Melatonin ameliorates bupivacaine-induced spinal neurotoxicity in rats by suppressing neuronal NLRP3 inflammasome activation.

Bupivacaine is a common local anesthetic that causes neurotoxicity when used at clinical concentrations. Melatonin (MT), is a potent neuroprotective molecule. The study aimed to characterize the neuroprotective effects of MT on spinal neurotoxicity induced by bupivacaine in rats. It showed that bupivacaine, by intrathecal injection, induced spinal injury, and that the protein levels of Nod-like receptor protein 3 (NLRP3), cleaved caspase-1, and the N-terminal region of gasdermin D (GSDMD-N) were significantly increased. NLRP3 was expressed mainly in neurons and microglia. MT treatment ameliorated bupivacaine-induced spinal cord injury in rats by suppressing activation of neuronal NLRP3 inflammasomes.

Standardization of critical care management of non-critically ill patients with COVID-19.

The large global outbreak of coronavirus disease 2019 (COVID-19) has seriously endangered the health care system in China and globally. The sudden surge of patients with severe acute respiratory syndrome coronavirus 2 infection has revealed the shortage of critical care medicine resources and intensivists. Currently, the management of non-critically ill patients with COVID-19 is performed mostly by non-intensive care unit (ICU) physicians, who lack the required professional knowledge, training, and practice in critical care medicine, especially in terms of continuous monitoring of the respiratory function, intervention, and feedback on treatment effects. This clinical problem needs an urgent solution. Therefore, here, we propose a series of clinical strategies for non-ICU physicians aimed at the standardization of the management of non-critically ill patients with COVID-19 from the perspective of critical care medicine. Isolation management is performed to facilitate the implementation of hierarchical monitoring and intervention to ensure the reasonable distribution of scarce critical care medical resources and intensivists, highlight the key patients, timely detection of disease progression, and early and appropriate intervention and organ function support, and thus improve the prognosis. Different management objectives are also set based on the high-risk factors and the severity of patients with COVID-19. The approaches suggested herein will facilitate the timely detection of disease progression, and thus ensure the provision of early and appropriate intervention and organ function support, which will eventually improve the prognosis.

[Spatiotemporal variations of natural wetland CH4 emissions over China under future climate change].

Based on a new process-based model, TRIPLEX-GHG, this paper analyzed the spatio-temporal variations of natural wetland CH4 emissions over China under different future climate change scenarios. When natural wetland distributions were fixed, the amount of CH4 emissions from natural wetland ecosystem over China would increase by 32.0%, 55.3% and 90.8% by the end of 21st century under three representative concentration pathways (RCPs) scenarios, RCP2. 6, RCP4.5 and RCP8.5, respectively, compared with the current level. Southern China would have higher CH4 emissions compared to that from central and northern China. Besides, there would be relatively low emission fluxes in western China while relatively high emission fluxes in eastern China. Spatially, the areas with relatively high CH4 emission fluxes would be concentrated in the middle-lower reaches of the Yangtze River, the Northeast and the coasts of the Pearl River. In the future, most natural wetlands would emit more CH4 for RCP4.5 and RCP8.5 than that of 2005. However, under RCP2.6 scenario, the increasing trend would be curbed and CH4 emissions (especially from the Qinghai-Tibet Plateau) begin to decrease in the late 21st century.

Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury, involving heme oxygenase-1.

NLRP3 inflammasome activation contributes to acute lung injury (ALI), accelerating caspase-1 maturation, and resulting in IL-1ß and IL-18 over-production. Heme oxygenase-1 (HO-1) plays a protective role in ALI. This study investigated the effect of hemin (a potent HO-1 inducer) on NLRP3 inflammasome in sepsis-induced ALI. The sepsis model of cecal ligation and puncture (CLP) was used in C57BL6 mice. In vivo induction and suppression of HO-1 were performed by pretreatment with hemin and zinc protoporphyrin IX (ZnPP, a HO-1 competitive inhibitor) respectively. CLP triggered significant pulmonary damage, neutrophil infiltration, increased levels of IL-1ß and IL-18, and edema formation in the lung. Hemin pretreatment exerted inhibitory effect on lung injury and attenuated IL-1ß and IL-18 secretion in serum and lung tissue. In lung tissues, hemin down-regulated mRNA and protein levels of NLRP3, ASC and caspase-1. Moreover, hemin reduced malondialdehyde and reactive oxygen species production, and inhibited NF-κB and NLRP3 inflammasome activity. Meanwhile, hemin significantly increased HO-1 mRNA and protein expression and HO-1 enzymatic activity. In contrast, no significant differences were observed between the CLP and ZnPP groups. Our study suggests that hemin-inhibited NLRP3 inflammasome activation involved HO-1, reducing IL-1ß and IL-18 secretion and limiting the inflammatory response.

[Artesunate suppresses human endometrial carcinoma RL95-2 cell proliferation by inducing cell apoptosis].

OBJECTIVE: To investigate the inhibitory effect of artesunate on human endometrial carcinoma RL95-2 cell line proliferation in vitro and the possible mechanisms. METHODS: The inhibitory effect of artesunate on the cell proliferation was assessed with MTT assay. Transmission electron miscrosopy was used to observe the morphological change of the cells after the treatment. Flow cytometry was performed to examine the changes in the cell cycle, reactive oxygen species (ROS) levels (with DCFH-DA labeling) and mitochondrial membrane potential (rhodamine123 staining), and caspase-3 activity was detected by immunohistochemistry. RESULTS: Artesunate inhibited the proliferation of RL95-2 cells with an IC(50) of 26.29 microg/ml. Transmission electron microscopy revealed early apoptotic changes of the cells with obvious chromatin fragmentation. The cell cycle arrest at G(0)/G(1) phase was observed by flow cytometry, and immunohistochemistry demonstrated caspase-3 positivity in cytoplasm. ROS generation in the cells increased obviously after treatment with artesunate for 72 h, which also resulted in lowered mitochondrial membrane potential. CONCLUSION: Artesunate suppressed the proliferation of RL95-2 cells in vitro possibly by inducing cell apoptosis.

[Molecular biologic study on heme oxygenase in experiment pulmonary thromboembolism].

OBJECTIVE: To investigate the changes in heme oxygenase (HO) system expression in pulmonary thromboembolism (PTE), and the influence to the pulmonary artery blood pressure as a result of the changes. METHODS: In 23 healthy adult male dogs, autologous thrombus was injected through the jugular vein to reproduce the PTE model. They were divided randomly into 4 groups: A (pulmonary embolism 3 hours group), B (pulmonary embolism 8 hours group), C (pulmonary embolism 24 hours group) and D (control group). Swan-Ganz catheter was placed via the femoral vein to observe the changes in hemodynamics. Pulmonary artery was obtained to detect the expression of HO-1 using semi-quantity reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical method. RESULTS: The pulmonary artery mean pressure (PAMP), pulmonary artery systolic pressure (PASP) and pulmonary artery diastolic pressure (PADP) of the experimental groups were increased obviously after the pulmonary embolism as compared with those of before the embolism (all P<0.05), and were decreased obviously 1 hour after the embolism (all P<0.05). The decrease was gradual and stopped after 4-5 hours, but the pressure 8 hours after embolism was still higher than that of before embolism. HO-1 was not expressed in pulmonary artery in control group, but expressed after embolism in each experimental group. The expression was increased gradually after pulmonary embolism, and it was remarkable 24 hours after embolism (all P<0.05). CONCLUSION: The expression of HO-1 increased in PTE, and the increased pulmonary artery blood pressure decreased at the same time. The results suggest that HO-1 is related with dilatation of pulmonary artery after PTE.

Interaction between cisplatin, 5-fluorouracil and vincristine on human hepatoma cell line (7721).

AIM:To evaluate the killing effects of CDDP, 5-Fu and VCR on human hepaoma cell line (7721).METHODS:The median-effect principle was used.RESULTS:Killing effects of the individual drug were enhanced as the median concentration increased. Antagonism was produced when two drugs were used at a higher concentration (CI > 1), and synergism was achiened when CI < 1. Finally, the effect was influenced by both the ratios of drug concentration and the sequence of administration.CONCLUSION:The drug administration order and drug concentrations are significant factors that need to be considered in clinical practice.