OBJECTIVE: To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved. METHODS: MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-β (TGF-β1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively. RESULTS: PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-β1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05). CONCLUSIONS PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

BACKGROUNDPropofol is increasingly used during partial support mechanical ventilation such as pressure support ventilation (PSV) in postoperative patients. However, breathing pattern, respiratory drive, and patient-ventilator synchrony are affected by the sedative used and the sedation depth. The present study aimed to evaluate the physiologic effects of varying depths of propofol sedation on respiratory drive and patient-ventilator synchrony during PSV in postoperative patients.

METHODSEight postoperative patients receiving PSV for <24 h were enrolled. Propofol was administered to achieve and maintain a Ramsay score of 4, and the inspiratory pressure support was titrated to obtain a tidal volume (VT) of 6-8 ml/kg. Then, the propofol dose was reduced to achieve and maintain a Ramsay score of 3 and then 2. At each Ramsay level, the patient underwent 30-min trials of PSV. We measured the electrical activity of the diaphragm, flow, airway pressure, neuro-ventilatory efficiency (NVE), and patient-ventilator synchrony.

RESULTSIncreasing the depth of sedation reduced the peak and mean electrical activity of the diaphragm, which suggested a decrease in respiratory drive, while VT remained unchanged. The NVE increased with an increase in the depth of sedation. Minute ventilation and inspiratory duty cycle decreased with an increase in the depth of sedation, but this only achieved statistical significance between Ramsay 2 and both Ramsay 4 and 3 (P < 0.05). The ineffective triggering index increased with increasing sedation depth (9.5 ± 4.0%, 6.7 ± 2.0%, and 4.2 ± 2.1% for Ramsay 4, 3, and 2, respectively) and achieved statistical significance between each pair of depth of sedation (P < 0.05). The depth of sedation did not affect gas exchange.

CONCLUSIONSPropofol inhibits respiratory drive and deteriorates patient-ventilator synchrony to the extent that varies with the depth of sedation. Propofol has less effect on breathing pattern and has no effect on VT and gas exchange in postoperative patients with PSV.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Pressure ; drug effects ; physiology ; Female ; Hemodynamics ; drug effects ; physiology ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Positive-Pressure Respiration ; methods ; Propofol ; therapeutic use ; Prospective Studies ; Respiration, Artificial ; methods ; Tidal Volume ; drug effects ; physiology ; Young Adult

BACKGROUNDEarly goal-directed therapy (EGDT) has become an important therapeutic management in early salvage stage of septic shock. However, splenic organs possibly remained hypoperfused and hypoxic despite fluid resuscitation. This study aimed to evaluate the effect of EGDT on hepatic perfusion in septic shock patients.

METHODSA prospective observational study was carried out in early septic shock patients who were admitted to Intensive Care Unit within 24 h after onset and who met all four elements of the EGDT criteria after treatment with the standard EGDT procedure within 6 h between December 1, 2012 and November 30, 2013. The hemodynamic data were recorded, and oxygen metabolism and hepatic functions were monitored. An indocyanine green clearance test was applied to detect the hepatic perfusion. The patients' characteristics were compared before treatment (T0), immediately after EGDT (T1), and 24 h after EGDT (T2). This study is registered at ClinicalTrials.org, NCT02060773.

RESULTSTwenty-one patients were included in the study; however, the hepatic perfusion data were not included in the analysis for two patients; therefore, 19 patients were eligible for the study. Hemodynamics data, as monitored by pulse-indicator continuous cardiac output, were obtained from 16 patients. There were no significant differences in indocyanine green plasma disappearance rate (ICG-PDR) and 15-min retention rate (R15) at T0 (11.9 ± 5.0%/min and 20.0 ± 13.2%), T1 (11.4 ± 5.1%/min and 23.6 ± 14.9%), and T2 (11.0 ± 4.5%/min and 23.7 ± 15.3%) (all P > 0.05). Both of the alterations of ICG-PDR and R15 showed no differences at T0, T1, and T2 in the patients of different subgroups that achieved different resuscitation goal numbers when elected (P > 0.05).

CONCLUSIONThere were no hepatic perfusion improvements after EGDT in the early phase of patients with septic shock.

TRIAL REGISTRATIONClinicaltrials.gov NCT02060773 (https://clinicaltrials.gov/ct2/show/NCT02060773).

Aged ; Aged, 80 and over ; Cardiac Output ; physiology ; Disease Management ; Female ; Fluid Therapy ; Hemodynamics ; physiology ; Humans ; Intensive Care Units ; statistics & numerical data ; Male ; Middle Aged ; Prospective Studies ; Shock, Septic ; therapy

BACKGROUNDThere are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer (MBC) in older Chinese patients.

METHODSMBC patients aged > 65 years pretreated with 1 - 5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m(2) twice daily, days 1 - 14, plus docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles (median 4, range 2 - 8) and were evaluable for efficacy.

RESULTSThe overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia (12%), alopecia (7%), grade 3 nausea and vomiting (2%) and grade 3 nail toxicity (2%).

CONCLUSIONSCapecitabine 825 mg/m(2) twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women > 65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.

Aged ; Anthracyclines ; therapeutic use ; Antimetabolites, Antineoplastic ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; Capecitabine ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Drug Resistance, Neoplasm ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; therapeutic use ; Humans ; Taxoids ; administration & dosage ; therapeutic use

OBJECTIVETo evaluate the correlation between the lactate in artery blood and lactate clearance rate and prognosis in patients with septic shock in intensive care unit (ICU).

METHODSProspectively studied 221 consecutive patients with septic shock from December 2005 to December 2007, the diagnosis of septic shock was made based on the criteria of 2001 ACCP/SCCM. For inclusion in the study, we required admission of the patients within 24 h of septic shock diagnosed. The criteria for exclusion from the study were an age of less than 18 years, pregnancy, serious inadequacy of liver and renal, needing blood purification, or acidosis result of biguanides drugs, or do-not-resuscitate. The eligible patients assigned to early goal-directed therapy. The 6-, 24- and 72-hour lactate clearance rate were calculated, the relationship between the level of lactate, lactate clearance rate, the APACHE II score, the number of failed organ and the 28-day mortality were evaluated.

RESULTSOne hundred and five patients with septic shock were admitted, 74 male and 31 female, the mean age was 70 +/- 12 years. The 28-day mortality was 54.3%. The average APACHE II score at baseline was 20 +/- 8, the number of failed organs was 3.0 +/- 1.1 and the average concentration of lactate in artery blood at baseline was (3.8 +/- 3.6) mmol/L. Significant differences of the lactate at 0-, 6-, 24- and 72-hour were found between death group and survival group. There were 69 patients whose lactate in artery blood at baseline was > 2 mmol/L, 24 survived. The lactate clearance rate of 6- and 24-hour in survival group were significantly higher than death group (P < 0.01, P < 0.05, respectively), but the lactate clearance rate of 72-hour was not (P > 0.05). By using a multivariate logistic regression analysis, it showed that the lactate clearance rate of 6-hour was the independent predictive factor of survival. The area under the receiver operating characteristic curve (ROC) was 0.564, 0.649, 0.754, 0.784, respectively according to the level of the lactate at 0-, 6-, 24-hour and the 6-hour lactate clearance rate. The cutoff of 6-hour lactate clearance rate was >or= 30.0%, resulting in a sensitivity of 60.0% and a specificity of 77.3%.

CONCLUSIONSDynamic observation of lactate level is very important for the survival in the patients with septic shock. Patients with elevated lactate and not decreased rapidly have a worse outcome. The 6-hour lactate clearance rate might be the indicator for predicting the prognosis of patients with septic shock.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lactic Acid ; blood ; Male ; Middle Aged ; Monitoring, Ambulatory ; Prognosis ; Prospective Studies ; Shock, Septic ; blood ; Young Adult

OBJECTIVESevere acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in November 2002. The SARS-associated coronavirus (SARS-CoV) has been identified as the causal agent, but the pathology and pathogenesis are still not quite clear.

METHODSPost-mortem lung samples from six patients who died from SARS from April to July 2003 were studied by light and electron microscopy, Masson trichromal staining and immunohistochemistry. Evidence of infection with the SARS-CoV was determined by reverse-transcription PCR (RT-PCR) , serological examination and electron microscopy.

RESULTSFour of six patients had serological and RT-PCR evidence of recent infection of SARS-CoV. Morphologic changes are summarized as follows: (1) Diffuse and bilateral lung consolidation was seen in all patients (6/6) with increasing lung weight. (2) Diffuse alveolar damage was universal (6/6) with hyaline membrane formation (6/6), intra-alveolar edema/hemorrhage (6/6), fibrin deposition (6/6), pneumocyte desquamation (6/6). A marked disruption in the integrity of the alveolar epithelium was confirmed by immunostaining for the epithelial marker AE1/AE3 (6/6). (3) Type II pneumocytes, with mild hyperplasia, atypia, cytomegaly with granular amphophilic cytoplasm and intracytoplasmic lipid accumulation (5/6). (4) Giant cells in the alveoli were seen in five of 6 patients (5/6) , most of which were positive for the epithelial marker AE1/AE3 (5/6), but some cells were positive for the macrophage marker CD68(2/6). (5) A pronounced increase of macrophages were seen in the alveoli and the interstitium of the lung (6/6), which was confirmed by histological study and immunohistochemistry. (6) Haemophagocytosis was present in five of the 6 patients(5/6). (7) Lung fibrosis was seen in five patients(5/6), with alveolar septa and interstitium thickening(5/6), intraalveolar organizing exudates (6/6) and pleura thickening (4/6). Proliferation of collagen was confirmed by Masson trichromal staining, most of which was type III collagen by immunostaining. The formation of distinctive fibroblast/myofibroblast foci was seen in five patients (5/6) by light microscopy and immunochemistry. (8) Squamous metaplasia of bronchial mucosa was seen in five patients(5/6). (9) Thrombi was seen in all patients(6/6). (10) Accompanying infection was present in two patients, one was bacteria, the other was fungus. In addition, electron microscopy revealed viral particles in the cytoplasm of alveolar epithelial cells and endothelial cells corresponding to coronavirus.

CONCLUSIONDirect injury of SARS-CoV on alveolar epithelium, prominent macrophage infiltration and distinctive fibroblast/myofibroblast proliferation may play major roles in the pathogenesis of SARS.

Adult ; Antibodies, Monoclonal ; metabolism ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Epithelium ; pathology ; Female ; Humans ; Keratins ; immunology ; Lung ; pathology ; ultrastructure ; virology ; Male ; Middle Aged ; Pulmonary Alveoli ; pathology ; Pulmonary Fibrosis ; etiology ; pathology ; SARS Virus ; isolation & purification ; Severe Acute Respiratory Syndrome ; complications ; metabolism ; pathology ; virology