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Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that causes progressive angiogenesis and lymphangiogenesis, which often occurs in the skin or soft tissue, with an acute onset and rapid progression. A 4-year-old girl was admitted to our hospital with a 2-year history of thrombocytopenia, combined with right hepatic atrophy and pancreatic lesion for 3 months. At the age of two, she developed purpura and thrombocytopenia was detected, after treatment with gamma globulin and corticosteroids, the platelet count normalized, but it dropped immediately at lower doses. One year after the cessation of corticosteroids therapy, the patient presented with abdominal pain and abnormal liver function and the magnetic resonance imaging (MRI) revealed right hepatic atrophy and pancreatic occupancy, but the first liver biopsy did not reveal any positive pathological results. By analyzing the clinical manifestations in conjunction with MRI and abnormal coagulation, we considered that the patient might be diagnosed as KHE with Kasabach-Merritt phenomenon, however, sirolimus treatment was ineffective and pancreatic biopsy only showed a tendency for tumors of vascular origin. Finally, we performed a Whipple operation after the right hepatic artery embolization, histological and immunohistochemical examination suggested KHE. Three months postoperatively, the patient's liver function, pancreatic enzymes and blood clotting function gradually returned to normal. KHEs may result in significant blood loss with worsening of the coagulopathy and functional impairment, timely surgical intervention for KHE is necessary when non-invasive or minimally invasive treatment is ineffective, or the symptoms of tumor compression are obvious.
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Background: Early Kasai surgery before 60 days of life results in better clinical outcomes in patients with biliary atresia (BA). We aimed to develop and validate a prediction tool for the early diagnosis of BA in infants younger than 60 days old. Methods: This prospective study recruited consecutive infants younger than 60 days old with conjugated hyperbilirubinemia who were evaluated with an ultrasound (US) scan, including B-mode US with color Doppler flow imaging (CDFI) features and liver two-dimensional shear wave elastography (2D SWE), from March 2017 to July 2021. The reference standard for diagnosis was intraoperative cholangiography, liver biopsy, or the resolution of jaundice. Area under the receiver operating characteristic curve (AUC) analysis, logistic regression analysis, and establishment of a nomogram were performed. Results: A total of 174 patients (mean age, 46 days), including 87 infants with BA and 87 non-BA cholestatic infants, were included in the study. The established nomogram based on gallbladder (GB) abnormality, liver 2D SWE, and serum γ-glutamyl transferase (GGT) and alanine aminotransferase (ALT) had an AUC of 0.99 [95% confidence interval (CI): 0.94-1.00], a sensitivity of 92%, and a specificity of 100%. The nomogram in the validation cohort also had good diagnostic performance in the diagnosis of BA, with an AUC of 0.98 (95% CI: 0.95-1.00). Conclusions: The new prediction tool had a good diagnostic performance in the early prediction of BA in infants younger than 60 days old and will facilitate timely Kasai surgery.
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Background: Cavernous transformation of the portal vein (CTPV) causes portal hypertension in children. Among Meso-Rex treatments, it is unclear whether the Meso-Rex bypass shunt (MRB) or the Meso-Rex transposition shunt (MRT) offers lower postoperative morbidity. Our objective was to evaluate postoperative outcomes, comparing MRB and MRT for children with CTPV. Methods: A retrospective study was conducted on children undergoing Meso-Rex for CTPV from January 2010 to December 2020. The primary outcome was shunt complications, including shunt stenosis and thrombus. The secondary outcome was re-operation. Results: Of the 43 patients included, 21 underwent MRT and 22 underwent MRB. MRT was associated with a higher rate of shunt complications when compared to MRB (23.8 vs. 9.1%, p = 0.191). The patients exhibited a higher rate of re-operation under the MRT than under the MRB (19 vs. 4.5%, p = 0.138). The operative time in the MRT group was significantly shorter than in the MRB group. Compared to MRT, the reduction in the length and thickness of the spleen was significantly greater in the MRB group. The increases in platelets were significantly higher in the MRB group than in the MRT group. The postoperative shunt velocity of MRB was notably faster than MRT. There was no significant difference in postoperative portal pressure between the two groups (p > 0.05). Conclusion: Both MRB and MRT result in acceptable postoperative outcomes, but MRT is associated with higher post-shunt complications, which often increase the re-operation rate. This study suggests that MRB may offer advantages for children with CTPV.
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Background: In 2017, the World Health Organization (WHO) defined a new category of pancreatic neuroendocrine neoplasms named G3 pancreatic neuroendocrine tumors (p-NETs), whose surgical outcomes, long-term survivals and staging systems have not been well documented. Methods: Data from eligible patients with G3 p-NETs defined using the WHO 2017 grading classification at our institute were retrospectively analyzed. Results: Our study enrolled 80 patients with WHO G3 p-NETs, including 50 women and 30 men. The accumulative 5-year overall survival (OS) of G3 p-NETs was 29.7%. The current staging system by the American Joint Committee on Cancer (AJCC) failed to discriminate the survival difference between Stage II and Stage III (p = 0.172), while notable differences with regard to the OS were statistically offered between each stage using the modified tumor−node−metastasis (mTNM) staging system (all p < 0.05). The OS of patients receiving surgical resection was significantly better than those with palliative operation (p < 0.05). Both the current AJCC system and proposed mTNM system were independent predictors for the OS of G3 p-NETs (p = 0.017 and p = 0.032, respectively). The 95% confidence intervals of the proposed mTNM staging system were smaller than that of the current AJCC system (0.626−8.217 and 0.329−10.013, respectively), indicating a relatively more accurate predictive ability. Conclusion: Our demonstration revealed that surgical resection was an independent predictor for the favorable prognosis of patients with G3 p-NETs. Moreover, the new mTNM staging system was more suitable and practical than the current AJCC system for stratifying G3 p-NETs into prognostic groups.
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BACKGROUND: The failed clearance of jaundice (CJ) in patients with biliary atresia (BA) after the Kasai procedure (KP) often leads to a shorter native liver survival (NLS) time and earlier liver transplantation. We aimed to investigate risk factors of failed CJ and establish a novel nomogram model to predict the status of CJ. METHODS: We retrospectively reviewed institutional medical records from January 2015 to April 2020 and enrolled BA patients post-KP, randomly divided into training and testing cohorts at a ratio of 7:3, and further subdivided into cleared and uncleared jaundice groups. Univariate and multiple logistic regression analyses were used to select risk factors to establish the nomogram in the training cohort. The performance of the nomogram was evaluated by calculating the areas under the receiver operating curve (AUC) in both cohorts. RESULTS: This study included 175 BA patients post-KP. After univariate and multiple logistic regression analyses, Cytomegalovirus IgM +ve associated BA (OR = 3.38; 95% CI 1.01-11.32; P = 0.04), ln γ-glutamyl transpeptidase (GGT) (OR = 0.41; 95% CI 0.22-0.80; P = 0.009), thickness of the fibrous portal plate (OR = 0.45; 95% CI 0.27-0.76; P = 0.003), liver stiffness measurement (LSM) (OR = 1.19; 95% CI 1.06-1.34; P = 0.002), and multiple episodes of cholangitis (OR = 1.65; 95% CI 1.13-2.41; P = 0.01) were identified as independent risk factors of unsuccessful CJ to construct the nomogram. The receiver operating characteristic curve (ROC) analysis suggested good nomogram performance in both the training (AUC = 0.96) and testing cohorts (AUC = 0.91). CONCLUSION: Our nomogram model including several risk factors effectively predicts CJ in patients post-KP, which could aid in clinical decision-making.
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BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare condition that has a variety of clinical manifestations. But LCH in children localized only in the hepatobiliary system is unusual. CASE PRESENTATION: Here we reported a rare case of a 2-year-old boy who was serendipitously found to have elevated liver enzymes while undergoing treatment of a perianal abscess. After a period of earlier conservative treatment in another hospital, the perianal abscess had resolved but the levels of liver enzymes were still rising slowly. The child was then referred to our institution for a definitive diagnosis. After laboratory tests, imaging and pathological examinations, a diagnosis of liver cirrhosis and sclerosing cholangitis was established, although the cause was unclear. Subsequently, living-donor liver transplantation was performed due to deterioration in liver function. Following successful liver transplantation, a diagnosis of LCH localized only within the hepatobiliary system was finally confirmed, based on additional pathological and imaging investigation. Additionally, the BRAF V600E mutation in this patient was also confirmed. The child has now recovered without evidence of LCH recurrence. CONCLUSIONS: LCH localized only within the hepatobiliary system is unusual. The presence of unexplainable sclerosing cholangitis and liver cirrhosis in any child should raise the suspicion of LCH.
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Colangitis Esclerosante , Histiocitosis de Células de Langerhans , Trasplante de Hígado , Niño , Preescolar , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/cirugía , Histiocitosis de Células de Langerhans/complicaciones , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/cirugía , Humanos , Cirrosis Hepática/complicaciones , Trasplante de Hígado/efectos adversos , Donadores Vivos , MasculinoRESUMEN
BACKGROUND: Despite surgical treatment, children with biliary atresia (BA) may face many problems which seriously affect their quality of life. However, there is a paucity of studies in China examining the quality of life of these children after BA treatment. This study investigated the current status of the quality of life of children after BA treatment and analyzed the influencing factors so as to provide a scientific basis for the development of targeted interventional measures. METHODS: From May 1 to May 31, 2021, the STAR questionnaire method was used to conduct cross-sectional surveys in children following BA surgery in the West China Hospital of Sichuan University, China. The basic information questionnaire was used to investigate the general characteristics of the children. The children were also given quality of life questionnaires during follow-up sessions after surgical treatment for BA. In addition, a 12-point health survey was used to assess the physical and mental health of the children's caregivers. Age- and gender-matched healthy children were recruited as controls. Correlation analysis and multiple linear regression equations were established to explore the influencing factors of the quality of life of children after surgery for BA. RESULTS: After surgery, children with BA experienced significantly lower physical health, emotional function, social function, cognitive function, and quality of life compared to healthy children (P<0.050). Co-existing diseases had a statistically significant impact on the quality of life of children with BA (b=-12.566; t=-2.343; P=0.021), and the caregiver's understanding level of liver transplantation also had a statistically significant impact on the quality of life of these children (b=6.481; t=2.376; P=0.021). CONCLUSIONS: The quality of life of children after BA surgery was significantly lower than that of age-matched healthy children. Co-existing diseases and the caregiver's understanding level of liver transplantation were the main factors affecting the quality of life of these children.
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BACKGROUND: ΔNp63α and c-Myc are key transcription factors controlling proliferation and senescence in epithelial cells. We previously reported that the c-Myc modulator MM1 and its E3 ligase, HERC3, together with the transcription factor ΔNp63α, compose a feedback loop, which regulates proliferative senescence in MCF-10A mammary epithelial cells. However, it is unknown whether this loop is involved in skin ageing. On the other hand, ultraviolet B (UVB) rays are assumed to be the main culprits for photoageing of the epidermis, but the underlying mechanisms are obscure. AIMS: To investigate whether MM1/ΔNp63α axis is involved in UVB-induced photoageing of the epidermis. MATERIALS AND METHODS: HaCaT human immortalized keratinocytes overexpressed with MM1, knocked down with c-Myc or irradiated with UVB, were subjected to MTT assays to measure cell proliferation, as well as RT-qPCR or immunoblot to detect the members of MM1/ΔNp63α loop and the cellular senescence markers. Meanwhile, primary normal human keratinocytes (NHKs) or mice were irradiated with UVB, followed by immunoblot analysis, SA-ß-gal, haematoxylin-eosin or immunohistochemistry staining. RESULTS: Overexpression of MM1 down-regulated ΔNp63α and induced proliferative senescence in the HaCaT cells. In the HaCaT cells, NHKs and the mouse epidermis, UVB irradiation increased MM1 mRNA level and led to a down-regulation of ΔNp63α, HERC3 and c-Myc, concomitant with cellular senescence or photoageing. Additionally, knock-down of c-Myc induced proliferative senescence in the HaCaT cells and abrogated UVB-induced cellular senescence. CONCLUSIONS: UVB up-regulates MM1 and consequently modulates ΔNp63α and c-Myc, which may account for the proliferative senescence of keratinocytes and photoageing of the epidermis.
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Epidermis , Envejecimiento de la Piel , Animales , Línea Celular , Humanos , Queratinocitos , Ratones , Transactivadores , Factores de Transcripción , Proteínas Supresoras de Tumor , Rayos UltravioletaRESUMEN
OBJECTIVES: Laparoscopic Kasai portoenterostomy (LKPE) has been shown to be a safe and feasible procedure in patients with biliary atresia (BA). The purpose of this study was to investigate the efficacy of modified LKPE (MLKPE) in the treatment of BA. METHODS: Data of 58 BA patients undertaken MLPKE from July 2014 to December 2015 were retrospectively analyzed (group B), and compared with that of 43 BA patients received open Kasai portoenterostomy (OKPE) during the same period (group C). In addition, 195 BA patients who had undergone LKPE during May 2009 to June 2014 were also included (group A). RESULTS: All 296 patients enrolled in this study were non-syndromic type III BA. Compared with group A, group B had shorter operative time (ORT) (P < 0.01) and fewer intraoperative blood transfusion (IOBT) (P < 0.05). The conversion rate and cholangitis rate were also significantly lower in group B than that in group A (P < 0.05). The postoperative oral intake resumed (POOR), any postoperative complications (APOC), clearance of jaundice (CJ), 1-year and 3-year survival rate with native liver (SNL) were not significantly different between group A and group B (P > 0.05). The ORT, IOBT, POOR, APOC, CJ, 1-year and 3-year SNL in group B were much better than that of group C (P < 0.05). CONCLUSION: The MLKPE was associated with good perioperative with ORT, IOBT, POOR, and APOC. The short-term outcomes in MLKPE were no worse than that of OKPE and LKPE. MLKPE can be regarded as a treatment option for BA.
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Atresia Biliar/cirugía , Laparoscopía , Portoenterostomía Hepática , Algoritmos , Anastomosis Quirúrgica , Femenino , Humanos , Lactante , Estimación de Kaplan-Meier , Hígado/cirugía , Masculino , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Laparoscopic inguinal repair use is rapidly growing because it is a minimally invasive surgery (MIS) technique. However, there is insufficient evidence to support the use of one MIS over others. We compared laparoscopic intracorporeal suture (LIS) and laparoscopic percutaneous extraperitoneal closure (LPEC) to determine which technique is superior. METHODS: Between February 2017 and December 2019, 260 children who underwent LPEC and 214 children who underwent LIS were enrolled. Operative time, recovery score, and patient cosmetic satisfaction were compared. A total of 108 propensity score-matched pairs were analyzed using paired t-test for continuous measurements and McNemar test for categorical variables. RESULTS: The mean surgery time was lower in the LPEC group for both unilateral (15.76 ± 5.35 vs. 19 ± 5.71 min; p = 0.04) and bilateral (21.56 ± 5.7 vs. 26.38 ± 6.94 min; p = 0.01) surgeries. The LPEC group required shorter time for complete recovery (p = 0.017). The mean rating for scar visibility was higher in the LIS group (p = 0.02); however, both groups had high levels of cosmetic satisfaction (p = 0.125). CONCLUSION: LPEC for hernia repair is safe and efficient in children and reduced operative time, hastened recovery, and provided excellent cosmetic results.
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Hernia Inguinal , Laparoscopía , Niño , Hernia Inguinal/cirugía , Herniorrafia , Humanos , Lactante , Estudios Retrospectivos , Técnicas de Sutura , Suturas , Resultado del TratamientoRESUMEN
This retrospective study was conducted to examine the development and current status of pediatric liver transplantation (LT) in western China. Clinical, demographic, morbidity, and mortality data were collected to analyze. It included 260 consecutive pediatric LTs performed at three centers in western China between January 2000 and May 2019. Kaplan-Meier graft survival rates at 1, 3, 5, and 10 years were 82.1%, 77.2%, 76.6%, and 76.6%, respectively; corresponding patient survival rates were 84.7%, 80.7%, 80.0%, and 80.0%, respectively. More patients underwent living donor liver transplantation (LDLT; n = 188 (73.4%)) than deceased-donor liver transplantation (DDLT; n = 68 (26.6%)). Survival was better after LDLT (91.5%, 86.6%, and 80.6% at 1, 3, and 5 years, respectively) than after DDLT (80.9%, 72.4%, and 63.9%, respectively; P < .05). Biliary atresia was the leading LT indication (n = 141 (55.1%)), followed by metabolic disease (n = 36 (14.1%)), which was associated with the best recipient survival (88.5% at 5 years). The transplant era and graft-to-recipient body weight ratio (GRWR) also significantly predicted overall survival. Survival rates at 5 years were worst in 2000-2005 (54.5%) and best for GRWRs of 0.8%-4% (80.4%). The development of pediatric LT in western China began slowly, but the quantity and quality of pediatric LT has progressed in recent years. This procedure is now a promising and reliable treatment for children with end-stage liver disease in western China.
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Trasplante de Hígado/estadística & datos numéricos , Adolescente , Niño , Preescolar , China , Femenino , Supervivencia de Injerto , Humanos , Lactante , Estimación de Kaplan-Meier , Trasplante de Hígado/mortalidad , Masculino , Estudios RetrospectivosRESUMEN
Objective: To summarize and analyze the technique and experience of laparoscopic liver resection (LLR) in children. Methods: From Dec 2015 to Dec 2018, surgical outcomes were evaluated in 30 pediatric patients with liver tumors. LLR was performed in 21 patients, including 15 males and 6 females with a mean age of 7.6 ± 3.8 years (range, 2-13 years) and a mean liver tumor diameter of 7.2 ± 2.0 cm (range, 4-10 cm). During the same period, 9 cases of traditional open liver resection were selected as controls, including 6 males and 3 females with a mean age of 7.0 ± 3.7 years (range, 2-13 years) and a mean liver tumor diameter of 7.5 ± 2.2 cm (range, 4.4-10.0 cm). Results: The mean operation time and mean hepatic inflow occlusion time were longer in the laparoscopic group, with values of 182.3 ± 66.1 minutes and 83.2 ± 38.2 minutes, respectively, than in the open group, with values of 120.0 ± 54.3 minutes and 49.6 ± 26.5 minutes, respectively. There were no significant differences between the two groups in blood loss (164.4 ± 107.4 mL versus 133.8 ± 87.1 mL), blood transfusion volume (102.2 ± 100.2 mL versus 69.2 ± 81.8 mL), and alanine aminotransferase levels 24 hours after surgery (212.0 ± 101.4 IU/L versus 173.3 ± 97.2 IU/L) and 72 hours after surgery (74.0 ± 32.5 IU/L versus 81.7 ± 57.3 IU/L). The average hospital stay in the laparoscopic group (6.2 ± 1.6 days) was significantly shorter than that in the open group (8.2 ± 2.0 days). The children in both groups recovered well after surgery without serious complications. Conclusion: LLR contributes to improved recovery of patients after surgery without increasing the incidence of complication, therefore, LLR is a safe option for liver tumors in children.
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Carcinoma Hepatocelular/cirugía , Hepatectomía , Laparoscopía , Neoplasias Hepáticas/cirugía , Adolescente , Transfusión Sanguínea , Niño , Preescolar , Femenino , Humanos , Tiempo de Internación , Masculino , Tempo Operativo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Acute kidney injury (AKI) may contribute to high mortality rates after liver transplantation. Few studies have investigated AKI in pediatric liver transplantation. This retrospective study was conducted to investigate the risk factors for and associated outcomes of AKI in pediatric liver transplant recipients. METHODS: Eighty pediatric liver transplant patients were included. The occurrence of AKI was defined by the KDIGO Clinical Practice Guidelines for Acute Kidney Injury. A multivariate regression analysis model was used to investigate risk factors for AKI in the pediatric liver recipients. RESULTS: The final multivariable regression model showed that biliary atresia (odds ratio [OR]â¯=â¯0.097, pâ¯=â¯0.03), increased time of the anhepatic phase (ORâ¯=â¯0.871, pâ¯=â¯0.005) and lower postoperative jaundice clearance (ORâ¯=â¯13.936, pâ¯=â¯0.02) were independently associated with the development of AKI in pediatric patients. Additionally, cumulative 3-year patient (pâ¯=â¯0.15) and graft (pâ¯=â¯0.26) survival rates between the non-acute kidney injury (NAKI) and AKI groups were 95.2% vs 86.8% and 90.5% vs 84.2%, respectively. CONCLUSION: Pediatric liver transplant recipients with a presence of biliary atresia, increased time of anhepatic phase, and a lower postoperative jaundice clearance had an increased risk of AKI. The long-term outcomes of patients who developed AKI appears to be worse compared with those having NAKI. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level III.
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Lesión Renal Aguda , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/epidemiología , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Niño , Humanos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Liver transplantation can lead to post-traumatic stress disorder (PTSD) in recipients, but the risk factors associated with PTSD in living donors are unknown. To investigate this progression in pediatric living donors, a cross-sectional investigation was carried out.All participants completed 2 questionnaires: a PTSD self-rating scale (PTSD-SS) and a validated Chinese version of the Medical Outcomes Study Short Form-36 (SF-36). Clinical and demographic data were collected from medical records and self-report questionnaires. Univariate analysis was conducted to identify statistical differences.The prevalence of full PTSD (all symptom clusters) and partial PTSD (2 out of 3 symptom clusters) was 12.1% and 31.1%, respectively. Those with an educational status of elementary school (Pâ=â.001), who were donors to their children (Pâ=â.008), who were in the first 6 months after transplant (Pâ<â.001), or were involved in transplants where the recipients had severe complications (Pâ=â.02) were more likely to have higher PTSD-SS scores than other groups. The non-PTSD group had a higher health-related quality-of-life score compared with the full and partial PTSD groups in the domains of physical function, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. In addition, the occurrence of PTSD was related to a poorer quality of life.The occurrence of PTSD was common in living donors after pediatric liver transplantation. Those with a lower educational status, who were donors to their children, were in the first 6 months after transplant, or were involved in transplants where the recipients had severe complications were most likely to experience PTSD. Post-traumatic stress symptom severity was significantly associated with a poorer quality of life after transplant.
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Trasplante de Hígado/psicología , Donadores Vivos/psicología , Trastornos por Estrés Postraumático/epidemiología , Adulto , Niño , China/epidemiología , Estudios Transversales , Emociones , Femenino , Estado de Salud , Humanos , Masculino , Salud Mental , Padres/psicología , Calidad de Vida , Factores de Riesgo , Factores Socioeconómicos , Factores de Tiempo , Adulto JovenAsunto(s)
Anomalías del Sistema Digestivo/fisiopatología , Anomalías del Sistema Digestivo/cirugía , Duodeno/fisiopatología , Duodeno/cirugía , Vólvulo Intestinal/fisiopatología , Vólvulo Intestinal/cirugía , Páncreas/anomalías , Enfermedades Pancreáticas/cirugía , Niño , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Páncreas/fisiopatología , Páncreas/cirugía , Enfermedades Pancreáticas/fisiopatologíaRESUMEN
Dibutyl phthalate (DBP) has significant male reproductive toxicity, and the Sertoli cells are the target cells of DBP. This study was to investigate the injury effect induced by DBP on rat testicular Sertoli cells in vitro. MTT results showed that DBP can significantly reduce the survival rate of Sertoli cells; Hoechst staining results showed that the Sertoli cells treated with DBP emerged with typical morphological characteristics of apoptosis, nuclear condensation and chromatin condensation; flow cytometry results showed that DBP significantly increased the apoptotic rate of Sertoli cells, and dose-dependent; Western blotting showed that the expression of PTEN protein in Sertoli cells was significantly higher than that in the control group after treated with different concentrations of DBP for 24h, while the expression of p-PI3K1, p-AKT, p70S6K and 4E-BP1 protein in the PI3K/AKT/mTOR signal pathway were significantly decreased. It is speculated that PTEN/PI3K/AKT/mTOR signaling pathway plays an important role in DBP-induced apoptosis of testicular Sertoli cells in rats.
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Dibutil Ftalato/toxicidad , Disruptores Endocrinos/toxicidad , Células de Sertoli/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Masculino , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Células de Sertoli/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Terminal hindgut deformity is the leading digestive tract malformation, however, the etiology and pathogenesis remained unknown. To date, gene expression abnormalities were considered the primary cause of these diseases. miRNAs have been found to play an important role in regulating the expression of genes. METHODS: A total of 24 pregnant rats were randomly divided into two groups. The experimental group (n=12) received 1% ethylenethiourea (125mg/kg) by gavage on gestational day 11, while the control group (n=12) received the same volume of distilled water. From each group, fetal rats were obtained by cesarean section on gestational day 16. For the extraction of total RNA, 1 cm rectum samples were obtained from four fetal rats that had similar weights. Chip hybridization was conducted after poly(A) and biotin were added to the RNA samples, and this was followed by washing, dyeing, and scanning of the chip. Differences identified in the miRNA expression profiles and the target gene analysis results were further analyzed to identify potential regulators of terminal hindgut development. RESULTS: Compared with the control group, 111 miRNAs expressed in the terminal hindgut of the experimental group were up-regulated on gestational day 16, while 117 miRNAs were down-regulated. The ten miRNAs with the greatest differential expression profiles between the experimental and control samples were selected for target gene prediction, pathway analysis, and gene ontology analysis. A subset of these miRNAs was found to be closely related to rat fetus terminal hindgut growth and development. In addition, target gene analysis showed that miR-193 may have an important role in regulating a key gene in anorectal development, Hoxd13. This role was confirmed in a dual luciferase reporter assay when miR-193 was able to inhibit expression of a reporter gene under the control of the 3' untranslated region of the Hoxd13 gene in the human embryonic kidney cell line, 293T. Real-time PCR and Western blotting experiments further showed that the expression of Hoxd13 was significantly lower when miR-193 was highly expressed in rat intestinal epithelial cells. The differences in both sets of experiments were statistically significant compared with the negative control group (P<0.05). CONCLUSION: These data support an important regulatory role for miRNAs in the expression of target genes during terminal hindgut development in fetal rats. In particular, miR-193-mediated inhibition of Hoxd13 was found to be significant in rat intestinal epithelial cells.
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Modelos Animales de Enfermedad , MicroARNs/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Recto/metabolismo , Animales , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos , Embarazo , Ratas , Recto/anomalías , Factores de Transcripción/genética , Regulación hacia ArribaRESUMEN
Flexible bronchoscopy is more and more used for diagnosis and management of various pulmonary diseases in pediatrics. As poor coordination of children, the procedure is usually performed under general anesthesia with spontaneous or controlled ventilation to increase children and bronchoscopists' safety and comfort. Previous studies have reported that dexmedetomidine (DEX) could be safely and effectively used for flexible bronchoscopy in both adulate and children. However, there is no trial to evaluate the dose-finding of safety and efficacy of dexmedetomidine-remifentanil (DEX-RF) in children undergoing flexible bronchoscopy.The objective of this study is to evaluate the dose-finding of safety and efficacy of DEX-RF in children undergoing flexible bronchoscopy.One hundred thirty-five children undergoing flexible bronchoscopy with DEX-RF were divided into 3 groups: Group DR1 (nâ=â47, DEX infusion at 0.5âµg·kg for 10âminutes, then adjusted to 0.5-0.7âµg kg h; RF infusion at 0.5âµg kg for 2âminutes, then adjusted to 0.05-0.2âµg kg min), Group DR2 (nâ=â43, DEX infusion at 1âµg kg for 10âminutes, then adjusted to 0.5-0.7âµg kg h; RF infusion at 1âµg kg for 2âminutes, then adjusted to 0.05-0.2âµg kg min), Group DR3 (nâ=â45, DEX infusion at 1.5âµg kg for 10âminutes, then adjusted to 0.5-0.7âµg kg h; RF infusion at 1âµg kg for 2âminutes, then adjusted to 0.05-0.2âµg kg min). Ramsay sedation scale of the 3 groups was maintained 3. Anesthesia onset time, total number of intraoperative children movements, hemodynamics (heart rate, arterial pressure, pulse oxygen saturation (SpO2), respiratory rate), total cumulative dose of dexmedetomidine and remifentanil, the amount of midazolam and lidocaine, time to first dose of rescue midazolam and lidocaine, postoperative recovery time, adverse events, bronchoscopist satisfaction score were recorded.Anesthesia onset time was significantly shorter in DR3 group (14.23â±â5.45 vs 14.45â±â5.12 vs 11.13â±â4.51âminutes, respectively, of DR1, DR2, DR3, Pâ=â0.003). Additionally, the perioperative hemodynamic profile was more stable in group DR3 than that in the other 2 groups. Total number of children movements during flexible bronchoscopy was higher in DR1 group than the other 2 groups (46.81% 22/47 vs 34.88% 15/43 vs 17.78% 8/45, respectively, of DR1, DR2, DR3, Pâ=â0.012). Total doses of rescue midazolam and lidocaine were significantly higher in DR1 and DR2 groups than that of DR3 group (Pâ=â0.000). The time to first dose of rescue midazolam and lidocaine was significantly longer in DR3 group than DR1 and DR2 groups (Pâ=â0.000). Total cumulative dose of dexmedetomidine was more in DR2 and DR3 groups (Pâ=â0.000), while the amount of remifentanil was more in DR1 and DR2 groups (Pâ=â0.000). The time to recovery for discharge from the PACU was significantly shorter in DR1 group compared with the other 2 groups (Pâ=â0.000). Results from bronchoscopist satisfaction score showed significantly higher in DR2 and DR3 groups than that of DR1 group (Pâ=â0.025). There were significant differences among the 3 groups in terms of the overall incidence of hypertension, tachycardia, hypoxemia, and cough (Pâ<â0.05).Though it required longer recovery time, high dose of DEX-RF, which provided better stable hemodynamic profiles and bronchoscopist satisfaction score, less amount of rescue scheme, and children movements, could be safely and efficacy used in children undergoing flexible bronchoscopy.
Asunto(s)
Broncoscopía/métodos , Dexmedetomidina/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Piperidinas/uso terapéutico , Periodo de Recuperación de la Anestesia , Niño , Dexmedetomidina/administración & dosificación , Dexmedetomidina/efectos adversos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Hemodinámica , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Lidocaína/administración & dosificación , Masculino , Midazolam/administración & dosificación , Movimiento/efectos de los fármacos , Piperidinas/administración & dosificación , Piperidinas/efectos adversos , Remifentanilo , Estudios RetrospectivosRESUMEN
BACKGROUND: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal mortality; effective interventions are lacking with limited understanding of the pathogenesis of NEC. The importance of Toll-like receptor 4 (TLR4) signaling in NEC is well documented; however, the potential mechanisms that regulate enterocyte inflammation and apoptosis remain unclear. The aim of this study was to characterize the role of TLR4-mediated inflammation and apoptosis in the development of NEC and to determine the major apoptotic pathways and regulators in the process. METHODS: TLR4-deficient C57BL/10ScNJ mice and lentivirus-mediated stable TLR4-silent cell line (IEC-6) were used. NEC was induced by formula gavage, cold, hypoxia, combined with lipopolysaccharide in vivo or lipopolysaccharide stimulation in vitro. Enterocyte apoptosis was evaluated by TUNEL or Annexin analysis. The expression of TLR4, caspase3, caspase8, caspase9, Bip, Bax, Bcl-2, and RIP was detected by Western blot and immunofluorescence. Inflammatory factors such as tumor necrosis factor-α and interleukin-2 were examined by Luminex. RESULTS: Defect of TLR4 led to suppressed enterocytes apoptosis both in vitro and in vivo; the expression of caspase3, caspase8, Bip, and Bax was decreased; and caspase9 and Bcl-2 were increased. NEC severity was attenuated in TLR4-deficient mice compared with wild-type counterparts, and enterocytes apoptosis was correlated with NEC severity. RIP and cytokine level of tumor necrosis factor-α and interleukin-2 were also decreased. CONCLUSIONS: TLR4-induced inflammation and apoptosis play a critical role in the pathogenesis of NEC. TLR4 inhibition, combined with extrinsic (caspase8) and/or endoplasmic reticulum stress (Bip) apoptosis signaling blockade could serve as a potential effective treating strategy for NEC.