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Since its first application in 2016, spatial transcriptomics has become a rapidly evolving technology in recent years. Spatial transcriptomics enables transcriptomic data to be acquired from intact tissue sections and provides spatial distribution information and remedies the disadvantage of single-cell RNA sequencing (scRNA-seq), whose data lack spatially resolved information. Presently, spatial transcriptomics has been widely applied to various tissue types, especially for the study of tumor heterogeneity. In this review, we provide a summary of the research progress in utilizing spatial transcriptomics to investigate tumor heterogeneity and the microenvironment with a focus on solid tumors. We summarize the research breakthroughs in various fields and perspectives due to the application of spatial transcriptomics, including cell clustering and interaction, cellular metabolism, gene expression, immune cell programs and combination with other techniques. As a combination of multiple transcriptomics, single-cell multiomics shows its superiority and validity in single-cell analysis. We also discuss the application prospect of single-cell multiomics, and we believe that with the progress of data integration from various transcriptomics, a multilayered subcellular landscape will be revealed.
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Neoplasias , Transcriptoma , Humanos , Transcriptoma/genética , Perfilación de la Expresión Génica , Neoplasias/genética , Análisis por Conglomerados , Multiómica , Análisis de Secuencia de ARN , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Chronic kidney disease (CKD) has been demonstrated to be associated with adverse clinical outcomes for patients with coronary artery disease (CAD). However, data on relation of CKD and stent thrombosis (ST) after drug-eluting stent (DES) implantation are limited. OBJECTIVES: This study was designed to examine whether CKD is associated with higher incidence of ST after elective coronary DES implantation compared with patients with normal renal function. METHODS: We consecutively enrolled 2,862 patients undergoing elective percutaneous coronary intervention (PCI) with DES. Demographic and clinical data were collected preoperatively. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min, calculated using the modified MDRD equation. The primary outcome was 1-year definite or probable ST. RESULTS: Four hundred and forty-five participants (15.5%) had CKD before procedure. The incidence of 1-year definite or probable ST was significantly higher in CKD patients compared with patients with normal renal function (1.8% vs. 0.6%, P = 0.014). After adjustment for multiple clinical and biochemical covariates, CKD was an independent predictor of 1-year definite or probable ST (hazard rate [HR] 0.396, 95% CI 0.165-0.951, P = 0.038). CONCLUSION: CKD is significantly associated with increased incidence of 1-year definite or probable ST in patients undergoing PCI with DES.
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Enfermedad de la Arteria Coronaria/terapia , Trombosis Coronaria/epidemiología , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Insuficiencia Renal Crónica/epidemiología , Anciano , Distribución de Chi-Cuadrado , China/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Trombosis Coronaria/mortalidad , Femenino , Tasa de Filtración Glomerular , Humanos , Incidencia , Estimación de Kaplan-Meier , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Intervención Coronaria Percutánea/mortalidad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Diseño de Prótesis , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
The purpose of this review is to bridge the gap between clinical and basic research through providing a comprehensive and concise description of the cellular and molecular aspects of cardioprotective mechanisms and a critical evaluation of the clinical evidence of high-energy phosphates (HEPs) in ischemic heart disease (IHD). According to the well-documented physiological, pathophysiological and pharmacological properties of HEPs, exogenous creatine phosphate (CrP) may be considered as an ideal metabolic regulator. It plays cardioprotection roles from upstream to downstream of myocardial ischemia through multiple complex mechanisms, including but not limited to replenishment of cellular energy. Although exogenous CrP administration has not been shown to improve long-term survival, the beneficial effects on multiple secondary but important outcomes and short-term survival are concordant with its pathophysiological and pharmacological effects. There is urgent need for high-quality multicentre RCTs to confirm long-term survival improvement in the future.
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OBJECTIVE@#To access the efficacy and safety of the double-ProGlide technique for the femoral vein access-site closure in cryoballoon ablation with uninterrupted oral anticoagulants (OAC), and its impact on the electrophysiology laboratory time as well as hospital stay after the procedure in this observational study.@*METHODS@#Patients with atrial fibrillation undergoing cryoballoon ablation with uninterrupted OAC at Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China from May 2019 to May 2021 were enrolled in this study. From October 2020, double-ProGlide technique was consistently used for hemostasis (ProGlide group), and before that conventional manual compression was utilized (manual compression group). The occurrence of vascular and groin complications was accessed during the hospital stay and until the three-month follow-up.@*RESULTS@#A total of 140 participants (69.30% of male, mean age: 59.21 ± 10.29 years) were evaluated, 70 participants being in each group. Immediate hemostasis was achieved in all the patients with ProGlide closure. No major vascular complications were found in the ProGlide group while two major vascular complications were occurred in the manual compression group. The incidence of any groin complication was obviously higher in subjects with manual compression than patients with ProGlide devices (15.71% vs. 2.86%, P = 0.009). In addition, compared with the manual compression group, the ProGlide group was associated with significantly shorter total time in the electrophysiology laboratory [112.0 (93.3-128.8) min vs. 123.5 (107.3-158.3) min, P = 0.006], time from sheath removal until venous site hemostasis [3.8 (3.4-4.2) min vs. 8.0 (7.6-8.5) min, P < 0.001], bed rest time [8.0 (7.6-8.0) h vs. 14.1 (12.0-17.6) h, P < 0.001] and hospital stay after the procedure [13.8 (12.5-17.8) h vs. 38.0 (21.5-41.0) h, P < 0.001].@*CONCLUSIONS@#Utilization of the double-ProGlide technique for hemostasis after cryoballoon ablation with uninterrupted OAC is feasible and safe, which has the clinical benefit in reducing the total electrophysiology laboratory time and the hospital stay length after the procedure.
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Aim To evaluate the pharmacokinetics and bioequivalence of two osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers.Methods The fed test each enrolled twenty-six Chinese healthy volunteers in a randomized-sequence, open-label, two-period crossover single-dose oral test and reference preparations of hydrochloride venlafaxine extended-release tablets.The plasma concentrations of venlafaxine and its active metabolites O-desmethylvenlafaxine were determined by a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method, and the pharmacokinetic parameters and bioequivalence of the two tablets were analyzed using PhoenixTM WinNonlin 6.4 software.Results The pharmacokinetic parameters of venlafaxine after single dose for the test and reference tablets were as follows: Cmax(58.50±19.47)vs(60.14±22.18)μg•L-1, AUC0-t(1 074.1±526.7)vs(1 057.9±539.7)μg•h•L-1, AUC0-∞(1 084.7±536.8)vs(1 067.8±554.0)μ g•h•L-1.The pharmacokinetic parameters of O-desmethylvenlafaxine were as follows: Cmax(101.63±29.64)vs(101.45±31.62)μg•L-1, AUC0-t(2 694.0±834.5)vs(2 702.9±946.4)μg• h•L-1, AUC0-∞(2 753.9±885.5)vs(2 753.2±988.4)μg•h•L-1.The 90% confidence intervals of the geometric mean ratios of Cmax, AUC0-t, AUC0-∞ for the test preparation and the reference preparationwere all within the equivalent interval of 80.00%-125.00%.Conclusion The test and reference preparations of hydrochloride venlafaxine extended-release tablets are bioequivalent in Chinese healthy volunteers under fed conditions.
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OBJECTIVE: To evaluate the effect of exogenous creatine phosphate (CP) on myocardial injury after percutaneous coronary intervention (PCI). METHOD: Four hundred patients were divided to receive conventional therapy (control group) or 3-day intravenous infusion of CP after PCI (CP group). Levels of creatine kinase MB (CK-MB) and troponin I (TnI) were measured before and on postprocedural day 3. RESULTS: Postprocedural CK-MB and TnI in the CP group were significantly increased compared to the control group. In the CP group, 8.0% and 5.0% of patients had an increase in CK-MB 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (19.0% and 9.0%, respectively); 12.0% and 10.0% of patients had an increase in TnI 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (21.0% and 18.0%, respectively). CONCLUSION: Exogenous CP was helpful to reduce myocardial injury after PCI.
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Daño por Reperfusión Miocárdica/prevención & control , Intervención Coronaria Percutánea/efectos adversos , Fosfocreatina/administración & dosificación , Anciano , Biomarcadores/sangre , China , Forma MB de la Creatina-Quinasa/sangre , Citoprotección , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Daño por Reperfusión Miocárdica/sangre , Daño por Reperfusión Miocárdica/diagnóstico , Daño por Reperfusión Miocárdica/etiología , Factores de Tiempo , Resultado del Tratamiento , Troponina I/sangre , Regulación hacia ArribaRESUMEN
Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
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Niño , Humanos , Factor VIII/uso terapéutico , Hemartrosis , Hemofilia A/tratamiento farmacológico , Hemorragia , Estudios RetrospectivosRESUMEN
We assessed the impact of preprocedural high-sensitivity C-reactive protein (hsCRP) on the incidence of contrast-induced nephropathy (CIN) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (p-PCI). We retrospectively studied 1452 patients with STEMI undergoing p-PCI. Baseline clinical characteristics, CIN incidence, and other inhospital clinical outcomes were compared among hsCRP quartiles; 212 (14.6%) patients developed CIN. The overall inhospital mortality rate was 4.5% (65 patients). Univariate analysis revealed CIN incidence was significantly associated with hsCRP, with 7.44% for quartile Q1 (<3.00 mg/L), 12.6% for Q2 (3.00-5.90 mg/L), 16.9% for Q3 (5.91-11.4 mg/L), and 21.49% for Q4 (>11.4 mg/L; P < .001). Patients with a higher hsCRP experienced a higher rate of inhospital complications. After adjusting for potential confounders, hsCRP >6.50 mg/L was significantly associated with the occurrence of CIN. Preprocedural hsCRP levels are significantly related to the incidence of CIN in patients with STEMI undergoing p-PCI.
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Proteína C-Reactiva/análisis , Medios de Contraste/efectos adversos , Enfermedades Renales/inducido químicamente , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea , Anciano , Biomarcadores/sangre , China/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Incidencia , Enfermedades Renales/diagnóstico , Enfermedades Renales/mortalidad , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico por imagen , Radiografía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE@#To study the clinical effect of psychological and behavioral intervention combined with biofeedback in the treatment of preschool children with attention deficit hyperactivity disorder (ADHD).@*METHODS@#Sixty children each with inattentive, hyperactive/impulsive or combined type ADHD were enrolled. According to the intervention measure, they were randomly divided into 4 groups: control, psychological and behavioral intervention, biofeedback treatment and comprehensive treatment (psychological and behavioral intervention + biofeedback). Attention concentration time and impulse/hyperactivity and hyperactivity index scores of the Conners Parent Symptom Questionnaire (PSQ) were evaluated after 4 months of treatment.@*RESULTS@#The attention concentration time increased in all types children with ADHD after psychological and behavioral intervention, biofeedback treatment or comprehensive treatment (P<0.05). In children with inattentive ADHD, hyperactive/impulsive ADHD or combined-type ADHD, biofeedback or comprehensive treatment reduced the impulse/hyperactivity index score (P<0.05). In children with inattentive or combined-type ADHD, psychological and behavioral intervention or comprehensive treatment reduced the hyperactivity index score (P<0.05). In children with hyperactive/impulsive ADHD, biofeedback treatment, psychological and behavioral intervention or comprehensive treatment reduced the hyperactivity index score (P<0.05).@*CONCLUSIONS@#In children with ADHD, psychological and behavioral intervention combined with biofeedback treatment can improve the attention concentration and impulsive/hyperactive and hyperactive symptoms. The treatment strategies are slightly different for children with different types of ADHD.
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Preescolar , Humanos , Trastorno por Déficit de Atención con Hiperactividad , Biorretroalimentación Psicológica , Padres , Encuestas y CuestionariosRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of ATO on the proportion of Treg in the peripheral blood of patients with severe aplastic anemia (SAA) in vitro.</p><p><b>METHODS</b>The peripheral blood of 20 newlydiagnosed patients were collected, and the peripheral blood monomuclear cells (PBMNC) were extracted. After the PBMNC were treated with ATO of different concentrotions (0, 1, 2.5 and 5 µmol/L) for 96 hours, the proportion of CD44 CD25CD127 regulatatory T cells (Treg) were detected by flow cytometry. The expression levels of Foxp3 mRNA were detected by RT-PCR, and the levels of IFN-γ,IL-4,IL-17 and TGF-β1 were detected by ELTSA to verify the results of flow cytomery.</p><p><b>RESULTS</b>ATO significantly increased the proportion of Treg (P<0.01) at the concentration of 2.5 and 5 µmol/L, and the rising degree of Treg proportion improved with the increasing ATO concentration(r= 0.524). Treg proportion increased at a concentration of 1 µmol/L, but without statistical significance (P>0.05). At 1(P<0.05), 2.5(P<0.01) and 5 µmol/L(P<0.01), ATO significantly up-regulated the expression of Foxp3 mRNA, and the increase of Foxp3 mRNA positively and linearly correlated with the increase of Treg cell-frequency(r=0.523). ATO significantly reduced the levels of IFN-γ (at ATO 1,2.5 and 5 µmol/L, P<0.01), IL-4 (at ATO 2.5 µmol/L, P<0.01; at ATO 5 µmol/L, P<0.01) and IL-17(at ATO 2.5 µmol/L, P<0.05; at ATO 5 µmol/L, P<0.01). ATO had no significant effect on TGF-β1 at 1(P>0.05) and 2.5 µmol/L (P>0.05), but significantly reduced TGF-β1 level at 5 µmol/L (P<0.05).</p><p><b>CONCLUSION</b>ATO can mediate the immune regulation through up-regulating the proportion of Treg in peripheral blood of patients with SAA and reducing the levels of IFN-γ, IL-4 and IL-17.</p>
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Humanos , Anemia Aplásica , Trióxido de Arsénico , Arsenicales , Factores de Transcripción Forkhead , Óxidos , ARN Mensajero , Linfocitos T ReguladoresRESUMEN
Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ2=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ2=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ2=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ2=0.230, P=0.891; χ2=2.628, P=0.269; χ2=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ2=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS. Conclusion: The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.
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Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Anemia Aplásica/terapia , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Estudios Retrospectivos , Resultado del Tratamiento , Donante no EmparentadoRESUMEN
<p><b>OBJECTIVE</b>To investigate the difference in the efficacy between clonidine transdermal patch and haloperidol tablets in the treatment of moderate to severe tic disorders in children.</p><p><b>METHODS</b>A total of 134 children with moderate to severe tic disorders were randomly divided into clonidine group (n=70) and haloperidol group (n=64). The clonidine and haloperidol groups were treated with clonidine transdermal patch and haloperidol tablets respectively, and the treatment lasted for 8 weeks in both groups. The Yale Global Tic Severity Scale (YGTSS) was used to evaluate the conditions of the children before and after treatment, and the adverse events during the treatment were recorded.</p><p><b>RESULTS</b>The haloperidol group had a significantly better treatment outcome than the clonidine group after one week of treatment (P<0.05); the treatment outcome showed no significant difference between the two groups after 3, 5, and 8 weeks of treatment (P>0.05). The clonidine group had significantly less reductions in the motor tics, vocal tics, and function impairment scores and total score of YGTSS than the haloperidol group after one week of treatment (P<0.05); there were no significant differences in YGTSS score reductions between the two groups after 3, 5, and 8 weeks of treatment (P>0.05). The clonidine group had a significantly lower overall incidence of adverse events than the haloperidol group (8% vs 37%; P<0.01).</p><p><b>CONCLUSIONS</b>Clonidine transdermal patch and haloperidol are both effective in the treatment of moderate to severe tic disorders in children. The clonidine transdermal patch, despite slow action, has comparable efficacy and fewer adverse effects compared with haloperidol.</p>
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Niño , Preescolar , Femenino , Humanos , Masculino , Clonidina , Haloperidol , Usos Terapéuticos , Índice de Severidad de la Enfermedad , Trastornos de Tic , Quimioterapia , Parche TransdérmicoRESUMEN
<p><b>OBJECTIVE</b>To observe the clinical efficacy on spastic pelvic floor syndrome (SPFS) treated with electroacupuncture (EA) at Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34).</p><p><b>METHODS</b>Thirty-six cases of SPFS were treated with EA at Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34), intermittent wave, 60 times/min in frequency, retained for 20 min. In general, the acupoints on one side were stimulated in each treatment. The bilateral acupoints stimulation was applied in serious cases. The treatment was given once every two days, five treatments made one session and totally three sessions were required. Before and after treatment, the clinical symptoms, anal kinetic indices defecation radiographic changes were observed. The follow-up observation was done in three months after the end of treatment.</p><p><b>RESULTS</b>In three-months follow-up after treatment, 14 cases were cured, 18 cases improved and 4 cases failed. The total effective rate was 88. 9%. After treatment, the cases of incomplete defecation, difficult defecation, anal pain and anal obstruction were reduced apparently as compared with those before treatment, indicating the statistically significant differences (all P<0.01). After treatment, rectal anal reflex threshold (ARA) was increased, anal maximal contraction pressure (AMCP) was reduced to (16.62±1.54) kPa and anal rest pressure (ARP) was significantly reduced to (7.22±0.36) kPa, indicating the statistical differences as compared with those before treatment (all P<0.01). After treatment, anorectal angle (ARA) in forceful defecation was increased to (116.55±9.42)°, the distance between the anorectal junction and the pubococcygeal line was decreased, and the impression of puborectal muscle was alleviated apparently as compared with that before treatment (P<0.01).</p><p><b>CONCLUSION</b>EA at Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34) achieves definite efficacy on SPFS and this therapeutic method obviously relieves the symptoms and deserves to be promoted in clinic.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntos de Acupuntura , Enfermedades del Ano , Terapéutica , Estreñimiento , Terapéutica , Defecación , Electroacupuntura , Espasticidad Muscular , Terapéutica , Diafragma Pélvico , PatologíaRESUMEN
<p><b>OBJECTIVE</b>Restrictive cardiomyopathy (RCM) is rare in children, and little is known about the molecular basis of RCM. The aim of this study was to investigate the clinical and myopathological characteristics and to detect mutations on cardiac sarcomere protein genes in three idiopathic pediatric RCMs.</p><p><b>METHODS</b>Detailed clinical characteristics and familiar history were obtained in three idiopathic pediatric RCMs. One hundred healthy pediatric individuals were recruited as controls. Histological evaluation was performed with heart tissue retrieved at catheterization in case-1 and case-2. The entire coding sequences of four cardiac sarcomere protein genes, including cardiac troponin T (TNNT2), cardiac troponin I(TNNI3), β-myosin heavy chain (MYH7), and α-actin (ACTC)were screened for mutations. Sequence variants were then tested in the family as well as in 100 healthy control DNAs.</p><p><b>RESULTS</b>All three index cases were diagnosed as primary RCMs without family history, and their clinical conditions deteriorated rapidly. Case-1 was in combination with ventricular septal defect. Case-2 was in combination with mid- and inferoseptal hypertrophy. In case-1, myocardial biopsies displayed extensive an isomorphism and disarray of cardiomyocytes; electron microscopy showed large stacks of severely dysmorphic megamitochondria and focal Z-disc streaming. In case-2, endomyocardial biopsy revealed moderate myocyte hypertrophy with mild interstitial fibrosis; transmission electron microscopy showed misalignment of Z-bands and unequal Z-Z band distances. Genetic analysis identified two heterozygous missense mutations in TNNI3, with R204H in case-1 and R192H in case-3 respectively. A de novo heterozygous deletion in TNNT2 (p. Asn100_Glu101del) was identified in case-2. Sequence analysis shows that all three mutations are located in a position highly conserved across many species. The three mutations were negative for their parents and controls.</p><p><b>CONCLUSION</b>The clinical conditions in all three index cases are deteriorated rapidly after diagnosed as primary RCM. Three heterozygous mutations including two in TNNI3 and one in TNNT2 gene are identified in the three RCMs respectively, which are considered as causative mutations. These findings provide new insights into the molecular etiology responsible for pediatric RCM.</p>
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Niño , Femenino , Humanos , Secuencia de Aminoácidos , Cardiomiopatía Restrictiva , Genética , Análisis Mutacional de ADN , Datos de Secuencia Molecular , Mutación , Troponina I , Genética , Troponina T , GenéticaRESUMEN
<p><b>OBJECTIVE</b>To explore the relationship between gene polymorphism of GABAA receptors and childhood autism by detecting rs140682, rs2081648 and rs140679 site of single nucleotide polymorphism (SNP) in GABAA receptors gene.</p><p><b>METHODS</b>A total of 94 children with autism and 124 normal children were enrolled in a hospital from November 2010 to May 2011. Childhood autism rating scale (CARS) and autism behavior checklist (ABC) were used to evaluate or investigate the case group. After collecting venous blood and extracting the genome DNA, the allele and genotype of SNP rs140682, rs2081648 and rs140679 site in GABAA receptors gene were detected by PCR-RFLP. The allele and genotype of case group and control group were analyzed by χ(2) test, while the score of scales was analyzed by Spearman rank correlation analysis.</p><p><b>RESULTS</b>The age of the case group was 5.12 ± 0.32, and it was 5.25 ± 0.27 in the control group (P < 0.05). In case group, the frequency of genotype CC, CT and TT of rs140682 site was 44, 41 and 9, while it was 48, 65, and 11 in control group (P > 0.05), respectively. The frequency of genotype AA, AG and GG of rs2081648 site was 8, 58 and 28 in case group, while it was 12, 49 and 63 in control group (P < 0.05), respectively. In case group, the frequency of genotype CC, CT and TT of rs140679 site was 15, 36 and 43, while it was 18, 59 and 47 in control group (P > 0.05), respectively. It was revealed by Spearman rank correlation analysis that of rs2081648 site, there was a positive correlation between genotype AG and sensation factor (S), social intercourse factor (R), and language factor (L) of autism behavior checklist (ABC) (r values were 0.149, 0.165 and 0.155, all P values < 0.05). A negative correlation between genotype GG and S, R, L and self-help factor (V) was proved (r values were -0.140, -0.173, -0.158 and -0.135, all P values < 0.05). There was a positive correlation between allele A and R and L factors (r values were 0.153 and 0.137, all P values < 0.05), while a negative correlation between allele G and R and L factors (r values were -0.153 and -0.137, all P values < 0.05). In case group, 42 children were diagnosed with mild-to-moderate autism, while 52 children were severe autism. There was no statistically significant correlation between allele or genotype of SNP rs140682 and rs140679 site and the degree of autism (P > 0.05). There was a positive correlation between allele A and genotype AG and the degree of autism (r values were 0.147 and 0.616, all P values < 0.05), while a negative correlation between allele G and genotype GG and the degree of autism (r values were -0.159 and -0.616, all P values < 0.05).</p><p><b>CONCLUSION</b>The SNP rs2081648 site which located in GABAA receptors gene may be related to autism. No evidence for significant association between rs140682 and rs140679 site and autism was found.</p>
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Niño , Preescolar , Femenino , Humanos , Masculino , Alelos , Trastorno Autístico , Genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo de Nucleótido Simple , Receptores de GABA-A , GenéticaRESUMEN
<p><b>BACKGROUND</b>Transradial coronary intervention (TRI) introduces injury to the radial artery (RA) which will affect repeat transradial coronary procedure and the quality as a bypass conduit. We sought to compare the early radial injury after TRI between first-TRI and repeat-TRI by ultrasound biomicroscopy (UBM).</p><p><b>METHODS</b>A total of 1116 patients who underwent the transradial coronary procedures were enrolled. The patients depending on whether for the first time to accept transradial coronary procedure were divided into first-TRI group and repeat-TRI group. The RA was examined by UBM before and one day after the procedure.</p><p><b>RESULTS</b>Compared with first-TRI group, the mean RA diameter of repeat-TRI one day after the procedure decreased significantly (P < 0.05). In first-TRI group, the mean RA diameter was (2.32 ± 0.53) and (1.93 ± 0.57) mm before procedure and one day after the procedure respectively (P < 0.05). In repeat-TRI group, the mean RA diameter was (2.37 ± 0.51) and (1.79 ± 0.54) mm before procedure and one day after the procedure, respectively (P < 0.01). Compared with first-TRI group, the mean RA diameter was reduced significantly in repeat-TRI group one day after the procedure (P < 0.05). The early radial injuries and intimal thickening were compared between first-TRI and repeat-TRI. The mean intima-media thickness of RA was (0.24 ± 0.13) mm and (0.59 ± 0.28) mm before procedure and one day after the procedure in first-TRI group. The mean intima-media thickness of RA was (0.29 ± 0.16) mm and (0.68 ± 0.32) mm before procedure and one day after the procedure in repeat-TRI group. Compared with first-TRI group, the mean intimal thickening was increased significantly in repeat-TRI group one day after the procedure (P < 0.05). Intimal dissection, stenosis and occlusion were all significantly greater in repeat-TRI RAs (P < 0.05). Linear regression analysis revealed that diameter, repeated TRI procedure and PCI procedure were the independent predictors of intimal thickening.</p><p><b>CONCLUSIONS</b>RA early injuries were greater in repeat-TRI patients than in first-TRI patients. We first use high-resolution UBM imaging to demonstrate the rate of radial injury and revealed that diameter, repeated TRI procedure and PCI procedure were the independent predictors of intimal thickening.</p>
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angioplastia Coronaria con Balón , Grosor Intima-Media Carotídeo , Microscopía Acústica , Métodos , Arteria Radial , Diagnóstico por Imagen , Heridas y LesionesRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of exogenous nitric oxide (NO) on the migration of HaCaT cell and its possible mechanism.</p><p><b>METHODS</b>Sodium nitroprusside (SNP) was used as the donor of NO. Different concentrations of SNP (0.1, 1.0, 10.0, 100.0, 1000.0 micromol/L) were added into nutrient culture medium of HaCaT cells. Cell migration rate was observed and calculated at post scratching hour (PSH) 0 (immediately after scratching), 6, 12, 24, 48. The most suitable concentration of SNP and culture duration were selected as stimulation condition. Cytoskeletons of HaCaT cells were observed under confocal laser scanning microscope. The expressions of integrin beta 1, RhoA, Rac1 and Cdc42 of cells in experiment group (cultured with 10.0 micromol/L SNP for 24 hours) and negative control group were determined at mRNA and protein levels with RT-PCR and Western blot respectively. Data were processed with one-way analysis of variance (ANOVA) and repeated measure ANOVA.</p><p><b>RESULTS</b>Migration rate of HaCaT cells in each group increased gradually as time after scratching went on. There were significant differences between PSH 6-48 and PSH 0 in cells cultured with 10.0 micromol/L SNP (F = 31.002, P values all below 0.05). Pili were rarely observed in negative control group with slender stress fibers in cells. In comparison, the amount of pili amount increased obviously in experiment group with thickened stress fibers. Compared with those of cells in control group (RhoA protein expression = 0.64 +/- 0.04), integrin beta 1 expression decreased obviously (F = 8.25, P = 0.015), RhoA (0.92 +/- 0.04), Cdc42 and Rac1 were up-regulated at both protein (with F value respectively 7.25, 14.10, 6.50, P values all below 0.05) and mRNA levels (with F value respectively 23.67, 10.39, 9.52, P values all below 0.05).</p><p><b>CONCLUSIONS</b>Exogenous NO in suitable concentration can promote the proliferation and migration of HaCaT cell, suggesting it exerts significant effect in wound repair. The changed cytoskeletons and the down-regulated integrin beta 1 expression may be involved in this process.</p>
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Humanos , Línea Celular , Movimiento Celular , Citoesqueleto , Metabolismo , Óxido Nítrico , Farmacología , ARN Mensajero , Genética , Proteína de Unión al GTP rhoA , Genética , MetabolismoRESUMEN
<p><b>BACKGROUND</b>Transradial approach, which is now widely used in coronary angiography and intervention, may be advantageous with respect to the femoral access due to the lower incidence of vascular complications. Transulnar approach has been proposed for elective procedures in patients not suitable for transradial approach. The objective of this study was to evaluate the safety and efficacy of the transulnar approach versus the transradial approach for coronary angiography and intervention.</p><p><b>METHODS</b>Two hundred and forty patients undergoing coronary angiography, followed or not by intervention, were randomized to transulnar (TUA) or transradial approach (TRA). Doppler ultrasound assessments of the forearm vessels were scheduled for all patients before procedures, 1 day and 30 days after procedures. The primary end point was access site vascular complications during hospitalization and 30 days follow-up. Major adverse cardiac events (MACE) as secondary end point was recorded till 30 days follow-up.</p><p><b>RESULTS</b>Successful puncture was achieved in 98.3% (118/120) of patients in the TUA group, and in 100% (120/120) of patients in the TRA group. Coronary angiographies were performed in 40 and 39 patients in TUA and TRA group. Intervention procedures were performed in 78 and 83 patients in TUA and TRA group, respectively. The incidence of artery stenosis 1 day and 30 days after procedures was 11.0% vs.12.3% and 5.1% vs. 6.6% in TUA and TRA group, respectively. Asymptomatic access site artery occlusion occurred in 5.1% vs.1.7% of patients 1 day and 30 days after transulnar angioplasty, and in 6.6% vs. 4.9% of patients 1 day and 30 days after transradial angioplasty. Minor bleeding was still observed at the moment of the ultrasound assessment in 5.9% and 5.7% of patients in TUA and TRA group, respectively (P = 0.949). No big forearm hematoma, and A-V fistula were observed in both groups. Freedom from MACE at 30 days follow-up was observed in all patients.</p><p><b>CONCLUSIONS</b>The transulnar approach is as safe and effective as the transradial approach for coronary angiography and intervention. It is an attractive opinion for experienced operators who are skilled in this technique, particularly in cases of anatomic variations of the radial artery, radial artery small-caliber or thin radial pulse.</p>
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angiografía Coronaria , Métodos , Arteria Radial , Diagnóstico por Imagen , Resultado del Tratamiento , Arteria Cubital , Diagnóstico por Imagen , UltrasonografíaRESUMEN
<p><b>BACKGROUND</b>Radial artery spasm (RAS) is the most common complication in transradial coronary angiography and intervention. In this study, we designed to investigate the incidence of RAS during transradial procedures in Chinese, find out the independent predictors through multiple regression, and analyze the clinical effect of RAS during follow-up.</p><p><b>METHODS</b>Patients arranged to receive transradial coronary angiography and intervention were consecutively enrolled. The incidence of RAS was recorded. Univariate analysis was performed to find out the influence factors of RAS, and logistic regression analysis was performed to find out the independent predictors of RAS. The patients were asked to return 1 month later for the assessment of the radial access.</p><p><b>RESULTS</b>The incidence of RAS was 7.8% (112/1427) in all the patients received transradial procedure. Univariate analysis indicates that young (P = 0.038), female (P = 0.026), small diameter of radial artery (P < 0.001), diabetes (P = 0.026), smoking (P = 0.019), moderate or severe pain during radial artery cannulation (P < 0.001), unsuccessful access at first attempt (P = 0.002), big sheath (P = 0.004), number of catheters (> 3) (P = 0.048), rapid baseline heart rate (P = 0.032) and long operation time (P = 0.021) were associated with RAS. Logistic regression showed that female (OR = 1.745, 95%CI: 1.148 - 3.846, P = 0.024), small radial artery diameter (OR = 4.028, 95%CI: 1.264 - 12.196, P = 0.008), diabetes (OR = 2.148, 95%CI: 1.579 - 7.458, P = 0.019) and unsuccessful access at first attempt (OR = 1.468, 95%CI: 1.212 - 2.591, P = 0.032) were independent predictors of RAS. Follow-up at (28 +/- 7) days after the procedure showed that, compared with non-spasm patients, the RAS patients had higher portion of pain (11.8% vs. 6.2%, P = 0.043). The occurrences of hematoma (7.3% vs. 5.6%, P = 0.518) and radial artery occlusion (3.6% vs. 2.6%, P = 0.534) were similar.</p><p><b>CONCLUSIONS</b>The incidence of RAS during transradial coronary procedure was 7.8%. Logistic regression analysis showed that female, small radial artery diameter, diabetes and unsuccessful access at first attempt were the independent predictors of RAS.</p>
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Edad , Angiografía Coronaria , Vasoespasmo Coronario , Epidemiología , Modelos Logísticos , Arteria Radial , Factores SexualesRESUMEN
The Bj1 gene encodes the Drosophila homolog of RCC1, the guanine-nucleotide exchange factor for RanGTPase. Here, we provide the first phenotypic characterization of a RCC1 homolog in a developmental model system. We identified Bj1 (dRCC1) in a genetic screen to identify mutations that alter central nervous system development. We find that zygotic dRCC1 mutant embryos exhibit specific defects in the development and differentiation of lateral CNS neurons although cell division and the cell cycle appear grossly normal. dRCC1 mutant nerve cords contain abnormally large cells with compartmentalized nuclei and exhibit increased transcription in the lateral CNS. As RCC1 is an important component of the nucleocytoplasmic transport machinery, we find that dRCC1 function is required for nuclear import of nuclear localization signal sequence (NLS)-carrying cargo molecules. Finally, we show that dRCC1 is required for cell proliferation and/or survival during germline, eye and wing development and that dRCC1 appears to facilitate apoptosis.