Objective To evaluate the relevance of MSCT pulmonary function parameters and pulmonary function test (PFT) parameters, and to define the reference value of MSCT pulmonary function parameters. Methods Thirty male volunteers received clinical PFT and MSCT scan. MSCT scan was perfomed at the end of the maximum inspiratory and maximum expiratory. All data were analyzed with the lung analysis software of computer-aided inspection system correlatedly with pulmonary function parameters. Results The lung volume at full inspiratory volume (Vin) and full expiratory volume (Vex) in MSCT scan had good correlation with total lung capacity (TLC) and residual volume (RV) (r=0.90, P<0.01; r=0.74, P<0.01). Vex/Vin was correlated with RV/TLC (r=0.74, P<0.01), and Vin-Vex was correlated with MVC (r=0.85, P<0.01). In inspiration, the average lung density was (-879.51±32.82) HU, the density per unit volume was (0.12±0.03) g/cm3, while in expiratory they were (-688.14±62.38) HU and (0.31±0.06) g/cm3. Conclusion MSCT pulmonary function tests with the analysis software of computer-aided inspection system have good correlation with PFT.

Objective To compare the anesthetic effects,safety and side effects of the mixture with different ratios of etomidate to propofol in painless gastroscopy.Methods Two hundred patients scheduled for painless gastroscopy,95 males and 105 females,aged 18 to 65 years,BMI 18.5-27.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were randomized into two groups,group A (the ratio of eto-midate and propofol volume 1:1);group B (the ratio of etomidate and propofol volume 1:2).All of the patients were injected with sufentanil 0.1 μg/kg at first.All patients were given the first dose of 0.15-0.2 ml/kg intravenously slowly.Repeated doses of 1-2 ml etomidate-propofol were administered to maintain an adequate level of sedation.HR,SBP,DBP and SpO2were monitored.The dosages of etomidate and propofol were recorded.At the same time the induction time,the operation time,the recovery time and the leaving time were recorded.And low blood pressure,hypoxia saturation,re-spiratory obstruction,muscle fibrillation,nausea and vomiting and other adverse reactions were re-corded.Results There was no significant difference between group A and group B in the induction time,the operation time,the recovery time,the leaving time,perioperative hypotension,periopera-tive hypoxia and injection pain.The dosage of etomidate in the group A was significantly more than in the group B (P<0.01).The dosage of propofol in the group A was significantly less than in the group B(P<0.05).The incidence of myoclonus in group A was notably higher than that in the group B (P<0.01),The incidence of nausea and vomiting in group A was higher than that in the group B (P<0.05).Conclusion Etomidate plus propofol (1:2)had less incidence of myoclonus and nausea and vomiting,and it is more suitable for gastroscopy than 1:1 EP mixture.

Objective:The activation of astrocytes is an important process in the formation of chronic pain.This study aims to observe the activation of A1 reactive astrocytes in the medullary dorsal horn in the rat model of trigeminal neuralgia,and to explore the mechanism of central sensitization caused by A1 reactive astrocyte. Methods:The adult male rats were randomly divided into a sham group and a chronic constriction injury of infraorbital nerve(ION-CCI)group.The facial mechanical pain threshold and thermal withdrawal latency were measured before the operation and on the 1st,3rd,7th,10th,and 14th day after the operation.After pain behavior observation,the expression of glial fibrillary acidic protein(GFAP)in the medullary dorsal horn was observed by immunohistochemistry and immunofluorescence colocalization of GFAP,complement 3(C3)/S100A10,and 4',6-diamidino-2-phenylindole(DAPI)was analyzed.Primary astrocytes were cultured and randomly divided into a naive group and a DHK group.The DHK group was treated with 1 mmol/L of astrocyte activation inhibitor dihydrokainic acid(DHK).Fura-2/AM was used to stain the astrocytes and the calcium wave of the 2 groups under the stimulation of high potassium was recorded and compared.The expression of C3 was detected by Western blotting. Results:The facial mechanical pain threshold and thermal withdrawal latency of the ION-CCI group were significantly lower than those of the sham group(both P<0.05).There were a large number of GFAP positive astrocytes in the medullary dorsal horn of the ION-CCI group.The fluorescence intensity of GFAP in the ION-CCI group was higher than that in the sham group(P<0.05).GFAP and C3/S100A10 were co-expressed in astrocytes.Compared with the sham group,the fluorescence intensity of C3 and the protein expression of C3 in the ION-CCI group were increased(both P<0.05).The expression of C3 in ION-CCI group was significantly increased(P<0.05).Compared with the naive group,the C3 protein expression was significantly decreased in the DHK group(P<0.05).The intensity of calcium fluorescence was increased after high potassium stimulation in both groups.Furthermore,the peak and increase amplitude of calcium fluorescence in the naive group were much higher than those in the DHK group(both P<0.05). Conclusion:A1 reactive astrocytes in the medullary dorsal horn of trigeminal neuralgia model rats are increased significantly,which may participate in central sensitization of trigeminal neuralgia by impacting astrocyte calcium wave.

OBJECTIVE: To explore the analgesic mechanism of intrathecal trichostatin A (TSA) injection in a rat model of neuropathic pain induced by chronic constrictive injury (CCI). METHODS: Male SD rats were randomized into sham operation+ DMSO group (group S), CCI +DMSO group (group C), CCI +10 μg TSA group (group T), and in the latter two groups, rat models of neuropathic pain were established induced by CCI. The rats were given intrathecal injections of 10 μL 5% DMSO or 10 μg TSA (in 5% DMSO) once a day on days 7 to 9 after CCI or sham operation. The rats were euthanized after behavioral tests on day 10, and the lumbar segment of the spinal cord was sampled to determine the expression of histone deacetylase 4 (HDAC4) protein and mRNA and detect the differentially expressed miRNAs using a miRNA chip. MiR-190b-5p and miR-142-3p were selected for validation of the results using RT-qPCR. RESULTS: Compared with those in group S, the rats in group C showed significantly decreased paw withdrawal mechanical threshold (PWMT) from day 3 to day 10 after CCI ( < 0.05); intrathecal injection of TSA significantly reversed the reduction of PWMT following CCI ( < 0.05). Positive HDAC4 expression was detected mainly in the cytoplasm of the neurons in the gray matter of the spinal cord, and was obviously up-regulated after CCI ( < 0.05). Intrathecal injection of TSA significantly suppressed CCI-induced up-regulation of HDAC4 at 10 days after the operation ( < 0.05). Compared with the miRNA profile in group S, miRNA profiling identified 83 differentially expressed miRNAs in group C (fold change ≥2 or ≤0.5, < 0.05); TSA treatment reversed the expressions of 58 of the differentially expressed miRNAs following CCI, including 41 miRNAs that were decreased after CCI but up-regulated following TSA treatment. The results of real-time PCR validated the changes in the expressions of miR-190b-5p and miR-142-3p. CONCLUSIONS TSA suppresses CCI-induced up-regulation of HDAC4 and reverses differential expressions of miRNAs in the spinal cord of rats, which may contribute to the analgesic effect of TSA on neuropathic pain.
Animals ; Histone Deacetylases ; Hydroxamic Acids ; Male ; MicroRNAs ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; Up-Regulation

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3C^pro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we re-purpose these hits towards the main protease (M^pro) of SARS-CoV-2 which shares the 3C-like fold and a similar active site. The hit fragments covalently link to the catalytic cysteine of M^pro to inhibit its activity. We demonstrate that targeting the active site cysteine of M^pro can have profound allosteric effects, distorting secondary structures to disrupt the active dimeric unit.