Objective To study the changes in the central nervous system in adult mice after various degrees of acute heat stress. Methods Adult mice placed in insulated cages were exposed to 24℃, 34℃, 37℃, 38.5℃, 40℃ or 42℃ for 60min respectively with a constant humidity of 60%. The behavior response was carefully monitored. Rectal temperature was measured before the exposure and after the exposure. Electroencephagrams were taken. Then the hippocampal neurons of these animals were examined with transmission electron microscope. Results Heat stress at 34℃ for 60 min only raised the rectal temperature, and heat stress above 37℃ for 60 min not only raised rectal temperature, but also induced water loss and irritability and attempt to escape. Abnormal EEG with increased amplitude and retarded rhythm could be observed. However, when mice were exposed to 24℃ and 34℃ such behavior did not appear. After exposure to 42℃, EEG frequency increased and pathological changes in hippocampus neurons were found. The main ultrastructural changes included degeneration of hippocampal neurons, expansion of space around capillary, decrease in number of synaptic vesicle, and decomposition of synapse. Conclusion Mice were very sensitive to heat stress. An increase in core temperature could induce behavioral thermoregulation. EEG and electron microscopic study revealed changes in the central nervous system after heat stress. Following exposure to high environmental temperature under 40℃, acute dysfunction of brain was reversible. At 42℃, damage to the brain tissue occurred, and most mice died of heat stroke.

Objective:Based on relevant database data analysis,to explore the correlation of the abnormal expression of EMT related factors and chronic obstructive pulmonary disease and its related non-small cell lung cancer.Methods: Based on some data sets of GEO in the NCBI database,to perform express analysis,survival analysis and correlation analysis.Results: ①Snai1 and other EMT related regulatory factors exist significantly higher expression in non-small cell lung cancer patients,and E-cadherin (CDH1) was showed significantly lower expression. ②A large number of COPD patients samples were analyzed,and some EMT-related molecules in patients with COPD also showed significant abnormal expression and consistented with the changes in patients with non-small cell lung cancer.Conclusion: The results showed that dysregulation expression of EMT related regulatory factors may have some correlation with disease progression of COPD patients through the EMT markers and their expression and correlation analysis in COPD patients.

Objective:To explore the clinical characteristics and influencing factors of myocarditis induced by immune checkpoint inhibitors (ICIs).Methods:Using programmed death receptor-1 (PD-1), nivolumab, pembrolizumab, programmed cell death receptor ligand-1 (PD-L1), atezolizumab, durvalumab, avelumab, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), ipilimumab, tremelimumab as keywords respectively, we combined these words with myocarditis or the corresponding Chinese to search.Results:A total of 49 articles were reported, including 64 patients. Nivolumab was the most reported, followed by pembrolizumab and ipilimumab. The average age was (65.47±13.24)years, mainly elderly patients; 37 cases (57.81%) were male; the overall mortality rate was 31.25%(20/64). The clinical symptoms were diverse and nonspecific, with dyspnea being the most common (39/64, 60.94%). Heart biomarkers were elevated in 94.64%(53/56) of the patients. 35 patients (54.69%, 35/64) developed myocarditis after 1-2 doses and 17 patients died. 60 patients received steroids as initial treatment, and immunosuppressive therapies such as infliximab, intravenous immunoglobulin, antithymic globulin, and/or plasmapheresis were used in 25 patients, symptoms improved in 17 cases (68.00%).Conclusions:ICIs can cause myocarditis, with high mortality, and should be closely monitored and timely treatment. Steroids can be used as initial first-line therapy and immunosuppressants and/or plasmapheresis may improve clinical symptoms and survival rate.

Codon bias is an important factor which influences heterologous gene expression. Optimizing codon sequence could improve expression level of heterologous gene. In order to improve the expression level of BmK AngM1 gene encoding the analgesic peptide from Buthus martensii Karsch in Pichia pastoris, the codon-optimized BmK AngM1 gene according to its cDNA sequence and the preference codon usage of P. pastoris were cloned into expression vector pPIC9K and then transformed into P. pastoris. The expersion of recombinant BmK AngM1 (rBmK AngM1) was inducced by methanol in the medium, and the expression level of the optimized BmK AngM1 gene was 3.7 times of the native one. These results suggested that the expression of BmK AngM1 in P. pastoris could be successfully improved by codon optimization.

Objective To investigate the protective effects of Digoxin on cardioventricular function in rats after simulated weightlessness.Methods Eighty rats were divided randomly into 5 groups:control(Con)group,tail-suspended+sham feeding(TS+SF)group,tail-suspended+Digoxin 2 wk(TS+D2)group and tail-suspended+Digoxin 3 wk(TS+D3)group.The TS+SF group was given the distilled water.At the end of tail-suspended for 3 weeks,the heart function of 10 rats in each group was examined with echocardiography.The level of atrial natriuretic polypeptide(ANP)in serum was measured with immunoradiometric assay in other 6 rats.Results Compared with TS+SF group,the contractile function of LV improved in TS+D2 and TS+D3 groups(P0.05).Conclusion Digoxin can improve muscle contractile and blood ejection of LV and retard the tendency of atrophy in simulated weightlessness.

OBJECTIVE: To investigate the main point of long backbone fracture caused by blunt force in forensic clinical identification and to provide a reference for the inspection and appraisal practices of such injury. METHODS: Ninety-nine cases of adult long backbone fractures were collected from January 2006 to December 2013 in Gutian County of Fujian Province. According to the terms of fracture location, mode of injury, type, the data were summarized. RESULTS: In the 99 cases, there were 36 cases caused by hitting, kicking, and falling and 63 cases caused by vehicle collision. The majority of the former was ulna, and those of the latter were tibia and fibula. The types of fracture were transverse one, short oblique one, long oblique one, and spiral one. CONCLUSION Different types of long backbone fracture, not only causing stress load of fractures as well as structural differences related to each segment.
Fibula/pathology* ; Forensic Pathology ; Fractures, Bone/pathology* ; Humans ; Tibial Fractures/pathology*

OBJECTIVETo examine the protective effect of ecdysterone (ECR) against beta-amyloid peptide fragment(25-35) (Abeta(25-35))-induced PC12 cells cytotoxicity, and to further explore its mechanism.

METHODSExperimental PC12 cells were divided into the Abeta group (treated by Abeta(25-35) 100 micromol/L), the blank group (untreated), the positive control group (treated by Vit E 100 micromol/L after induction) and the ECR treated groups (treated by ECR with different concentrations of 1, 50 and 100 micromol/L). The damaged and survival condition of PC12 cells in various groups was monitored by lactate dehydrogenase (LDH) release and MTT assay. The content of malondialdehyde (MDA) was measured by fluorometric assay to indicate the lipid peroxidation. And the antioxidant enzymes activities in PC12 cells, including superoxide dismutases (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), were detected respectively.

RESULTSAfter PC12 cells were treated with Abeta(25-35) (100 micromol/L) for 24 hrs, they revealed a great decrease in MTT absorbance and activity of antioxidant enzymes, including SOD, CAT and GSH-Px as well as a significant increase of LDH activity and MDA content in PC12 cells (P < 0.01). When the cells was pretreated with 1-100 micromol/L ECR for 24 hrs before Abeta(25-35) treatment, the above-mentioned cytotoxic effect of Abeta(25-35) could be significantly attenuated dose-dependently, for ECR 50 micromol/L, P < 0.05 and for ECR 100 micromol/L, P < 0.01. Moreover, ECR also showed significant inhibition on the Abeta(25-35) induced decrease of SOD and GSH-Px activity, but not on that of CAT.

CONCLUSIONECR could protect PC12 cells from cytotoxicity of Abeta(25-35), and the protective mechanism might be related to the increase of SOD and GSH-Px activities and the decrease of MDA resulting from the ECR-pretreatment.

Amyloid beta-Peptides ; toxicity ; Animals ; Catalase ; analysis ; Ecdysterone ; pharmacology ; Glutathione Peroxidase ; analysis ; L-Lactate Dehydrogenase ; analysis ; Malondialdehyde ; analysis ; PC12 Cells ; Peptide Fragments ; toxicity ; Rats

AIMTo establish separation methods of five sulfonamides by using capillary high performance liquid chromatography(mu-HPLC) and electrochromatography. The effect of mobile phase varies such as methanol content, pH, buffer solution concentration and voltage on their chromatographic behavior and electroosmesis flow was investigated. Capillary electrochromatography (CEC) was compared with mu-HPLC at the same condition.

METHODSStationary phase was ODS, mobile phase was methanol and 2 mmol.L-1 H3PO4 buffer solution (pH 3.0-7.0), voltage was 0- -15 kV, flow rate was 10 microL.min-1, pressure was approximately 70 MPa and UV detection wavelength was 254 nm.

RESULTSSeparations on base line have been respectively accomplished for five sulfonamides by mu-HPLC with mobile phase of methanol-2 mmol.L-1 H3PO4 buffer solution (30:70) at pH 5.0 in 67 min, and CEC with the same mobile phase at -5 kV voltage in 25 min.

CONCLUSIONElectroosmesis flow of CEC decreased with the increase in methanol content, buffer solution concentration, increased with the increase in voltage and increase slightly with the increase in pH of mobile phase. Retention values (k) of solutes to be examined decreased with increasing methanol content of mobile phase in mu-HPLC and CEC. Retention values (k) of solutes increased slightly with increasing buffer solution concentration, decreased with increasing voltage in CEC. Trimethoprim(TMP) decreased obviously with increasing voltage in CEC. The effect of pH of mobile phase on retention values (k) was more complex. Five sulfonamides were separated at the same mobile phase condition by mu-HPLC and CEC. And separation speed of CEC was much faster than that of mu-HPLC. CEC was very fit for rapid separation of sulfonamides.

Anti-Infective Agents ; isolation & purification ; Buffers ; Chromatography, High Pressure Liquid ; methods ; Chromatography, Micellar Electrokinetic Capillary ; methods ; Hydrogen-Ion Concentration ; Sulfonamides ; isolation & purification ; Trimethoprim ; isolation & purification

In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.

OBJECTIVETo observe the effect of total coptis alkaloids (TCA) on beta -amyloid peptide (A beta 25-35) induced learning and memory dysfunction in rats, and to explore its mechanism.

METHODSForty male Wistar rats were randomly divided into four groups: the control group, the model group, the TCA low dose (60 mg/kg) group and the TCA high dose (120 mg/kg) group, 10 in each. A beta 25-35 (5microl, 2 microg/microl) was injected into bilateral hippocampi of each rat to induce learning and memory dysfunction. TCA were administered through intragavage for consecutive 15 days. Morris Water Maze test was used to assess the impairment of learning and memory; concentration of malondialdehyde (MDA) in cerebral cortex was determined by thiobarbituric acid reactive substance to indicate the level of lipid peroxidation in brain tissues; activity of manganese-superoxide dismutase (Mn-SOD) in cerebral cortex was determined by xanthine-oxidase to indicate the activity of the enzyme; and NF- kappa B protein expression in cerebral cortex was measured by SP immunohistochemistry.

RESULTS(1) Morris Water Maze test showed that, during the 4 consecutive days of acquisition trials, the rats in the model group took longer latency and searching distance than those in the control group (P<0.01), which could be shortened by high dose TCA (P<0.05); during the spatial probe trial on the fifth day, the rats in the model group took shorter searching time and distance on the previous flat area than those in the control group (P<0.01), which could be prolonged after TCA treatment (for low dose group, P<0.05; for high dose group, P<0.01). (2) Analysis of cerebral cortical tissues showed that, compared with the control group, MDA level got significantly increased and Mn-SOD activity decreased in the model group (both P<0.01). After having been treated with TCA, the MDA level got significantly decreased (P<0.05 and P<0.01 respectively for low and high dose group), while relative increase of Mn-SOD activity only appeared in high dose group (P<0.05). (3) Immunohistochemistry analysis showed the protein expression of NF- kappa B got significantly increased after modeling, while high dose TCA can significantly inhibit it.

CONCLUSIONTCA could improve A beta 25-35 induced dysfunction of learning and memory in rats, and its protective mechanism is associated with its actions in decreasing MDA level, increasing Mn-SOD activity and inhibiting the expression of NF-kappa B in cerebral cortex.

Alkaloids ; administration & dosage ; pharmacology ; Amyloid beta-Peptides ; administration & dosage ; Animals ; Cerebral Cortex ; metabolism ; Coptis ; chemistry ; Dose-Response Relationship, Drug ; Hippocampus ; drug effects ; Injections ; Learning Disorders ; chemically induced ; psychology ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory ; drug effects ; Memory Disorders ; chemically induced ; psychology ; NF-kappa B ; metabolism ; Peptide Fragments ; administration & dosage ; Rats ; Rats, Wistar ; Reaction Time ; drug effects ; Superoxide Dismutase ; metabolism ; Swimming