The research of the secondary damage remote from middle cerebral artery territory infarction has made significant progress in recent years.More animal experiments from the cellular,biochemical and molecular levels have been performed for in-depth and detailed research on remote site damage. The injury mechanisms such as oxidative damage and β amyloid deposition have been found.The new imaging detection technologies,such as magnetic resonance diffusion tensor imaging(DTI),have gradually been applied to the diagnosis of remote site damage.

Objective To investigate the effects of angiotensin Ⅱ (Ang Ⅱ) on the expression of TLR4 and its role in lipopolysaccharide (LPS)-induced NF-κB activation and CD40 expression in rat peritoneal mesothelial cells (RPMCs). Methods RPMCs were harvested from Spragne-Dawley rat peritoneal cavity and maintained under defined in vitro condition. The cells were treated with Ang Ⅱ at different concentrations (10-9, 10-8, 10-7, 10-6 mol/L) and exposed to Ang Ⅱ (10-7 mol/L) for different times (1, 2, 4, 8, 12, 24, 48 h for mRNA and 6, 12, 24, 36, 48 h for protein, respectively). Meanwhile, the influence of AT1 receptor antagonist (AT1R, losartan, 10-5 mol/L) and AT2 receptor blocker (AT2R, PD123177, 10-5 mol/L) on the TLR4 induced by Ang Ⅱ was observed. After synchronization for 24 hours, the cells were randomly assigned to four groups: the control group, the Ang Ⅱ (10-7 tool/L) group, the LPS (1 mg/L) group, the Ang Ⅱ (10-7 mol/L) plus LPS (1 mg/L) group, which were used to investigate the effects of Ang Ⅱ on the NF-κB activation and CD40 expression induced by LPS. The mRNA expression of TLR4 and CD40 was measured by RT-PCR and the protein abundance of TLR4, NF-κB p65, phospho-p65, IKBα and phospho-IκBα were analyzed by Western blot. Immunofluorescence was performed to determine the subcellular localization of p65 subunit of NF-κB. Results (1) Treatment of RPMCs with Ang Ⅱ resulted in a concentration-dependent increase in the expression of TLR4. Ang Ⅱ at 10-9, 10-8, 10-7 and 10-6 mol/L increased TLR4 mRNA expression by 70.5%, 89.5%, 102.9%, and 121.9%, respectively and protein expression by 12.1%, 27.7%, 51.2%, and 41.6%, respectively (P<0.01). Treatment of RPMCs with 10-7 mol/L Ang Ⅱ resulted in a time-dependent increase in the expression of TLR4, with the peak of mRNA expression at 8 and 12 h (P<0.01) and the protein expression at 12 and 24 h (P<0.01). (2) Losartan antagonized Ang Ⅱ-stimulated expression of TLR4 by 33.5% (P<0.05), PD123177 had no such effect (P0.05). (3) Treatment of RPMCs with LPS (1 mg/L) for 60 rain significantly increased the ratio of phospho-IκBα to IκBα by 362.6% (P< 0.01) , phospho-p65 to p65 by 67.4% (P<0.05), and LPS (1 mg/L) for 4 h significantly increased the expression of CD40 mRNA by 299.9% (P<0.01) compared to the control group. In comparison to the LPS (1 mg/L) group, preincubation of RPMCs with AngⅡ (10-7 mol/L) for 24 h then treated with LPS (1 mg/L) for 60 rain significantly increased the ratio of phospho-IκBα to IκBα by 49.1% (P<0.01), phospho-p65 to p65 by 29.3%(P<0.05), and LPS (1 mg/L) for 4 h significantly increased the expression of CD40 mRNA by 56.8%(P<0.01). (4) The p65 subunit of NF-κB was dominantly distributed in the cytoplasm in the control and Ang Ⅱ group. Following exposure to LPS for 60 min, p65 subunit labeling was upregulated and translocated into the nuclei. A significantly increased nuclear staining of p65 in ceils treated with Ang Ⅱ plus LPS were observed. Conclusions Ang Ⅱ induces the expression of TLR4 in dose- and time-dependent manner in RPMCs, resulting in enhanced NF-κB signaling and induction of CD40 expression, Locally produced Ang Ⅱ in the peritoneum may play an amplified role in LPS-induced peritoneal inflammation.

Objective Dilated cardiomyopathy (DCM) is generally considered to be accompanied by both left and right ventricular dysfunction,but most studies only analyze the left ventricular function. In this study, we evaluated the effect of arotinolol on right ventricular function in patients with DCM. Methods Right ventricular ejection fraction (RVEF) and right ventricular diameter (RVD) were measured by two-dimensional echocardiography (2-DE) in 33 DCM patients; RVEF measured by first-pass radionuclide angiography (FPRA) was compared with that by 2-DE. Results The treatment with arotinolol for one year resulted in a reduction in the right ventricular diameter (baseline, 23.0 ± 8.3 mm vs after one-year treatment, 20.7 ± 5.4 mm; P=0.004 ) and an associated increase in ejection fraction (baseline, 36.9 ± 10.3% vs after one-year treatment, 45.8 ± 9.6%; P ＜ 0.001 ); there is a high correlation between the 2-DE method and radionuclide ventriculographic method. The correlation coefficient is 0.933 (P＜0.001). Conclusion Arotinolol therapy could not only improve left ventricular function, but also improve right ventricular function in DCM patients.

BACKGROUNDTo explore the sequential variation of pulmonary flow spectrum and its value on evaluation of risk for pulmonary resection in perioperative patients with lung cancer.

METHODSForty-nine patients with lung cancer who underwent pneumonectomy (12 cases) and lobectomy (37 cases) were observed for the values of Doppler pulmonary flow spectrum before operation, on the 3-5 days and 8-10 days postoperatively. Moreover the patients were divided into different groups according to the different operative procedures and with or without postoperative cardiac arrhythmia.

RESULTSDoppler pulmonary flow spectrum changed in all cases who underwent pneumonectomy and lobectomy from 3 to 5 days postoperatively. These changs included prolonged preejection period (PEP), shortened acceleration time (ACT), increased PEP/ACT ratio, increased pulmonary artery mean pressure (PAMP), and increased pulmonary vascular resistance (PVR). There were significant differences comparing with those before operation ( P < 0.01). The patients who underwent lobectomy recovered to the same level of pre operation on the 8th to 10th postoperative days. However, the changes of pulmonary flow spectrum continuously existed in the patients who underwent pneumonectomy on the 8th to 10th postoperative days. There were significant differences of pulmonary flow spectrum between patients with postoperative arrhythmia and without postoperative arrhythmia before operation.

CONCLUSIONSPulmonary hemodynamic obviously changes after pulmonary resection in the patients with lung cancer and the changes last longer in pneumonectomy patients. Patients with postoperative cardiac arrhythmia have marked pulmonary hemodynamic changes before operation. Doppler pulmonary flow spectrum can not only be used to analyse the pulmonary hemodynamic changes for those cases undergoing pulmonary resection after operation, but also to evaluate the risk of pulmonary resection before operation.

We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.
Base Sequence ; China ; Cluster Analysis ; Gene Components ; Genetic Variation ; Genome, Viral ; Genotype ; Molecular Sequence Data ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; SARS Virus ; genetics ; Sequence Analysis, DNA ; Severe Acute Respiratory Syndrome ; genetics

OBJECTIVETo compare the effect of first-line treatment with platinum-based chemotherapy and non-platinum-based chemotherapy in patients with lung metastases from triple negative breast cancer (TNBC).

METHODSSixty-five eligible patients were divided into platinum-treated group and non-platinum-treated group according to the first-line therapy. Factors predicting the chemotherapeutic efficacy included overall survival (OS), progression-free survival (PFS) and objective response (OR).

RESULTSIn the platinum-treated group of 32 patients, 2 cases (6.3%) achieved CR, 16 cases (50.0%) achieved PR, 11 (34.4%) cases achieved SD, and 3 patients (9.4%) achieved PD. In the non-platinum-treated group of 33 patients, 2 cases (6.1%) achieved CR, 6 cases (18.2%) achieved PR, 16 cases (48.5%) achieved SD, and 9 cases (27.3%) achieved PD. Median PFS was significantly longer in the platinum-treated group than in the non-platinum-treated group (10 months vs. 6.0 months, P = 0.012), and OS was also improved (32 months vs. 22 months, P = 0.006). Multivariate analysis of several factors including local-regional lymph node involvement, lung metastasis-related symptoms, first-line platinum-based chemotherapy, disease-free interval, size and number of lung lesions, showed that first-line platinum-based chemotherapy was an independent prognostic factor for TNBC patients with lung metastases.

CONCLUSIONSCompared with non-platinum-based chemotherapy, the first-line platinum-based chemotherapy can improve PFS and OS in TNBC patients with metastases confined to the lungs.

Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Disease-Free Survival ; Humans ; Lung Neoplasms ; drug therapy ; Neoplasms, Second Primary ; Platinum ; therapeutic use ; Triple Negative Breast Neoplasms ; drug therapy