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BACKGROUND: Transanal endoscopic intersphincteric resection (ISR) surgery currently lacks sufficient clinical research and reporting. AIM: To investigate the clinical effectiveness of transanal endoscopic ISR, in order to promote the clinical application and development of this technique. METHODS: This study utilized a retrospective case series design. Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included. All patients underwent transanal endoscopic ISR as the surgical approach. We conducted this study to determine the perioperative recovery status, postoperative complications, and pathological specimen characteristics of this group of patients. RESULTS: This study included 45 eligible patients, with no perioperative mortalities. The overall incidence of early complications was 22.22%, with a rate of 4.44% for Clavien-Dindo grade ≥ III events. Two patients (4.4%) developed anastomotic leakage after surgery, including one case of grade A and one case of grade B. Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients. The mean distance between the tumor lower margin and distal resection margin was found to be 2.30 ± 0.62 cm. The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens. CONCLUSION: Transanal endoscopic ISR is safe, feasible, and provides a clear anatomical view. It is associated with a low incidence of postoperative complications and favorable pathological outcomes, making it worth further research and application.
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Atrial fibrillation (AF) is a common arrhythmia. Radiofrequency ablation (RFA) is the major AF treatment. Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is related to AF diagnosis. This study explored the clinical roles of PVT1 in AF. Totally, 168 AF patients and 100 healthy controls were selected. Plasma lncRNA PVT1 in AF patients before/after RFA was detected and the diagnostic efficacy and postoperative recurrence prediction value in AF were analyzed. Effects of plasma PVT1 expression on AF recurrence and its correlation with transforming growth factor beta 1 (TGF-ß1) in the recurrence and non-recurrence groups were analyzed by Pearson coefficient. The risk factors of AF recurrence were evaluated. Plasma PVT1 was highly expressed in AF patients and diminished after RFA. PVT1 level >1.255 assisted AF diagnosis. The plasma PVT1 level in the recurrence group was higher than that of the non-recurrence group. PVT1 level >1.525 assisted the prediction for postoperative recurrence. AF postoperative recurrence incidence in high PVT1 expression group was clearly higher than that in low PVT1 expression group, and plasma PVT1 expression in patients of the recurrence and non-recurrence groups was positively correlated with TGF-ß1 content. High PVT1 expression was an independent risk factor for postoperative recurrence. Briefly, high PVT1 level assisted AF diagnosis and recurrence evaluation after RFA and was an independent risk factor for AF postoperative recurrence.
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Fibrilación Atrial , Ablación por Catéter , ARN Largo no Codificante , Fibrilación Atrial/genética , Fibrilación Atrial/cirugía , Humanos , ARN Largo no Codificante/genética , Recurrencia , Factores de Riesgo , Factor de Crecimiento Transformador beta1/genética , Resultado del TratamientoRESUMEN
BACKGROUND: This study aims to discuss the application value of serum cystatin C (Cys C) in detecting early renal function injury in elderly patients with malignant tumors after chemotherapy. METHODS: The data at different chemotherapy time points (before chemotherapy, after two cycles of chemotherapy, and after four cycles of chemotherapy) were analyzed. RESULTS: Serum Cys C was significantly higher after chemotherapy than before chemotherapy in elderly patients with malignant tumors, and the endogenous creatinine clearance rate (CCr) significantly decreased. These were significantly correlated. However, there was no significant change in serum creatinine (SCr) and blood urea nitrogen (BUN). Cys C continued to increase with the prolonged time of chemotherapy. In addition, Cys C was sensitive for detecting renal impairment caused by platinum-based chemotherapy drugs. CONCLUSIONS: The diagnostic effect of Cys C on early renal function injury after chemotherapy in elderly patients with malignant tumors is better, when compared to traditional renal function test items, such as SCr, BUN and CCr.
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OBJECTIVE: We aimed to describe the heterogeneity in the clinical presentation of acute mountain sickness (AMS) and to identify its primary risk factors. METHODS: The participants (n = 163) received case report form questionnaires, and their heart rate (HR), oxygen saturation (SpO2), echocardiographic and transcranial Doppler variables, ability to perform mental and physical work, mood and psychological factors were assessed within 18 to 22 hours after arriving at 3700 m from sea level (500 m) by plane. First, we examined the differences in all variables between the AMS-positive and the AMS-negative groups. Second, an adjusted regression analysis was performed after correlation and principal component analyses. RESULTS: The AMS patients had a higher diastolic vertebral artery velocity (Vd; p = 0.018), a higher HR (p = 0.006) and a lower SpO2. The AMS subjects also experienced poorer sleep quality, as quantified using the Athens Insomnia Scale (AIS). Moreover, the AMS population exhibited more negative mood states, including anxiety, depression, hostility, fatigue and confusion. Five principal components focused on diverse aspects were also found to be significant. Additionally, more advanced age (p = 0.007), a higher HR (p = 0.034), a higher Vd (p = 0.014), a higher AIS score (p = 0.030), a decreased pursuit aiming capacity (p = 0.035) and decreased vigor (p = 0.015) were risk factors for AMS. CONCLUSIONS: Mood states play critical roles in the development of AMS. Furthermore, an elevated HR and Vd, advanced age, elevated AIS sores, insufficient vigor and decreased mental work capacity are independent risk factors for AMS.
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Mal de Altura/diagnóstico , Modelos Teóricos , Enfermedad Aguda , Adolescente , Adulto , Mal de Altura/fisiopatología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Oximetría , Análisis de Componente Principal , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
AIM: To investigate the prevalence of nature tyrosine-methionine-aspartic acid-aspartic acid motif mutations in chronic hepatitis B (CHB) patients and to evaluate the efficacy of lamivudine. METHODS: A total of 1268 CHB patients were recruited from the outpatient and inpatient departments of six centers. Tyrosine-methionine-aspartic acid-aspartic acid (YMDD) mutations were analyzed using the hepatitis B virus (HBV) drug resistance line probe assay. Forty voluntary patients were selected from those with positive or negative natural YMDD mutations to undergo treatment with lamivudine. RESULTS: YMDD mutations were detected in 288 (22.71%) of the 1268 CHB patients. Multivariate analysis revealed that the patients' HBV DNA level (P=0.0282) and hepatitis B e antigen status (P=0.0133) were also associated with natural YMDD mutations. The rates of normalization of alanine aminotransferase levels and HBV DNA nondetection at 6, 24, 36, and 48 wk were compared between the patients with natural YMDD mutations and those without, and the differences were not significant. However, there was a significant difference in the cumulative emergence rates of virological breakthrough at 48 wk in the patients with natural YMDD mutations and those without (32.5% vs 12.5%, P=0.032). CONCLUSION: Naturally occurring YMDD mutations are detectable in a large proportion of CHB patients; breakthrough hepatitis tended to occur in patients with natural YMDD mutations.
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Secuencias de Aminoácidos/genética , Antivirales/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Mutación , Adulto , Alanina Transaminasa/sangre , Biomarcadores/sangre , China , Análisis Mutacional de ADN , ADN Viral/sangre , Farmacorresistencia Viral/genética , Femenino , Genotipo , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Carga ViralRESUMEN
A method was developed for the determination of 59 glucocorticoids, sex hormones, nonsteroidal anti-inflammatory drugs, antibiotics, and other contaminants in cosmetics simultaneously by ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Acetonitrile was used to extract the sample, and the mixed sorbents were dispersed for purification. With the optimal conditions, the optimized pretreatment processes led to no significant interference on analysis from an extremely complicated sample matrix, and the linear ranges of 59 analytes were 0-480.0 µg/kg with the correlation coefficients above 0.99 and the limits of quantification (S/N≥10) were 5-40 µg/kg. Statistical evaluation revealed that the average recoveries were in the range of 61.2-131.2%, and relative standard deviations were in the range of 2.0-22.8%, meanwhile the interday precision ranged from 3.8 to 21.8%. This method is simple, fast, and credible, and it can be applied to simultaneous screening and determination of various classes of substances under investigations illegally presented in cosmetic products, covering a wide diversity of polarities, and pKa values.
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Antibacterianos/análisis , Antiinflamatorios no Esteroideos/análisis , Cosméticos/química , Glucocorticoides/análisis , Hormonas Esteroides Gonadales/análisis , Cromatografía Líquida de Alta Presión , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en TándemRESUMEN
This study aimed to develop a sensitive and reliable multi-residue method for the determination of trace amounts of endocrine disrupting chemicals including five phthalate esters (PAEs), five monoalky phthalate esters (MPEs), four alkylphenols (APs) and bisphenol A (BPA) in seafood. Ultrasonic liquid extraction was selected for extraction based on acetonitrile, instead of frequently-used n-hexane, due to its lower background of PAEs. Application of solid phase extraction (SPE) with primary secondary amine (PSA, 1g/6 mL) cartridge achieved the relatively low matrix effects for MPEs and BPA in seafood. To our knowledge, it is the first study reporting about simultaneous extraction and purification of PAEs, MPEs, APs and BPA in biota samples. To obtain the maximum sensitivity, both liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS) were applied for analysis. This method was validated and tested on fish, mollusk and prawn. Sufficient linearity was verified by Mandel's fitting test for the matrix-matched calibrations used in this study for MPEs, APs and BPA, between 0.5 ng/g and 200 ng/g or 400 ng/g. And correlation coefficients of all calibrations suppressed 0.99 for all analytes. Good recoveries were obtained, ranging from 60% to 127% for most compounds. The sensitivity was good with method detection limits (MDLs) of 0.015-2.2 ng/g wet weight (ww) for all compounds. Most MDLs are much lower than those in previous reports. The sensitive method was then applied on real fish, mollusk and prawn samples from the Yangtze River Delta sea area (China), and all the target compounds were detected with the maximum concentrations of PAEs, MPEs, APs and BPA up to 219.3 ng/g ww, 51.4 ng/g ww, 62.0 ng/g ww and 8.6 ng/g ww, respectively.
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Disruptores Endocrinos/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Ácidos Ftálicos/análisis , Alimentos Marinos/análisis , Extracción en Fase Sólida/métodos , Animales , China , Cromatografía Liquida , Peces , Modelos Lineales , Moluscos , Penaeidae , Reproducibilidad de los Resultados , Ríos , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem/métodosRESUMEN
A quantitative multi-class analytical method covering more than 226 veterinary drugs and other contaminants in muscle, belonging to different drug families, was developed. The method is based on liquid-liquid extraction, purification by low-temperature clean-up and dispersive solid-phase extraction (D-SPE), and analysis was conducted in two analytical runs by column-switching UPLC coupled with electrospray ionisation and tandem mass spectrometry (UPLC-ESI-MS/MS). For most of the target analytes, the optimised pre-treatment processes led to no significant interference from the sample matrix. The limit of quantification varied from 0.05 to 10 µg kg(-1). Statistical evaluation indicated that average recoveries spiked into pork were in the range from 62.4% to 138.8%, and the relative standard deviations were in the range from 2.8% to 26.6% (intra-day precision). The availability of this method will contribute to a better safety assurance of meat with a significant reduction of both effort and time.
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Cromatografía Líquida de Alta Presión/métodos , Residuos de Medicamentos/análisis , Contaminación de Alimentos/análisis , Carne/análisis , Espectrometría de Masas en Tándem/métodos , Drogas Veterinarias/análisis , Animales , Bovinos , China , Músculo Esquelético/química , Reproducibilidad de los Resultados , PorcinosRESUMEN
A rapid, simple and generic analytical method which was able to simultaneously determine 220 undesirable chemical residues in infant formula had been developed. The method comprised of extraction with acetonitrile, clean-up by low temperature and water precipitation, and analysis by ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS-MS) using multiple reaction monitoring (MRM) mode. Most fat materials in acetonitrile extract were eliminated by low temperature clean-up. The water precipitation, providing a necessary and supplementary cleanup, could avoid losses of hydrophobic analytes (avermectins, ionophores). Average recoveries for spiked infant formula were in the range from 57% to 147% with associated RSD values between 1% and 28%. For over 80% of the analytes, the recoveries were between 70% and 120% with RSD values in the range of 1-15%. The limits of quantification (LOQs) were from 0.01 to 5 µg/kg, which were usually sufficient to verify the compliance of products with legal tolerances. Application of this method in routine monitoring programs would imply a drastic reduction of both effort and time.
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Cromatografía Líquida de Alta Presión/métodos , Residuos de Medicamentos/análisis , Contaminación de Alimentos/análisis , Fórmulas Infantiles/química , Espectrometría de Masas en Tándem/métodos , Drogas Veterinarias/análisisRESUMEN
Exposure to thermal environment is one of the main concerns for manned space exploration. By focusing on the works performed on thermoregulation at microgravity or simulated microgravity, we endeavored to review the investigation on space thermal environmental physiology. First of all, the application of medical requirements for the crew module design from normal thermal comfort to accidental thermal emergencies in a space craft will be addressed. Then, alterations in the autonomic and behavioral temperature regulation caused by the effect of weightlessness both in space flight and its simulation on the ground are also discussed. Furthermore, countermeasures like exercise training, simulated natural ventilation, encouraged drink, etc., in the protection of thermoregulation during space flight is presented. Finally, the challenge of space thermal environment physiology faced in the future is figured out.
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Medicina Aeroespacial , Regulación de la Temperatura Corporal , Vuelo Espacial , Ambiente , Ejercicio Físico , Humanos , Ingravidez , Simulación de IngravidezRESUMEN
A generic, rapid and simple analytical method able to identify 255 veterinary drug residues and other contaminants in raw milk had been developed. The method was based on two-step simple precipitation and ultra performance liquid chromatography coupled with electrospray ionization and tandem mass spectrometry (UPLC-ESI-MS/MS) operating both in positive and negative multiple reaction mode (MRM). For most of the target analytes, the optimized pretreatment processes led to no significant interference on analysis from complicated sample matrix. For quantification, matrix-fortified calibration curves were performed to compensate for the matrix effect and loss in sample preparation. Competent linearity was found for over 90% of target compounds with linear regression coefficients (R) higher than 0.99. Detection limits ranged from 0.05 to 10µg/kg. Average recoveries spiked into raw milk were in the range from 63% to 141% with associated RSD values from 1% to 29% under the selected conditions. The method had been validated for its extraction sensitivity, linearity, recoveries and precision. The results clearly demonstrated the feasibility of the approach proposed. Application of this method, which improved efficiency and coverage of residues, would imply a drastic reduction of both effort and time in routine monitoring programs.
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Cromatografía Líquida de Alta Presión/métodos , Residuos de Medicamentos/análisis , Leche/química , Residuos de Plaguicidas/análisis , Espectrometría de Masas en Tándem/métodos , Drogas Veterinarias/análisis , Animales , Modelos Lineales , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.
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Antivirales/uso terapéutico , Ácido Aspártico/genética , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Metionina/genética , Mutación/genética , Tirosina/genética , Adulto , Secuencias de Aminoácidos/efectos de los fármacos , Secuencias de Aminoácidos/genética , ADN Viral/análisis , Femenino , Genotipo , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/virología , Humanos , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.
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Adulto , Femenino , Humanos , Masculino , Antivirales/uso terapéutico , Ácido Aspártico/genética , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Metionina/genética , Mutación/genética , Tirosina/genética , Secuencias de Aminoácidos/efectos de los fármacos , Secuencias de Aminoácidos/genética , ADN Viral/análisis , Genotipo , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/virología , Reacción en Cadena de la PolimerasaRESUMEN
A novel analytical method employing MCX (mixed-mode cationic exchange) based solid phase extraction (SPE) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed to detect 31 endocrine-disrupting compounds (EDCs) in surface water samples simultaneously. The target EDCs belong to five classes, including seven estrogens, eight androgens, six progesterones, five adrenocortical hormones and five industrial compounds. In order to simultaneously concentrate the target EDCs and eliminate matrix interferences in the water samples, MCX SPE cartridges were employed for SPE, and then followed by a simple and highly efficient three-step sequential elution procedure. Two electrospray ionization (ESI) detection modes, positive (ESI+) and (ESI-), were optimized for HPLC-MS/MS analysis to obtain the highest sensitivity for all the EDCs. The limits of detection (LODs) were 0.02-1.9 ng L(-1), which are lower than or comparable to these reported in references. Wide linear ranges (LOD-100 ng L(-1) for ESI+ mode, and LOD-200 ng L(-1) for ESI- mode) were obtained with determination coefficients (R(2)) higher than 0.99 for all the compounds. With five internal standards, good recoveries (84.4-103.0%) of all the target compounds were obtained in selected surface water samples. The developed method was successfully applied to investigate the EDCs occurrence in the surface water of Shanghai by analyzing surface water samples from 11 sites. The results showed that nearly all the target compounds (30 in 31) were present in the surface water samples of Shanghai, of which three industrial compounds (4-t-OP, BPA, and BPF) showed the highest concentrations (median concentrations were 11.88-23.50 ng L(-1)), suggesting that industrial compounds were the dominating EDCs in the surface water of Shanghai, and much more attention should be paid on these compounds. Our present research demonstrated that SPE with MCX cartridges combined with HPLC-MS/MS was convenient, efficient and reliable for multiclass analysis of EDCs in surface water.
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Cromatografía Líquida de Alta Presión/métodos , Disruptores Endocrinos/química , Monitoreo del Ambiente/métodos , Extracción en Fase Sólida/métodos , Espectrometría de Masas en Tándem/métodos , Contaminantes Químicos del Agua/química , Adsorción , Resinas de Intercambio de Catión/química , China , Disruptores Endocrinos/aislamiento & purificación , Extracción en Fase Sólida/instrumentación , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
AIM: Myocardial contrast echocardiography (MCE) is effective in predicting myocardial viability and functional recovery on a segmental level in patients with acute myocardial infarction (AMI). In this study, we investigated whether insufficient myocardial reperfusion plays an important role in left ventricular (LV) remodeling and functional recovery in patients with thrombolysis in myocardial infarction (TIMI) flow grade 3 and corrected TIMI frame count (CTFC) < 40 after recanalization of the infarct-related artery. METHOD: Patients underwent intracoronary injection of microbubbles for echocardiographic assessment of myocardial microvascular perfusion, wall motion score, LV volume and ejection function (EF) at baseline, 30 minutes, one month and six months after recanalization. The patients with MCESI < 1 were considered to have insufficient myocardial reperfusion (group A, n=11), while the patients with MCESI≥1 were considered to have sufficient myocardial reperfusion (group B, n=47) after AMI recanalization. RESULTS: The wall motion score index (WMSI) and the left ventricular ejection fraction (LVEF) showed significant improvement at 1 month and 6 months in group B, but only at six months in group A. Left ventricular end-systolic and end-diastolic volumes (LVESV and LVEDV) were also significantly decreased at one and six months in group B. WMSI, LVESV, LVEDV and LVEF were significantly improved in group B in comparison with group A at one month and six months (P < 0.01). By six months, significant correlations were seen in all patients between MCESI and changes in LVESV, LVEDV and LVEF at 6 months. Similar correlations were observed between the myocardial regional blood flow (Q) and changes in LVESV , LVEDV and LVEF. CONCLUSION: Insufficient myocardial reperfusion was a strong independent predictor of LV remodeling and functional recovery in AMI patients with TIMI flow grade 3 and CTFC < 40 after recanalization. MCE has important additional value for prognosis and risk assessment in patients with acute myocardial infarction following recanalization.
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Infarto del Miocardio/fisiopatología , Remodelación Ventricular/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Angioplastia Coronaria con Balón , Angiografía Coronaria , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/terapia , Reperfusión Miocárdica , Volumen Sistólico/fisiologíaRESUMEN
Risk factors for coronary heart disease can reduce the number of endothelial progenitor cells (EPCs) and impair EPC function, thus hindering their utility in the treatment of cardiovascular diseases. In the present study, we began exploring the feasibility of genetic modification of EPCs with hepatocyte growth factor (HGF) to counter the effects of these risk factors and enhance the biological functions of EPCs. The effects of HGF transfection on proliferation, migration and angiogenesis of EPCs were investigated. Additionally, the role of ERK1/2 in this process was evaluated through the observation of ERK1/2 and ERK1/2 phosphorylation as well as by pharmacological analysis. Finally, we evaluated the effect of HGF-transfected EPCs (HGF-EPCs) on neointima formation after balloon-induced arterial injury in hypercholesterolemic rats. Our data showed that EPCs transfected with the HGF gene released high levels of soluble HGF protein, which were maintained for at least nine days. Transfection with HGF also enhanced the proliferative, migratory and angiogenic capabilities of EPCs, and promoted the activation of ERK1/2 without affecting its expression. ERK1/2 blockade by the chemical inhibitor PD98059 partially inhibited these effects. In hypercholesterolemic rats, HGF-EPCs homed to the site of vascular injury at a significantly higher rate than did EPCs without the exogenous HGF gene. Furthermore, systemically applied HGF-EPCs were more effective in decreasing neointima formation and increasing re-endothelialization. These data suggest that gene delivery combined with EPC transplant may be a practical and promising therapy for the prevention of neointimal formation after vascular injury.
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Traumatismos de las Arterias Carótidas/terapia , Células Endoteliales/fisiología , Factor de Crecimiento de Hepatocito/genética , Trasplante de Células Madre , Células Madre/fisiología , Análisis de Varianza , Angioplastia Coronaria con Balón , Animales , Células de la Médula Ósea , Enfermedades Cardiovasculares/terapia , Movimiento Celular , Proliferación Celular , Células Cultivadas , Colesterol en la Dieta/administración & dosificación , Células Endoteliales/enzimología , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Expresión Génica , Terapia Genética , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Hipercolesterolemia/etiología , Hipercolesterolemia/patología , Hipercolesterolemia/fisiopatología , Inmunohistoquímica , Neovascularización Fisiológica , Fosforilación , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión , Células Madre/enzimología , Transfección , Túnica Íntima/patología , Túnica Íntima/fisiopatologíaRESUMEN
BACKGROUND/AIMS: Human coronary artery-derived endothelial cells (ECs) seem to be the most appropriate cells for the pathogenesis study of coronary artery disease. But limited availability of endothelial tissue is a major constraint. In this study, we developed a method to isolate human coronary artery ECs in vivo from patients. METHODS: Coronary guidewires were used to obtain EC samples from coronary arteries in 76 patients. Cells were eluted from wire tips and purified by immunomagnetic beads. Von Willebrand factor and CD31 were used as immunocytochemical markers to identify cells as endothelium. Cell viability was evaluated in terms of cell membrane integrity, energy-dependent uptake of DiI-labeled acetylated low-density lipoprotein, and apoptosis. Nitric oxide synthase (eNOS) expression and nitric oxide (NO) production of cells were detected to evaluate cell function. RESULTS: About 96 coronary artery ECs were obtained per guidewire. Cells manifested endothelial morphology and immunoreactivity for von Willebrand factor and CD31 with good viability. But eNOS expression and NO production of cells were decreased. CONCLUSIONS: Viable coronary endothelium could be obtained during routine percutaneous coronary interventions combined with immunomagnetic beads. These cells may be used for advanced cellular functional analyses such as immunocytochemistry and molecular biology. Such information could aid in understanding mechanisms of coronary artery diseases.
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Angioplastia Coronaria con Balón , Vasos Coronarios/citología , Células Endoteliales/citología , Separación Inmunomagnética/métodos , Anciano , Apoptosis , Biomarcadores/metabolismo , Antígeno CD146/metabolismo , Supervivencia Celular , Células Cultivadas , Células Endoteliales/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismoRESUMEN
OBJECTIVE: To develop a method to obtain and identify human coronary artery endothelial cells obtained during percutaneous coronary interventions (PCI). METHODS: Coronary guide wires were used to obtain endothelial cells from coronary arteries in 28 patients undergoing PCI. The cells were eluted from the wire tips and then purified by magnetic beads coated with anti-CD146 antibody. von Willebrand factor (vWF) was used as an immunocytochemical marker for endothelial cells. The cellular viability was evaluated by observing cell membrane integrity and energy-dependent uptake of DiI-labeled acetylated low-density lipoprotein. RESULTS: An average of 96 coronary artery endothelial cells with good viability per patient were obtained by one guide wire. vWF identification showed their endothelial morphology and immunoreactivity. CONCLUSION: The viable coronary endothelial cells could be obtained during routine percutaneous coronary interventions combined with magnetic beads isolation technique. These cells may be used for further cellular functional analyses (such as immunocytochemistry and molecular biology) and expand our understanding on mechanisms of coronary artery diseases.
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Vasos Coronarios/patología , Endotelio Vascular/citología , Biopsia/métodos , Vasos Coronarios/citología , Endotelio Vascular/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The aim of this study was to evaluate the efficacy, toxicity and safety of doxorubicin combined with domestically produced docetaxel versus with taxotere, and to investigate whether these two regimens result in similar outcomes in the treatment for non-small-cell lung cancer (NSCLC) patients who failed previous platinum-based chemotherapy. METHODS: Eighty-eight NSCLC patients were enrolled into this clinical phase II trial. The patients randomly received either domestic docetaxel (study arm) or taxotere (control arm) at a dose of 70 mg/m2 on D2, while doxorubicin at a dose of 40 mg/m2 on D1 was administered in both groups. It was repeated every 3 weeks, totally for three cycles. No granulocyte colony-stimulating factor was used to prevent granulocytopenia. The response rate and toxicity were evaluated using World Health Organization toxicity scale and Karnofsky performance status scale. RESULTS: Of the 88 patients, 81 were evaluable in terms of efficacy. There was no complete responder in this series. The response rate (RR) was 17.1% in the study arm versus 7.5% in the control arm, and the clinical benefit rate (CBR) was 80.5% in the study group versus 72.5% in the control group. The most frequent grade 3 or 4 toxicities were neutropenia, leucopenia and gastrointestinal symptoms. Other toxicities such as alopecia and vomiting were mild and generally well tolerated. No fluid retention was noticed. CONCLUSION: The administration of doxorubicin 40 mg/m2 on D1 combined with domestic docetaxel 70 mg/m2 on D2 is proved to be as effective and tolerable as with taxotere. The domestic drug docetaxel may be considered as an alternative for patients with non-small-cell lung cancer who failed previous platinum-based chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Docetaxel , Doxorrubicina/administración & dosificación , Femenino , Humanos , Leucopenia/inducido químicamente , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Inducción de Remisión , Terapia Recuperativa , Taxoides/administración & dosificación , Insuficiencia del Tratamiento , Vómitos/inducido químicamenteRESUMEN
BACKGROUND: Collateral circulation is considered key for left ventricular (LV) function recovery in patients with chronic total occlusion (CTO). However, there are conflicting reports about the influence of collaterals on LV recovery after revascularization. METHODS: Echocardiographic assessment of regional myocardial perfusion, wall motion score (WMS), and left ventricular ejection fraction (LVEF) were performed in patients with angiographically visible collateral circulation of grades 2 and 3. RESULTS: The WMS and LVEF of group B (with presence of myocardial regional perfusion) were significantly improved at one month and six months compared to those of group A (with absence of myocardial regional perfusion). The correlation between myocardial regional blood flow and changes in WMS and LVEF was significant at 6 months in patients with angiographically visible collateral circulation of grade 2 and 3. Similar correlations were observed on myocardial contrast echocardiography (MCE) score index. CONCLUSION: Myocardial function recovery in patients with CTO is determined by myocardial regional perfusion. MCE has important value for prognosis and risk stratification in patients with CTO undergoing cardiac catheterization.