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1.
Fetal Pediatr Pathol ; 42(1): 123-130, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35403555

RESUMEN

Inflammatory myofibroblastic tumor (IMT) infrequently involves the sigmoid colon, and has not previously been described in an infant sigmoid colon.An inflammatory myofibroblastic tumor arose from the sigmoid colon of an 11-month-old boy, confirmed by anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA) and desmin immunohistochemical staining. The patient recovered well after complete resection of the tumor.Sigmoid IMT can occur in infancy. This eighth case is the youngest so far. The child did well after surgical resection.


Asunto(s)
Neoplasias de Tejido Muscular , Neoplasias del Colon Sigmoide , Masculino , Niño , Humanos , Lactante , Colon Sigmoide/patología , Neoplasias del Colon Sigmoide/diagnóstico , Neoplasias del Colon Sigmoide/cirugía , Neoplasias de Tejido Muscular/diagnóstico , Neoplasias de Tejido Muscular/cirugía , Neoplasias de Tejido Muscular/patología , Inflamación/patología
2.
Pediatr Surg Int ; 38(9): 1263-1271, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35852594

RESUMEN

BACKGROUND: Anastomotic leakage (AL) is one of the most perplexing complications that can occur following a radical operation to treat Hirschsprung disease (HSCR). The purpose of this study was to document our experience with anastomotic leakage following radical HSCR surgery to enhance therapeutic effect and prognosis. METHODS: Between January 2007 and April 2021, a retrospective study was conducted on 12 children who developed anastomotic leakage following radical surgery for HSCR. Medical records were analyzed to determine the clinical manifestations, primary surgical procedures, evaluation methods, surgical plans, and outcomes of the patients. To assess postoperative bowel function, the Rintala score was used. RESULTS: The Soave procedure was used as the primary surgical method in seven cases (58.3%), the Swenson procedure was used in four cases (33.3%), and the Rehbein procedure was used in one case (8.3%). Enterostomy (10, 83.3%) and conservative treatment (2, 16.7%) were performed when anastomotic leakage was diagnosed. Two patients who directly closed stoma without redoing pull-through both accepted enterostomy within 48 h. One female with anastomotic fistula who was closed leakage or fistula in situ had to endure lifelong stoma. Other patients who underwent redo pull-through procedures had normal bowel function. Seven patients underwent a redo pull-through procedure. Three of them preferred the transanal full-thickness pull-through (FTPT) approach, while four preferred the Soave technique. Three children had mild postoperative soiling, which improved with conservative treatment. Bowel function score was 17.5 ± 1.1. CONCLUSION: Enterostomy should be performed immediately if anastomotic leakage occurs. After leakage, it is necessary to redo the pull-through procedure in an anastomotic fistula or anastomotic stricture. Transanal FTPT reconstruction is an effective method for repairing anastomoses and leakage.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Enfermedad de Hirschsprung , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Niño , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Femenino , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/cirugía , Humanos , Lactante , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
3.
Phys Chem Chem Phys ; 22(8): 4715-4730, 2020 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-32057037

RESUMEN

Benziporphyrins are versatile macrocycles exhibiting aromaticity switching behaviors. The existence of both Hückel and Möbius (anti)aromaticity has been reported in these systems, whose validity is respectively governed by the [4n + 2] and [4n] π-electron rule on the macrocyclic pathway. Despite the experimental evidence on the floppiness of benziporphyrins, the switching mechanism between Hückel and Möbius structures is still not clear, as well as the factors influencing the stability of the different π-conjugation topologies. For these reasons, we performed a systematic study on A,D-di-p-benzihexaphyrins(1.1.1.1.1.1) with two redox states corresponding to [28] and [30] π-electron conjugation pathways. Whereas benzi[28]hexaphyrin obeys Möbius aromaticity, benzi[30]hexaphyrin follows Hückel aromaticity. The dynamic interconversion between Möbius and Hückel aromaticity is investigated through the rotation of a phenylene ring, which acts as the topology selector. Further analyses of the energy profiles using energy decomposition and information-theoretic approaches provide new insights into conformational stability, aromaticity and antiaromaticity for these species. Strong and opposite cross correlations between aromaticity indexes and information-theoretic quantities were found for the two macrocyclic systems with opposite global aromaticity and antiaromaticity behaviors. These results indicate that Hückel and Möbius aromaticity and antiaromaticity, though qualitatively different, are closely related and can be interchanged, and information-theoretic quantities provide a novel understanding about their relevance. Our present results should provide in-depth insights to appreciate the nature and origin about Möbius (anti)aromaticity and its close relationship with Hückel (anti)aromaticity.

4.
J Phys Chem A ; 124(24): 5033-5041, 2020 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-32436382

RESUMEN

To provide feasible methods for the extraction of valuable metals from spent batteries or low-grade primary ores, the extraction behavior of some representative acidic phosphorus-containing compounds (APCCs) as extractants is evaluated from the perspective of experimental and theoretical investigations in this work. Aqueous solutions containing five metal ions, Ca(II), Co(II), Mg(II), Mn(II), and Ni(II), were made to simulate leaching liquids, and the extraction of these metals was investigated. A simplified calculated model was used to evaluate the interaction between each extractant and metal ions. The calculation results agree well with the experimental tests in trend. This work not only provides potential extractants for the extraction of valuable metals from spent batteries or low-grade primary ores but also demonstrates the practicability of the simplified calculation model.

5.
Phys Chem Chem Phys ; 21(33): 18195-18210, 2019 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-31389933

RESUMEN

In this work, we report a systematic study on the global and local aromaticity of acenes using a series of model structures from 2-acene to 11-acene. A recently developed ansatz, an information-theoretic approach coached into density functional reactivity theory has been employed, which essentially provides different density functionals characterizing the molecular electron density distribution. Based on the correlation analysis of six conventional aromaticity indices with eight information-theoretic quantities, we examined the aromaticity of acenes from both global and local perspectives. From the global aromaticity viewpoint, our results suggest that different descriptors based on various physicochemical properties are intrinsically dependent. A novel laminated feature ruling local aromaticity of acenes has been unveiled, from which we found that the distance from the terminal rings plays the critical role. Based on the shape of the correlation plots between the conventional aromaticity indices and information-theoretic quantities, the latter could be separated into three subgroups. The seemingly contradictory results from global and local aromaticity perspectives not only present us the uniqueness of the acene systems but all demonstrate the effectiveness of the information-theoretic approach from density functional reactivity theory. Besides strengthening the validity of a series of new aromaticity descriptors, our results should lead to more clear insights into the chemical significance of the information-theoretic quantities.

6.
J Phys Chem A ; 123(31): 6751-6760, 2019 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-31305075

RESUMEN

The oxidation state, also called oxidation number, of atoms in molecules is a fundamental chemical concept. It is defined as the charge of an atom in a molecule after the ionic approximation of its heteronuclear bonds is applied. Even though for simple molecules the assignment of oxidation states is straightforward, redundancy and ambiguity do exist for others. In this work, we present a density-based framework to determine the oxidation state using the quantities from the information-theoretic approach. As a proof of concept, we examined six elements for a total of 49 molecules. Strong linear correlations were obtained with Shannon entropy, Ghosh-Berkowitz-Parr entropy, information gain, relative Rényi entropy of orders 2 and 3, and Hirshfeld charge. We also discovered that the crystal radius of elements plays the key role in rationalizing the system dependent nature of these strong linear correlations. The validity and effectiveness of our results were demonstrated by the examples of molecules containing elements with two or more oxidation states. Our results should be applicable to more complicated systems in assigning different oxidation states.

7.
J Am Chem Soc ; 140(48): 16553-16559, 2018 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-30421611

RESUMEN

All-aza smaragdyrin, a historic but elusive pentapyrrolic macrocycle, was successfully synthesized and characterized for the first time. [22]Smaragdyrin BF2-complex 3 was smoothly synthesized by 2-fold SNAr reaction of 1,9-dibromo-5-mesityldipyrrin with 5,10-dimesityltripyrrane. Treatment of 3 with methanesulfonic acid gave [20]smaragdyrin 5 as a stable antiaromatic compound. Reduction of 5 with NaBH4 under inert conditions gave [22]smaragdyrin 6 as an aromatic congener, which was easily oxidized back to 5 in the air. Complex 3 was interconvertible with its 20π-congener 4 via oxidation with MnO2 and reduction with NaBH4. Treatment of 3 or 4 with CuCl2 in the presence of NaOAc gave hetero bimetal complex 8.

8.
Phys Chem Chem Phys ; 20(26): 17990-17998, 2018 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-29927447

RESUMEN

Cooperativity is a widely used chemical concept whose existence is ubiquitous in chemical and biological systems but whose quantification is still controversial and origin much less appreciated. In this work, using the interaction energy of a molecular system, which is composed of multiple copies of a building block, we propose a quantitative measurement to evaluate the cooperativity effect. This quantification approach is then applied to six molecular systems, i.e., water cluster, argon cluster, protonated water cluster, zinc atom cluster, water cluster on top of a graphene sheet, and alpha helix of glycine amino acids, each with up to 20 copies of the building block. Cooperativity is seen in all these systems. Both positive and negative cooperativity effects are observed. Employing the two energy partition schemes in density functional theory and the information-theoretic quantities such as Shannon entropy, Fisher information, information gain, etc., we then examine the origin of the cooperativity effect for these systems. Strong linear correlations between the cooperativity measure and some of these theoretical quantities have been unveiled. With these correlations, we are able to quantitatively account for their origin of cooperativity. Our results show that the interactions governing the existence and validity of the cooperativity effect are complicated. An opposite mechanism in enthalpy-entropy compensation for positive and negative cooperativity has been unveiled. These results should provide new insights and understandings from a different viewpoint about the nature and origin of cooperativity to appreciate this vastly important chemical concept.

9.
Phys Chem Chem Phys ; 20(3): 1408-1420, 2018 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-29299564

RESUMEN

The steric effect is one of the most widely used chemical concepts in chemistry, yet a generally accepted implementation of its formulation and quantification from a theoretical viewpoint, if even possible, is still an unaccomplished task. Based on the energetics viewpoint of our earlier proposal using the Weizsäcker kinetic energy as a quantification of the energy contribution from the steric effect as well as our recent work using steric force as a reliable local descriptor to account for the origin of the stereoselective propensity in chemical reactions, in this work, we systematically examine the local behavior and general applicability of another closely related quantity, steric charge. To this end, its physical origin and physiochemical properties are formalized and highlighted, and are shown with numerical illustrations and verifications. To showcase its usefulness in appreciating chemical reactivity, we present three case studies of steric charge in this work. In the case of ethane flexible rotation, we found that the eclipsed conformer is more sterically charged than the staggered conformer, leading to the reduced stability and higher energy of the former. For the case of SN2 reactions, a remarkable linear correlation has been obtained between the steric charge on the central atom in the transition state and the reaction barrier height of SN2 reactions, in good agreement with experimental findings. In the case of stereoselectivity properties for the nucleophilic addition of carbonyl compounds, we found that steric charge is equally applicable as steric force to justify the stereoselective origin for the nucleophilic attack to the carbonyl carbon atom with different substituent groups. Put together, our results from the present study should pave the way towards the general use of steric charge, together with steric energy and steric force, as an insightful global and local descriptor to appreciate and quantify chirality and stereoselectivity related phenomena in chemical processes and transformations.

10.
J Phys Chem A ; 122(2): 700-707, 2018 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-29260874

RESUMEN

Molecular acidity of trivalent rare-earth metal cations in aqueous solution is an important factor dedicated to the efficiency of their extraction and separation processes. In this work, the aqueous acidity of these metal ions has been quantitatively investigated using a few theoretical approaches. Our computational results expressed in terms of pKa values agree well with the tetrad effect of trivalent rare-earth ions extensively reported in the extraction and separation of these elements. Strong linear relationships have been observed between the acidity and quantum electronic descriptors such as the molecular electrostatic potential on the acidic nucleus and the sum of the valence natural atomic orbitals energies of the dissociating proton. Making use of the predicted pKa values, we have also predicted the major ionic forms of these species in the aqueous environment with different pH values, which can be employed to rationalize the behavior difference of different rare-earth metal cations during the extraction process. Our present results should provide needed insights not only for the qualitatively understanding about the extraction and separation between yttrium and lanthanide elements but also for the prediction of novel and more efficient rare-earth metal extractants in the future.

11.
Pediatr Surg Int ; 34(8): 897-901, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29872885

RESUMEN

Congenital biliary dilatation (CBD) is usually associated with complications such as recurrent cholangitis, manifested as abdominal pain, vomiting, and jaundice. If cholangitis cannot be controlled by conservative treatment, a good therapeutic effect can be obtained through percutaneous biliary drainage or open T-tube drainage. We aimed to evaluate our experiences in biliary drainage through endoscopic retrograde cholangiopancreatography in children with cholangitis caused by CBD. From January 2014 to December 2017, 167 children with CBD were treated in our hospital. 17 patients (10.18%) with serious cholangitis caused by CBD underwent ERCP. There were 4 males and 13 females with an age range of 10-120 months (average 56.4 months). Placement of a biliary stent was attempted for biliary drainage through endoscopic retrograde cholangiopancreatography. Of the 17 patients studied, 13 children had jaundice and 15 had elevated aminotransferases. ERCP showed CBD in all patients and a common biliopancreatic duct in 12 of 17 patients (70.6%). Five patients underwent nasobiliary drainage and 12 patients underwent biliary drainage through double pigtail tubes. All patients achieved successful biliary drainage. Postoperative pancreatitis occurred in one patient. Biochemical indicators decreased significantly in 12 patients (70.6%) on the second postoperative day. The average length of hospital stay after surgery was 4.5 (range 3-7) days. No major complications related to ERCP were observed and all children had a good prognosis so far. Endoscopic biliary drainage is a safe, simple, and reliable technique. It can be used to resolve CBD-associated cholangitis, evaluate the biliary tract and pancreatobiliary duct junction, and guide pediatric surgeons to choose the right time and the correct procedure for CBD.


Asunto(s)
Enfermedades de las Vías Biliares/complicaciones , Colangitis/terapia , Dilatación Patológica/complicaciones , Drenaje/métodos , Endoscopía del Sistema Digestivo , Enfermedades de las Vías Biliares/congénito , Preescolar , Colangiopancreatografia Retrógrada Endoscópica , Colangitis/etiología , Dilatación Patológica/congénito , Femenino , Humanos , Lactante , Masculino
12.
Phys Chem Chem Phys ; 19(28): 18635-18645, 2017 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-28692080

RESUMEN

Even though the concept of aromaticity and antiaromaticity is extremely important and widely used, there still exist lots of controversies in the literature, which are believed to be originated from the fact that there are so many aromatic types discovered and at the same time there are many aromaticity indexes proposed. In this work, using seven series of substituted fulvene derivatives as an example and with the information-theoretic approach in density functional reactivity theory, we examine these concepts from a different perspective. We investigate the changing patterns of Shannon entropy, Fisher information, Ghosh-Berkowitz-Parr entropy, information gain, Onicescu information energy, and relative Renyi entropy on the ring carbon atoms of these systems. Meanwhile, we also consider variation trends of four representative kinds of aromaticity indexes such as FLU, HOMA, ASE and NICS. Statistical analyses among these quantities show that with the same ring structure of the derivatives, both information-theoretic quantities and aromaticity indexes obey the same changing pattern, which are valid across all seven systems studied. However, cross correlations between these two sets of quantities yield two completely opposite patterns. These ring-structure dependent correlations are in good agreement with Hückel's 4n + 2 rule of aromaticity and 4n rule of antiaromaticity. Our results should provide a novel and complementary viewpoint on how aromaticity and antiaromaticity should be appreciated and categorized. More studies are in progress to further our understanding about the matter.

13.
Int Psychogeriatr ; 29(10): 1595-1608, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28884657

RESUMEN

BACKGROUND: It has been reported that up to 42% of the population aged over 60 are affected by mild cognitive impairment (MCI) worldwide. This study aims to investigate the prevalence and progression of MCI through a meta-analysis. METHODS: We searched Embase and PubMed for relevant literature. Stable disease rate (SR), reversion rate (RR), dementia rate (DR), and Alzheimer's disease rate (AR) were used to evaluate the progression of MCI. The prevalence and progression rates were both obtained by reported percentile and indirect data analysis. Additionally, we carried out sensitivity analysis of each index by excluding some studies due to influence analysis with the most publication bias. RESULTS: Effect size (ES) was used to present adjusted overall prevalence (16%) and progression rates including SR (45%), RR (15%), DR (34%), and AR (28%) of MCI. Compared with clinic-based outcomes, MCI prevalence, SR, and RR are significantly higher in community, while DR and AR are lower. Despite significant heterogeneity found among the studies, no publication bias was observed. CONCLUSIONS: Age and gender were observed to be associated with MCI, in which age was considered as an impact factor for DR. The strong heterogeneity may result from variations in study design and baselines. Standardized MCI criteria were suggested to systematically evaluate MCI in the future.


Asunto(s)
Envejecimiento/psicología , Disfunción Cognitiva/epidemiología , Demencia/complicaciones , Demencia/epidemiología , Anciano , Progresión de la Enfermedad , Humanos , Factores de Riesgo
14.
Angew Chem Int Ed Engl ; 56(12): 3196-3200, 2017 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-28194833

RESUMEN

Trifluoromethylthiolation by sulfuration of difluorocarbene with elemental sulfur is described for the first time, which overrides long-standing trifluoromethyl anion-based theory. Mechanistic elucidation reveals an unprecedented chemical process for the formation of thiocarbonyl fluoride and also enables transition-metal-mediated trifluoromethylthiolation and [18 F]trifluoromethylthiolation of α-bromo carbonyl compounds with broad substrate scope and compatibility.

15.
J Comput Chem ; 37(18): 1668-71, 2016 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-27218266

RESUMEN

Ninety-six acidic phosphorus-containing molecules with pKa 1.88 to 6.26 were collected and divided into training and test sets by random sampling. Structural parameters were obtained by density functional theory calculation of the molecules. The relationship between the experimental pKa values and structural parameters was obtained by multiple linear regression fitting for the training set, and tested with the test set; the R(2) values were 0.974 and 0.966 for the training and test sets, respectively. This regression equation, which quantitatively describes the influence of structural parameters on pKa , and can be used to predict pKa values of similar structures, is significant for the design of new acidic phosphorus-containing extractants. © 2016 Wiley Periodicals, Inc.

16.
Paediatr Anaesth ; 26(9): 891-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27346807

RESUMEN

BACKGROUND: Postoperative pain can cause physiological distress, postoperative complications, and extended lengths of hospitalized stay. In children, management of postoperative pain is still recognized as being inadequate. OBJECTIVE: The aim of this trial was to investigate the effects of intraperitoneal ropivacaine on postoperative pain, and recovery of bowel function and emetic events after laparoscopic herniorrhaphy in toddlers. METHODS: Seventy-six children aged from 9 months to 3 years were recruited between August 2013 and June 2014 at Tongji Hospital and randomly assigned into two groups. One group received intraperitoneal ropivacaine right before surgery and the control group received intraperitoneal saline. A standard combined general anesthesia procedure was performed under regular monitoring. Postoperative pain was assessed by the FLACC scale. Postoperative analgesic consumption, time to flatus, time to first stool, and postoperative emetic events were also recorded. RESULTS: When compared with the control group, children who received intraperitoneal ropivacaine experienced less pain 0-4 h after surgery [P < 0.001, difference in median FLACC (95% CI) for 2 h time point is 2.00 (0.87-3.13), for 4 h time point is 1.00 (0.55-1.45)]. In addition, the number of toddlers who received analgesia 0-24 h after surgery in the ropivacaine group was lower than that in the control group [P < 0.001, difference in proportions (95% CI) is 0.575 (0.3865-0.7638)]. Compared with the control group, time to flatus in ropivacaine group was also much shorter [21.1 h vs 16.7 h, P = 0.04, difference in mean (95% CI) is 4.4 (1.49-7.28)], and the time to first stool after surgery was earlier in the ropivacaine group [30.7 h vs 25.6 h, P = 0.003, difference in mean (95% CI) is 5.1 (1.78-8.45)]. Furthermore, the incidence of emetic events in the ropivacaine group was significantly lower than the control group [32.4% vs 11.1%, P = 0.03, difference in proportions (95% CI) is 0.212 (0.0246-0.4002)]. CONCLUSION: The present results indicate that intraperitoneal ropivacaine reduces early postoperative pain and improves recovery after laparoscopic herniorrhaphy in toddlers. Therefore, IPLA is a good stratagem for postoperative pain management after laparoscopic surgery in toddlers.


Asunto(s)
Amidas/uso terapéutico , Anestésicos Locales/uso terapéutico , Herniorrafia , Laparoscopía , Dolor Postoperatorio/tratamiento farmacológico , Amidas/administración & dosificación , Anestésicos Locales/administración & dosificación , Preescolar , Femenino , Humanos , Lactante , Inyecciones Intraperitoneales , Tiempo de Internación/estadística & datos numéricos , Masculino , Manejo del Dolor/métodos , Ropivacaína , Resultado del Tratamiento
17.
Cell Mol Neurobiol ; 35(2): 255-64, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25301495

RESUMEN

With the increasing use of bone marrow mesenchymal stem cells (BMSCs) in cell therapies, factors regulating BMSC differentiation have become the interest of current research. In this study, we investigated the effects of glial cell-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) on the course of BMSC differentiation. BMSCs were isolated from rat bone marrow and transfected with GDNF and NT-3 genes. Compared to mock-transfected BMSCs, GDNF and NT-3 induced BMSC differentiation to reveal neuron-like characteristics, i.e., the positive expression of neuronal marker MAP-2 and astrocyte marker GFAP, as detected by immunofluorescence assays. Semi-quantitative polymerase chain reaction (PCR) and western blot analyses showed that the increase of expression of GDNF and NT-3 in BMSCs also simultaneously elevated the mRNA expression of NSE, nestin, and MAP-2. Furthermore, the cell patch-clamp test demonstrated that the overexpression of GDNF and NT-3 in BMSCs enhanced voltage-activated potassium currents, implying that BMSCs possess great potential as a cell-based therapeutic candidate to treat neurological diseases.


Asunto(s)
Huesos/citología , Diferenciación Celular , Medios de Cultivo/farmacología , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Células Madre Mesenquimatosas/citología , Neuronas/citología , Neurotrofina 3/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Separación Celular , Forma de la Célula/efectos de los fármacos , Células Cultivadas , Feto/citología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Tracto Gastrointestinal/citología , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Técnicas de Placa-Clamp , Fenotipo , Canales de Potasio/metabolismo , Ratas Sprague-Dawley
18.
J Pediatr Surg ; 59(8): 1498-1514, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38508971

RESUMEN

OBJECTIVE AND DESIGN: Hirschsprung disease-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). We aimed to investigate the effectiveness, long-term safety and the underlying mechanisms of Mesenchymal stem cells (MSCs) based therapy for HAEC. MATERIAL OR SUBJECTS: Specimens from HSCR and HAEC patients were used to assess the inflammatory condition. Ednrb knock-out mice was used as HAEC model. MSCs was intraperitoneally transplanted into HAEC mice. The therapy effects, long-term outcome, safety and toxicity and the mechanism of MSCs on the treatment of HAEC were explored in vivo and in vitro. RESULTS: Intestinal M1 macrophages infiltration and severe inflammation condition were observed in HAEC. After the injection of MSCs, HAEC mice showed significant amelioration of the inflammatory injury and inhibition of M1 macrophages infiltration. The expression levels of pro-inflammatory cytokines (TNF-α and IFN-γ) were decreased and anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. In addition, we found that effective MSCs homing to the inflamed colon tissue occurred without long-term toxicity response. However, COX-2 inhibitor could diminish the therapeutic effects of MSCs. Using MSCs and macrophages co-culture system, we identified that MSCs could alleviate HAEC by inhibiting M1 macrophages activation through COX-2-dependent MAPK/ERK signaling pathway. CONCLUSIONS: MSCs ameliorate HAEC by reducing M1 macrophages polarization via COX-2 mediated MAPK/ERK signaling pathway, thus providing novel insights and potentially promising strategy for the treatment or prevention of HAEC.


Asunto(s)
Ciclooxigenasa 2 , Enterocolitis , Enfermedad de Hirschsprung , Macrófagos , Trasplante de Células Madre Mesenquimatosas , Enfermedad de Hirschsprung/terapia , Enfermedad de Hirschsprung/patología , Animales , Enterocolitis/etiología , Trasplante de Células Madre Mesenquimatosas/métodos , Macrófagos/metabolismo , Ratones , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Humanos , Masculino , Modelos Animales de Enfermedad , Femenino , Ratones Noqueados , Células Madre Mesenquimatosas , Receptor de Endotelina B
19.
Dev Cell ; 59(13): 1689-1706.e8, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38636517

RESUMEN

During enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung's disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders.


Asunto(s)
Movimiento Celular , Sistema Nervioso Entérico , Cresta Neural , Transducción de Señal , Animales , Cresta Neural/metabolismo , Cresta Neural/citología , Ratones , Sistema Nervioso Entérico/metabolismo , Sistema Nervioso Entérico/embriología , Sistema Nervioso Entérico/citología , Embrión de Mamíferos/metabolismo , Embrión de Mamíferos/citología , Diferenciación Celular , Regulación del Desarrollo de la Expresión Génica , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/metabolismo , Enfermedad de Hirschsprung/patología , Humanos
20.
Int J Colorectal Dis ; 28(5): 689-96, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23568714

RESUMEN

PURPOSE: To create a simple diagnostic scoring system to differentiate Hirschsprung's disease (HD) from Hirschsprung's disease-allied disorders (HAD) in patients with suspected intestinal dysganglionosis (IDs). METHODS: Between 1998 and 2008, 967 patients with suspected intestinal dysganglionosis underwent surgical treatment at the pediatric surgery department of Tongji Hospital. The diagnosis of HD or HAD was confirmed by postoperative pathological examination. All patients underwent preoperative work-up including barium enema, anorectal manometry, and histochemical acetylcholinesterase staining of rectal mucosa. Known risk factors for IDs were recorded. The predicting score was calculated by summing the scores of the risk factors and three preoperative tests. The sensitivity, specificity, accuracy, positive predictive values, negative predictive values, positive likelihood ratios, and negative likelihood ratios of the predicting score were calculated. The cutoff score for predicting HD was determined using receiver operating characteristic (ROC) analysis. The accuracy of the predicting score was measured by the area under the ROC curve. RESULTS: Failed or delayed passage of meconium, age <3 years and male gender were risk factors associated with HD. The area under the ROC curve of the predicting score was 0.927 (95 % confidence interval, 0.910-0.944). A predicting score of more than 5 was used as a cutoff for predicting HD. The scoring system achieved 83.1 % sensitivity, 89.5 % specificity, and 85.9 % accuracy in predicting HD. CONCLUSION: Patients with a predicting score of more than 5 are more likely to be diagnosed with HD, whereas a score less than 5 are mostly indicative of HAD.


Asunto(s)
Ganglios/patología , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/diagnóstico , Proyectos de Investigación , Área Bajo la Curva , Preescolar , Demografía , Diagnóstico Diferencial , Pruebas Diagnósticas de Rutina , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Curva ROC
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