Hernia Diafragmatica Izquierda. Reporte de un caso / Left Diaphragmatic Hernia: A case report

Se presenta un caso clínico de diagnóstico ecográfico de hernia diafragmática realizado a partir de signos de sospecha. La paciente se presenta a control prenatal cursando 18 semanas de gestación, donde se visualiza alteración de la posición de la silueta cardiaca y cambios en la ecogenicidad en el campo pulmonar izquierdo. Se evalúan los signos pronósticos de las hernias diafragmáticas como la presencia de estómago e hígado en tórax y se calcula el índice pulmóncabeza ( LHR). En el presente caso el LHR arrojo un valor de 2,3 %, lo cual indica un buen pronóstico ya que el LHR mayor a 1,4 % se asocia a 93 % de posibilidades de sobrevivir

A clinical case of ultrasound diagnosis of diaphragmatic hernia performed from signs of suspicion is presented. The patient is presented to prenatal control studying 18 weeks gestation, where alteration of the position of the cardiac silhouette and changes in ecogenicity in the left pulmonary field is displayed. The prognostic signs of diaphragmatic hernias such as the presence of stomach and thorax liver and the lung-headed index (LHR) are evaluated. In the present case, the LHR shows a value of 2.3 %, which indicates a good prognosis since the LHR greater than 1.4 % is associated with 93 % possibilities to survive

Hiperenrollamiento con torsión del cordón umbilical como causa de muerte fetal: reporte de caso / Hypercoiled umbilical cord torsion as a cause of fetal death: case report

Resumen La torsión del cordón umbilical como causa de muerte fetal es rara, con pocos casos reportados. No se conoce con claridad la causa y se presenta principalmente en el segundo trimestre de embarazo. Los factores de riesgo descritos son la longitud del cordón umbilical y el aumento del número de giros. Se reporta el caso de una paciente de 37 años, grávida 2, para 1 con embarazo de 23 semanas, con hallazgo ecográfico de muerte fetal. En el estudio de histopatología se evidenció el cordón umbilical con hiperenrollamiento y torsión a nivel de la unión feto-umbilical con oclusión de la luz de los vasos umbilicales como causa de muerte fetal. Se requiere la investigación de esta patología para determinar los factores de riesgo y el riesgo de recurrencia en futuros embarazos con el fin de establecer métodos de vigilancia fetal antenatal.

Abstract Torsion of the umbilical cord as a cause of fetal death is a rare occurrence, with few reported cases. The cause is not clearly known, and it transpires mainly in the second trimester of pregnancy; the risk factors described are the length of the umbilical cord with increased number of twists. The case of a 37-year-old woman is reported, gravida 2 para 1, 23 weeks pregnant with ultrasound diagnosis of fetal death. Histopathology revealed hypercoiled umbilical cord torsion at the point where the umbilical cord attaches to the fetus, with occlusion of the lumen of the umbilical vein, as a cause of fetal death. Further research of this pathology is required to determine the risk factors and risk of recurrence in future pregnancies that will allow the preparation of antenatal fetal surveillance methods.

Efficiency and safety of umbilical cord mesenchymal stromal/ stem cells in multiple sclerosis combined treatment / Eficacia y seguridad de las células madre / estromales mesenquimales del cordón umbilical en el tratamiento combinado de la esclerosis múltiple

SUMMARY: Multiple sclerosis is a demyelinating disease of the nervous system that affects young people of working age and quickly leads to disability. Treatment of this pathology with umbilical cord mesenchymal stem cells is promising, given their immunomodulatory and neurotrophic properties. The study involved 27 patients diagnosed with multiple sclerosis, 12 of whom underwent combined treatment (intravenous and intrathecal administration) of umbilical cord multipotent mesenchymal stromal/stem cells. The effectiveness of treatment was determined by the degree of neurological deficit and spasticity. Combined treatment with umbilical cord mesenchymal stem cells significantly improves the condition of patients with multiple sclerosis and promotes the regression of neurological deficits and spasticity. This treatment is safe, but for a deeper study, it is necessary to continue research in this area.

RESUMEN: La esclerosis múltiple es una enfermedad desmielinizante del sistema nervioso que afecta a los jóvenes en edad laboral y conduce rapidamente a la discapacidad. El tratamiento de esta patología con células madre mesenquimales de cordón umbilical es prometedor, debido a sus propiedades inmunomoduladoras y neurotróficas. En el estudio participaron 27 pacientes diagnosticados de esclerosis múltiple, 12 de los cuales fueron sometidos a un tratamiento combinado (administración intravenosa e intratecal) de células madre / estromales mesenquimales multipotentes del cordón umbilical. La efectividad del tratamiento estuvo determinada por el grado de déficit neurológico y espasticidad. El tratamiento combinado con células madre mesenquimales del cordón umbilical mejora significativamente la condición de los pacientes con esclerosis múltiple y promueve la regresión de los déficits neurológicos y la espasticidad. Este tratamiento es seguro, sin embargo, es necesario continuar investigando en esta area.

Jujuboside A inhibits oxidative stress damage and enhances immunomodulatory capacity of human umbilical cord mesenchymal stem cells through up-regulating IDO expression / 中国天然药物

Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy. The present study was aimed to investigate the effects of jujuboside A (JuA) on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells (hUC-MSCs). Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs, while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs. Furthermore, Hoechst 33258 staining, lactate dehydrogenase test, measurement of malondialdehyde, Western blot, high-performance liquid chromatography; and flow cytometry were performed. Our results indicated that JuA (25 μmol·L-1) promoted the proliferation of hUC-MSCs, but did not affect the differentiating capability of these cells. JuA pre-treatment inhibited apoptosis, prevented oxidative damage, and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H2O2. In addition, JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs, which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase. In conclusion, our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress, providing a new option for the improvement of hUC-MSCs in the clinical setting.

MicroRNA-204 Carried by Exosomes of Human Umbilical Cord-derived Mesenchymal Stem Cells Regulates the Polarization of Macrophages in a Mouse Model of Myocardial Ischemia-reperfusion Injury / 中国医学科学院学报

Objective To explore the role and mechanism of microRNA-204(miR-204) carried by the exosomes of human umbilical cord-derived mesenchymal stem cells(hUC-MSC) in regulating the polarization of macrophages in a mouse model of myocardial ischemia-reperfusion(I/R) injury. Methods After the hUC-MSCs were isolated,cultured,and identified,their adipogenic and osteogenic differentiation capabilities were determined.The exosomes of hUC-MSCs were separated by ultracentrifugation,and the expression of CD81,CD63,tumor susceptibility gene 101(Tsg101),and calnexin in the exosomes was determined by Nanoparticle Tracking Analysis software,transmission electron microscopy,and Western blotting.Three groups(hUC-MSC,miR-204 mimic,and negative control) were designed for the determination of the expression of miR-204 in the cells and their exosomes by qRT-PCR.The C57BL/6J mice were randomly assigned into a sham operation group,an I/R group,a hUC-MSC exosomes group,a negative control group,and a miR-204 mimic group.Except the sham operation group,the I/R model was established by ligating the left anterior descending artery.The echocardiography system was employed to detect the heart function of mice.HE staining was employed to observe the pathological changes of mouse myocardium.ELISA was employed to determine the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),arginase 1(Arg-1),and IL-10 in the myocardial tissue.After the macrophages of mouse myocardial tissue were isolated,flow cytometry was employed to determine the expression of CD11c and CD206,and ELISA to measure the levels of IL-1β,TNF-α,Arg-1,and IL-10 in the macrophages. Results hUC-MSCs had adipogenic and osteogenic differentiation capabilities,and the exosomes were successfully identified.Compared with the negative control group,the miR-204 mimic group showed up-regulated expression of miR-204 in hUC-MSCs and their exosomes(P<0.001,P<0.001).Compared with the sham operation group,the modeling of I/R increased the left ventricular end-diastolic diameter(LVEDD)(P<0.001),left ventricular end-systolic diameter(LVESD)(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1β(P<0.001),TNF-α(P<0.001),and CD11c(P<0.001).Meanwhile,it lowered the left ventricular ejection fraction(LVEF)(P<0.001),left ventricular fractional shortening(LVFS)(P<0.001),Arg-1(P<0.001),IL-10(P<0.001),and CD206(P<0.001).Compared with those in the I/R group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1β(P<0.001),TNF-α(P=0.010),and CD11c(P<0.001) reduced,while LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.028),and CD206(P=0.022) increased in the hUC-MSC exosomes group.Compared with those in the negative control group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P=0.001),and the levels of IL-1β(P=0.048),TNF-α(P<0.001),and CD11c(P=0.007) reduced,while the LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.001),and CD206(P=0.001) increased in the miR-204 mimic group. Conclusion The hUC-MSC exosomes overexpressing miR-204 can inhibit the polarization of macrophages in the I/R mouse model to M1-type and promote the polarization to M2-type.

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance the Osteoblastic Differentiation of Periodontal Ligament Stem Cells Under High Glucose Conditions Through the PI3K/AKT Signaling Pathway / 生物医学与环境科学（英文）

OBJECTIVE@#High glucose (HG) can influence the osteogenic differentiation ability of periodontal ligament stem cells (PDLSCs). Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-exo) have broad application prospects in tissue healing. The current study aimed to explore whether hUCMSC-exo could promote the osteogenic differentiation of hPDLSCs under HG conditions and the underlying mechanism.@*METHODS@#We used a 30 mmol/L glucose concentration to simulate HG conditions. CCK-8 assay was performed to evaluate the effect of hUCMSC-exo on the proliferation of hPDLSCs. Alkaline phosphatase (ALP) staining, ALP activity, and qRT-PCR were performed to evaluate the pro-osteogenic effect of hUCMSC-exo on hPDLSCs. Western blot analysis was conducted to evaluate the underlying mechanism.@*RESULTS@#The results of the CCK-8 assay, ALP staining, ALP activity, and qRT-PCR assay showed that hUCMSC-exo significantly promoted cell proliferation and osteogenic differentiation in a dose-dependent manner. The Western blot results revealed that hUCMSC-exo significantly increased the levels of p-PI3K and p-AKT in cells, and the effect was inhibited by LY294002 (PI3K inhibitor) or MK2206 (AKT inhibitor), respectively. Moreover, the increases in osteogenic indicators induced by hUCMSC-exo were significantly suppressed by LY294002 and MK2206.@*CONCLUSION@#hUCMSC-exo promote the osteogenic differentiation of hPDLSCs under HG conditions through the PI3K/AKT signaling pathway.

Influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks.@*METHODS@#PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis.@*RESULTS@#A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05).@*CONCLUSIONS@#Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.

Human umbilical cord Wharton's jelly-derived mesenchymal stem cell transplantation could improve diabetic intracavernosal pressure / 亚洲男科学杂志(英文版)

Mesenchymal stem cells (MSCs) secrete various cytokines with angiogenic and neuroprotective effects. This study aimed to assess the effects of human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on diabetes-related intracavernosal pressure (ICP) impairment in rats. hWJ-MSCs were isolated from human umbilical cord Wharton's jelly and transplanted into the corpus cavernosum of streptozotocin (STZ)-induced diabetic rats by unilateral injection. The erectile function was evaluated at 4 weeks, as well as the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS), and insulin-like growth factor 1 (IGF1). STZ-induced diabetic rats showed impaired ICP, which was significantly improved by hWJ-MSC treatment. VEGF, eNOS, IGF1, and bFGF expression levels were higher in hWJ-MSC injection sites than those in control ones in STZ-induced diabetic rats. These results suggest that hWJ-MSC transplantation might improve diabetic erectile dysfunction through increased production of paracrine growth factors, highlighting a novel potential therapeutic option for erectile dysfunction.

Comparison of biological characteristics of placenta mesenchymal stem cells derived from fetus / 生物工程学报

Mesenchymal stem cells (MSCs) have broad application potentials in regenerative medicine and translational medicine. Obtaining large quantities of primary-cultured MSCs and select the most suitable cell origin for targeted diseases are critical to research. To select the most suitable seed cells of MSCs from different origins for clinical treatment and research, biological characteristics of MSCs from human umbilical cord and placenta were compared. These include cell morphology, surface marker expression, differentiation and karyotype. Transcriptome sequencing of four MSCs from fetus were performed and the results were analyzed from the perspective of proliferation and cytokine secretion. The results revealed that MSCs from umbilical cord (UC), amniotic membrane (AM), chorionic membrane (CM), chorionic villi (CV) and deciduae (DC) met the minimum standards of the International Society of Cell Therapy (ISCT) in 2006 and had the general characteristics of stem cells. Karyotype analysis showed that MSCs derived from UC, AM, CM and CV were all from fetus except that the DC-MSCs were from mother. Transcriptome sequencing analysis showed that hMSCs from umbilical cord and placenta had similar gene expression patterns, while different expression patterns were observed in specific genes involved in cell cycle, cell division, cell death, cell growth and development. These genes play important roles in transcriptional regulation, DNA repair, DNA replication and chromosome stability, which were momentous components of cellular or subcellular fraction movement, cell communication, cell tissue protrusions, cytokine secretion and hormone metabolism. Transcriptome sequencing analysis explained the differences in biological characteristics among MSCs from different sources, while verification experiments based on the transcriptome sequencing results showed that the proliferation and cytokine secretion capabilities of MSCs from different sources were significantly different. In all, UC-MSCs and CV-MSCs with stronger proliferation and higher levels of paracrine factors secretion may show their respective advantages in treating diseases.

HucMSC-Ex alleviates inflammatory bowel disease via the lnc78583-mediated miR3202/HOXB13 pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

As a group of nonspecific inflammatory diseases affecting the intestine, inflammatory bowel disease (IBD) exhibits the characteristics of chronic recurring inflammation, and was proven to be increasing in incidence (Kaplan, 2015). IBD induced by genetic background, environmental changes, immune functions, microbial composition, and toxin exposures (Sasson et al., 2021) primarily includes ulcerative colitis (UC) and Crohn's disease (CD) with complicated clinical symptoms featured by abdominal pain, diarrhea, and even blood in stools (Fan et al., 2021; Huang et al., 2021). UC is mainly limited to the rectum and the colon, while CD usually impacts the terminal ileum and colon in a discontinuous manner (Ordás et al., 2012; Panés and Rimola, 2017). In recent years, many studies have suggested the lack of effective measures in the diagnosis and treatment of IBD, prompting an urgent need for new strategies to understand the mechanisms of and offer promising therapies for IBD.

Identification of new human mesenchymal stem cell biomarker by aptamers / Identificação de novos biomarcadores de células tronco mesenquimais de origem humana por meio de aptâmeros

Stem cells are undifferentiated cells that can be distinguished from others by their ability to self-renew and to differentiate into new specific cell types. Mesenchymal stem cells (MSC) are adult stem cells that can be obtained from different sources, such as adipose tissue, bone marrow, dental pulp, and umbilical cord. They can either replicate, originating new identical cells, or differentiate into cells of mesodermal origin and from other germ layers. MSC have been studied as new tools for regenerative therapy. Although encouraging results have been demonstrated, MSC-based therapies still face a great barrier: the difficulty of isolating these cells from heterogeneous environments. MSC are currently characterized by immunolabelling through a set of multiple surface membrane markers, including CD29, CD73, CD90 and CD105, which are also expressed by other cell types. Hence, the present work aimed to identify new specific biomarkers for the characterization of human MSC using DNA aptamers produced by the SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technique. Our results showed that MSC from different origins bound to DNA candidate aptamers, that is, DNA or RNA oligonucleotides selected from random libraries that bind specifically to biological targets. Aptamer-bound MSC could be isolated by fluorescenceactivated cell sorting (FACS) procedures, enhancing the induction of differentiation into specific phenotypes (chondrocytes, osteocytes and adipocytes) when compared to the whole MSC population. Flow cytometry analyses revealed that candidate aptamers bound to 50% of the MSC population from dental pulp and did not present significant binding rates to human fibroblasts or lymphocytes, both used as negative control. Moreover, immunofluorescence images and confocal analyses revealed staining of MSC by aptamers localized in the surfacemembrane of these cells. The results also showed internal staining of human monocytes by our investigated aptamers. A non-specific control aptamer (CNTR APT) obtained from the random pool was then utilized to compare the specificity of the aptamers bound to the analyzed non-apoptotic cells, showing no staining for MSC. However, 40% of the monocytes bound to the CNTR APT. Normalized data based on the cells bound to candidate aptamers compared to those bound to the CNTR APT, revealed a 10 to 16-fold higher binding rate for MSC against 2-fold for monocytes. Despite its low specificity, monocyte-aptamer binding occurs probably due to the expression of shared markers with MSC, since monocytes are derived from hematopoietic stem cells and are important for the immune system ability to internalize/phagocyte external molecules. Given that, we performed a pull-down assay followed by mass spectrometry analysis to detect which MSC-specific protein or other target epitope not coexpressed by monocytes or the CNTR APT would bind to the candidate aptamer. Distinguishing between MSC and monocyte epitopes is important, as both cells are involved in immunomodulatory effects after MSC transplantations. ADAM17 was found to be a target of the APT10, emerging as a possible biomarker of MSC, since its involvement in the inhibition of the TGF signaling cascade, which is responsible for the differentiation of MSC. Thus, MSC with a higher stemness profile should overexpress the protein ADAM17, which presents a catalytic site with affinity to APT10. Another target of Apt 10 is VAMP3, belonging to a transmembrane protein complex that is involved in endocytosis and exocytosis processes during immune and inflammatory responses. Overall, proteins identified as targets of APT10 may be cell surface MSC biomarkers, with importance for MSC-based cell and immune therapies

Células tronco são células indiferenciadas que podem ser distinguidas de outros tipos celulares por meio da habilidade de se auto renovarem e de se diferenciarem em novos tipos celulares. Células tronco mesenquimais (MSC) são células tronco adultas encontradas em diferentes tecidos como tecido adiposo, polpa de dente e cordão umbilical. Estas células podem se autodividir em células idênticas ou se diferenciarem em células de origem mesodermal. Estas células têm sido estudadas em novas aplicações que envolvem terapia regenerativas. Embora resultados encorajadores tenham sido demonstrados, terapias que utilizam MSC ainda encontram uma grande barreira: a dificuldade no isolamento destas células a partir de um ambiente heterogêneo. MSC são caracterizadas por populações positivas em ensaios de imunomarcação para os epítopos membranares CD29, CD73, CD90 e CD105, presentes também em outros tipos celulares. Assim, o presente trabalho tem o objetivo de identificar novos biomarcadores de MSC de origem humana, utilizando aptâmeros de DNA produzidos pela técnica SELEX (Systematic Evolution of Ligands by EXponential Enrichment) como ferramenta. Nossos resultados mostraram que MSC de diferentes origens ligam-se a aptâmeros (oligonucleotídeos de DNA ou RNA que atuam como ligantes específicos de alvos moleculares) de DNA candidatos que atuam no isolamento de MSC por meio da técnica FACS de separação celular, promovendo uma maior indução de diferenciação em células específicas (condrócitos, osteócitos e adipócitos) comparada com a população total de MSC. Análises de citometria de fluxo mostraram que os aptâmeros candidatos se ligam a 50% das MSC de polpa de dente e não apresentam taxa de ligação significante para fibroblastos e linfócitos de origem humana - utilizados como controles negativo. Além domais, imagens de imunofluorescência e confocal mostraram ligação na superfície da membrana de MSC e a marcação interna de monócitos a estes aptâmeros. Portanto, um aptâmero controle (CNTR APT) foi utilizado para comparar a especificidade dos aptâmeros ligados a células viáveis, mostrando a não ligação deste aptâmero a MSC. Porém, 40% da população de monócitos ligou-se ao CNTR APT. Uma normalização baseada na comparação entre as taxas de ligação entre células ligadas com aptâmeros candidatos e o aptâmero controle gerou uma taxa de especificidade entre 10-16 vezes maior para MSC contra 2,5 vezes para os monócitos. Deste modo, embora os resultados tenham mostrado uma taxa de ligação entre monócitos e aptâmeros, as MSC ligadas aos aptâmeros candidatos possuem uma maior taxa de especificidade devido a uma maior presença de antígenos que são expressos em ambas as células. Um ensaio de Pull Down seguido de espectrometria de massas foi utilizado para a identificação de biomarcadores que se ligariam aos aptâmeros candidatos, e que não seriam co-expressos por monócitos e por antígenos ligados ao aptâmero controle. Deste modo, a proteína ADAM17 foi identificada nas amostras de APT10 ligadas às MSC. Tal proteína está relacionada à inibição de uma cascata de sinalização da família de proteínas TGF, responsável pela diferenciação de MSC. Assim, MSC com maior potencial tronco deveriam expressar ADAM17 em maior quantidade. Tal proteína apresenta um sítio catalítico que demonstra interagir com o APT10, de acordo com predição Docking entre proteína e DNA. Foi identificada também, a proteína VAMP3, que pertence a um complexo proteico transmembranar responsável pelos processos de endocitose e exocitose, e que podem ter um papel importante na liberação de citocinas e outras moléculas relacionadas às respostas imune e inflamatórias. Deste modo, o APT10 identificou proteínas importantes que devem estar relacionas com a melhora de imunoterapias que utilizam MSC

Factors associated with umbilical cord clamping in term newborns / Factores asociados al clampaje del cordón umbilical en recién nacidos a término / Fatores associados ao clampeamento do cordão umbilical em recém-nascidos a termo

ABSTRACT OBJECTIVE: To identify factors associated with umbilical cord clamping in term newborns and to compare the recording of clamping time in the medical record with what was observed. METHOD: Cross-sectional study, with 300 mothers-infants, in a university hospital. Clamping time and medical records were observed, and a structured questionnaire was applied to postpartum women for sociodemographic variables. Bivariate analysis, multivariate Poisson Regression model, and Kappa concordance test were performed. RESULTS: The percentage of late/optimal clamping observed was 53.7%. The associated factors were skin-to-skin contact in the delivery room (PR = 0.76; 0.61-0.95; p = 0.014), position of the newborn below the vaginal canal (PR = 2.6; CI95%: 1.66-4.07; p < 0.001), position of the newborn at the vaginal level (PR = 2.03; CI95%: 1.5-2.75; p < 0.001), and need for newborn resuscitation in the delivery room (PR = 1.42; CI95%; 1.16-1.73; p = 0.001). Kappa concordance level of the professionals, records compared to the observation was: nurse 0.47, obstetrician 0.59, and pediatrician 0.86. CONCLUSION: the identification of associated factors and the comparison between recording and observing the clamping time can help in the planning and implementation of improvements for adherence to good practices at birth.

RESUMEN Objetivo: Identificar factores asociados al clampaje del cordón umbilical en neonatos a término y comparar el registro del tiempo de clampaje en el prontuario con el observado. Método: Estudio transversal, con 300 madres-hijos, en hospital universitario. Se observó tiempo de clampaje y registros en prontuario, siendo aplicado cuestionario estructurado a las puérperas para variables sociodemográficas. Se utilizó análisis bivariado, modelo de Regresión de Poisson multivariado e índice de concordancia Kappa. Resultados: el porcentaje de clampaje tardío/oportuno observado fue 53,7%. Los factores asociados fueron contacto piel con piel en sala de partos (RP = 0,76; 0,61-0,95; p = 0,014), posición del recién nascido abajo del canal vaginal (RP = 2,6; IC95%: 1,66-4,07; p < 0,001), posición del recién nacido en el nivel vaginal (RP = 2,03; IC95%: 1,5-2,75; p < 0,001) y necesidad de reanimación del recién nacido en sala de partos (RP = 1,42; IC95%; 1,16-1,73; p = 0,001). El nivel de concordancia Kappa del registro de los profesionales comparado a la observación fue: enfermera 0,47, obstetra 0,59 y pediatra 0,86. Conclusión: la identificación de los factores asociados y la comparación entre registro y observación del tiempo de clampaje puede auxiliar en la planificación e implementación de mejorías para la adhesión a las buenas prácticas de nacimiento.

RESUMO Objetivo: identificar fatores associados ao clampeamento do cordão umbilical em neonatos a termo e comparar o registro do tempo de clampeamento no prontuário com o observado. Método: estudo transversal, com 300 mães-bebês, em hospital universitário. Observaram-se tempo de clampeamento e registros em prontuário, sendo aplicado questionário estruturado às puérperas para variáveis sociodemográficas. Procedeu-se análise bivariada, modelo de Regressão de Poisson multivariado e teste de concordância Kappa. Resultados: o percentual de clampeamento tardio/oportuno observado foi 53,7%. Os fatores associados foram contato pele-a-pele em sala de parto (RP = 0,76; 0,61-0,95; p = 0,014), posição do recém-nascido abaixo do canal vaginal (RP = 2,6; IC95%: 1,66-4,07; p < 0,001), posição do recém-nascido no nível vaginal (RP = 2,03; IC95%: 1,5-2,75; p < 0,001) e necessidade de reanimação do recém-nascido em sala de parto (RP = 1,42; IC95%; 1,16-1,73; p = 0,001). O nível de concordância Kappa do registro dos profissionais comparado à observação foi: enfermeira 0,47, obstetra 0,59 e pediatra 0,86. Conclusão: a identificação dos fatores associados e a comparação entre registro e observação do tempo de clampeamento podem auxiliar no planejamento e implementação de melhorias para adesão às boas práticas no nascimento.

Recovery of motor function in rats with complete spinal cord injury following implantation of collagen/silk fibroin scaffold combined with human umbilical cord-mesenchymal stem cells

SUMMARY OBJECTIVE: This study aimed to assess the effect of the collagen/silk fibroin scaffolds seeded with human umbilical cord-mesenchymal stem cells on functional recovery after acute complete spinal cord injury. METHODS: The fibroin and collagen were mixed (mass ratio, 3:7), and the composite scaffolds were produced. Forty rats were randomly divided into the Sham group (without spinal cord injury), spinal cord injury group (spinal cord transection without any implantation), collagen/silk fibroin scaffolds group (spinal cord transection with implantation of the collagen/silk fibroin scaffolds), and collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (spinal cord transection with the implantation of the collagen/silk fibroin scaffolds co-cultured with human umbilical cord-mesenchymal stem cells). Motor evoked potential, Basso-Beattie-Bresnahan scale, modified Bielschowsky's silver staining, and immunofluorescence staining were performed. RESULTS: The BBB scores in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group were significantly higher than those in the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). The amplitude and latency were markedly improved in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). Meanwhile, compared to the spinal cord injury and collagen/silk fibroin scaffolds groups, more neurofilament positive nerve fiber ensheathed by myelin basic protein positive structure at the injury site were observed in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (p<0.01, p<0.05). The results of Bielschowsky's silver staining indicated more nerve fibers was observed at the lesion site in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.01, p< 0.05). CONCLUSION: The results demonstrated that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen/silk fibroin scaffolds could promote nerve regeneration, and recovery of neurological function after acute spinal cord injury.

Diagnóstico posnatal de hematoma de cordón umbilical: reporte de un caso / Postnatal diagnosis of umbilical cord hematoma: case report

ANTECEDENTES: El hematoma espontáneo del cordón umbilical es una complicación rara del embarazo que representa una causa grave de morbilidad y mortalidad fetal. Se han descrito numerosos factores de riesgo, pero aún se desconoce su etiología exacta. CASO CLÍNICO: Mujer de 28 años, en su octava gestación, que consultó en urgencias por disminución de los movimientos fetales de varias horas de evolución tras una caída accidental traumática. La monitorización fetal mostró un patrón cardiotocográfico no tranquilizador, con disminución de la variabilidad y sin aceleraciones. Se realizó una cesárea urgente, sin complicaciones, con el nacimiento de un varón vivo de 4560 g, con Apgar 8/10/10 y pH de sangre de cordón umbilical 7.08, que precisó ingreso en la unidad de neonatología por hallazgo de un soplo cardíaco. Tras el alumbramiento se objetivó una gran colección hemática en el cordón umbilical. MÉTODO: Se aplicó una estrategia de búsqueda sistemática en Medline, PubMed y Cochrane de todos los artículos en inglés y español que tuvieran como palabras clave "Umbilical", "Cordón" y "Hematoma". RESULTADOS: Se encontraron 13 publicaciones de 15 casos de hematoma del cordón umbilical en los años 2008-2020. Se realizó una revisión sistemática de los informes de casos descritos en los últimos 12 años en la literatura para evaluar la epidemiología, los factores predisponentes, los resultados potenciales, el diagnóstico prenatal y el manejo clínico. CONCLUSIONES: Debido a la rareza de esta afección, se deben informar todos los casos nuevos de hematoma del cordón umbilical para mejorar el conocimiento de los factores predisponentes, el diagnóstico prenatal y el manejo clínico.

BACKGROUND: Spontaneous umbilical cord hematoma is a rare complication of pregnancy which represents a serious cause of fetal morbidity and mortality. There are many risk factors, but the exact etiology is still unknown. CASE REPORT: 28-year-old woman, eighth gestation, who consulted due to decreased fetal movements of several hours of evolution after traumatic accidental fall. Fetal monitoring showed a non-reassuring cardiotocographic pattern, with decreased fetal variability, without accelerations. An emergency cesarean section was performed without complications, with the birth of a living male weighing 4560 grams, with an 8/10/10 Apgar test, and an arterial pH of the umbilical cord 7.08, which required admission to the neonatology unit. After delivery, a large blood collection was observed in the umbilical cord. METHOD: A systematic search strategy was applied to several electronic bibliographic databases: Medline, PubMed and Cochrane. Key words used were "Umbilical", "Cord", "Hematoma". RESULTS: 13 publications of 15 cases of umbilical cord hematoma were reported in the years 2008-2020. A systematic review of the reports of cases, described in the last twelve years in the literature was carried out to evaluate the epidemiology, predisposing factors, potential results, prenatal diagnosis and clinical management of this phenomenon. CONCLUSIONS: Due to the rarity of this condition, every new case of umbilical cord hematoma should be reported in order to improve the knowledge of predisposing factors, prenatal diagnosis, and clinical management.

Ligadura del cordón umbilical en recién nacidos prematuros / Umbilical cord clamping in preterm infants

La prematiridad fue aumentando la supervivencia desde hace varios años, y eso produce, sobre todo, una preocupación en los prematuros nacidos antes de las 28 semanas de gestación. El tiempo del clampeo del cordón umbilical puede generar diversos trastornos, principalmente, cuando se realiza temprano (10-15 segundos). Ya desde hace 20 años, a través de varias investigaciones, se pudieron demostrar los notorios beneficios del clampeo demorado del cordón (de 2 a 3 minutos). Esta práctica fue instalada en la asistencia obstétrica y neonatal por las recomendaciones de sociedades científicas y de las revisiones sistemáticas, que señalaron las sólidas evidencias que apoyaban esta conducta para prematuros. En esta revisión, se describen los artículos más relevantes en los últimos años, que sustentan notoriamente la aplicación del clampeo demorado del cordón versus el clampeo temprano. Asimismo, esta práctica genera una disminución de los trastornos graves en prematuros.

For several years now, the survival of preterm infants has been increasing, which has shifted our concern to preterm infants born before 28 weeks of gestation in particular. The timing of umbilical cord clamping may lead to several disorders, especially when done early (10-15 seconds). In the last two decades, several investigations have shown the considerable benefits of delayed cord clamping (2-3 minutes). Delayed cord clamping has been practiced in obstetrics and neonatal care based on the recommendations made by scientific societies and in systematic reviews, which have provided solid evidence to support this practice in preterm infants. This review describes the most relevant articles from the last years, which strongly support the use of delayed cord clamping versus early cord clamping. In addition, this practice reduces the rate of severe disorders in preterm infants.

Síndrome de cordón umbilical corto / Short umbilical cord syndrome

El síndrome de cordón umbilical corto es una anomalía poco común e incompatible con la vida que se asocia a defectos de la pared anterior del feto, cordón umbilical corto o ausente y anomalías de los miembros. Esta entidad es la más severa y más infrecuente entre los defectos de la pared anterior del abdomen, con una incidencia de 1 en 14 000 nacimientos. Se presenta el caso de un recién nacido de término, de sexo indeterminado, producto de primer embarazo, de parto abdominal. A las 28 semanas de gestación se diagnosticó un defecto en pared abdominal anterior y una imagen quística de columna vertebral por ultrasonografía. Al nacimiento se observaron los órganos abdominales expuestos, el cordón umbilical grueso, de 10 cm de longitud, eventración de intestinos e hígado y cifoescoliosis marcada, ausencia de genitales externos y de ano, un remanente de miembro inferior derecho y miembro inferior izquierdo completo con pie equinovaro. Se le dio apoyo ventilatorio y falleció a los 15 minutos de vida

Short umbilical cord syndrome is a rare and life-incompatible abnormality associated with fetal anterior wall defects, absent or short umbilical cord, and limb abnormalities. This entity is the most severe and rarest of anterior abdominal wall defects, with an incidence of 1 in 14,000 births. We present the case of a full-term newborn, of undetermined sex, product of first pregnancy, of abdominal delivery. At 28 weeks' gestation, an anterior abdominal wall defect and a cystic image of the spine were diagnosed by ultrasonography. At birth, the exposed abdominal organs, the thick umbilical cord, 10 cm in length, eventration of the intestines and liver and marked kyphoscoliosis, absence of external genitalia and anus, a remnant of the right lower limb and complete left lower limb with foot were observed. equinovarus. Ventilatory support was given and died at 15 minutes of life

Inserción "velamentosa", encefalopatía hipóxico-isquémica y rehabilitación neurológica: reporte de caso / Velamentous cord insertion, ischemic-hypoxic encephalopathy, and neurological rehabilitation: A case report

Resumen. La encefalopatía hipóxico-isquémica es una causa frecuente e importante de daño neurológico en recién nacidos a término y prematuros. Un evento centinela de esta condición es la vasa previa, específicamente cuando existe anormalidad de la placenta como la inserción "velamentosa" del cordón umbilical. Algunos reportes evidencian la asociación entre estas dos condiciones, pero son escasos los que dan cuenta del proceso de recuperación y del pronóstico neurológico de los niños afectados por ellas. Se presenta el caso de un paciente, con antecedentes de inserción "velamentosa" del cordón umbilical y encefalopatía hipóxico-isquémica, que recibió hipotermia terapéutica (cool cap). Se describe su proceso de rehabilitación neurológica y se calculó el porcentaje de probabilidad de presentar esta condición frente a la población sin estos factores. El niño tenía cinco años y el puntaje en su prueba de Apgar fue de 0 al minuto y de 2 a los 15 minutos. Desarrolló encefalopatía hipóxico-isquémica grave secundaria a una inserción "velamentosa" del cordón umbilical sin diagnóstico prenatal, con gran compromiso neurológico y multisistémico inicial. El proceso de recuperación incluyó el manejo inicial multidisciplinario en la unidad de cuidados intensivos neonatales y el inicio temprano de habilitación neurológica. Hoy el niño está escolarizado y en terapia integral, no presenta deficiencias motoras ni sensoriales en el examen físico, aunque la prueba neuropsicológica sugiere un riesgo de trastorno por déficit de atención e hiperactividad. Habitualmente, los niños con encefalopatía hipóxico-isquémica grave presentan discapacidad por deficiencias motoras, cognitivas o conductuales. El haber recibido hipotermia terapéutica y un manejo estructurado de rehabilitación redujo en gran medida las deficiencias esperadas y ha promovido un satisfactorio desarrollo físico y neurológico.

Abstract. Hypoxic-ischemic encephalopathy is a frequent and important cause of neurological problems in term and preterm newborns. A sentinel event of this entity is the vasa previa, specifically when there is an abnormality of the placenta such as a velamentous cord insertion. Some reports have shown the association between these two entities, but those regarding the recovery process and the neurological prognosis of children with both conditions are scarce. We present the case of a patient with a history of velamentous cord insertion and hypoxic-ischemic encephalopathy who received therapeutic hypothermia (cool cap). We describe his neurological rehabilitation process and we calculated the percentage of probability of presenting this condition compared to the population without these factors. The patient was a five-year-old boy with an Apgar index at birth equal to zero at one minute and equal to two at fifteen minutes who developed severe hypoxic-ischemic encephalopathy secondary to a velamentous cord insertion without prenatal diagnosis and a marked initial neurological and multisystemic compromise. The recovery process included early multidisciplinary management in the neonatal intensive care unit and a focus on early neurological habilitation. The patient is currently in school and he undergoes comprehensive therapies; on physical examination, he presents no motor or sensory deficiencies. His neuropsychological test suggests the risk of attention deficit hyperactivity disorder. Children with severe hypoxic-ischemic encephalopathy usually have disabilities due to motor, cognitive, and/or behavioral deficiencies. Having received therapeutic hypothermia and a structured rehabilitation process greatly reduced the expected deficiencies according to prognosis and have promoted satisfactory physical and neurological development.

Expression of Twist1, SIRT1, FGF2 and TGF-β3 genes and its regulatory effect on the proliferation of placenta, umbilical cord and dental pulp mesenchymal stem cells / 中华医学遗传学杂志

OBJECTIVE@#To compare the mRNA level of cell proliferation-related genes Twist1, SIRT1, FGF2 and TGF-β3 in placenta mesenchymal stem cells (PA-MSCs), umbilical cord mensenchymals (UC-MSCs) and dental pulp mesenchymal stem cells (DP-MSCs).@*METHODS@#The morphology of various passages of PA-MSCs, UC-MSCs and DP-MSCs were observed by microscopy. Proliferation and promoting ability of the three cell lines were detected with the MTT method. Real-time PCR (RT-PCR) was used to determine the mRNA levels of Twist1, SIRT1, FGF2, TGF-β3.@*RESULTS@#The morphology of UC-MSCs and DP-MSCs was different from that of PA-MSCs. Proliferation ability and promoting ability of the PA-MSCs was superior to that of UC-MSCs and DP-MSCs. In PA-MSCs, expression level of Twist1 and TGF-β3 was the highest and FGF2 was the lowest. SIRT1 was highly expressed in UC-MSCs. With the cell subcultured, different expression levels of Twist1, SIRT1, FGF2, TGF-β3 was observed in PA-MSCs, UC-MSCs and DP-MSCs.@*CONCLUSION@#Up-regulated expression of the Twist1, SIRT1 and TGF-β3 genes can promote proliferation of PA-MSCs, UC-MSCs and DP-MSCs, whilst TGF-β3 may inhibit these. The regulatory effect of Twist1, SIRT1, FGF2 and TGF-β3 genes on PA-MSCs, UC-MSCs and DP-MSCs are different.

Effect of delayed cord clamping and umbilical cord milking on cerebral hemodynamics in preterm infants: a randomized double-blind controlled trial / 中国当代儿科杂志

OBJECTIVE@#To compare the effect of delayed cord clamping (DCC) versus umbilical cord milking (UCM) on cerebral blood flow in preterm infants.@*METHODS@#This was a single-center, prospective, double-blind, randomized controlled trial. A total of 46 preterm infants, with a gestational age of 30-33@*RESULTS@#A total of 21 preterm infants in the DCC group and 23 in the UCM group were included in the statistical analysis. There was no significant difference in PSV, EDV, and RI between the two groups at all time points after birth (@*CONCLUSIONS@#DCC and UCM have a similar effect on cerebral hemodynamics in preterm infants with a gestational age of 30-33