Objective To investigate the reliability and feasibility of spectral entropy in evaluate the effectiveness of analgesic sedation in patients with ischemic stroke.Methods A total of 64 patients with acute ischemic stroke admitted to Hongqi Hospital Affiliated to Mudanjiang Medical University from July 2021 to November 2022 were selected as study objects,and the included patients were divided into control group and experimental group according to random number table method,with 32 cases in each group.Patients in control group adjusted analgesia and sedation regimen according to Richmond agitation-sedation scale(RASS)score and critical-care pain observation tool(CPOT)score.Patients in experimental group adjusted the analgesic and sedation regimen according to the results of spectral entropy.The vital signs,C-reactive protein(CRP),dose of sedative and analgesic drugs and incidence of adverse reactions were compared between two groups.The correlation between spectral entropy and RASS score and CPOT score was used Spearman correlation analysis.Results The spectral entropy values were positively correlated with the RASS score and CPOT score,respectively(r=0.719,0.556,P<0.001).There were no significant differences in mean arterial pressure and percutaneous arterial oxygen saturation between two groups at different time points(P>0.05).The heart rate at T3 in experimental group was significantly lower than that in control group(P<0.05).At T1,T2 and T3,CRP levels in experimental group were significantly lower than those in control group(P<0.05).The dosage of sufentanil and midazolam in experimental group were significantly lower than those in control group(P<0.05).The incidence of adverse reactions in experimental group was significantly lower than that in control group(12.50%vs.34.38%,χ2=4.267,P=0.039).Conclusion Spectral entropy can be used as an objective method to monitor the depth of analgesia and sedation in patients with ischemic stroke,and has a good correlation with RASS score and CPOT score,which can reduce the incidence of adverse reactions,effectively avoid stress reactions,and reduce the application of analgesia and sedation drugs.

Objective:To evaluate the effect of berberine on acute kidney injury (AKI) in rats undergoing liver transplantation and the role of AMP-activated protein kinase (AMPK).Methods:Twenty-four SPF-grade adult male Sprague-Dawley rats, aged 12 weeks, weighing 210-230 g, were divided into 4 groups ( n=6 each) using the random number table method: sham operation group (S group), AKI group, berberine group (BBR group), and berberine + AMPK inhibitor Compound C group (BBR-Comp C group). In BBR group, berberine 200 mg/kg was given by gavage starting from 2 weeks before surgery, once a day for 14 consecutive days. In BBR-Comp C group, Compound C 1 mg/kg was injected into the tail vein at 30 min before surgery. The rat AKI model was prepared by in situ liver transplantation in AKI group, BBR group and BBR-Comp C group. Blood specimens were taken from the inferior vena cava at 24 h postoperatively, and serum BUN and Cr concentrations were determined by enzyme-linked immunosorbent assay. Then the rats were sacrificed, and the kidney tissues were taken for microscopic examination of the pathological changes (with the light microscope after HE staining) and for determination of the expression of phosphorylated AMPK (p-AMPK), receptor-interacting protein kinase-1 (RIPK-1), receptor-interacting protein kinase-3 (RIPK-3) and mixed lineage kinase domain-like protein (MLKL) (by Western blot). Results:Compared with S group, the serum BUN and Cr concentrations were significantly increased, the p-AMPK expression was down-regulated, the expression of RIPK-1, RIPK-3 and MLKL was up-regulated ( P<0.05), and the pathological damage to renal tissues occurred in AKI group. Compared with AKI group, the serum BUN and Cr concentrations were significantly decreased, the p-AMPK expression was up-regulated, the expression of RIPK-1, RIPK-3 and MLKL was down-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in BBR group. Compared with BBR group, the serum BUN and Cr concentrations were significantly increased, the p-AMPK expression was down-regulated, and the expression of RIPK-1, RIPK-3 and MLKL was up-regulated in BBR-Comp C group ( P<0.05). Conclusions:Berberine can attenuate AKI in rats undergoing liver transplantation, and the mechanism may be related to the promotion of AMPK phosphorylation and inhibition of programmed necrosis.

On March 24, 2017, a patient with Von Hippel-Lindau syndrome (VHL) characterized by bilateral adrenal pheochromocytoma and pancreatic tumors was admitted to our hospital, who underwent simultaneous pancreatic body and tail tumor resection, bilateral adrenal tumor resection and Omentum transplantation of the right adrenal gland.Intraoperative hormone therapy was used. Part of the normal adrenal tissue was preserved and embedded in the omentum, but an adrenal crisis occurred on the first day after the operation.The hormone replacement was used. Postoperative hormone replacement therapy was performed for 6 months. After 4 years of follow-up, blood pressure was normal, no cortical dysfunction, no tumor recurrence or other related lesions appeared. The preserved part of adrenal tissue during simultaneous multi-organ tumor resection for such patients can reduce long-term hormone replacement after surgery and prevent late adrenal cortex dysfunction.

The teaching contents of graduate medical developmental biology are rich and abstruse, which makes it insufficient to reach the goal of cultivating higher-quality graduate students by traditional teaching methods. In current years, we have constructed and practiced the modular teaching model for the course of graduate medical developmental biology. By dividing the teaching contents into models, including basic development principle, model organisms, hotspot of medicinedevelopmentalbiologyresearch and main technologies and methods, we aim to meet all needs of students, enhance the practicality of our course, improve students' innovation abilities and comprehensive quality, and efficiently increase the quality of our education.

Tong-Mai(TM) granules were composed ofRadix Salviae Miltiorrhizae(Danshen),Rhizoma Chuanxiong(Chuanxiong) andRadix Puerariae(Gegen). It had the effect of activating blood circulation. It had been used to treat ischemic cardio-cerebrovascular diseases in the clinical practice. This research combined serum pharmacochemistry and serum pharmaocology to study the material basis of active components in TM granules. After single or multiple intragastric administrations of TM granules, serum blood samples of rats were collected at different time points. LC-MS/MS method was developed to analyze chemical components of TM in blood serum samples. The cardiomyocyte hypoxia / reoxygenation (H/R) model was used in the evaluation of cardiomyocyte protection by TM. The correlation analysis was also conducted between serum concentration of TM and cardiomyocyte activity. The results showed that 8 components of pueraria flavonoid, 5 components of salvianolic acids and 2 components fromGegen were promptly absorbed and reached their highest concentrations at 5 or 30 min after administration. After 3 times of medication, the serum concentration was obviously higher compared to single medication. The drug-serum of TM showed significant protective effect on the cardiomyocyte H/R injury with dose-effect relationship. Daidzein, lithospermic acid, salvianolic acid A, salvianic acid A and rosmarinic acid presented as the most correlated components linked to the effect of activating blood circulation by TM. The serum pharmacochemistry / serum pharmacology related studies provided references for the verification of material basis of active components in compound Chinese medicine.

Since alkaloids are the major active constituents of Rhizoma corydalis (RC), a convenient and accurate analytical method is needed for their identification and characterization. Here we report a method to profile the alkaloids in RC based on liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS/MS). A total of 16 alkaloids belonging to four different classes were identified by comparison with authentic standards. The fragmentation pathway of each class of alkaloid was clarified and their differences were elucidated. Furthermore, based on an analysis of fragmentation pathways and alkaloid profiling, a rapid and accurate method for the identification of unknown alkaloids in RC is proposed. The method could also be useful for the quality control of RC.

Sai-Luo-Tong (SLT) is a compound preparation composed of ginseng, ginkgo and saffron for the treatment of vascular dementia. In order to identify its material foundation and provide evidence for therapeutic regimen, the plasma concentration, pharmacokinetics and brain distribution of ginkgolides were investigated after intragastric ad-ministration of SLT. An LC-MS/MS method was developed for the determination of 4 ginkgolides in rat plasma and brain simultaneously. Statistical analysis of obtained data demonstrated that the method had achieved the desired lin-earity, precision, accuracy and sensitivity. The results showed that after administration of SLT at the dose of 60 mg·kg-1, 4 ginkgolides were all absorbed into systemic circulation with AUC value in the order of bilobalide B (BB) >ginkgolide A (GA) > ginkgolide B (GB) > ginkgolide C (GC). All ginkgolides exhibited short half lives less than 2.8 h among which BB showed the shortest t1/2 of 1.61 h. The determination of brain distribution at different time after dos-ing revealed ginkgolides entered into brain promptly dominated by GA and BB. The concentrations of 4 ginkgolides in brain were much lower than these in plasma and declined along with time rapidly. It was concluded that ginkgolides can be absorbed in blood and penetrated into brain rapidly. GA, BB and GB might be main components which effect both periphery and brain collectively by means of their specific mechanism to achieve the therapeutic efficacy on vascular dementia of SLT.

OBJECTIVETo observe the protective effect of serum containing Tanyu Tongzhi formula (TYTZF) on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) injury and detect its mechanism on anti-artherosclerosis.

METHODHUVECs were pretreated with serum containing TYTZF and simvastatin respectively for 2 hours and then added with 100 mg x L(-1) of ox-LDL and laid aside for 24 hours. The activity of HUVECs were measured by the methyl thiazolyl tetrazolium (MTF) method and the NO content in cell culture supernatants were examined by the Griess method. The mRNA levels of Cav-1 and eNOS were measured by the Real-time PCR method. The protein expression of Cav-1 and eNOS were detected by Western blotting.

RESULTThe activity of HUVECs was significantly decreased after ox-LDL treatment (P < 0.01) and this decrease was significantly inhibited by serum containing TYTZF and simvastatin of different doses (P < 0.05). They could enhance the NO content in cell culture supernatants, down-regulate the expression of Cav-1 and up-regulate the expression of eNOS at mRNA and protein levels, which was especially notable after treatment with serum containing TYTZF and simvastatin in large doses.

CONCLUSIONTYTZF has the protective effect on HUVECs by increasing the production of NO and up-regulating Cav-1 expression and down-regulating eNOS expression.

Animals ; Caveolin 1 ; metabolism ; Cell Line ; Drugs, Chinese Herbal ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Lipoproteins, LDL ; pharmacology ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum ; chemistry

OBJECTIVEA sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method has been developed and validated for the determination of brucine and strychnine in rat plasma.

METHODSamples were extracted by ethyl acetate-n-butanol (7: 3). Chromatographic separation was operated on ZORBAX XDB-C18 column with gradient elution of acetonitrile-methanol-water (0.05% acetic acid and 10 nmol x L(-1) ammonium formate contained), followed by LC-MS/MS in positive electrospray ionization. Quantification was carried out on multiple reaction monitoring (MRM) of the transition m/z 395.2/324.2, m/z 335.2/184.2 and m/z 199.1/171.1 for brucine, strychnine and tacrine (internal standard), respectively.

RESULTThe method was linear in the range of 0.195-100 and 0.07840 microg x L(-1) for brucine and strychnine, with coefficient correlation 0.994 and 0.996 respectively. The recoveries of extraction were 78.9% - 102.4% for brucine and 95.2% - 106.1% for strychnine. Precision, accuracy, stability and matrix effect of the analytes met the requirement. The method was applied to a pharmacokinetic study of brucine and strychnine after cutaneous administration of Semen Strychni niosome gel. The C(max) were (26.20 +/- 5.81) and (12.50 +/- 3.00) microg x L(-1) while the AUC(0-infinity), were (193.75 +/- 39.43) and (98.25 +/- 28.54) microg x h x L(-1) of the two components.

CONCLUSIONWe conclude that the niosomes may reduce the systemic exposures and prolong the local release of brucine and strychnine.

Administration, Cutaneous ; Analgesics ; analysis ; pharmacokinetics ; Animals ; Chromatography, Liquid ; Convulsants ; analysis ; pharmacokinetics ; Female ; Gels ; chemistry ; Liposomes ; chemistry ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Seeds ; chemistry ; Semen ; chemistry ; Specific Pathogen-Free Organisms ; Strychnine ; analogs & derivatives ; analysis ; pharmacokinetics ; Strychnos nux-vomica ; chemistry ; Tandem Mass Spectrometry

The rat model of multi-infarct was adopted in this study to elucidate the protective mechanism of Sailuotong capsule (Sailuotong) in recovery period of multiple cerebral infarction. The effects of Sailuotong on levels of Glu, GABA and the expression of NMDA receptor subtypes including NR1, NR2A and NR2B, were detected. The multi-infarct model rats were established by injecting embolizing microsphere via internal carotid artery, and were given Sailuotong treatment (16.5 and 33.0 mg x kg(-1)) for 60 days. The pathological changes in brain ultrastructure were observed by transmission electron microscope. The levels of Glu and GABA in brain tissue were measured with high performance liquid chromatography. The expression of NMDA receptors including NR1, NR2A and NR2B in neurons was evaluated by immunohistochemical staining. Compared with the sham rats, abnormal changes were observed in ultrastructures of neurons, neuroglia cells and synapses of model rat brains. Moreover, significant decrease of Glu and GABA, as well as the elevated expression of NR1, NR2A and NR2B were detected in brain tissues. Sailuotong (16.5 and 33.0 mg x kg(-1)) could improve ultrastructure of cerebral tissue, facilitate synthesis of Glu and GABA, and down-regulate expression of NR1, NR2A and NR2B in neurons. The results demonstrated that Sailuotong could exert neuroprotective effects to some extent in the recovery phase of multiple cerebral infarction by promoting expression of NMDA receptors and synthesis of Glu and GABA.