The primary intravenous anesthetics employed in clinical practice encompass dexmedetomidine (Dex), propofol, ketamine, etomidate, midazolam, and remimazolam. Apart from their established sedative, analgesic, and anxiolytic properties, an increasing body of research has uncovered neuroprotective effects of intravenous anesthetics in various animal and cellular models, as well as in clinical studies. However, there also exists conflicting evidence pointing to the potential neurotoxic effects of these intravenous anesthetics. The role of intravenous anesthetics for neuro on both sides of protection or toxicity has been rarely summarized. Considering the mentioned above, this work aims to offer a comprehensive understanding of the underlying mechanisms involved both in the central nerve system (CNS) and the peripheral nerve system (PNS) and provide valuable insights into the potential safety and risk associated with the clinical use of intravenous anesthetics.
Animals ; Humans ; Anesthetics, Intravenous/adverse effects* ; Neuroprotective Agents/pharmacology* ; Propofol ; Neurotoxicity Syndromes/prevention & control* ; Central Nervous System/drug effects* ; Dexmedetomidine

Objective: To evaluate the effect and safety of molecular targeted therapy of apatinib mesylate combined with multiple antigen stimulatiing cellular therapy in treatment of osteosarcoma and soft tissue sarcoma. Methods:Six patients with sarcoma were collected by the failure of surgery, radiation and chemotherapy treatment or refusal surgery, radiation and chemotherapy, and at least one month from the last treatment of surgery, radiation and chemotherapy. All of the patients at least received three cycle MASCTTM . From Day 1,everyone were given Apatinib 500 mg,po,qd ,until the disease progression. To measure the patient’s quality of life depending on EORTC QLQ-C30,meanwhile,detecting the cellular immunity function and circulating tumor cells(CTCs) of patients before treatment and one month after 3 cycle MASCTTM . At last, monitoring the cellular immune responses by the Enzyme-linked immuno spot ( ELISPOT) assay. Results: All of the four patients completed the treatment of 3 cycle MASCTTM . Only one patient reduced apatinib from 500 mg to 250 mg because of palmar-plantar erythrodyses-thesia. The response rates of the four patients received MASCTTM and apatinib mesylate after treatment were 1 for complete response (CR),3 for partial response (PR). The life quality and cellular immunity function were improved in all of the patients. ELISPOT assay suggested that the majority of antigen peptides could induce specific cytotoxic T lymphocytes( CTLs) response. The Progression-Free-Survival ( PFS) of four patients received MASCTTM and apatinib mesylate was 7,6,9 and 4 months ,while the response rates of the two patients received apatinib mesylate were 1 for ( Stable disease) SD,one for ( Progression disease) PD. And PFS of the two patients were one month and two months. Conclusion:Combination of MASCTTM and apatinib mesylate is safe,effective and were good prospects for application.

Objective To investigate the radiosensitivity of stem cells in pancreatic adenocarcinoma PANC‐1 cell line and the possible mechanism of its radiation resistance .Methods Using flow cytometry ,the cells were isolated and sorted into CD44+CD24+ ,CD44-CD24+ ,CD44+CD24- ,and CD44-CD24- .Multi‐target click model was used to fit cell survival curves and deter‐mine the sensitizer enhancement ratio .The apoptosis and cycle distribution of the four cell subsets were determined using flow cy‐tometry ,and the level of ROS was determined by DCFH‐DA probe .Results The ratio of CD44+ and CD24+ in the sorted PANC‐1 cell line was 92 .0% and 4 .7% respectively .Before radiation ,there was no statistically significant difference between four groups (P>0 .05);After treated with 6MV‐X ray ,The ratio of apoptosis was the lowest in CD44+CD24+ (P<0 .01);The percentage G0/G1 cell was the highest in CD44+CD24+ (P<0 .01) ,the sensitizer enhancement ratio of CD44+ CD24- ,CD44-CD24+ and CD44-CD24- were 1 .61 ,1 .81 ,1 .94 ,respectively .The level of ROS in CD44+CD24+ was lower (P<0 .01) .Conclusion Tumor stem cells of pancreatic adenocarcinoma have properties of a lower level of ROS and relative stationary that maybe the reasons of radio resist‐ance .

Objective To evaluate the effect of raltitrexed plus oxaliplatin combined with concurrent radiotherapy on life quality of advanced esophageal carcinoma.Methods Oesophageal cancer specific health related quality of life questionnaire(QLQ-OES18) was used to evaluate the life quality of 54 patients with esophageal carcinoma respectively at 1 day pre-treatment(baseline level),1 day post-treatment and 1month post-treatment.Total 54 patients were treated with raltitrexed plus oxaliplatin combined with con-current radiotherapy.Comparing the differences of quality of life scores at different time points,and analyzing the correlation of the differences between the 1month post-treatment and baseline score and short term effect.Results The scores of difficulty swallo-wing,eating difficulties,saliva decreased significantly at 1 day post-treatment than that of pre-treatment(P<0.05),the scores of eating pain increased significantly at 1 day post-treatment than that of pre-treatment(P<0.05)and there was no significantly differ-ences in other items(P>0.05).The scores of 1 day post-treatment were significantly reduced compared to baseline levels except re-flux and speech(P<0.05).It was positive correlation between the difference of 1 month post-treatment and baseline score and short term effect,and the correlation coefficients was 0.85,0.55,0.73,0.32(P<0.05),respectively.Conclusion There is a transient im-pact of raltitrexed plus oxaliplatin combined with concurrent radiotherapy on quality of life for advanced esophageal carcinoma after treatment,but most of the life quality of the patients could be improved after 1 month obviously.

AIM:To investigate the effects of thalidomide ( THD) on the activation of connective tissue growth factor ( CTGF) gene promoter induced by transforming growth factor β1 ( TGF-β1 ) in human embryonic lung fibroblasts ( HELF) .METHODS:DNA sequence of CTGF gene promoter was cloned into luciferase reporter gene vector to construct the recombinant eukaryotic expression vector pGL 3-CTGFP, and the recombinant vector was transfected into HELF cell line.The effects of TGF-β1 and THD on the activation of CTGF gene promoter were detected by dual-luciferase analysis . RESULTS:TGF-β1 increased the reporter gene activity dose-dependently (P<0.05), with a plateau at 5 μg/L being 2.16 folds as high as the control .TGF-β1-induced increase in the reporter gene activity was also time-dependent ( P<0.05).After exposure to TGF-β1(5 μg/L), the level of luciferase activity reached its peak at 12 h and was 2.52 folds as high as the control .THD significantly inhibited TGF-β1-induced increase in the reporter gene activity in a dose-dependent manner , but its basal activity was not changed .CONCLUSION: TGF-β1 stimulates the transcriptional activity of CTGF gene promoter in HELF cells in a dose-and time-dependent manner , while THD may inhibit the effects dose-dependently .

OBJECTIVETo observe triclabendazole effect on Paragonimus skrjabini in experimentally infected rats,and to develop a new drug for treating paragonimiasis.

METHODSMetacercariae of Paragonimus skrjabini were isolated from crabs (Sinopotamon) collected from endemic area. Wistar rats were infected intraperitoneally. One and two months after infection, they were treated with triclabendazole at the dosage of 300 mg.kg(-1).2 d(-1), 450 mg.kg(-1).3 d(-1) and 600 mg.kg(-1).3 d(-1) respectively. Five patients with Paragonimus skrjabini were treated, with Triclabendazole dosage of 10 mg/kg bid x 3 days.

RESULTSThe worm reduction rates were 50.3%, 80.8% and 86.7% respectively one month after completion of treatment. Dead worms of sesame size recovered from muscles, liver, abdominal cavity, chest cavity and lung were greatly diminished in size and weight in comparison with that of the control group. Many large (about 1 cm) black-colored distended worm cysts were found in the lungs of the control rats. Usually there were two adult worms pairs with numerous eggs in each worm cyst. Most worm cysts in the treated groups of rats were changed into hemorrhagic-necrotic patches. All five patients were cured.

CONCLUSIONTriclabendazole was highly active against Paragonimus skrjabini in rats experimentally infected and patients.

Adult ; Animals ; Anthelmintics ; therapeutic use ; Benzimidazoles ; therapeutic use ; Child ; Female ; Humans ; Male ; Paragonimiasis ; drug therapy ; Parasite Egg Count ; Rats ; Rats, Wistar

AIM: To investigate intracellular free calcium ([Ca 2+ ]i ) alterations in hypothalamus of febrile rabbits induced by endotoxin (ET), and compare with the effect of ET and IL-1? on [Ca 2+ ]i in hypothalamic neurocytes from normothermia rabbits. METHOD: The concentration of [Ca 2+ ]i was determined by using spectrofluorometer and fluorescent Ca 2+ probe fura-2 /Am. RESULTS: 1. A minute dose of ET (2 ng/mL) induced a significant rise in [Ca 2+ ]i in hypothalamic neurocytes from normothermia rabbits. The rise in [Ca 2+ ]i in hypothalamic neurocytes from febrile rabbits induced by intravenous injection of ET was also observed. 2. In hypothalamic neurocytes from normotheria rabbits, IL-1? failed to affect [Ca 2+ ]i at concentrations of 100, 500, 1 000 ng/mL, respectively. CONCLUSION:The action site of low concentration of calcium that plays a regulatory role during fever seems unlikely to be in cytosolic compartment of hypothalamic neurons. The change of [Ca 2+ ]i in hypothalamic neurocytes by ET can not be considered the direct effect of IL-1?.

AIM: To investigate the relationship among MCP-1 and monocyte chemoattract protein activity (MCA) and pathogenesis of lung cancer. METHODS: 173 patients were involved in the study and divided into three groups: group A: lung cancer group (60 patients); group B: benign lung disease group (55 patients) and group C: healthy control group (58 patients). MCP-1 level and MCA in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: The concentration of MCP-1 and MCA in BALF in group A were much higher than those in group B and group C (P

In order to determine further whether cAMP and PGE takes part in the mechanism of EGTA-induced fever in the present experiment with 40 New Zealand rab bits, the influence of intravenous infusion of sodium salicylate (SS) on the febrile response and the rise of cAMP and PGE_2 concentration in c.s.f. produced by intraventricular perfusion of EGTA were observed. The results showed that intravenous infusion of SS (9.6?M/min. following an initial dose of 1.25mM) could inhibit the rise of PGE_2 concentration in c.s.f. (P0.05) after 0.6 mM EGTA was perfused into lateral cerebroventricle. The concentration of cAMP in c.s.f. was correlated apparently positively with the febrile response in EGTA-induced fever (r=0.9839, P