Effect of Xuebijing injection on myocardium during cardiopulmonary bypass: A prospective, randomized, double blind trial.

BACKGROUND: Cardiopulmonary bypass (CPB) is an essential procedure for maintaining the blood supply to vital organs in patients undergoing cardiac surgery. However, perioperative cardiac injury related to CPB remains a severe complication in these patients. Cardiac protection is important for patients undergoing CPB. AIM: To evaluate the potential cardioprotective efficacy of the Chinese medicine preparation Xuebijing injection (XBJ) in patients undergoing CPB. METHODS: Sixty patients undergoing cardiac surgery with CPB were randomly allocated to the XBJ and control groups (saline). XBJ was administered intravenously three times: 12 h prior to surgery, at the beginning of the surgery, and 12 h after the second injection. Cardiac function was evaluated by echocardiography 48 h after surgery. Circulating inflammation- and oxidative-stress-related markers were measured. Clinical outcomes related to intensive care unit (ICU) stay were recorded. RESULTS: Compared to control treatment, XBJ was associated with improved PaO2/FiO2 and cardiac systolic function, but reduced troponin I and creatine kinase fraction after surgery (all P < 0.05). The circulating concentrations of tumor necrosis factor-α, interleukin (IL)-1ß and IL-8 in the XBJ group were significantly lower than those in the control group (all P < 0.05), whereas the circulating concentration of IL-10 was significantly higher in the XBJ group (P < 0.05). In addition, the lengths of ICU stay and hospitalization after surgery tended to be shorter in the XBJ group than in the control group, although the differences were not significant. CONCLUSION: Perioperative administration of XBJ was associated with attenuated cardiac injury during CPB, likely via anti-inflammatory and antioxidative mechanisms.

Ac2-26 Alleviates Brain Injury after Cardiac Arrest and Cardiopulmonary Resuscitation in Rats via the eNOS Pathway.

BACKGROUND: Brain injury is the leading cause of death following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Ac2-26 and endothelial nitric oxide synthase (eNOS) have been shown to reduce neuroinflammation. This study is aimed at determining the mechanism by which Ac2-26 protects against inflammation during brain injury following CA and CPR. METHODS: Sixty-four rats were randomized into sham, saline, Ac2-26, and Ac2-26+L-NIO (endothelial nitric oxide synthase (eNOS) inhibitor) groups. Rats received Ac2-26, Ac2-26+L-NIO, or saline after CPR. Neurologic function was assessed at baseline, 24, and 72 hours after CPR. At 72 hours after resuscitation, serum and brain tissues were collected. RESULTS: Blood-brain barrier (BBB) permeability increased, and the number of surviving neurons and neurological function decreased in the saline group compared to the sham group. Anti-inflammatory and proinflammatory factors, neuron-specific enolase (NSE) levels, and the expression of eNOS, phosphorylated (p)-eNOS, inducible nitric oxide synthase (iNOS), and oxidative stress-related factors in the three CA groups significantly increased (P < 0.05). BBB permeability decreased, and the number of surviving neurons and neurological function increased in the Ac2-26 group compared to the saline group (P < 0.05). Ac2-26 increased anti-inflammatory and reduced proinflammatory markers, raised NSE levels, increased the expression of eNOS and p-eNOS, and reduced the expression of iNOS and oxidative stress-related factors compared to the saline group (P < 0.05). The effect of Ac2-26 on brain injury was reversed by L-NIO (P < 0.05). CONCLUSIONS: Ac2-26 reduced brain injury after CPR by inhibiting oxidative stress and neuroinflammation and protecting the BBB. The therapeutic effect of Ac2-26 on brain injury was largely dependent on the eNOS pathway.

Ac2-26 ameliorates lung ischemia-reperfusion injury via the eNOS pathway.

BACKGROUND: Lung ischemia-reperfusion injury (LIRI) is a major complication after lung transplantation. Annexin A1 (AnxA1) ameliorates inflammation in various injured organs. This study aimed to determine the effects and mechanism of AnxA1 on LIRI after lung transplantation. METHODS: Thirty-two rats were randomized into sham, saline, Ac2-26 and Ac2-26/L groups. Rats in the saline, Ac2-26 and Ac2-26/L groups underwent left lung transplantation and received saline, Ac2-26, and Ac2-26/L-NIO, respectively. After 24 h of reperfusion, serum and transplanted lung tissues were examined. RESULTS: The partial pressure of oxygen (PaO2) was increased in the Ac2-26 group compared to that in the saline group but was decreased by L-NIO treatment. In the Ac2-26 group, the wet-to-dry (W/D) weight ratios, total protein concentrations, proinflammatory factors and inducible nitric oxide synthase levels were notably decreased, but the concentrations of anti-inflammatory factors and endothelial nitric oxide synthase levels were significantly increased. Ac2-26 attenuated histological injury and cell apoptosis, and this improvement was reversed by L-NIO. CONCLUSIONS: Ac2-26 reduced LIRI and improved alveoli-capillary permeability by inhibiting oxygen stress, inflammation and apoptosis. The protective effect of Ac2-26 on LIRI largely depended on the endothelial nitric oxide synthase pathway.

Endothelial Colony-forming Cells Attenuate Ventilator-induced Lung Injury in Rats with Acute Respiratory Distress Syndrome.

BACKGROUND: Mechanical ventilation (MV) can cause ventilator-induced lung injury (VILI). AIM OF THE STUDY: This study investigated whether endothelial colony-forming cells (ECFC) could inhibit VILI in a rat model of acute respiratory distress syndrome (ARDS). METHODS: Male Wistar rats received the femoral artery and venous cannulation (sham group) or were injected intravenously with 500 µg/kg lipopolysaccharide to induce ARDS. The ARDS rats were subjected to MV. Immediately after the MV, the rats were randomized and injected intravenously with vehicle (ARDS group) or ECFC (ECFC group, n = 8 per group). The oxygen index, lung wet-to-dry weight (W/D) ratios, cytokine protein levels in serum or bronchoalveolar lavage fluid (BALF), neutrophil counts, neutrophil elastase and total protein levels in BALF, histology and cell apoptosis in the lung were detected. The protein levels of endothelin-1, inducible nitric oxide synthase (iNOS), endothelial NOS, matrix metalloproteinase (MMP)-9, Bax, Bcl-2, gelsolin, cleaved caspase-3, phosphorylated NF-κBp65 and myosin light chain (MLC) in the lung were analyzed. RESULTS: Compared with the ARDS group, treatment with ECFC significantly increased the oxygen index, and decreased the lung W/D ratios and injury, and the numbers of apoptotic cells in the lungs, neutrophils counts, total protein and elastase concentrations in BALF of rats. ECFC treatment significantly minimized the protein levels of pro-inflammatory cytokines in BALF and serum, but increased interleukin 10 in rats. Furthermore, ECFC treatment significantly reduced the protein levels of endothelin-1, iNOS, Bax, Gelsolin, MMP-9, cleaved caspase-3, phosphorylated NF-κBp65 and MLC, but enhanced eNOS and Bcl-2 in the lungs of rats. CONCLUSIONS: Therefore, ECFC attenuated inflammation, cell apoptosis and VILI in ARDS rats.

Yangzheng Sanjie decoction regulates proliferation and apoptosis of gastric cancer cells by enhancing let-7a expression.

AIM: To explore the let-7a-mediated anti-cancer effect of Yangzheng Sanjie decoction (YZSJD) in gastric cancer (GC) cells. METHODS: YZSJD-containing serum (YCS) was prepared using traditional Chinese medicine serum pharmacology methods. After YCS treatment, cell proliferation and apoptosis were assessed by cell counting kit-8 assay and flow cytometry, respectively, and miRNA expression profiles were determined using qPCR arrays. Let-7a expression was examined by in situ hybridization in GC tissues and by qPCR in GC cells. c-Myc protein expression was detected by immunohistochemistry in GC tissues, and by Western blot in cell lines. RESULTS: YZSJD significantly inhibited proliferation and induced apoptosis in AGS and HS-746T GC cells. After treatment with YCS, the miRNA expression profiles were altered and the reduced let-7a levels in both cell lines were up-regulated, accompanied by a decrease in c-Myc expression. Moreover, decreased let-7a expression and increased c-Myc expression were observed during the progression of gastric mucosa cancerization. CONCLUSION: YZSJD inhibits proliferation and induces apoptosis of GC cells by restoring the aberrant expression of let-7a and c-Myc.

[Combined external radiotherapy and 125I-particle implantation for treatment of head and neck cancers].

OBJECTIVE: To evaluate the relative incidence of local control and toxicity in patients with head and neck cancers who underwent external beam radiotherapy (EBRT) plus (125)I seeds implantation. METHODS: Ten patients diagnosed as head and neck cancers at the department of oral and maxillofacial surgery of Peking University School of Stomatology during the period of February 2008 to July 2010 were collected. The histologic types included squamous cell carcinoma in 8 patients, poorly differentiated adenocarcinoma of salivary gland in 2 patients. All patients could not receive surgical treatment due to poor medical status or unresectable advanced-stage tumors and underwent EBRT plus (125)I seeds implantation. Eight patients with squamous cell carcinoma had conventional fractionated EBRT with a total dose of 50 Gy; two patients with poorly differentiated adenocarcinoma had conventional fractionated EBRT with a total dose of 70 Gy. They all then had (125)I seeds implantation with matched peripheral dose of 60 Gy (TNM stage I-II) or 80 Gy (TNM stage III-IV ). The apparent activity per seed ranged from 25.9 to 29.6 MBq. follow-up of the patients was done to analyze acute and late toxicity, local control, and survival. RESULTS: After a median follow-up of 12 months (range 2-28 months), soft tissue necrosis was seen in one patient, dysphagia and hemorrhage in another. No other serious side effects were observed. All the tumor mass of 10 cases disappeared within 6 months, regional metastases was observed in one patient, and distant metastases was observed in another. Seven of 10 patients survived till the date of investigation. CONCLUSION: External beam radiotherapy plus (125)I seeds implantation is a safe and effective therapy regimen for patients with unrectable head and neck cancers.