Immunomodulatory effect of pachymaran on cyclosporine A (CsA)-induced lung injury in mice / 数字中医药（英文）

@#Objective To investigate the immunomodulatory effect of pachymaran on cyclosporine A (CsA)-induced lung injury in mice. Methods (i) Fifty male BALB/c mice were randomly divided into five groups (10 mice in each group): normal control (NC) group, 30, 45, and 60 mg/kg CsA groups, and lipopolysaccharide (LPS) group. Except for the NC group, other groups underwent CsA modeling. The NC group was treated with phosphate-buffered saline (PBS), the LPS group with 10 mg/kg LPS eight hours before mice euthanized, and the 30, 45, and 60 mg/kg CsA groups with corresponding doses of CsA for seven consecutive days. After treatment, the body and organ mass of each group were weighed, and the lung, thymus, and spleen indexes were calculated. Hematoxylin-Eosin (HE) staining was performed to observe histopathological changes in the lungs of the mice. The protein expression levels of interleukin (IL)-2 and IL-1β in the blood were detected using enzyme-linked immunosorbent assay (ELISA), and those of surfactant protein D (SP-D), IL-2, and IL-6 in lung tissues were detected by immunohistochemistry (IHC). The mRNA expression levels of SP-D, IL-1β, IL-6, and myeloperoxidase (MPO) in the lung tissues were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). (ii) Another 60 BALB/c mice were divided into six groups (10 mice in each group) : NC group, model control (MC) group, 50, 100, and 200 mg/kg pachymaran groups, and polyinosinic-polycytidylic acid [poly(I:C)] group. Except for the NC group, other groups underwent 45 mg/kg CsA modeling. The NC and MC groups were treated with distilled water, the pachymaran groups with corresponding doses pachymaran, and the poly(I:C) group with 0.1 mg/kg poly(I:C) for seven days.The mice were euthanized to obtain tissues and serum for detection. Detection methods were identical to those described in (i) above. Results (i) CsA (30 mg/kg) increased the lung index of mice (P < 0.001), and decreased the spleen index (P < 0.01), thymus index (P < 0.05), and the serum level of IL-2 (P < 0.05). CsA (45 mg/kg) decreased the spleen, thymus indexes, and the serum level of IL-2 (P < 0.01) in mice, and increased the serum level of IL-1β (P < 0.05) and the protein level of lung SP-D (P <0.001). CsA (60 mg/kg) increased the lung index of mice (P < 0.01), the serum level of IL-1β (P < 0.05), the protein level of lung SP-D (P < 0.01), and the mRNA levels of lung MPO and SP-D ( P < 0.05), and decreased the thymus index of mice (P < 0.01). HE staining showed that 30, 45, and 60 mg/kg CsA, and LPS caused pathological changes in the lung tissue of mice. (ii) After pachymaran intervention in MC mice, the spleen and thymus indexes (P < 0.05) were increased in the 100 and 200 mg/kg pachymaran groups, and the lung index was decreased (P < 0.05). Moreover, 50 mg/kg pachymaran increased the thymus index (P < 0.05) and decreased the lung index (P < 0.01) in MC group. Pachymaran (50, 100, and 200 mg/kg) improved lung tissue injury, reduced the serum level of IL-1β (P < 0.001), and the mRNA levels of MPO and SP-D in lung tissues (P < 0.05) of mice. Pachymaran (100 mg/kg) increased the protein level of lung IL-2 (P < 0.01), decreased the protein level of lung SP-D (P < 0.01), and the mRNA level of IL-1β (P < 0.001) in the lung tissues of mice. Pachymaran (200 mg/kg) increased the serum level of IL-2 (P < 0.01) and lung IL-6 of mice (P < 0.05). Pachymaran (50 and 200 mg/kg) increased the mRNA level of IL-6 in the lung tissues of mice (P < 0.05). Conclusion While the immune function of mice was suppressed by CsA, the lung tissue was also damaged. Pachymaran can improve the immunosuppression induced by CsA and improve the lung tissue injury in immunosuppressed mice.

Study on cardiovascular monitoring and diagnosis of athletes / Estudo de monitoramento cardiovascular e diagnóstico de atletas / Estudio de monitoreo cardiovascular y diagnóstico de atletas

ABSTRACT Introduction: The study and collection of athletes' heart function index parameters and the correct and reasonable evaluation of body functions can effectively adjust training plans and avoid athletes' bodily exhaustion. Objective: To study the diagnosis of myocardial injury by cardiovascular monitoring in athletes from two aspects: extraction of characteristic parameters of heart function and research of signal processing. Methods: The heart function intelligent evaluation algorithm was studied by using multi-source information fusion, and embedded technology; miniature sensors were used as well. Results: The incidence of severe ventricular arrhythmia was lower in both groups. The incidence of sinus arrhythmia and intermittent second degree I atrioventricular block in the high-intensity group was significantly higher than that in the control group. The number of atrial and ventricular premature beats was lower in the control group, but increased significantly in the high-intensity group. Conclusions: This study applied the theory of multi-source information fusion to carry out representative research on the intelligent monitoring and evaluation of the heart function of elite athletes, centering on the application requirements of the heart function monitoring of elite athletes. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: O estudo e a coleta de parâmetros indiciais da função cardíaca em atletas e a avaliação correta e razoável das funções corporais podem, efetivamente, levar ao ajuste de planos de treinamento e evitar a sobrecarga física de atletas. Objetivo: Estudar o diagnóstico da lesão miocárdica pelo monitoramento cardiovascular em atletas a partir de dois aspectos: a extração de parâmetros característicos da função cardíaca e a pesquisa do processamento de sinais. Métodos: O algoritmo de avaliação inteligente da função cardíaca foi estudado usando a fusão de informações de múltiplas fontes, além da tecnologia embarcada. Sensores em miniatura também foram usados. Resultados: A incidência de arritmia ventricular severa era menor nos dois grupos. A incidência de arritmia sinusal e o bloqueio atrioventricular de segundo grau do tipo I intermitente no grupo de alta intensidade foi significativamente mais alta do que no grupo de controle. O número de batidas prematuras atriais e ventriculares era menor no grupo de controle, mas aumentava consideravelmente no grupo de alta intensidade. Conclusões: Este estudo aplicou a teoria da fusão de informações de múltiplas fontes para conduzir uma pesquisa importante sobre o monitoramento e avaliação inteligentes da função cardíaca de atletas de elite, enfocando as exigências de aplicação do monitoramento da função cardíaca de atletas de elite. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: El estudio y la recogida de parámetros indíciales de la función cardíaca en atletas y la evaluación correcta y razonable de las funciones corporales pueden efectivamente llevar al ajuste de planes de entrenamiento y evitar la sobrecarga física de atletas. Objetivo: Estudiar el diagnóstico de la lesión miocárdica a través del monitoreo cardiovascular en atletas a partir de dos aspectos: la extracción de parámetros característicos de la función cardíaca y la investigación del procesamiento de señales. Métodos: El algoritmo de evaluación inteligente de la función cerebral se estudió utilizando la fusión de informaciones de múltiples fuentes, además de la tecnología embebida. Sensores en miniatura también se utilizaron. Resultados: La incidencia de taquicardia ventricular severa era menor en los dos grupos. La incidencia de arritmia sinusal y bloqueo auriculoventricular de segundo grado del tipo I intermitente en el grupo de alta intensidad fue significativamente más alta que en el grupo de control. El número de contracciones prematuras auriculares y ventriculares era menor en el grupo de control, pero aumentaba considerablemente en el grupo de alta intensidad. Conclusiones: Este estudio aplicó la teoría de la fusión de informaciones de múltiples fuentes para conducir una investigación importante sobre el monitoreo y evaluación inteligentes de la función cardiaca de atletas de élite, centrando las exigencias de aplicación del monitoreo de la función cardíaca de atletas de élite. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Medical promotion effect of physical exercise on parkinson's disease / O efeito médico do exercício físico na doença de parkinson / El efecto médico del ejercicio físico en la enfermedad de parkinson

ABSTRACT Introduction: Parkinson's disease is a common neurodegenerative disease in middle-aged and older people. Some studies have shown that sports can reduce its impact on physical functions. Objective: Based on the abovementioned research background, this paper explores the effect of moderate physical exercise on muscle tone and body posture of patients with Parkinson's disease. Methods: The article selected 72 Parkinson patients admitted to our hospital's Parkinson's Medical Center from 2019 to 2020. These were divided into a basic drug treatment group and a sports intervention group. The Ashworth score, walking speed, walking cycle, and walking distance of the two groups were recorded. At the same time, we performed statistical data analysis on the two sets of data obtained. Results: Compared with the basic treatment group, the modified Ashworth score of the sports intervention group decreased after treatment (P<0.01). The walking speed of the sports intervention group increased, the walking cycle was shortened, and the distance of repeated steps increased (P<0.01). Conclusion: Appropriate physical exercise can reduce muscle tone in patients with Parkinson's disease. It helps them increase their pace and improve small gait symptoms. Sports can help Parkinson patients adjust their body posture and promote their clinical treatment. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: A doença de Parkinson é uma doença neurodegenerativa comum em pessoas de meia idade ou idade avançada. Alguns estudos mostram que o esporte pode reduzir seu impacto nas funções físicas das pessoas. Objetivo: Com base em pesquisas sobre o contexto mencionado acima, este estudo explora o efeito de exercício físico moderado no tônus muscular e postura corporal de pacientes com a doença de Parkinson. Métodos: O artigo selecionou 72 pacientes com Parkinson, internados no Centro Médico de Parkinson em nosso hospital, de 2019 a 2020. Estes foram divididos em dois grupos: um de tratamento medicamentoso básico e outro de intervenção esportiva. O escore Ashworth, velocidade de caminhada, ciclo de caminhada e distância de caminhada dos dois grupos foram registrados. Ao mesmo tempo, fizemos uma análise estatística de dados no conjunto de dados obtidos nos dois grupos. Resultados: Ao compararmos o grupo de intervenção esportiva com o de tratamento básico, o escore Ashworth modificado do primeiro grupo diminuiu após o tratamento (P<0.01). A velocidade de caminhada do grupo de intervenção esportiva aumentou, o ciclo de caminhada foi reduzido e a distância de passos repetidos aumentou (P<0.01). Conclusão: Exercícios físicos adequados podem diminuir o tônus muscular em pacientes com a doença de Parkinson. Auxilia no aumento de passos e melhora os sintomas dos passos curtos. Os esportes podem ajudar os pacientes ajustar sua postura e promover seu tratamento clínico. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: La enfermedad de Parkinson es una enfermedad neurodegenerativa común en personas de mediana edad o edad avanzada. Algunos estudios muestran que el deporte puede reducir su impacto en las funciones físicas de las personas. Objetivo: Con base en investigaciones sobre el contexto mencionado antes, este estudio explora el efecto de ejercicio físico moderado en el tono muscular y postura corporal de pacientes con la enfermedad de Parkinson. Métodos: El artículo seleccionó 72 pacientes con Parkinson, internados en el Centro Médico de Parkinson en nuestro hospital, de 2019 a 2020. Se los dividió en dos grupos: uno de tratamiento medicamentoso básico y otro de intervención deportiva. Se registró la escala Ashworth, velocidad de caminata, ciclo básico de caminata y distancia de caminata de los dos grupos. Al mismo tiempo, hicimos un análisis estadístico de datos en el conjunto de datos obtenidos en los dos grupos. Resultados: Al comparar el grupo de intervención deportiva con el de tratamiento básico, la escala Ashworth modificada del primer grupo disminuyó tras el tratamiento (P<0.01). La velocidad de caminata del grupo de intervención deportiva aumentó, el ciclo de caminata se redujo y la distancia de pasos repetidos disminuyó (P<0.01). Conclusión: Ejercicios físicos adecuados pueden disminuir el tono muscular en pacientes con la enfermedad de Parkinson. Auxilia en el aumento de pasos y mejora los síntomas de los pasos cortos. Los deportes pueden ayudar a los pacientes a ajustar su postura y promover su tratamiento clínico. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Risk factors analysis for development of acute kidney injury in elderly patients with respiratory distress syndrome / 中华老年医学杂志

Objective:To investigate the incidence, risk factors and prognosis of acute renal injury(AKI)in elderly patients with respiratory distress syndrome(ARDS).Methods:The elderly patients with ARDS treated in the Department of Respiratory Medicine, Emergency Department and Geriatrics of the Second People's Hospital of Lianyungang from July 2016 to July 2019 were divided into AKI group and non-AKl group according to KDIGO diagnostic criteria.The clinical data and the differences were compared and analyzed between the two groups.Binary Logistic regression was used to analyze Risk factors for AKI.Kaplan-Meier cure was used to analyze the influence of different stages of AKI on the prognosis of ARDS patients.The Cox proportional hazards model was used to analysis risk factors for AKI and ARDS on elderly patients＇prognosis.Results:A total of 432 elderly patients with ARDS were enrolled in the study, in which the mean age was 74.7 ± 8.8 years, and AKI occurred in 129 cases(29.9%). Compared with non-AKI group, AKI group showed older age, and higher proportion of the incidences of hypertension, diabetes, atrial fibrillation, consciousness disturbance, mechanical ventilation and a low mean arterial pressure(all P<0.05). The incidence of AKI was increased significantly in patients with moderate to severe ARDS( P< 0.001). The levels of basal creatinine, AST and NT-proBNP were significantly higher in AKI Group than in non-AKI Group( P= 0.001, P< 0.001, P< 0.001). AKI Group patients had the more elevated inflammatory marker level of neutrophil / lymphocyte ratio(NLR)( P= 0.003)and D-dimer( P< 0.001), and the level of high-sensitivity c-reactive protein(hsCRP)( P=0.040). AKI group showed the increased incidence of urine protein( P< 0.001), low ejection fraction( P= 0.040), and positive rate of pleural effusion( P= 0.003). Logistic Regression analysis showed the following independent risk factors for the development of ARDS-associated AKI, included hypertension( OR: 1.789, 95%, CI: 1.105-2.894, P=0.018), diabetes( OR: 1.976, 95% CI: 1.076-3.628, P=0.028), consciousness disturbance( OR: 2.531, 95% CI: 1.203-5.251, P=0.014), mechanical ventilation( OR: 3.421, 95% CI: 1.521-7.694, P=0.003), AST>40 U/L( OR: 2.495, 95% CI: 1.431-4.348, P=0.001), increased basal creatinine levels( OR: 1.014, 95% CI: 1.002-1.027, P=0.024), and NLR( OR: 1.015, 95% CI: 1.001-1.029, P=0.042). Kaplan-Meier survival curve showed that there was a significant difference in the prognosis between patients with different AKI stages( χ2=19.790, P<0.001), and there was no significant difference in the prognosis between stage 1-AKI and non-AKI( χ2=2.188, P=0.139). The risk of poor prognosis was higher in AKI(stage 2-3)group( χ2=18.268, P<0.001; χ2=6.347, P=0.012)than in patients without AKI or stage 1 AKI.Multivariate Cox Proportional Hazard Model Analysis elucidated that AKI( HR: 1.858, 95% CI: 1.207-2.861, P= 0.005)and moderate-severe ARDS( HR: 1.815, 95% CI: 1.167-2.822, P=0.008)were independent risk factors for poor prognosis of ARDS in the elderly. Conclusions:Hypertension, diabetes, disturbance of consciousness, mechanical ventilation, AST>40 U/L, elevated levels of basal creatinine and NLR are independent risk factors for ARDS-associated AKI in elderly patients with ARDS.Patients with moderate-severe ARDS and AKI(2-3 phases)have the increased risk of poor prognosis.

Vein valve function following pharmacomechanical thrombectomy versus simple catheter-directed thrombolysis for lower extremity deep vein thrombosis: A case control study / 中国胸心血管外科临床杂志

@#Objective To compare vein valve function following pharmacomechanical thrombolysis (PMT) with simple catheter-directed thrombolysis (CDT) for deep vein thrombosis. Methods We retrospectively analyzed the clinical data of sixty patients who suffered acute lower extremity deep vein thrombsis in our hospital between October 2016 and March 2017. All patients underwent contralateral preprocedural duplex and bilateral postprocedure duplex to access patency and valve function. The patients were divided into three groups including a group A with catheter-directed thrombolysis (CDT) alone (36 patients with 20 males and 16 females at average age of 56 years), a group B with PMT alone (15 patients with 8 males and 7 females at average age of 55 years), and a group C with PMT combined CDT (9 patients with 4 males and 5 females at average age of 56 years). The valve function was compared among the Group A, Group B and Group C. Results There were 40.0% (24/60) patients with bilateral femoral vein valve reflux, 40.0% (24/60) patients with unilateral femoral vein valve reflux (all in the treated limbs), 20% (12/60) patients had no reflux in both limbs. Of the limbs treated with CDT alone, PMT alone and PMT combined CDT, the rate of valve reflux was 38.9% (14/36), 33.3% (5/15), and 55.6% (5/9) respectively (P=0.077). Conclusion In the patients suffering acute DVT, PMT or PMT combined CDT does not hamper valve function compared with CDT alone.

The diagnostic value of fiberoptic ductoscopy of the breast as an examination tool for pathological nipple discharge / 中华内分泌外科杂志

Objective To investigate the diagnostic value of fiberoptic ductoscopy (FDS) in pathological milky white nipple discharge.Methods The data of 1688 patients with pathological milky white nipple discharge who underwent FDS examination in Chengdu Third People's Hospital from Oct.2011 to Oct.2016 were analyzed retrospectively.Results Among the 1688 cases,the proportion of patients with milky white nipple discharge was 30％,higher than that of the bloody discharge (15％) and yellow liquid (24.5％).The detection rate of lesions in patients with milk nipple discharge was 9.3％,among whom 6.1％ was breast cancer.Conclusions FDS should be routinely performed in patients with pathological milky white nipple discharge,as an examination tool to exclude the intra ductal lesion.The disease should be paid more attention by physicians.

Effect of shRNA-mediated silencing of BDNF gene on VEGF expression of RPMI8226 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of vascular endothelial growth factor (VEGF) of human multiple myeloma (MM) cell line RPMI8226 regulated by brain-derived neurotrophic factor (BDNF), and preliminarily approach the close relationship between BDNF and angiogenesis of MM.</p><p><b>METHODS</b>The recombinant eukaryotic BDNF siRNA expression vector was designed and constructed. The empty vector pGenesil-1, and the recombinant plasmid, pGenesil-shRNA-BDNF were transfected into RPMI8226 cells using Lipofectamine™ 2000 (groups P0 and P1, respectively). BDNF mRNA and protein level in RPMI8226 cells were detected by RT-PCR and Western blotting, respectively; the cellular proliferation activity was determined by MTT assay, while the cell apoptosis was measured by flow cytometry; the variation of VEGF mRNA level in RPMI8226 cells via transfection was determined by RT-PCR, the secretion of VEGF was detected by ELISA.</p><p><b>RESULTS</b>(1)The recombinant eukaryotic BDNF siRNA expression vectors were successfully constructed. BDNF mRNA expression and protein level in P1 group were significantly inhibited compared to those in non-transfected group (Pn) and P0 groups (P<0.05); (2)MTT tests demonstrated that the cellular proliferation activities were obviously decreased in Pn (0.42 ± 0.06) vs P0 (0.56 ± 0.06) and P1 (0.50 ± 0.04) groups (P<0.05); (3)The early cell apoptosis rates were statistically increased in P1 [(53.84 ± 9.95)%] vs Pn [(5.23 ± 2.46)%] and P0 [(9.10 ± 3.46)%] groups (P<0.01); (4)The silence of endogenous BDNF significantly decreased the expression of VEGF in RPMI8226 cells:the relative expression level of VEGF121, VEGF145 and VEGF165 in P1 group were (0.62 ± 0.07), (0.47 ± 0.09) and (0.57 ± 0.02) folds compared to Pn group (P<0.05); (5)ELISA demonstrated that secretion of VEGF in P1 group were (0.36 ± 0.05) and (0.44 ± 0.06) folds compared to Pn and P0 group, respectively (P<0.05).</p><p><b>CONCLUSION</b>BDNF gene silence can obviously increase apoptosis of RPMI8226 cells, inhibit their proliferation and decrease the expression of VEGF. BDNF might mediate the expression of VEGF in MM cells, which may be involved in MM angiogenesis.</p>

Role of brain-derived neurotrophic factor in bone marrow angiogenesis in multiple myeloma / 华中科技大学学报（医学）（英德文版）

This study examined the expression of brain-derived neurotrophic factor (BDNF) in multiple myeloma (MM) and its role in bone marrow angiogenesis. The peripheral blood plasma was harvested from 71 MM patients and 63 patients without hematological malignancy. The BDNF level in the blood plasma was determined by ELISA. Human bone marrow endothelial cells (HBMECs) were cultured. The mRNA and protein expression levels of the BDNF receptor TrkB in HBMECs were detected by using RT-PCR and flow cytometry, respectively. The viability of HBMECs treated with recombinant human (rh) BDNF or not was measured by using MTT assay. The migration of HBMECs in the presence of rhBDNF or not was determined by modified Boyden chamber assay. In vitro tube formation assay was used to assess the effect of rhBDNF on HBMECs differentiation. The results of ELISA revealed that the BDNF level was significantly higher in peripheral blood plasma of MM patients than in that of control patients (4.39±0.67 vs. 1.96±0.39 ng/mL, P<0.05). The BDNF receptor TrkB was expressed in HBMECs at mRNA and protein level. MTT assay manifested that rhBDNF could significantly concentration-dependently promote the HBMECs proliferation. The number of HBMECs treated with 160 ng/mL rhBDNF for 48 h was 1.57±0.10 folds higher than that in control group (P<0.05). Moreover, rhBDNF could enhance HBMECs migration in a concentration-dependent manner and the maximal migration was reached in the presence of 100 ng/mL rhBDNF. The migration indexes were 1.40±0.11, 1.64±0.16, 2.06±0.25 and 2.18±0.21 in 25, 50, 100 ng/mL rhBDNF groups and 25 ng/mL rhVEGF group, respectively. In vitro tube formation assay demonstrated that the area of the formed tubular structure was increased with the rhBDNF concentration. In control group, there was no formation of intact tubular structure and the HBMECs on the matrigel were irregularly dispersed. HBMECs treated with 100 ng/mL rhBDNF could form intact tubular structure and the area and the diameter of tubes were significantly greater than those in control group (P<0.05). There was no significant difference in the formed tubular area between 25 ng/mL VEGF group and 100 ng/mL rhBDNF group. It was concluded that BDNF plays an important role in myeloma cell-induced angiogenesis, and it may become a new target of anti-angiogenesis treatment for MM.

Role of brain-derived neurotrophic factor in bone marrow angiogenesis in multiple myeloma / 华中科技大学学报（医学）（英德文版）

This study examined the expression of brain-derived neurotrophic factor (BDNF) in multiple myeloma (MM) and its role in bone marrow angiogenesis. The peripheral blood plasma was harvested from 71 MM patients and 63 patients without hematological malignancy. The BDNF level in the blood plasma was determined by ELISA. Human bone marrow endothelial cells (HBMECs) were cultured. The mRNA and protein expression levels of the BDNF receptor TrkB in HBMECs were detected by using RT-PCR and flow cytometry, respectively. The viability of HBMECs treated with recombinant human (rh) BDNF or not was measured by using MTT assay. The migration of HBMECs in the presence of rhBDNF or not was determined by modified Boyden chamber assay. In vitro tube formation assay was used to assess the effect of rhBDNF on HBMECs differentiation. The results of ELISA revealed that the BDNF level was significantly higher in peripheral blood plasma of MM patients than in that of control patients (4.39±0.67 vs. 1.96±0.39 ng/mL, P<0.05). The BDNF receptor TrkB was expressed in HBMECs at mRNA and protein level. MTT assay manifested that rhBDNF could significantly concentration-dependently promote the HBMECs proliferation. The number of HBMECs treated with 160 ng/mL rhBDNF for 48 h was 1.57±0.10 folds higher than that in control group (P<0.05). Moreover, rhBDNF could enhance HBMECs migration in a concentration-dependent manner and the maximal migration was reached in the presence of 100 ng/mL rhBDNF. The migration indexes were 1.40±0.11, 1.64±0.16, 2.06±0.25 and 2.18±0.21 in 25, 50, 100 ng/mL rhBDNF groups and 25 ng/mL rhVEGF group, respectively. In vitro tube formation assay demonstrated that the area of the formed tubular structure was increased with the rhBDNF concentration. In control group, there was no formation of intact tubular structure and the HBMECs on the matrigel were irregularly dispersed. HBMECs treated with 100 ng/mL rhBDNF could form intact tubular structure and the area and the diameter of tubes were significantly greater than those in control group (P<0.05). There was no significant difference in the formed tubular area between 25 ng/mL VEGF group and 100 ng/mL rhBDNF group. It was concluded that BDNF plays an important role in myeloma cell-induced angiogenesis, and it may become a new target of anti-angiogenesis treatment for MM.

The role of gender difference on the prognosis of ST-segment elevation myocardial infarction (STEMI) in patients treated with primary percutaneous coronary intervention / 中华流行病学杂志

Objective To investigate and analyze the impact of gender difference on outcome and prognosis of ST-segment elevation myocardial infarction (STEMI) in patients treated with primary percutaneous coronary intervention (PCI).Methods This was a prospective and multicentered observation study.All the patients with acute STEMI admitted to the hospitals from June 1st 2009 to June 1st 2010 were continuously recruited.In this study,a unified questionnaire was applied and the 382 patients satisfied the criteria.A unified follow-up questionnaire was used on patients who were discharged from the hospital.Results On average,the female patients were 8 years older than the males.The median “symptom-to-balloon time” was 312.5 minutes in females and 270.0 minutes in males,and it was significantly different (P=0.007).During hospitalization,a higher proportion of female patients developed heart failure,angina and bleeding.No gender differences were found on the in-hospital mortality rates and medical therapy recommended by the guideline.The female patients were more prone to multi-vessel disease than males (P=0.002).Success rates of primary PCI did not show any gender differences.One-month mortality and other cardiovascular events also did not show gender difference when the patients were followed for one month after being discharged.The rates of heart failure and re-hospitalization due to cardiac incidents among female patients were obviously higher than the males,three months after being discharged (P=0.007,respectively).However,the three-month and long-term cardiac mortality did not show differences related to gender.Female patients were associated with higher all-cause mortality than that in males,but there was no statistically significant difference (female 4.2％ vs.male 1.6％;P=0.056).Data from multi-factor regression analysis showed that being female was not an independent predictor related to in-hospital mortality or during the follow-up period.Conclusion Being female was not an independent predictor of in-hospital mortality or during follow-up period among patients who were treated with primary PCI.Worse long-term outcome seen in female patients was likely to be explained by older age or longer pre-hospital delayed time.

LUNX mRNA in regional lymph nodes of non-small cell lung cancer patients by RT-PCR and its clinical significance / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the detection of humen-lung-specific X protein (LUNX) gene in micrometastases of patients with non-small cell lung cancer.@*METHODS@#The expression of LUNX gene in tumor tissue, lung and lymph nodes was detected by reverse transcriptase-polymerase chain reaction(RT-PCR) both in 43 non-small-cell lung cancer patients (the experimental group) and 15 lung benign patients (the control group). LUNX mRNA expression in clinic pathology,stage of cancer cell differentiation, clinic stage, age, sex, smoking history, and 4 lung cancer blood markers (CEA,CA125,NSE, and CYFRA211) were evaluated.@*RESULTS@#The expression of LUNX gene was positive in the 2 groups. LUNX gene expression was positive in 33 of the 87 lymph nodes of the 43 patients in the experimental group (37.93%), and in 2 of the 26 lymph nodes in the control group (7.69%). The LUNX mRNA positive in the lymph nodes was closely related to the pathological type, cancer cell differentiation and clinic stage(r=0.660,0.500,0.460; P=0.011,0.017,0.022, all P0.05).@*CONCLUSION@#The LUNX mRNA expression detected by RT-PCR is more sensitive than by traditional ways. The expression of LUNX gene mRNA in the lymph nodes is a valuable index for the detection of micrometastases in patients with non-small cell lung cancer.

The Effect of Brain-derived Neurotrophic Factor on Angiogenesis / 华中科技大学学报（医学）（英德文版）

To investigate the in vitro and in vivo proangiogenic effects of brain-derived ncurotrophic factor (BDNF),human umbilical vein endothelial cells (HUVECs) were isolated and cultured in primary culture.The effect of BDNF on the proliferation of HUVECs was examined by MTT assay.The effects of BDNF on HUVEC migration and tube formation were studied by modified Boyden chamber assay and tube formation assay,respectively.Matrigel plug assay and chorioaUantoic membrane assay were used to evaluate the effects of BDNF on angiogencsis in vivo.Our results showed that BDNF substantially stimulated the migration and tube formation of HUVECs in vitro,although it did not induce HUVEC proliferation.BDNF also induced angiogenesis both in matrigcl plug of mouse model and in chick chorioallantoic membrane.In conclusion,BDNF can promote angiogenesis both in vitro and in vivo,and may be a proangiogenic factor.

Effect of RNA interference targeting brain-derived neurotrophic factor gene on HeLa cell proliferation and apoptosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To screen effective sequences of short hairpin RNA on brain-derived neurotrophic factor (BDNF) gene and the effect of RNA interference on the proliferation and apoptosis of HeLa cells, a cervix carcinoma cell line with high expression of BDNF.</p><p><b>METHODS</b>Two recombinant eukaryotic human-BDNF siRNA expression vectors were designed and constructed. Sequences were confirmed by restrictive endonuclease digestion and DNA sequencing. The empty vector pGenesil-1 and two recombinant plasmids, pGenesil-shRNA-BDNF1 and pGenesil-shRNA-BDNF2, were transfected into HeLa cells using Lipofectamine 2000 (groups: P(0), P(1) and P(2), respectively). The mRNA and protein levels of BDNF in HeLa cells were detected by RT-PCR and Western blot, respectively. The cellular proliferation rates were determined by MTT assay and the apoptotic rates were measured by flow cytometry and Hoechest 33258.</p><p><b>RESULTS</b>The recombinant eukaryotic BDNF siRNA expression vectors were successfully constructed. The expression of mRNA and protein of BDNF in P(1) group were significantly decreased, comparing with non-transfected group, P(0) and P(2) groups (F = 48.19, P < 0.01). P(2) group failed to meet the expected results (P > 0.05). In addition, the proliferation activity was reduced in P(1) group and the peak point of proliferation curve was prolonged. Moreover, the early cell apoptotic rates were statistically increased in P(1)[(53.4 +/- 4.2)%] VS. non-transfected [(0.8 +/- 0.4)%], P(0) [(5.1 +/- 1.8)%] and P(2)[(7.9 +/- 2.4)%] groups (F = 269.77, P < 0.01).</p><p><b>CONCLUSION</b>HeLa cells express a high level of BDNF. BDNF gene silencing by RNA interference increases the apoptosis of HeLa cells and inhibits cell proliferation, offering a possible target for efficient tumor therapy.</p>

Study of brain-derived neurotrophic factor activating TrkB signaling cascades in the pathogenesis of multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the significance of abnormal expression of brain-derived neurotrophic factor (BDNF)/TrkB in the development and evolution of multiple myeloma (MM) and the involved signaling pathways.</p><p><b>METHODS</b>The effect of BDNF on the cell viability of human myeloma cell line (HMCL) (RPMI8226, U266, KM3) was determined by trypan blue dye-exclusion. MTT assay was used to evaluate the cytotoxicity of tested chemotherapeutic agents. The effect of BDNF on the phosphorylation of TrkB was determined by Western blot. A human myeloma xenograft animal model was used to evaluate the effects of BDNF on tumor growth and survival time.</p><p><b>RESULTS</b>BDNF at 50 microg/L triggered significant increase in cell viability of HMCL. BDNF protected KM3 cells from melphalan and vincristine. The viability of KM3 cells exposed to varying concentrations of melphalan with and without 50 microg/L BDNF showed that BDNF induced almost a 2-fold and a 3-fold increase in melphalan and vincristine toxicity respectively. BDNF treatment increased MM cell growth in xenografted MM model (3240.9 mm3 vs 1032.7 mm3 ) (P <0.05). Intratumoral injection of BDNF also significantly reduced survival time (13 d vs 21 d) (P <0.05). The phosphorylated TrkB level was increased significantly after treated by exogenous BDNF. BDNF-triggered migration in RPMI8226 cells was completely abrogated by a Trk tyrosine kinase inhibitor K252a.</p><p><b>CONCLUSION</b>BDNF can activate TrkB signaling cascades resulting in MM cells growth, migration, and chemoprotection and appears to have a major contribution to the pathogenesis of MM.</p>

Brain-derived neurotrophic factor promotes the secretion of MMP-9 in human myeloma cell through modulation of nucleus factor-kappaB / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the mechanism of brain-derived neurotrophic factor (BDNF) promoting human multiple myeloma (MM) cells secreting matrix metalloproteinase-9 ( MMP-9).</p><p><b>METHODS</b>Gelatin zymography of culture supernatants was performed to visualize the content of MMPs in myeloma RPMI 8226 cells stimulated by BDNF. NF-kappaB activity was determined by chemiluminescent electrophoretic mobility shift assay (EMSA).</p><p><b>RESULTS</b>Treatment with 25, 50, 100 and 200 microg/L BDNF for 24 h significantly (P < 0.01) enhanced the level of MMP-9 (2.03+/-0.48, 2.99+/-0.046, 4.63+/-0.62 and 5.62+/-1.29 microg/L, respectively, vs 1.00 microg/L of the control) secreted by RPMI8226 cells in a dose-dependent manner, while that of MMP-2 was not changed significantly (P > 0.05). The BDNF-induced activation of MMP-9 was inhibited by pretreatment with pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, or K252 alpha, a specific tyrosine inhibitor of TrkB which is the receptor for BDNF. Pretreated with 1 mmol/L PDTC or 500 nmol/L K252 alpha significantly downregulated MMP-9 secreted by the 100 microg/L of BDNF stimulated RPMI 8226 cells (the optical density values were 867.52+/-101.81 and 727.98 +/-92.05, respectively, vs 1,159.01+/-233.15 of the control). The activity of NF-kappaB was enhanced by BDNF in a dose-dependent manner, and pretreatment with K252 alpha could significantly inhibit this activation at 1, 6, 12 and 24 h (P < 0.05) in a time-dependent manner.</p><p><b>CONCLUSION</b>BDNF plays an important role in the angiogenesis of MM to promote the up-regulation of MMP-9, which may be induced by enhanced NF-kappaB activity in MM cells.</p>

Antimyeloma effects of resveratrol through inhibition of angiogenesis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In multiple myeloma (MM), bone marrow angiogenesis parallels tumour progression and correlates with disease activity. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo. In this study, we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol on some important angiogenic factors of RPMI 8226 cells.</p><p><b>METHODS</b>RPMI 8226 cells were cocultured with human umbilical vein endothelial cells (HUVECs) to evaluate the effects of myeloma cells on angiogenesis. The RPMI 8226 cells were treated with various concentrations of resveratrol (6.25 - 50.00 micromol/L) for different times (12 - 72 hours). Reverse transcriptase polymerase chain reaction (RT-PCR) was used to assay vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinases (MMP)-2 and MMP-9 mRNA. Gelatin zymography was used to analyze MMP-2 and MMP-9 activity. VEGF and bFGF proteins secreted by the cells in the medium were quantified by enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Cell proliferation, migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226 cells. Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in a dose dependent manner. Treatment of RPMI 8226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity. Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Furthermore, decreased levels of VEGF, bFGF, MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrol confirmed its antiangiogenic action at the level of gene expression.</p><p><b>CONCLUSIONS</b>Resveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF, bFGF, MMP-2 and MMP-9. Resveratrol may be a potential candidate for the treatment of multiple myeloma.</p>

Role of Coagulation Factor Ⅶ in Pathogenesis of Ischemic Heart Disease / 华中科技大学学报（医学）（英德文版）

To study the variation and significance of plasma coagulation factor Ⅶ (FⅦ) in differ ent kinds of ischemia heart disease (IHD) and examine its relation with plasma lipid and gene polymorphism. FⅦa was determined with one stage clotting assay by using a recombinant soluble tissue factor (rsTF). FⅦc was measured with one stage clotting assay. FⅦag was quantified with an enzyme-linked immunosorbent assay (ELISA). Polymorphism was analyzed with PCR-urea-polyacrylamide gel electrophoresis. Our results showed that FⅦa in stable angina (SA),unstable angina (UA), obsolete and acute myocardial infraction (OMI, AMI) patients was higher than those of normal group with the differences being significant within any two groups. FⅦag in UA, OMI and AMI was higher than those in SA and normal groups. There were positive correlations between FⅦa and serum triglycerides, FⅦa and FⅦc, FⅦc and FⅦag. FⅦ-323 0/10 bp polymorphism analysis was performed in 60 patients and 0/10 bp polymorphism was found in 5 cases. FⅦc and FⅦag were much lower in cases of 0/10 bp groups than those in cases of 0/0 bp groups. It is concluded that there was activation of extrinsic coagulation pathway in every kind of IHD to different extent. FⅦa was the risk factor in the development of IHD, and more sensitive in reflecting the severity of cardiovacutar disease than FⅦc or FⅦag. FⅦa was higher in OMI, which may be one of the risk factors of re-infraction. Serum triglyceride may indirectly lead to the development of IHD by increasing the level of FⅦa. FⅦ-323 0/10 bp polymorphism was present in Chinese patients with IHD and it was correlated with the level of FⅦc, FⅦag in plasma. 10 bp allelomorphic gene was a protective factor against thrombogenesis.

Role of coagulation factor VII in pathogenesis of ischemic heart disease / 华中科技大学学报（医学）（英德文版）

To study the variation and significance of plasma coagulation factor VII (FVII) in different kinds of ischemia heart disease (IHD) and examine its relation with plasma lipid and gene polymorphism. FVIIa was determined with one stage clotting assay by using a recombinant soluble tissue factor (rsTF). FVIIc was measured with one stage clotting assay. FVIIag was quantified with an enzyme-linked immunosorbent assay (ELISA). Polymorphism was analyzed with PCR-urea-polyacrylamide gel electrophoresis. Our results showed that FVIIa in stable angina (SA), unstable angina (UA), obsolete and acute myocardial infraction (OMI, AMI) patients was higher than those of normal group with the differences being significant within any two groups. FVIIag in UA, OMI and AMI was higher than those in SA and normal groups. There were positive correlations between FVIIa and serum triglycerides, FVIIa and FVIIc, FVIIc and FVIIag. FVII-323 0/10 bp polymorphism analysis was performed in 60 patients and 0/10 bp polymorphism was found in 5 cases. FVIIc and FVIIag were much lower in cases of 0/10 bp groups than those in cases of 0/0 bp groups. It is concluded that there was activation of extrinsic coagulation pathway in every kind of IHD to different extent. FVIIa was the risk factor in the development of IHD, and more sensitive in reflecting the severity of cardiovacutar disease than FVIIc or FVIIag. FVIIa was higher in OMI, which may be one of the risk factors of re-infraction. Serum triglyceride may indirectly lead to the development of IHD by increasing the level of FVIIa. FVII-323 0/10 bp polymorphism was present in Chinese patients with IHD and it was correlated with the level of FVIIc, FVIIag in plasma. 10 bp allelomorphic gene was a protective factor against thrombogenesis.