BackgroundPerioperative hypertension requires careful management. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) have shown efficacy in treating hypertension associated with surgery. However, there is lack of consensus about whether they can prevent mortality and morbidity. ObjectivesTo systematically assess the benefits and harms of administration of ACEIs or ARBs perioperatively for the prevention of mortality and morbidity in adults (aged 18 years and above) undergoing any type of surgery under general anaesthesia.

The mainstay of malaria diagnosis relies on rapid diagnostic tests (RDTs) and microscopy, both of which lack analytical sensitivity. This leads to repeat testing to rule out malaria. A prospective diagnostic trial of the Meridian illumigene Malaria assay (loop-mediated isothermal amplification [LAMP]) was conducted comparing it with reference microscopy and RDTs (BinaxNOW Malaria) in returning travelers between June 2017 and January 2018. Returning travelers with signs and symptoms of malaria were enrolled in the study. RDTs, microscopy, and LAMP assays were performed simultaneously. A total of 298 patients (50.7% male; mean age, 32.5 years) were enrolled, most visiting friends and relatives (43.3%), presenting with fever (88.9%), not taking prophylaxis (82.9%), and treated as outpatients (84.1%). In the prospective arm (n = 348), LAMP had a sensitivity of 98.1% (95% confidence interval [CI], 90.0%–100%) and a specificity of 97.6% (95% CI, 95.2%–99.1%) vs microscopy. After discrepant resolution with real-time polymerase chain reaction, LAMP had a sensitivity of 100% (95% CI, 93.7%–100%) and a specificity of 100% (95% CI, 98.7%–100%) vs microscopy. After discrepant resolution, RDTs had a sensitivity of 83.3% (95% CI, 58.6%–96.4%) and a specificity of 96.2% (95% CI, 93.2%–98.1%) vs microscopy. When including retrospective specimens (n = 377), LAMP had a sensitivity of 98.8% (95% CI, 93.2%–100%) and a specificity of 97.6% (95% CI, 95.2%–99.1%) vs microscopy, and after discrepant resolution of this set, LAMP had a sensitivity of 100% (95% CI, 95.8%–100%) and a specificity of 100% (95% CI, 98.7%–100%). A cost-benefit analysis of reagents and labor suggests savings of up to USD$13 per specimen using a novel algorithm with LAMP screening.

To investigate the regulatory role of RhoA/Rho kinase in the effects of fluvastatin (Flu) on the tumor necrosis factor-(TNF-) induced expression of tissue factor (TF) in human umbilical vein endothelial cells (HUVECs) which may provide basis for the prevention of arterial thrombosis, HUVECs in logarithmic phase were divided into TNF-group, Flu group and TNF-+Flu group. enzyme-linked immunosorbent assay (ELISA), real time polymerase chain reaction (RT-PCR) and western blot assay were employed to detect the content of TF, messenger ribonucleic acid (mRNA) expression of TF and protein expressions of TF and activated RhoA, respectively. Then, angiotensin II (Ang II) and Y27632 were used to treat these cells which were then divided into control group, TNF+Ang II group, AngII group, TNF-group and TNF-+Y27632 group. Western blot assay was performed to detect the protein expression of TF. After TNF-treatment, the content and mRNA and protein expressions of TF were markedly increased when compared with the control group (P<0.05). However, the content and mRNA and protein expressions of TF in Flu group were significantly lower than those in TNF-group (P<0.05). Our results showed TNF-could induce TF expression in HUVECs and activate RhoA, which, however, were inhibited by Flu. Ang II treatment could increase the TNF-induced TF expression in HUVECs which however was inhibited Y27632. Flu could effectively inhibit the TNF-induced protein and mRNA expressions of TF in HUVECs in which RhoA/Rho signaling pathway may play an important role.

The parasympathetic nervous system has been known to modify innate immune responses. In animal models, acetylcholine (Ach) released from the distal ends of nerves has been shown to inhibit inflammatory responses such as endotoxic shock, pancreatitis, intestinal inflammation, etc. However, its role in LPSinduced fulminant hepatitis remains to be elucidated. Here, we demonstrate that the vagus nerve acts as a suppressor in the liver after challenge with LPS plus Dgal. The vagus nerve acts through the a7 AchR expressed on the surface of Kupffer cells, inhibiting the production of the proinflammatory cytokines TNF and IL-6. A mechanism study revealed that the suppressive effect of Ach may occur through the activation of Src kinase and subsequent inhibition of the Myd88 signal pathway. Our study has suggested a suppressive role of vagus nerve in the modulation of liver inflammatory responses, which should be noticed during clinical massive hepatectomy and liver transplantation. The nicotinic anti-inflammatory pathway may also be a potential target for sepsis after liver transplantation.

Neuroinflammation plays an important role in the induction and maintenance of chronic pain. Orchestra of pattern-recognition receptor-induced pro-inflammatory and anti-inflammatory cytokines is critical for inflammation homeostasis. CD11b on macrophages could inhibit toll-like receptor (TLR) activation-induced inflammatory responses. However, the function of CD11b on microglia remains unknown. In the current study, we demonstrated that CD11b-deficient microglia cells produced more inflammatory cytokines, such as interleukin-6 and tumor necrosis factor alpha, while less anti-inflammatory cytokines. Signal transduction assay confirmed that nuclear factor-κB activation was increased in CD11b-deficient microglia cells, which resulted from decreased activation of Src. Inhibition of Src by PP1 increased inflammation in wild-type microglia cells significantly, but not in CD11b-deficient microglia cells. In vivo, CD11b-deficient mice were more susceptible to chronic constrictive injury-induced allodynia and hyperalgesia with significantly more inflammatory cytokines expression. All these results indicated that the regulatory function of CD11b-Src signal pathway on both inflammatory and anti-inflammatory cytokines in microglia cells is a potential target in neuropathic pain treatment.