaches, we avoid the occurrence of COVID-19 in carrying out kidney transplantation in the epidemic period.
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Infecciones por Coronavirus/epidemiología , Trasplante de Riñón , Neumonía Viral/epidemiología , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/prevención & control , Humanos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Estudios Retrospectivos , SARS-CoV-2 , Centros de Atención Terciaria , Receptores de Trasplantes , Listas de EsperaRESUMEN
Liver fibrosis is characterized by the transdifferentiation of hepatic stellate cells (HSCs) to myofibroblasts and poor response to treatment. This can be attributed to the myofibroblast-specific resistance to phenotype reversal. In this study, we complemented miR-16 into miR-16-deficient myofibroblasts and analyzed the global role of miR-16 using transcriptome profiling and generating a pathway-based action model underlying transcriptomic regulation. Phenotypic analysis of myofibroblasts and fibrogenic characterization were used to understand the effect of miR-16 on phenotypic remodeling of myofibroblasts. miR-16 expression altered the transcriptome of myofibroblasts to resemble that of HSCs. Simultaneous targeting of Smad2 and Wnt3a, etc. by miR-16 integrated signaling pathways of TGF-ß and Wnt, etc., which underlay the comprehensive regulation of transcriptome. The synergistic effect of miR-16 on the signaling pathways abolished the phenotypic characteristics of myofibroblasts, including collagen production and inhibition of adipogenesis. In vivo, myofibroblast-specific expression of miR-16 not only eliminated mesenchymal cells with myofibroblast characteristics but also restored the phenotype of HSCs in perisinusoidal space. This phenotypic remodeling resolved liver fibrosis induced by chronic wound healing. Therefore, miR-16 may integrate signaling pathways crucial for the fate determination of myofibroblasts. Its global effect induces the reversal of HSC-to-myofibroblast transdifferentiation and, subsequently, the resolution of fibrogenesis. Taken together, these findings highlight the potential of miR-16 as a promising therapeutic target for liver fibrosis.
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Cirrosis Hepática/genética , MicroARNs/genética , Miofibroblastos/metabolismo , Animales , Transdiferenciación Celular , Células Cultivadas , China , Biología Computacional/métodos , Fibrosis/fisiopatología , Regulación de la Expresión Génica/genética , Células Estrelladas Hepáticas/metabolismo , Humanos , Hígado/metabolismo , Cirrosis Hepática/fisiopatología , MicroARNs/metabolismo , Ratas , Transducción de Señal/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Superoxide dismutase (SOD) is an acidic metalloenzyme that scavenges free radicals produced by endogenous and exogenous substances. In the present study, the tissue distribution of the superoxide dismutase HdhCu/Zn-SOD was investigated in Haliotis discus hannai Ino. The expression profile after lipopolysaccharide (LPS) challenge was determined using quantitative real-time polymerase chain reaction (qPCR). To study the antioxidant activity of a recombinant HdhCu/Zn-SOD protein, the HdhCu/Zn-SOD gene was cloned into the pPIC9K vector and transformed into the Pichia pastoris GS115 strain by electroporation. After induction by methanol, the recombinant product was purified using immobilized metal affinity chromatography and confirmed using mass spectrometry. The optimal expression conditions were determined to be incubation with 0.5% methanol at pH 6.0, resulting in a stable expressed product with the molecular weight of approximately 17 kDa and 21 kDa. The enzymatic activity of HdhCu/Zn-SOD consistently increased with increasing Cu2+ concentrations and showed good thermal stability. Recombinant HdhCu/Zn-SOD showed a strong ability to scavenge superoxide anions and hydroxyl radicals and protected L929 cells against the toxicity caused by H2O2 through its in vitro antioxidant activity. The heterologous expression of HdhCu/Zn-SOD in P. pastoris and the antioxidant activity of this enzyme are reported for the first time.
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Antioxidantes/metabolismo , Gastrópodos/genética , Superóxido Dismutasa/genética , Animales , Gastrópodos/metabolismo , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Peróxido de Hidrógeno/metabolismo , Concentración de Iones de Hidrógeno , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomycetales/genética , Saccharomycetales/metabolismo , Superóxido Dismutasa/metabolismo , TranscriptomaRESUMEN
The glycation of silver carp myosin (Ms) with konjac oligo-glucomannan (KOG) of different degrees of deacetylation (DD) was investigated. As DD increased, the physico-chemical and functional properties of glycoconjugates changed. The available lysine content decreased, while grafting degree and total sulfhydryl group increased, andmeanwhile, the isoelectric point (pI) reduced. SDS-PAGE analysis indicated that glycation can be promoted as the increase of DD. The solubility increased significantly both in 0.1â¯M and 0.5â¯M NaCl solution, and the thermal stability increased when heated for 60â¯min at 80⯰C. The emulsifying activity index (EAI) and emulsifying stability index (ESI) increased as well. These results showed that the highly deacetylated KOG (DKOG) was easier to glycate with myosin, leading to a great improvement in functional properties of myosin. It can be suggested that the reduction in steric hindrance of DKOG as a result of removal of acetyl groups facilitated the glycation.
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Carpas/metabolismo , Mananos/metabolismo , Miosinas/metabolismo , Acetilación , Animales , Electroforesis en Gel de Poliacrilamida , Glicosilación , Punto Isoeléctrico , Miosinas/química , Estabilidad Proteica , Compuestos de Sulfhidrilo/análisis , TemperaturaRESUMEN
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.
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Aorta Abdominal/cirugía , Peso Corporal , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Trombosis/prevención & control , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , PronósticoRESUMEN
BACKGROUND: Memory T cells (Tms) form a barrier against long-term allograft survival; however, CD4(+)Foxp3(+) regulatory T cells (Tregs) can suppress allograft rejection. The OX40/OX40L pathway is critical to the generation of Tms and turns off Treg suppressor function. METHODS: B6 mice that rejected BALB/c skin grafts after 4 weeks were used as the secondary heart transplant recipients. The skin recipient mice, termed S0, S2 and S3, were treated with the isotype antibodies, anti-CD40L/LFA-1 or anti-OX40L combined with anti-CD40L/LFA-1 mAbs, respectively. The secondary heart recipients, termed H0 and H2, received anti-CD40L/LFA-1 mAbs or not, respectively (Fig. 1). RESULTS: Four weeks after primary skin transplantation, the Tms in the S3 group that received anti-OX40L with anti-CD40L/LFA-1 mAbs were reduced compared to those in the S2 group (CD4(+) Tm: 32.61 ± 2.20% in S2 vs. 25.36 ± 1.16% in S3; CD8(+) Tm: 27.76 ± 1.96% in S2 vs. 20.95 ± 1.30% in S3; P < 0.01). Meanwhile, the proportions of Tregs in S3 increased compared to those in S2 (P < 0.05). The anti-OX40L with anti-CD40L/LFA-1 mAbs group (S3H2) prolonged the mean survival time (MST) following secondary heart transplantation from 9.5 days to 21 days (P < 0.001). Furthermore, allogeneic proliferation of recipient splenic T cells and graft-infiltrating lymphocytes were significantly inhibited in the S3H2 group. Additionally, a higher level of IL-10 was detected in sera and allografts. CONCLUSIONS: Anti-OX40L mAb could prolong secondary heart allograft survival based on CD40/CD40L and LFA-1/ICAM-1 blockade. The mechanism of protecting allografts using anti-OX40L mAb involved impairing the generation of Tm and up-regulating IL-10 producing Tregs, inhibiting the function of T cells.
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Anticuerpos Monoclonales de Origen Murino/farmacología , Antígenos CD40/inmunología , Ligando de CD40/inmunología , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Corazón , Antígeno-1 Asociado a Función de Linfocito/inmunología , Glicoproteínas de Membrana/inmunología , Factores de Necrosis Tumoral/inmunología , Aloinjertos , Animales , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/inmunología , Molécula 1 de Adhesión Intercelular/inmunología , Ratones , Ratones Endogámicos BALB C , Ligando OX40 , Trasplante de Piel , Factores de TiempoRESUMEN
Hepatic stellate cell (HSC) activation is the critical event of liver fibrosis. Abnormality of miR-16 expression induces their activation. However, the action model of miR-16 remains to be elucidated because of its multiple-targeted manner. Here, we report that miR-16 restoration exerted a wide-range impact on transcriptome (2,082 differentially expressed transcripts) of activated HSCs. Integrative analysis of both targetome (1,195 targets) and transcriptome uncovered the miR-16 regulatory network based upon bio-molecular interaction databases (BIND, BioGrid, Tranfac, and KEGG), cross database searching with iterative algorithm, Dijkstra's algorithm with greedy method, etc. Eight targets in the targetome (Map2k1, Bmpr1b, Nf1, Pik3r3, Ppp2r1a, Prkca, Smad2, and Sos2) served as key regulatory network nodes that mediate miR-16 action. A set of TFs (Sp1, Jun, Crebl, Arnt, Fos, and Nf1) was recognized to be the functional layer of key nodes, which mapped the signal of miR-16 to transcriptome. In result, the comprehensive action of miR-16 abrogated transcriptomic characteristics that determined the phenotypes of activated HSCs, including active proliferation, ECM deposition, and apoptosis resistance. Therefore, a multi-layer regulatory network based upon the integration of targetome and transcriptome may underlie the global action of miR-16, which suggesting it plays an inhibitory role in HSC activation.
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Regulación de la Expresión Génica/genética , Redes Reguladoras de Genes/fisiología , Células Estrelladas Hepáticas/fisiología , MicroARNs/genética , Factores de Transcripción/genética , Activación Transcripcional/genética , Transcriptoma/genética , Proliferación Celular/genética , Marcación de Gen , Células Estrelladas Hepáticas/citología , HumanosRESUMEN
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.
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Supervivencia de Injerto , Trasplante de Riñón , Donantes de Tejidos , Adulto , Humanos , Lactante , Riñón , Periodo PosoperatorioRESUMEN
Matrine is one of the main active components that is extracted from the dry roots of Sophora flavescens. The compound has potent antitumor activity in various cancer cell lines. However, the anticancer activity of matrine in colon cancer cells remains unclear. The purpose of the present study was to investigate the effects of matrine on the growth of human colon cancer cells and the expression of the associated proteins. Cancer cell proliferation was measured by 3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The cell cycle distribution and apoptosis were analyzed by flow cytometry (FCM). The activation of the caspases and the expression of pro-apoptotic and anti-apoptotic factors were examined using western blot analysis. Matrine was shown to significantly inhibit the proliferation of HT29 cells in a dose- and time-dependent manner, and also to reduce the percentage of cells in the G2/M phase, which was most frequently associated with an increase of cells arrested in the G0/G1 phase of the cell cycle. Western blot analysis revealed that matrine induced the activation of caspase-3 and -9 and the release of cytochrome C (Cyto C) from the mitochondria to the cytosol. Furthermore, the pro-apoptotic factor, Bax, was upregulated and the anti-apoptotic factor, Bcl-2, was downregulated, eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. The results demonstrated that matrine inhibits proliferation and induces apoptosis of HT29 human cells in vitro. The induction of apoptosis appears to occur through the upregulation of Bax, the downregulation of Bcl-2, the release of Cyto C from the mitochondria to the cytosol and the activation of caspase-3 and caspase-9, which subsequently trigger major apoptotic cascades. Matrine has potent antitumor activity in HT29 cells and may be used as a novel effective reagent in the treatment of colon cancer.
RESUMEN
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.