Efficacy of Xuebijing Injection () on Cardiopulmonary Bypass-Associated Pulmonary Injury: A Prospective, Single-center, Randomized, Double Blinded Trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of Xuebijing Injection (, XBJ) on the lung injury induced by cardiopulmonary bypass (CPB).</p><p><b>METHODS</b>Fifty patients undergoing CPB were randomized to either the saline group or XBJ group according to a random number table (25 cases in each group). The patients in the saline group received saline and patients in XBJ group received XBJ at 12 h prior to the operation, at the beginning of the operation, and at 12 h after the second injection. The PaO/FiO at extubation 3 days post-operation, duration of ventilation in the intensive care unit (ICU), and lengths of stay in the ICU and hospital were recorded. The levels of inflammatory mediators including interleukin (IL)-1β, IL-8, IL-10, and C-reactive protein (CRP) in bronchoalveolar lavage fluid (BALF) and plasma were measured. The neutrophil count and elastase neutrophil elastase in BALF were also measured. In addition, adverse events were monitored.</p><p><b>RESULTS</b>The PaO/FiO in the XBJ group was higher than that in the saline group from 12 to 72 h post-operation (all P<0.05). The blood levels of IL-1β, IL-8, and CRP in the XBJ group from 12 to 72 h were all significantly lower than those in the saline group (all P<0.05). In contrast, the level of the anti-inflammatory cytokine IL-10 was significantly higher in the XBJ group than in the saline group (P<0.05). In addition, 4 patients presented with atelectasis in the saline group and none in the XBJ group. Ten patients experienced mild acute respiratory distress syndrome (ARDS) during hospitalization, and 5 patients with mild ARDS were in the XBJ group (P<0.05).</p><p><b>CONCLUSION</b>XBJ shows protective potential against lung injury in patients who undergo CPB surgery, possibly through the downregulation of inflammatory mediators, reduction in neutrophil infiltration, and upregulation of IL-10 (Trial registry: ChiCTR-TRC-14004628).</p>

Drug-Resistant Mechanism of Multiple Myeloma and Its Therapy Combined with HDACi -Review / 中国实验血液学杂志

Drug resistance of multiple myeloma(MM) has become more and more common, and greatly decreased the survival rate of these patients. The occurence of drug-resistance involves in many factors such as bone marrow microenveronment, tumor cell self-metabolism, cytokines, specific targets and so on. In this review, the potential mechanisms of resistance to glucocorticoid/proteasome inhibitor/immunomodulatory druges are briefly expounded in the aspect of tumor cell self-metabolism, including the changes of heat slock protein expression, mRNA expression, related cytokine levels and down-regulation of thalidomid-effecting site CRBN expression. In this review, the researches on the effect of histone deacetylase inhibitors(HDACi) combined with glucocorticoid, proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies on multiple myeloma, specially, drug-resistant multiple myeloma are also summarized.

Preventive and therapeutic effects of penehyclidine hydrochloride on morphine-induced increased bladder pressure, urinary bladder sphincter pressure and histological damage in rabbits / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Morphine has become the preferred drug for analgesia. However, analgesic doses of morphine can result in urinary retention, which is an intractable problem in clinical practice. Though bladder catheterization is one available therapeutic option, data supporting the technique's effectiveness are controversial. As a novel anti-cholinergic medicine developed in China, penehyclidine hydrochloride (PHC) exhibits greater selectivity for M(3)/M(1) receptors than M(2) receptors. Therefore, this study aimed to determine the efficacy of PHC in treating urinary retention.</p><p><b>METHODS</b>Thirty-two healthy male New Zealand white rabbits were randomly divided in four groups (n = 8 each) as follows: control group (C group), PHC low-dose group (PL group, 0.01 mg/kg of PHC intramuscularly), PHC middle-dose group (PM group, 0.02 mg/kg of PHC intramuscularly), and PHC high-dose group (PH group, 0.05 mg/kg of PHC intramuscularly). All rabbits were injected intravenously with morphine (1 mg/kg) to induce urinary retention and different doses of PHC were injected intramuscularly in the PL, PM and PH groups. In the C group, 1 ml saline was administered instead of PHC. The bladder pressure and the bladder sphincter pressure were recorded at different time points. The plasma concentration of PHC was measured at different time points with high performance liquid chromatography. Arterial blood pressure and heart rate (HR) were recorded at different time points.</p><p><b>RESULTS</b>Bladder pressure and urinary bladder sphincter pressure rose significantly from 30 minutes after morphine administration until the end of the experiment. PHC markedly attenuated the elevations in pressure induced by morphine. Morphometric analysis also revealed histological damage, erythrocytes and ruptures of the microcirculation in regions of the submucosa and smooth muscle. Morphometric damage was ameliorated with PHC but not with saline. Hemodynamic data (mean arterial pressure (MAP) and HR) did not differ between groups over the observation period.</p><p><b>CONCLUSIONS</b>This study demonstrated that intravenous morphine significantly increased bladder pressure and urinary bladder sphincter pressure and induced histological damage in the bladder and urinary bladder sphincter. Importantly, preliminary data showed that PHC could decrease the extent of these changes.</p>

Effects of therapeutic hypercapnia on inflammation and apoptosis after hepatic ischemia-reperfusion injury in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Therapeutic hypercapnia (TH) has been demonstrated to protect several organs ischemia-reperfusion injury. The study aimed to investigate the effects of therapeutic hypercapnia on hepatic ischemia-reperfusion injury (HIRI).</p><p><b>METHODS</b>Thirty adult male Wistar rats weighing (250+/-20) g were randomized into 3 groups (n=10 in each), group C (control group), group A (hypercapnia group) and group B (CO2 preconditioning group). A segmental ischemia of the liver was induced by interrupting the blood vessels including the bile duct to the median and left lateral lobes for 60 minutes and all the animals were sacrificed after 240 minutes observation period of reperfusion. Mean arterial pressure (MAP) and the blood gases were measured before ischemia (baseline) and at 30, 60, 120, 180 and 240 minutes after reperfusion. Arterial blood samples were obtained for determination of serum levels of TNF-alpha, IL-10, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histopathology of liver tissues was evaluated by light microscopy. The NF-kappaB expression and apoptotic hepatocytes were respectively determined by immunohistochemistry and TUNEL assay.</p><p><b>RESULTS</b>The serum levels of liver enzymes and TNF-alpha were significantly decreased while the IL-10 level was significantly increased in groups A and B than in group C (P<0.05), and group B surpassed group A (P<0.05). The histopathological scores, the NF-kappaB immunohistochemical score (IHS) and apoptotic index were significantly lower in groups A and B than in group C (P<0.05), and the decrease in group B was more obvious than in group A (P<0.05).</p><p><b>CONCLUSION</b>Therapeutic hypercapnia attenuates ischemia-reperfusion injury to the liver. Moreover, the effects of CO2 preconditioning are outstandingly notable.</p>

Anti-apoptotic effect of morphine-induced delayed preconditioning on pulmonary artery endothelial cells with anoxia/reoxygenation injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Opioid preconditioning (PC) reduces anoxia/reoxygenation (A/R) injury to various cells. However, it remains unclear whether opioid-induced delayed PC would show anti-apoptotic effects on pulmonary artery endothelial cells (PAECs) suffering from A/R injury. The present study was conducted to elucidate this issue and to investigate the potential mechanism of opioid-induced delayed PC.</p><p><b>METHODS</b>Cultured porcine PAECs underwent 16-hour anoxia followed by 1-hour reoxygenation 24 hours after pretreatment with saline (NaCl; 0.9%) or morphine (1 micromol/L). To determine the underlying mechanism, a non-selective K(ATP) channel inhibitor glibenclamide (Glib; 10 micromol/L), a nitric oxide (NO) synthase blocker NG-nitro-L-arginine methyl ester (L-NAME; 100 micromol/L), and an opioid receptor antagonist naloxone (Nal; 10 micromol/L) were given 30 minutes before the A/R load. The percentage of apoptotic cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. eNOS mRNA level was measured by real-time polymerase chain reaction (PCR). NO content of PAECs supernatants was measured with the Griess reagent.</p><p><b>RESULTS</b>Compared to the A/R PAECs, morphine-induced delayed PC significantly reduced PAECs apoptosis ((18.1 +/- 1.9)% vs (5.5 +/- 0.3)%; P < 0.05), increased NO release ((11.4 +/- 1.3) micromol/L vs (20.5 +/- 2.1) micromol/L, P < 0.05), and up-regulated eNOS gene expression nearly 9 times (P < 0.05). The anti-apoptosis effect of morphine was abolished by pretreatment with Glib, L-NAME and Nal, but the three agent-selves did not aggravate the A/R injury. Furthermore, L-NAME and Nal offset the enhanced release of NO caused by pretreatment with morphine.</p><p><b>CONCLUSIONS</b>Morphine-induced delayed PC prevents A/R injury of PAECs. This effect may be mediated by activation of K(ATP) channel via opioid receptor and NO signaling pathways.</p>

Carbon monoxide inhalation ameliorates conditions of lung grafts from rat brain death donors / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Successful lung transplantation has been limited by the scarcity of donors. Brain death (BD) donors are major source of lung transplantation. Whereas BD process induces acute lung injury and aggravates lung ischemia reperfusion injury. Carbon monoxide (CO) inhalation at 50-500 parts per million (ppm) can ameliorate lung injury in several models. We examined in rats whether CO inhalation in BD donor would show favorable effects on lung grafts.</p><p><b>METHODS</b>Rats were randomly divided into 4 groups. In sham group, donor rats received insertion of a balloon catheter into the cranial cavity, but the balloon was not inflated. In BD-only group, donor rats were ventilated with 40% oxygen after BD confirmation. In BD+CO250 and BD+CO500 groups, donor rats inhaled, after BD confirmation, 250 ppm or 500 ppm CO for 120 minutes prior to lung procurement, and orthotopic lung transplantation was performed. The rats were sacrificed 120 minutes after the lung transplantation by exsanguination, and their blood and lung graft samples were obtained. A total of 8 rats fulfilling the criteria were included in each group.</p><p><b>RESULTS</b>The inhalation decreased the severity of lung injury in grafts from BD donors checked by histological examination. CO pretreatment reversed the aggravation of PaO2/FiO2 in recipients from BD donors. The CO inhalation down-regulated pro-inflammatory cytokines (TNF-alpha, IL-6) along with the increase of anti-inflammatory cytokine (IL-10) in recipient serum, and inhibited the activity of myeloperoxidase in grafts tissue. The inhalation significantly decreased cell apoptosis in lung grafts, inhibiting mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and caspase-3 in lung grafts. Further, the inhalation activated phosphorylation of p38 expression and inhibited phosphorylation of anti-extracellular signal-regulated kinase (ERK) expression in lung grafts. The effects of CO at 500 ppm were greater than those at 250 ppm.</p><p><b>CONCLUSIONS</b>CO exerts potent protective effects on lung grafts from BD donor, exhibiting anti-inflammatory and anti-apoptosis functions by modulating the mitogen-activated protein kinase (MAPK) signal transduction.</p>