Objective To observe the clinical value of dexmedetomidine combined with sufentanil in patients with acute myocardial infarction(AMI)after percutaneous coronary artery therapy(PCI).Methods A retrospective study was conducted on patients with AMI,and were divided into control group and treatment group according to different treatment plans.Both groups were given PCI.The control group was given sufentanil,and the treatment group was given dexmedetomidine combined sufentanil.Heart rate(HR),mean arterial pressure(MAP),visual analogue scale(VAS)and Ramsay score were compared between the two groups at different times,myocardial enzyme profile indexes(creatine kinase isoenzyme(CK-MB),N-terminal brain natriuretic peptide precursor(NT-proBNP),myoglobin(MYO),troponinⅠ(cTn Ⅰ)were recorded before and 48 h after surgery,and the occurrence of adverse drug reactions in the two groups were recorded.Results A total of 109 patients with AMI were included in this study,including 54 patients in control group and 55 patients in treatment group.In the control group and the treatment group,the initial 25 min HR were(112.32±10.32)and(97.52±11.32)beat·min-1,the MAP were(105.69±8.72)and(101.69±6.87)mmHg,there were significant differences between the two groups(all P＜0.05).The VAS scores at 6,12,24 and 48 h of control group were 4.58±1.12,4.10±0.78,2.32±0.85 and 2.12±0.59,which in treatment group were 4.12±0.32,3.85±0.92,2.02±0.68 and 1.89±0.42,the differences between the two groups were all statistically significant(all P＜0.05).At 48 h after operation,the CK-MB in control group and the treatment group were(149.42±20.78)and(110.49±17.13)ng·mL-1,the NT-proBNP were(1.09±0.42)and(0.92±0.15)ng·L-1,MYO were(78.51±7.85)and(59.42±7.10)pg·mL-1,cTn Ⅰ were(16.78±3.12)and(11.24±2.57)pg·mL-1,there were statistically significant differences between the two groups(all P＜0.05).There was no significant difference in the incidence of adverse drug reactions between treatment group(9.09％)and the control group(5.56％,P＞0.05).Conclusion Dexmedetomidine combined with sufentanil in the treatment of AMI patients after PCI can improve hemodynamic indexes,and reduce postoperative pain,myocardial enzyme spectrum,and have good safety.

With the rapid development of nanotechnology, the research and development of nanomedicines have become one of the development directions of drug innovation. Nanomedicines have special physical and chemical properties, such as nanoscale effects and nanostructure effects, so they have special biological properties, which may change the pharmacokinetic profiles such as absorption and tissue distribution of drug molecules, and thus affect their safety and effectiveness. There are many special concerns on the non-clinical safety evaluation of nanomedicines at the basis of ordinary drug because of the particularity of nanomedicines. On August 25, 2021, China issued Guidance on Non-clinical Safety Evaluation for Nanomedicines(interim). This article interprets comprehensively the guidance, focuses on the key points of non-clinical safety evaluation for nanomedicines, and expounds combined with some cases, aiming to provide reference for drug researchers.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.

OBJECTIVE: To quantitatively investigate the effects of Ringer's solution with different concentrations of alcohol (1%～80%) on biphasic compound action potentials (AP) from frog sciatic nerve trunk, and their recoveries from alcohol effects. METHODS: Individual segments of frog sciatic nerve trunk with a length of 6 to 8 cm were prepared. Ringer's solution with different concentrations of alcohol (0%, 1%, 2%, 4%, 8%, 16%, 32%, 48%, 64% and 80%) was applied onto the segment of the trunk between the stimulus and ground electrodes via an agent reservoir which was newly armed in a nerve trunk shielded chamber for 5 minutes. The nerve trunk was respectively electro-stimulated to generate the biphasic compound AP which was recorded using the experimental system of BL-420F. This was followed by 5 times washout plus 5 min administration with Ringer's solution before recovery recording of AP. RESULTS: Compared to normal Ringer's solution, Ringer's solution with alcohol at ≤4% did not have dramatic impacts on the AP amplitude and conduction velocity, while Ringer's solution with alcohol at ≥8% there was significant decrease in these two parameters. Ringer's solution with alcohol at the conentrations of 16%, 32% and ≥48% could prevent a small proportion (30%), a large proportion (90%) and all (100%) of sciatic nerve trunks, respectively, from generating AP. Washout with normal Ringer's solution after alcohol application at the concentration of ≤32%, AP could totally recover to normal status. While alcohol at the concentration of 48%, 64% and 80%, the probabilities to regenerate APs were 90%, 40% and 0%, and the AP amplitudes were decreased to 60%, 36% and 0%, respectively. After washout, AP conduction velocity showed no difference with alcohol at the concentration of ≤8% when compared with that before washout, while it could not be recovered to normal under alcohol at ≥16%. CONCLUSION Ringer's solution with different concentrations of alcohol exerts different effects on biphasic compound AP amplitude and conduction velocity. Hopefully, our findings could be helpful for the alcoholic usage and its recovery from alcoholic damage.
Action Potentials ; Animals ; Anura ; Ethanol ; pharmacology ; Ringer's Solution ; pharmacology ; Sciatic Nerve ; drug effects

Objective: To investigate the current status of the occupational hazards of welding fume, manganese, and manganese compounds in the welding environment of a large container manufacturing enterprise, as well as the status of occupational health examination of workers, and to provide a basis for improving the welding environment of this enterprise. Methods: In August 2016, July 2017, and August 2018, convenience sampling was used to perform an on-site occupational hygiene survey of the welding workshop for three consecutive years, and welding fume, manganese and, manganese compounds (counted as manganese dioxide) were measured for their workplace exposure concentrations and exposure levels in workers. A comprehensive analysis was performed for the results of occupational health examination. Results: Welding fume, manganese, and manganese compounds in the welding environment gradually increased from 2016 to 2018 (χ²_trend=5.14 and 5.54, P<0.05). The maximum over-standard rate of concentration-short term exposure limit was 43.3% (13/30) for welding fume and 40.0% (12/30) for manganese and its compounds, and the maximum over-standard rate of time-weighted average concentration was 26.7% (8/30) for welding fume and 23.3% (7/30) for manganese and its compounds. Abnormalities were observed in the occupational health examination of welding workers in 2016-2018, among which respiratory system abnormalities (cough, expectoration, and wheezing), nervous system abnormalities (dizziness, fatigue, sleep disorders, amnesia, hyperhidrosis, and palpitations), and electrocardiogram abnormalities (bundle conduction block) had an incidence rate of above 10.0%, and the incidence rate of abnormalities on posterior-anterior X-ray high-kV chest radiograph was close to 8.9% (30/336) . Conclusion There is severe exposure to welding fume, manganese, and manganese compounds among workers in this enterprise, which cause great hazards to the health of workers. It is necessary to strengthen occupational health management, take measures to improve the welding environment, and enhance occupational disease prevention.

Objective: To investigate the role of microRNA-29b-3p (miRNA-29b-3p) and miRNA-34c-3p in the process of pulmonary fibrosis, we detected the expression levels of miRNA-29b-3p and miRNA-34c-3p in the lung tissue of rats exposed to silica and A549 cells. Methods: SPF male Wistar rats were randomly divided into 1, 7, 14, 21, 28 d control group and silica (SiO₂) dusting group, with 6 rats in each group. One-time non-exposure method was used to infuse 1ml SiO₂ suspension. The rat SiO₂ dusting group was established in the liquid, and the control rats were intratracheally injected with 1 ml of sterile physiological saline in the same manner. The lung tissues of each group were collected at the corresponding time points after dusting. Three of the rats were taken out for pathological observation, and the other three were used to screen differentially expressed miRNAs in lung tissue by miRNA microarray technology. A549 cells were cultured at the in vitro cell level and divided into control group, SiO₂ stimulation group and TGF-β₁ stimulation group, and cells were collected at 12, 24 and 48 h after treatment. The expression levels of miRNA-29b-3p and miRNA-34c-3p in rat lung tissue and A549 cells were verified by real-time PCR (qRT-PCR), target gene prediction of miRNA-29b-3p and miRNA-34c-3p and perform GO enrichment analysis and KEGG pathway analysis. Results: The weight growth rate of the control group was significantly higher than that of the SiO₂ dusting group. Compared with the control group, the lung mass and lung coefficient of the SiO₂ dusting group were significantly increased (P<0.05). The inflammatory response of the lungs in the control group was significantly reduced at 21 and 28 days, and the inflammatory cells infiltrated in the lung tissue of the SiO2 group. The rats in the control group had a small amount of collagen at 21 and 28 days. A large amount of collagen fiber deposition began to appear in the lung tissue of rats exposed to SiO₂ for 21 days. Compared with the control group, the expression levels of miRNA-29b-3p and miRNA-34c-3p in the SiO₂ dusting group were significantly down-regulated, and there was significant difference compared with the control group (P<0.05). The expression levels of miRNA-29b-3p and miRNA-34c-3p in A549 cells treated with SiO₂ and human recombinant TGF-β1 were significantly lower than those in the control group at 24 h and 48 h, and the difference was statistically significant (P<0.05). Conclusion Down-regulation of miRNA-29b-3p and miR-34c-3p in rat lung tissue A549 cells may be associated with the development of early silicosis and is expected to be an indicator of early silicosis diagnosis and prognosis.

OBJECTIVE: To observe the effect and mechanism of crotonaldehyde sub-chronic exposure-induced pyroptosis in pulmonary inflammatory reaction in male rats. METHODS: Specific pathogen-free male Wistar rats were randomly divided into control group and low-, medium-and high-dose groups, with 10 rats in each group. Rats were treated with crotonaldehyde at concentrations of 0.0, 2.5, 4.5, and 8.5 mg/kg body weight by intra-gastric administration, once per day for 120 consecutive days. Rats′ body mass was recorded during exposure. After exposure, the rats were sacrificed, and the lung tissues were isolated. The relative expression of reactive oxygen species(ROS) in lung tissues was detected by fluorescent probes at the end of crotonaldehyde exposure. The fluorescent staining of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3) and Caspase-1 in lung tissues was observed by immunofluorescence microscope. The protein expression of NLRP3, apoptosis-associated spot-like protein(ASC), Caspase-1 precursor(pro-Caspase-1), Caspase-1, interleukin(IL)-1β and IL-18 in lung tissues was determined by Western blotting. RESULTS: At the end of exposure, the body weight gain of rats decreased with the increasing doses of crotonaldehyde(P<0.01). Among them, the body weight gain in the medium-and high-dose groups was lower than that of the control group(P<0.05). After exposure, the lung tissue of each group showed severe inflammatory change with the increasing doses of crotonaldehyde. Immunofluorescence staining showed that the expression of NLRP3 and Caspase-1 in the lung tissues of rats increased in a dose-dependent manner. The relative expression of ROS and the protein of NLRP3, ASC, pro-Caspase-1, Caspase-1, IL-1β and IL-18 in lung tissue of each group increased with the dose of crotonaldehyde(P<0.01). The above indexes of lung tissue in the medium-and high-dose groups were higher than that in the control group(P<0.05). CONCLUSION: Sub-chronic exposure to crotonaldehyde may cause pyroptosis by up-regulating ROS expression in the lung tissues of rats. The up-regulation of Caspase-1 classic dependent pathway leads to pyroptosis, thereby causing inflammatory responses in the lungs.

OBJECTIVETo investigate the effect of intermittent fasting on metabolize and gut microbiota in obese presenium rats fed with high-fat-sugar-diet.

METHODSWe fed the Wistar rats with high-fat and high-sugar diet to induce adiposity, and the rats for intermittent fasting were selected base on their body weight. The rats were subjected to fasting for 72 h every 2 weeks for 18 weeks. OGTT test was performed and fasting blood samples and fecal samples were collected for measurement of TC, TG, HDL-C and LDL-C and sequence analysis of fecal 16S rRNA V4 tags using Illumina. Gut microbial community structure was analyzed with QIIME and LEfSe.

RESULTSAfter the intervention, the body weight of the fasting rats was significantly lower than that in high-fat diet group (P<0.01). OGTT results suggested impairment of sugar tolerance in the fasting group, which showed a significantly larger AUC than compared with the high-fat diet group (P<0.05). Intermittent fasting significantly reduced blood HDL-C and LDL-C levels (P<0.05) and partially restored liver steatosis, and improved the gut microbiota by increasing the abundance of YS2, RF32 and Helicobacteraceae and reducing Lactobacillus, Roseburia, Erysipelotrichaceae and Ralstonia. Bradyrhizobiaceae was found to be positively correlated with CHOL and HDL-C, and RF39 was inversely correlated with the weight of the rats.

CONCLUSIONIntermittent fasting can decrease the body weight and blood lipid levels and restore normal gut microbiota but can cause impairment of glucose metabolism in obese presenium rats.

Animals ; Body Weight ; Diet, High-Fat ; Fasting ; Fatty Liver ; microbiology ; physiopathology ; Gastrointestinal Microbiome ; Lipids ; blood ; Obesity ; microbiology ; physiopathology ; RNA, Ribosomal, 16S ; Rats ; Rats, Wistar