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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(6): 865-868, 2021 Dec 30.
Artículo en Zh | MEDLINE | ID: mdl-34980323

RESUMEN

Objective To analyze the characteristics of high-risk maternal patients and evaluate the multidisciplinary medical care system we established correspondingly. Method We collected and analyzed the medical records of high-risk maternal patients who received medical care from January 1,2017 to December 31,2020 in Peking Union Medical College Hospital. Results Ninety-eight high-risk maternal patients were included in this study,and 84.7%(83/98)of them were combined with different severe systemic diseases.Under the multidisciplinary medical care system,91 patients showed improved conditions and were discharged,and the other 7 cases had poor prognosis. Conclusions General tertiary hospitals in Beijing are receiving maternal patients with more high-risk complications.Considering the high risk and diverse diseases of maternal patients admitted to our hospital,we established a medical care system composed of a multidisciplinary panel of experts for high-risk maternal patients to improve the medical care and prognosis of the patients with high efficiency.


Asunto(s)
Hospitalización , Hospitales Generales , Humanos , Pronóstico , Estudios Retrospectivos , Centros de Atención Terciaria
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 38(5): 528-533, 2016 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-27825408

RESUMEN

Objective To investigate the changes in preterm birth rate,its gestational age distribution,and possible contributors in Peking Union Medical College Hospital (PUMCH) over the last 25-year period. Methods The clinical data of premature deliveries,both singleton and twins,in PUMCH from January 1,1990 to December 31,2014 were retrospectively analyzed. We counted the number of premature fetuses and assessed the changes of preterm birth rate and its gestational age distribution (including extremely preterm birth,early preterm birth,and late preterm birth) over time. The etiologies (including spontaneous and iatrogenic) of preterm birth were also surveyed. Results The overall preterm birth rate was 7.8% in PUMCH,showing a slightly up-trend in both singletons and twins. Twin prematurity accounted for 23.8% of total preterm births,increased from 15.1% to 28.5%. Preterm births subgrouped by gestational age included 26 cases (0.7%) of extreme prematurity (<28 weeks),1199 cases (33.9%) of early preterm birth (28- 33+6 weeks),and 2310 cases (65.3%) of late preterm birth (34- 36+6 weeks). The gestational age distribution in singletons and twins showed no significant difference(z=0.844,P=0.398). Changes in the proportion of preterm birth before 28 weeks was little,gradually increased in the 28- 33+6 weeks group (from 23.8% to 36.1%) and gradually decreased in the 34- 36+6 weeks group (from 75.5% to 63.3%). Trends of gestational age distribution of singleton and twins were similar to that of the total. Spontaneous preterm labor,preterm premature rupture of membrane,and medically indicated (iatrogenic) preterm birth accounted for 20.2%,38.9%,and 40.9% respectively. There was no difference in singletons and twins(χ2=1.071,P=0.301).The proportion of iatrogenic preterm was increased. Common reasons for iatrogenic preterm birth included gestational hypertension,fetal indications (including fetal distress,fetal growth restriction),placenta previa,and pregnancy complicated by heart disease. Conclusions The overall preterm birth rate shows an upward trend in the general hospital as a result of more multifetal gestations and more medically indicated preterm births. Reducing multifetal gestations and effective control of pregnancy complications should be the priorieties in preterm birth intervention.


Asunto(s)
Recien Nacido Prematuro , Nacimiento Prematuro , Femenino , Edad Gestacional , Humanos , Recién Nacido , Trabajo de Parto Prematuro , Embarazo , Estudios Retrospectivos , Gemelos
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(1): 20-3, 2016 Jan.
Artículo en Zh | MEDLINE | ID: mdl-26781407

RESUMEN

OBJECTIVE: To investigate the correlation between neonatal and maternal vitamin D levels. METHODS: From June 1 to July 10, 2015, umbilical venous blood samples were collected from 102 full-term single neonates, and venous blood samples were collected from their mothers. Ultra-performance liquid chromatography with isotope dilution was applied to measure the serum 25(OH)D level. RESULTS: Vitamin D insufficiency was found in 39 mothers (38.2%) and 27 neonates (26.5%), and vitamin D deficiency was found in 25 mothers (24.5%) and 66 neonates (64.7%). Neonatal serum 25(OH)D level differed significantly between the groups of mothers with different serum 25(OH)D levels (P<0.001). Maternal 25(OH)D level was positively correlated with neonatal vitamin D level (r=0.914, P<0.001). When the receiver operating characteristic curve for maternal 25(OH)D level was used to predict neonatal vitamin D deficiency (≤15 ng/mL), the area under the curve was 0.962 (95%CI: 0.930-0.994; P<0.001). The sensitivity and specificity of maternal serum 25(OH)D level≤27.55 ng/mL to predict neonatal vitamin D deficiency were 97.2% and 80.3%, respectively. CONCLUSIONS: Neonatal vitamin D level is positively correlated with maternal vitamin D level. Maternal vitamin D level can help to predict neonatal vitamin D deficiency.


Asunto(s)
Embarazo/sangre , Vitamina D/análogos & derivados , Adulto , Femenino , Humanos , Recién Nacido , Masculino , Curva ROC , Vitamina D/sangre , Deficiencia de Vitamina D/diagnóstico
4.
Cancer Lett ; 580: 216493, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37977350

RESUMEN

Cholangiocarcinoma (CCA) is resistant to systemic chemotherapies that kill malignant cells mainly through DNA damage responses (DDRs). Recent studies suggest that the involvement of 2-oxoglutarate (2-OG) dependent dioxygenases in DDRs may be associated with chemoresistance in malignancy, but how 2-OG impacts DDRs in CCA chemotherapy remains elusive. We examined serum 2-OG levels in CCA patients before receiving chemotherapy. CCA patients are classified as progressive disease (PD), partial response (PR), and stable disease (SD) after receiving chemotherapy. CCA patients classified as PD showed significantly higher serum 2-OG levels than those defined as SD and PR. Treating CCA cells with 2-OG reduced DDRs. Overexpression of full-length aspartate beta-hydroxylase (ASPH) could mimic the effects of 2-OG on DDRs, suggesting the important role of ASPH in chemoresistance. Indeed, the knockdown of ASPH improved chemotherapy in CCA cells. Targeting ASPH with a specific small molecule inhibitor also enhanced the effects of chemotherapy. Mechanistically, ASPH modulates DDRs by affecting ATM and ATR, two of the major regulators finely controlling DDRs. More importantly, targeting ASPH improved the therapeutic potential of chemotherapy in two preclinical CCA models. Our data suggested the impacts of elevated 2-OG and ASPH on chemoresistance through antagonizing DDRs. Targeting ASPH may enhance DDRs, improving chemotherapy in CCA patients.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Ácido Aspártico/metabolismo , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/genética , Conductos Biliares Intrahepáticos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Daño del ADN , Ácidos Cetoglutáricos , Oxigenasas de Función Mixta/genética
5.
J Immunol ; 187(3): 1289-97, 2011 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-21724995

RESUMEN

In TNF-treated cells, TNFR1, TNFR-associated death domain protein (TRADD), Fas-associated death domain protein, and receptor-interacting protein kinase proteins form the signaling complex via modular interaction within their C-terminal death domains. In this paper, we report that the death domain SXXE/D motifs (i.e., S381DHE motif of TNFR1-death domain as well as S215LKD and S296LAE motifs of TRADD-death domain) are phosphorylated, and this is required for stable TNFR1-TRADD complex formation and subsequent activation of NF-κB. Phospho-S215LKD and phospho-S296LAE motifs are also critical to TRADD for recruiting Fas-associated death domain protein and receptor-interacting protein kinase. IκB kinase ß plays a critical role in TNFR1 phosphorylation of S381, which leads to subsequent T cell migration and accumulation. Consistently, we observed in inflammatory bowel disease specimens that TNFR1 was constitutively phosphorylated on S381 in those inflammatory T cells, which had accumulated in high numbers in the inflamed mucosa. Therefore, SXXE/D motifs found in the cytoplasmic domains of many TNFR family members and their adaptor proteins may serve to function as a specific interaction module for the α-helical death domain signal transduction.


Asunto(s)
Movimiento Celular/inmunología , Mediadores de Inflamación/metabolismo , Activación de Linfocitos/inmunología , Fosfoproteínas/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Subgrupos de Linfocitos T/inmunología , Proteína de Dominio de Muerte Asociada a Receptor de TNF/metabolismo , Secuencias de Aminoácidos/inmunología , Secuencia de Aminoácidos , Animales , Epítopos de Linfocito T/inmunología , Células HEK293 , Humanos , Mediadores de Inflamación/fisiología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Células Jurkat , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Fosfoproteínas/fisiología , Fosforilación/inmunología , Receptores Tipo I de Factores de Necrosis Tumoral/fisiología , Transducción de Señal/inmunología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/patología , Proteína de Dominio de Muerte Asociada a Receptor de TNF/fisiología
6.
Proc Natl Acad Sci U S A ; 107(45): 19314-9, 2010 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-20962278

RESUMEN

Cytokine-activated receptors undergo extracellular domain dimerization, which is necessary to activate intracellular signaling pathways. Here, we report that in prolactin (PRL)-treated cells, PRL receptor (PRLR) undergoes cytoplasmic loop dimerization that is acetylation-dependent. PRLR-recruited CREB-binding protein (CBP) acetylates multiple lysine sites randomly distributed along the cytoplasmic loop of PRLR. Two PRLR monomers appear to interact with each other at multiple parts from the membrane-proximal region to the membrane-distal region, relying on the coordination among multiple lysine sites neutralized via acetylation. Cytoplasmic loop-dimerized PRLR activates STAT5, which is also acetylated by CBP and undergoes acetylation-dependent dimerization. PRLR dimerization and subsequent signaling are enhanced by treating the cells with deacetylase sirtuin (SIRT) inhibitor nicotinamide or histone deacetylase (HDAC) inhibitor trichostatin A but inhibited by expressing exogenous deacetylase SIRT2 or HDAC6. Our results suggest that acetylation and deacetylation provide the rheostat-like regulation for the cytokine receptor PRLR in its cytoplasmic loop dimerization and subsequent STAT5 activation.


Asunto(s)
Multimerización de Proteína , Receptores de Prolactina/metabolismo , Acetilación , Sitios de Unión , Proteína de Unión a CREB/metabolismo , Línea Celular , Humanos , Lisina/metabolismo , Factor de Transcripción STAT5/metabolismo
7.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(1): 283-6, 2013 Jan.
Artículo en Zh | MEDLINE | ID: mdl-23586274

RESUMEN

The EUV imager is used to observe the 30.4 nm radiation of the earth's plasmasphere on the lunar surface. The 30.4 nm multilayer is the key optical part of the imager. According to the technical parameters, the B4 C/Mg, B4 C/Mg2Si, B4 C/Al, B4 C/Si, Mo/Si and so on were chosen. The period thickness, ratio of the material and the number of the periods were optimized and the reflectivity of those multilayers were calculated. In consideration of the lunar environment, the Mo/Si and the B4 C/Si multilayer were deposited by magnetron sputtering coating plant. The reflectivity of Mo/Si and B4 C/Si multilayer at 30.4 nm is 15.3% and 22.8% respectively.

8.
Quant Imaging Med Surg ; 13(12): 8587-8598, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38106337

RESUMEN

Background: Ultrasonography of the uterine artery (UtA) in the first and second trimesters of pregnancy can assess uterine-placental blood perfusion and guide early clinical prevention. Establishing normal ranges of the UtA pulsatility index (UtA-PI) at 11-14 weeks of pregnancy is helpful for the early identification of high-risk pregnant women and improving the prognosis. This study aimed to establish a reference range of UtA-PI based on crown-rump length (CRL) for spontaneous and in vitro fertilization (IVF) singleton pregnancy during 11-14 weeks, respectively. Methods: A prospective study was performed at Peking Union Medical College Hospital. Healthy, low-risk women with a singleton pregnancy at 11-14 gestational weeks were consecutively recruited for this study from December 2017 to December 2020. All participants underwent routine prenatal ultrasound examination. The CRL of the fetus and the UtA-PI were measured in both uterine arteries, and average values were calculated. The LMS method was used to fit the percentile (P)5, P10, P25, P50, P75, P90, and P95 curves of the UtA-PI value of spontaneous and IVF singleton pregnancy with CRL changes, respectively. Results: A total of 1,962 pregnant women with normal fetuses were included in this study, including 1,792 pregnancies conceived naturally and 170 IVF fetuses. The UtA-PI reference range in the spontaneous pregnancy group was consistently higher than that in the IVF group during 11-14 weeks, and showed a statistically significant difference in UtA-PI for spontaneous and IVF pregnancies (P<0.001). According to the LMS method, each percentile curve of UtA-PI decreased with the increase of CRL in both the natural pregnancy group and the IVF group. The P95 range of UtA-PI for pregnant women with naturally conceived and IVF pregnancy was 2.74 to 2.11 and 2.50 to 1.94, respectively. The overall change of UtA-PI differentials of the two groups showed a downward trend and decreased slightly with the increase of CRL. Conclusions: This study provided a single-center, large sample of data and constructed a CRL-based reference value of UtA-PI for spontaneous and IVF singleton pregnancy, which provides a reliable basis for early UtA evaluation and early clinical decision-making during 11-14 gestational weeks.

9.
Zhonghua Yi Xue Za Zhi ; 92(45): 3194-8, 2012 Dec 04.
Artículo en Zh | MEDLINE | ID: mdl-23328465

RESUMEN

OBJECTIVE: To explore the changes in serum protein levels of schizophrenics before and after treatment of risperidone and identify the potential markers of diagnosis, treatment and drug side effects of schizophrenia. METHODS: Eighty first-episode schizophrenics without other concurrent diseases and with positive and negative symptom scale (PANSS) score greater than or equal to 60 were recruited. And 15 of them were measured by proteomics. Different serum levels of proteins were obtained from these patients and were separated by two-dimensional electrophoresis (2-DE) before and after a single risperidone treatment for 8 weeks. These proteins were then identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and peptide mass fingerprinting. Enzyme-linked immunosorbent assay (ELISA) was used to verify the results. RESULTS: Almost 1400 spots were detected by 2-DE in each gel. Of these proteins, 23 protein spots showed significant differences in abundance before and after risperidone treatment. After MALDI-TOF peptide mass fingerprinting, 9 up-regulated proteins and 8 down-regulated proteins were validated after treatment. Of these proteins, the schizophrenics showed a significantly higher content of apolipoprotein A-1 (APOA-1) than those before treatment and haptoglobin (HP) protein was down-regulated after treatment. The results of ELISA were parallel with those of proteomic (P < 0.01). CONCLUSION: The serum proteins correlated with blood glucose and lipid metabolism are altered in schizophrenia after treatment of risperidone. A clinician should monitor the side effects of antipsychotic drugs according to the changes of serum proteins.


Asunto(s)
Proteómica , Risperidona/uso terapéutico , Esquizofrenia/sangre , Adolescente , Adulto , Femenino , Humanos , Masculino , Esquizofrenia/tratamiento farmacológico , Adulto Joven
10.
Zhonghua Fu Chan Ke Za Zhi ; 47(12): 883-7, 2012 Dec.
Artículo en Zh | MEDLINE | ID: mdl-23324185

RESUMEN

OBJECTIVE: To explore the pregnancy outcome and obstetric management of pregnancy and delivery after vaginal radical trachelectomy (VRT). METHODS: Forty-two cases of VRT from December 2003 to May 2012 in Peking Union Medical College Hospital were analyzed retrospectively. Among them ten cases got pregnant successfully. RESULTS: The average age of patient at VRT surgery was (30.6 ± 3.7) years old and average follow-up time was 29.5 months. There were 31 patients attempted conception. Ten of them got fourteen conceptions successfully. Overall conception rate was 45% (14/31). There were four cases of first trimester abortion. Among them, two were miscarriage, two were elective abortion. There was one case of ectopic pregnancy operation and non of second trimester loss. Nine cases reached the third trimester. The total preterm delivery rate was 4/9. There were two cases delivered before 32 gestational weeks (2/9). Cesarean section was performed through a transverse incision in all of nine cases. No uterine rupture and postpartum hemorrhage occurred. All newborns had good outcomes. The average follow-up time after postpartum was 22.9 months. All cases were disease-free. CONCLUSIONS: The conception rate of patients after VRT in our series is 45%. The preterm birth rate of pregnancy after VRT is higher. Routine cerclage of cervix during VRT procedure and pregnancy is not necessary. Cesarean section shortly after full term pregnancy through a transverse incision should be considered as a suitable and safe procedure.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Procedimientos Quirúrgicos Ginecológicos/métodos , Complicaciones del Embarazo/prevención & control , Resultado del Embarazo , Neoplasias del Cuello Uterino/cirugía , Adulto , Peso al Nacer , Carcinoma de Células Escamosas/patología , Cesárea , Femenino , Humanos , Recién Nacido , Estadificación de Neoplasias , Embarazo , Complicaciones del Embarazo/epidemiología , Índice de Embarazo , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología
11.
J Hand Surg Am ; 34(10): 1777-84.e1, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19969188

RESUMEN

PURPOSE: Transforming growth factor (TGF)-beta is considered to be responsible for the formation of scars such as adhesions around healing digital flexor tendons. We proposed to deliver microRNAs (miRNAs) to silence expression of the TGF-beta1 gene and to investigate the effectiveness of miRNAs in down-regulation of the TGF-beta1 gene in vitro and in vivo. METHODS: We designed and engineered 4 miRNAs according to genetic sequences of chicken TGF-beta1. Four plasmid vectors harboring the respective engineered miRNAs and 1 control vector were constructed. We transfected 30 wells of cultured tenocytes with these vectors and harvested them 48 hours later. The gene expression levels were quantified using real-time polymerase chain reactions. Subsequently, the miRNA that most effectively silenced TGF-beta gene in vitro was tested on 25 chickens in vivo. The miRNA and control vectors were injected into the injured tendons, respectively. At 1 and 6 weeks after surgery, the tendons were analyzed for gene expression and protein production. RESULTS: In both in vitro and in vivo settings, delivery of miRNA to the tendon substantially down-regulated expression of the TGF-beta gene but did not affect expression of the collagen I gene. In the healing tendon, TGF-beta gene expression was significantly down-regulated by 50% to 60% at 1 and 6 weeks. At 6 weeks, the collagen III gene expression was significantly down-regulated by 55% at 6 weeks and the connective tissue growth factor gene was significantly down-regulated by 25%. At 6 weeks, TGF-beta protein was substantially decreased. CONCLUSIONS: MicroRNA significantly down-regulates expression of the TGF-beta in vitro and in vivo. Application of miRNA did not down-regulate expression of the collagen I, but downregulated the collagen III gene. Application of miRNA treatment to modulate TGF-beta expression holds great promise in preventing tendon adhesion formation.


Asunto(s)
Regulación hacia Abajo/genética , MicroARNs/genética , Tendones/metabolismo , Adherencias Tisulares/genética , Transfección , Factor de Crecimiento Transformador beta1/genética , Cicatrización de Heridas/genética , Animales , Western Blotting , Células Cultivadas , Pollos , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Regulación de la Expresión Génica/genética , Ingeniería Genética , Vectores Genéticos , MicroARNs/farmacología , Plásmidos
12.
Dis Markers ; 2019: 6270187, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31396294

RESUMEN

The ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is elevated and proved to be useful in preeclampsia (PE) diagnosis. Its value in differential diagnosis with other pregnancy complications and prediction of pregnancy duration has yet to be clarified in Chinese population. We retrospectively analyzed 118 singleton pregnancies with suspected or diagnosed PE at the Peking Union Medical College Hospital (PUMCH) in China. Among these, 62 pregnancies were diagnosed as PE (48 early onsets and 14 late onsets, with 39 and 5 severe PE, respectively), 12 gestational hypertension (GH), 15 chronic hypertension (chrHTN), 16 autoimmune diseases, and 13 pregnancies with uncomplicated proteinuria. And 76 normal pregnancies were included as control. The results showed (1) the sFlt-1/PlGF ratio in early onset PE subgroup was significantly higher than that in GH, chrHTN, and control groups; the sFlt-1/PlGF ratio in late onset PE subgroup was significantly higher than that in chrHTN and control groups, but similar as GH group; the sFlt-1/PlGF ratio was similar among GH, chrHTN, and control groups. (2) The sFlt-1/PlGF ratio was significantly increased in the PE group compared with autoimmune disease and uncomplicated proteinuria pregnancies. (3) By ROC curve analysis, the cutoff value of the sFlt-1/PlGF ratio was less than 21.5 to rule out PE and higher than 97.2 to confirm the diagnosis of PE. (4) The sFlt-1/PlGF ratio was higher in PE pregnancies delivering within 7 days than those more than 7 days, either in early onset PE or severe PE. In conclusion, we show that maternal sFlt-1/PlGF ratio is an efficient biomarker in the diagnosis and differential diagnosis of PE. This ratio can be used to predict the timing of delivery for PE pregnancies.


Asunto(s)
Biomarcadores/sangre , Factor de Crecimiento Placentario/sangre , Preeclampsia/diagnóstico , Complicaciones del Embarazo/diagnóstico , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Estudios de Casos y Controles , China/epidemiología , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Preeclampsia/sangre , Preeclampsia/clasificación , Embarazo , Complicaciones del Embarazo/sangre , Pronóstico , Curva ROC
13.
Cancer Lett ; 429: 1-10, 2018 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-29733964

RESUMEN

Cholangiocarcinoma (CCA) is a highly lethal and aggressive disease. Recently, IDH1/2 mutations have been identified in approximately 20% of CCAs which suggests an involvement of 2-oxoglutarate (2-OG) -dependent dioxygenases in oncogenesis. We investigated if the 2-OG dependent dioxygenase, aspartate beta-hydroxylase (ASPH) was important in tumor development and growth. Immunoassays were used to clarify how ASPH modulates CCA progression by promoting phosphorylation of the retinoblastoma protein (RB1). A xenograft model was employed to determine the role of ASPH on CCA growth. Knockdown of ASPH expression inhibited CCA development and growth by reducing RB1 phosphorylation. Expression of ASPH promoted direct protein interaction between RB1, cyclin-dependent kinases, and cyclins. Treatment with 2-OG-dependent dioxygenase and ASPH inhibitors suppressed the interaction between RB1 and CDK4 as well as RB1 phosphorylation. Knockdown of ASPH expression inhibited CCA progression and RB1 phosphorylation in vivo and they were found to be highly expressed in human CCAs. Knockdown of ASPH expression altered CCA development by modulating RB1 phosphorylation, as one of the major factors regulating the growth of these tumors.


Asunto(s)
Neoplasias de los Conductos Biliares/metabolismo , Proteínas de Unión al Calcio/metabolismo , Colangiocarcinoma/enzimología , Proteínas de la Membrana/metabolismo , Oxigenasas de Función Mixta/metabolismo , Proteínas Musculares/metabolismo , Proteína de Retinoblastoma/metabolismo , Animales , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/terapia , Proteínas de Unión al Calcio/genética , Línea Celular Tumoral , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Progresión de la Enfermedad , Femenino , Humanos , Proteínas de la Membrana/genética , Ratones Noqueados , Ratones Desnudos , Oxigenasas de Función Mixta/genética , Proteínas Musculares/genética , Fosforilación , Unión Proteica , Interferencia de ARN , Tratamiento con ARN de Interferencia/métodos , Proteína de Retinoblastoma/genética , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
14.
Chin Med Sci J ; 22(1): 13-6, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17441311

RESUMEN

OBJECTIVE: To investigate ureteral injury during gynecological laparoscopic surgeries. METHODS: From January 1990 to December 2005, 12 868 gynecological laparoscopic surgeries were conducted in Peking Union Medical College Hospital with 12 ureteral injuries reported. The present study investigated several aspects, including surgical indications, uterine size, pelvic adhesion, operative procedures, symptoms, diagnostic time and methods, injury site and type, subsequent treatment, and prognosis. RESULTS: The incidence of ureteral injury was 0.093% (12/12 868) in all cases, 0.42% (11/2 586) in laparoscopic hysterectomy [laparoscopically assisted vaginal hysterectomy (LAVH) or total laparoscopic hysterectomy (TLH)], and 0.01% (1/10 282) in non-LAVH surgeries. Enlarged uterus, pelvic adhesion, and endometrosis were risk factors associated with ureteral injury. Only one injury was found intraoperatively while others were found postoperatively. The injury sites were at the pelvic brim (2 cases) or the lower part of ureter (10 cases). Patients were treated with ureteral stenting (effective in 2 cases) or laparotomy and open repair. Prognoses were favorable in most cases. CONCLUSIONS: Most laparoscopic ureteral injuries occur during laparoscopic hysterectomy. Further evaluation is required when ureteral injury is suspected, and surgical repair is the major treatment for ureteral injury.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Laparoscopía/efectos adversos , Uréter/lesiones , Femenino , Humanos , Histerectomía/efectos adversos , Ovariectomía/efectos adversos , Estudios Retrospectivos , Adherencias Tisulares/terapia , Resultado del Tratamiento
15.
Liver Cancer ; 4(3): 139-53, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26675015

RESUMEN

Abundant expression of aspartyl-(asparaginyl)-ß-hydroxylase (AAH) correlates with infiltrative growth of hepatocellular carcinoma (HCC). Herein, we examine the role of phosphorylation in relation to AAH's protein expression, hydroxylase activity, promotion of cell motility, and activation of Notch signaling in human Huh7 hepatoma cells. Predicted glycogen synthase kinase-3ß (GSK-3ß), protein kinase A (PKA), protein kinase C (PKC), and casein kinase 2 (CK2) phosphorylation sites encoded by human AAH cDNA were ablated by S/T→A site-directed mutagenesis using N-Myc-tagged constructs in which gene expression was controlled by a cytomegalovirus promoter. Functional consequences were assessed in transiently transfected Huh7 cells. Cells transfected with wildtype AAH had significantly increased AAH expression, catalytic activity, HES-1 expression, and directional motility relative to controls. Single phosphorylation site mutations in the C-terminus largely abrogated these effects and further inhibited catalytic activity relative to that in cells transfected with empty vector, whereas the effects of single point mutations within the N-terminus were more varied. In contrast, AAH cDNAs carrying multiple phosphorylation site mutations exhibited wildtype levels of AAH catalytic activity suggesting that the effects of AAH phosphorylation are complex and non-uniform. AAH expression and function can be modulated by direct phosphorylation of the protein. These findings suggest additional strategies for inhibiting infiltrative growth of HCC.

16.
J Nat Sci ; 1(4)2015 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-26029741

RESUMEN

BACKGROUND: Asparaginyl-ß-hydroxylase (AAH) promotes cell adhesion, migration, and invasion via Notch activation. AAH's expression is up-regulated by insulin/IGF signaling through PI3K-Akt, but its protein is independently regulated by GSK-3ß. The multiple predicted GSK-3ß phosphorylation sites suggest post-translational mechanisms may regulate AAH protein expression. METHODS: Human Huh7 hepatoma cells were transfected with recombinant plasmids that expressed full-length N-terminal Myc-tagged (N-Myc-AAH) or C-terminal HA-tagged (C-HA-AAH) cDNA. Effects of IGF-1 on AAH protein were examined using cellular ELISAs, immunofluorescence, and Western blotting. Effects of kinase inhibitors relevant to AAH's predicted phosphorylation sites were studied. RESULTS: IGF-1 stimulation increased AAH protein expression and shifted AAH's localization from the perinuclear zone to the cell periphery, including podocytes. Subsequently, Notch-1 intracellular domain was translocated to the nucleus, which is critical for Notch- modulated gene expression. Besides GSK-3ß, inhibition of PKC, PKA, and CK2, which could potentially phosphorylate AAH, increased IGF-1 stimulated AAH protein. Finally, insulin and LiCl independently and additively increased long-term AAH protein expression. CONCLUSION: Insulin/IGF-1 stimulation of AAH and Notch are enhanced by inhibiting kinases that could phosphorylate AAH protein. Targeted manipulation of AAH's phosphorylation state may have therapeutic value for reducing AAH-Notch activation and attendant infiltrative growth of hepatocellular carcinomas.

17.
Cancer Biol Ther ; 1(3): 263-5, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12432274

RESUMEN

Conventional anticancer drugs show non-specific vascular toxicity, and using anticancer drugs as angiogenesis inhibitors was suggested. However, our previous study suggested that vascular endothelial growth factor (VEGF) protected endothelial cells against chemotherapy drugs in vitro. To further test whether the vascular toxicity of anticancer drugs is active in vivo, epirubicin was i.p. injected into nude mice with s.c. xenografts of human nasopharyngeal carcinoma CNE-2 once (one-day schedule) or once a day from day 1 to day 7 (seven-day schedule). At 48 hours after the single injection or the 7th injection tumors were removed for detection of apoptosis of vascular endothelial cells vessels and the content of VEGF in tumor tissues. The results showed that epirubicin damaged tumor microvessels when the drug was given as a single dose, whereas epirubicin lost its vascular toxicity when the drug was given continuously for seven days, accompanied by higher levels of VEGF in tumor tissues. These results suggest the sensitivity of endothelial cells lining tumor vessels is variable during chemotherapy, and the protective effect of VEGF on endothelial cells might be related to the schedule of administration.


Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Endotelio Vascular/efectos de los fármacos , Epirrubicina/toxicidad , Neoplasias Nasofaríngeas/irrigación sanguínea , Animales , Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos , Factores de Crecimiento Endotelial/metabolismo , Endotelio Vascular/patología , Humanos , Etiquetado Corte-Fin in Situ , Inyecciones Intraperitoneales , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Linfocinas/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microcirculación/patología , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Trasplante de Neoplasias , Neovascularización Patológica , Trasplante Heterólogo , Células Tumorales Cultivadas/trasplante , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular
18.
Zhonghua Fu Chan Ke Za Zhi ; 39(3): 159-61, 2004 Mar.
Artículo en Zh | MEDLINE | ID: mdl-15130373

RESUMEN

OBJECTIVE: To retrospectively analyze the clinical characteristics and outcomes of endometrial carcinoma patients aged 45 years and younger. METHODS: Fifty-two cases of endometrial carcinoma aged 45 years and younger were treated in Peking Union Medical College Hospital. They were further divided into group A (35 years of age and younger) and group B (older than 35 years). Clinical data of these patients were reviewed and the two groups were compared. RESULTS: Patients aged 45 years and younger accounted for 12.7% of all the endometrial carcinoma cases. About 50% of the patients were nulliparous, infertile or had irregular menstruation and endometrial hyperplasia, 29% were obese, 23% had polycystic ovaries. Eighty-three percent of the patients were stage [International Federation of Gynecology and Obstetrics (FIGO), 1988]. Group A had more polycystic ovaries and atypical endometrial hyperplasia than group B (53% vs 9%, 59% vs 26% respectively, P < 0.05). All group A patients were stage I endometrial carcinoma. In group B, 26% had high risk factors, and compared with group A, FIGO stage was higher (P < 0.05). Operation was the main treatment. Two patients were treated successfully with conservative high dose progestin. Two patients relapsed. CONCLUSIONS: There were high incidences of infertility, irregular menstruation, endometrial hyperplasia, obese and polycystic ovaries in patients aged 45 years and younger, indicating the relationship between endometrial carcinoma and estrogen. Most patients, especially those younger than 35 years, were stage I with few risk factors and good prognosis. Conservation of fertility and ovarian function should be considered in these patients.


Asunto(s)
Adenocarcinoma de Células Claras/patología , Adenocarcinoma/patología , Neoplasias Endometriales/patología , Adenocarcinoma/complicaciones , Adenocarcinoma/terapia , Adenocarcinoma de Células Claras/complicaciones , Adenocarcinoma de Células Claras/terapia , Adulto , Factores de Edad , China , Hiperplasia Endometrial/etiología , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/terapia , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Síndrome del Ovario Poliquístico/etiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
19.
Zhonghua Fu Chan Ke Za Zhi ; 39(5): 311-4, 2004 May.
Artículo en Zh | MEDLINE | ID: mdl-15196412

RESUMEN

OBJECTIVE: To investigate the ureteral injury in gynecological laparoscopies and discuss its diagnosis, treatment and prevention. METHODS: Ureteral injury in gynecological laparoscopies during the past 13 years was reviewed retrospectively. The clinical features of initial operations including the types of disease, uterine size, pelvic adhesion, operative procedures and the methods of diagnosis, treatment and prognosis of ureteral injury were studied. RESULTS: There were 8 ureteral injuries (0.14%) in 5 541 gynecological laparoscopies with seven in laparoscopically assisted vaginal hysterectomy (LAVH)/total laparoscopic hysterectomy (TLH) (0.45%) and one in non-LAVH (0.03%). The main gynecological disorders included adenomyosis, endometriosis and leiomyoma. All patients had pelvic adhesions and 4 had previous pelvic operations. Uterine enlargement was found in 7. Patients presented increased vaginal drainage, flank pain, increased volumes of vaginal discharge, nausea and vomiting, fever, edema, or peritonitis from 0 to 13 days postoperatively. Ureteral injuries were mainly diagnosed via excretory urogram (IVP). The sites of injury were near the inferior margin of the sacroiliac joint in two women and at the inferior part of ureter (near the uterine vessel, uterosacral ligament and ureterovesical junction) in 6. Two patients whose injuries were found soon after operation received ureteral repair by laparotomy successfully. Two of the six patients whose injuries were found several days later were treated with internal ureteral stenting successfully, the other four failed with ureteral stenting and received ureteral repair by laparotomy. Outcomes were good in all cases. CONCLUSIONS: Ureteral injury is an uncommon and severe complication in gynecological laparoscopies. Symptoms like abnormally increased drainage, fever, flank pain, abnormal vaginal discharge and peritonitis after operation should be paid attention to and ureteral injury be considered. Surgical repair is the primary treatment.


Asunto(s)
Enfermedades de los Genitales Femeninos/cirugía , Complicaciones Intraoperatorias , Laparoscopía/efectos adversos , Uréter/lesiones , Enfermedades Ureterales/cirugía , Adulto , Femenino , Procedimientos Quirúrgicos Ginecológicos/instrumentación , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Histerectomía Vaginal/efectos adversos , Complicaciones Intraoperatorias/diagnóstico , Complicaciones Intraoperatorias/prevención & control , Complicaciones Intraoperatorias/terapia , Laparoscopía/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Uréter/cirugía
20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 25(4): 391-5, 2003 Aug.
Artículo en Zh | MEDLINE | ID: mdl-12974080

RESUMEN

OBJECTIVE: To evaluate clinical characteristics, prognosis, prognostic factors, and the ideal treatment of the young patients with cervical malignant tumor. METHODS: We analyzed retrospectively 52 cervical malignant tumor patients younger than 35 years (study group) and 45 cervical carcinoma patients older than 50 years (control group) who were admitted in Peking Union Medical College Hospital from 1985 to 2002. The data were analyzed statistically by SPSS10.0. The ovarian functions were evaluated by the questionnaire and the serum sex hormone assay. RESULTS: In study group, the median age was (31.0 +/- 0.6) years old. The most common clinical symptoms were contact bleeding and irregular bleeding; 55.8% of patients had more than one symptom. HPV positive rate was 20.5%, which was higher than control group significantly (P < 0.05). The percentage of advanced stage (stage II b-stage IV b) of disease in study group and control group were 30.8% and 22.2%, respectively, the difference was significant (P < 0.05). The most common histological type was squamous cell carcinoma (71.2%) in study group, while the percentage of non-squamous cell carcinoma (43.8%) in patients younger than 30 years was much higher than control group (P < 0.05). All the histological type was non-squamous cell carcinoma in the patients younger than 25 years. Histological grade showed that G1, G2, and G3 were 21.2%, 54.5%, and 24.2% respectively in study group. The percentage of bulky cervix (tumor diameter > 4 cm) in study group and control group was 27.9% and 2.7% respectively (P < 0.005). The overall 5-year survival rates were 75.7% in study group, lower than control group (P < 0.05). The COX hazards regression model showed histological type (P = 0.003) and bulky cervix (P = 0.001) were of significant prognostic values. CONCLUSIONS: There are more advanced stage carcinoma and non-squamous cell carcinoma patients with poor prognosis in study group. The treatment to younger patients should be concerned individually, as well as preservation of reproductive and female endocrine function should be considered.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino/cirugía , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirugía , Adenocarcinoma/virología , Adulto , Factores de Edad , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/virología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pruebas de Función Ovárica , Papillomaviridae/aislamiento & purificación , Pronóstico , Análisis de Regresión , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología
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