Oxidative Stress and Antioxidative Therapy in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is clinically characterized by a progressive increase in pulmonary artery pressure, followed by right ventricular hypertrophy and subsequently right heart failure. The underlying mechanism of PAH includes endothelial dysfunction and intimal smooth muscle proliferation. Numerous studies have shown that oxidative stress is critical in the pathophysiology of PAH and involves changes in reactive oxygen species (ROS), reactive nitrogen (RNS), and nitric oxide (NO) signaling pathways. Disrupted ROS and NO signaling pathways cause the proliferation of pulmonary arterial endothelial cells (PAECs) and pulmonary vascular smooth muscle cells (PASMCs), resulting in DNA damage, metabolic abnormalities, and vascular remodeling. Antioxidant treatment has become a main area of research for the treatment of PAH. This review mainly introduces oxidative stress in the pathogenesis of PAH and antioxidative therapies and explains why targeting oxidative stress is a valid strategy for PAH treatment.

Conserved function of crucian carp cGAS in the MITA-mediated interferon signaling.

Mammalian cyclic GMP-AMP synthase (cGAS) is pivotal for cytosolic DNA-triggered interferon (IFN) response. However, the function of cGAS in fish IFN response remains unclear. Our recent study has reported that cGAS from crucian and grass carps downregulates the IFN response by attenuating the K63-linked ubiquitination of retinoic acid-inducible gene-I (RIG-I) and its interaction with mitochondrial antiviral signaling protein (MAVS). Here, the function of crucian carp cGAS was further investigated. We found that crucian carp cGAS directly binds to poly deoxyadenylic-deoxythymidylic acid (poly (dA:dT)) and exhibits mediator of IFN regulatory factor 3 (IRF3) activation (MITA)-dependent activation of the IFN response, indicating a conserved function of crucian carp cGAS in the MITA-mediated IFN signaling. However, crucian carp cGAS could suppress the IFN activation stimulated by polyinosinic: polycytidylic acid (poly (I:C)) in time- and dose-dependent manners. These data collectively suggest complicated functions of crucian carp cGAS in the IFN antiviral response.

Finite element analysis for self-made femoral head brace device in the treatment of early femoral head necrosis / 中国组织工程研究

BACKGROUND: Core decompression for early adult ischemic necrosis of femoral head gets the identity of most scholars, but the postoperative femoral head easily experiences collapse. How to prevent collapse is still a problem to be solved currently. OBJECTIVE: To perform biomechanical analysis of femoral head ischemic necrosis by using the finite element method and to provide biomechanical basis for the treatment of early adult femoral head necrosis. METHODS: One fresh femur specimen died of accidental death in youth and young adults was obtained, and no deformity or fracture was found. X-ray confirmed that it did not have tumor or osteoporosis. Spiral CT was used to scan normal femoral head and neck, pulp core decompression of femoral head and neck, brace device placement and bone-graft of femoral head and neck for acquiring image data from the proximal to distal vertical longitudinal axis. Scanning data were input in the Mimics software. Finite element method was utilized for biomechanical analysis of femoral head and neck of three models. RESULTS AND CONCLUSION: (1) The stress dispersal and downward conduction of normal femoral head was concentrated in the shaft of the femur and the tensile stress was concentrated in the rotor socket. (2) After pulp core decompression, the stress concentration, displacement and strain increased in the weight-bearing area of femoral head. (3) The stress of the internal bracing was similar to that of normal femoral head. (4) The stress of weight bearing area of femoral head is concentrated, and the strain is increased, so that weight bearing area is easy to collapse after pulp core decompression. The more stress distribution, more bearing load and less strain of implant and bone graft model, are conformed to the normal mechanical properties of the normal femoral head and neck.

The survival analysis of metastatic prostate cancer / 中华外科杂志

<p><b>OBJECTIVES</b>To analyze the clinical and pathological informations of metastatic prostate cancer patients to find the predictive factors of the survival.</p><p><b>METHODS</b>To filter 364 cases of metastatic prostate cancer in the 940 cases of prostate cancer that were treated in Cancer Hospital Fudan University in Shanghai from March 1998 to June 2009, the cases had hormonal therapy and full clinical and pathological records. All the 364 cases were followed up and the clinical and pathological informations were analyzed, to find the predictive factors that related to the prognosis. Statistic software SPSS 15.0 was used for analysis. Cumulative survival was analyzed by the method of Kaplan-Meier. Cox regression was used for univariate and multivariate analysis. Log-rank method was used for the significance test.</p><p><b>RESULTS</b>The last follow-up date was 30th June 2009 and the median follow-up time was 24 months. At the final follow-up, 240 cases were alive, 109 cases were dead and 15 cases were lost to follow up. The median survival time of metastatic prostate cancer was 64 months, and the one-year, two-year, three-year, four-year, five-year survival rate was 92%, 78%, 66%, 60%, 54%. The univariate analysis indicated that Gleason score (P = 0.033), clinical stage (P < 0.001), the effectiveness of hormonal therapy (P < 0.001), the prostate specific antigen (PSA) nadir during hormonal therapy (P < 0.001) and the time from the start of hormonal therapy to the PSA nadir (P = 0.002) were predictive factors for the survival time of metastatic prostate cancer. The multivariate analysis indicated that the PSA nadir during hormonal therapy (P < 0.001) and the time from the start of hormonal therapy to the PSA nadir (P < 0.001) were independent factors that predict the survival time of metastatic prostate cancer.</p><p><b>CONCLUSION</b>The PSA nadir during hormonal therapy and the time from the start of hormonal therapy to the PSA nadir are independent factors that predict the survival time of metastatic prostate cancer.</p>

The survival analysis of the advanced metastatic castration-resistant prostate cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze predictive factors of advanced metastatic castration-resistant prostate cancer.</p><p><b>METHODS</b>From December 1996 to March 2008, 250 cases of advanced metastatic prostate cancer progressed into the stage of hormonal independent prostate cancer. The last follow-up date was 31 March 2008 and the median follow-up time was 24 months. During the follow-up, 131 cases were alive, 105 cases were dead and 14 cases were lost to follow-up. Clinical and pathological information of the cases was analyzed to find the predictive factors that related to the prognosis.</p><p><b>RESULTS</b>The median survival time of advanced metastatic castration-resistant prostate cancer was 30 months, and the one-year, two-year, three-year survival rate was 79%, 59%, and 41%. The univariate analysis indicated that prostate specific antigen (PSA) at diagnosis, clinical stage, the PSA nadir during hormonal therapy, the time form the start of hormonal therapy to the PSA nadir, the time of response duration during hormonal therapy, PSA velocity (PSAV) and PSA doubling time (PSADT) at the emergency of castration-resistant prostate cancer, age and PSA at the diagnosis of castration-resistant prostate cancer were factors that predicted the survival time of advanced metastatic castration-resistant prostate cancer. The multivariate analysis indicated that the PSA nadir during hormonal therapy, the time form the start of hormonal therapy to the PSA nadir, PSAV at the emergency of castration-resistant prostate cancer, the time of response duration during hormonal therapy were independent factors that predicted the survival time of advanced metastatic castration-resistant prostate cancer.</p><p><b>CONCLUSION</b>The PSA nadir during hormonal therapy, the time form the start of hormonal therapy to the PSA nadir, PSAV at the emergency of castration-resistant prostate cancer and the time of response duration during hormonal therapy are independent factors that predict the survival time of advanced metastatic castration-resistant prostate cancer.</p>