OBJECTIVETo observe the effect of obesity on pharmacokinetics and pharmacodynamics of isoflurane.

METHODSTwenty-six patients undergoing cholecystectomy were divided into obese group (Group A, BMI > or = 27, n = 13) and normal body weight group (Group N, BMI < or = 24, n = 13) according to body mass index (BMI). All patients were given to the same isoflurane anesthesia. Inspired and end-expired concentrations of isoflurane were monitored and uptake fraction of isoflurane were calculated.

RESULTSIsoflurane concentrations of vaporizer in Group A [(1.8 +/- 0.3)%] were evidently higher than those in Group N [(1.5 +/- 0.1)%] at all observed points (P < 0.05 or P < 0.01). Uptake fraction of isoflurane in Group A were higher than those in Group N at observed points (P < 0.05, P < 0.01 or P < 0.001), but there were no differences in the time when isoflurane concentration was lowered to 50% and awake time between the two groups after discontinuing inhaling isoflurane.

CONCLUSIONSObese patients demand higher inspired concentration and uptake of isoflurane than those in normal weight patients but discharge of isoflurane was influenced by obesity within the observed period of (66 +/- 33) min.

Adult ; Aged ; Anesthesia, Inhalation ; Anesthetics, Inhalation ; administration & dosage ; pharmacokinetics ; Body Mass Index ; Cholecystectomy, Laparoscopic ; Dose-Response Relationship, Drug ; Female ; Humans ; Isoflurane ; administration & dosage ; pharmacokinetics ; Male ; Middle Aged ; Obesity ; complications ; metabolism

Multilateral mechanisms are important platforms and vehicles for cooperation in traditional medicine.Relying on multilateral platforms,China is able to enhance the international influence of the domestic traditional Chinese medicine and form synergies with other member countries to enhance regional or cross-regional radiation effects in order to promote sustainable development of traditional medicine around the world.This paper focuses on China's participation in major multilateral health cooperation mechanisms,including global initiatives(WHO-led global cooperation framework,the Belt and Road Initiative),regional multilateral mechanisms(ASEAN countries,China-Japan-Korea Health Cooperation Mechanism,Shanghai Cooperation Organization(SCO),The Greater Mekong Subregion(GMS)),and cross-regional multilateral mechanisms(BRICS,Forum On China-Africa Cooperation(FOCAC),G20),and sorts out the cooperation policies and actions in traditional medicine under different mechanisms,to analyze the characteristics and challenges of the existing mechanisms in traditional medicine cooperation,and to provide evidence for China's promotion on multilateral cooperation in traditional medicine.

This study adopted the policy text analysis method,review the historical background of the enactment,aimed to comparatively analyze the international pharmaceutical trade policies of the BRICS countries.The main objectives of the BRICS countries'international pharmaceutical trade policies included ensuring stable and accessible drug supply,expanding exports of domestic products and creating a favorable political environment.For these purposes,Brazil,Russia,and South Africa all ensure drug supply through substantial imports.However,they have also taken measures such as compulsory patent licensing and promoting localization of production by foreign companies to reduce import dependence.India,on the other hand,protects its domestic industry by resisting drug imports to ensure drug supply while simultaneously promoting the export of pharmaceutical products.China continually optimizes approval and data monitoring procedures to align with international standards,creating a favorable trade environment and expanding exports.China should further refine its international pharmaceutical trade policies while ensuring the autonomy of domestic drug research and supply,fostering stronger collaboration within BRICS nations and promoting global access to public healthcare products.

Objective To observe the effects of ryanodine on rapamycin treated endothelial outgrowth cells (EOCs). Methods The mononuclear cells were harvested from umbilical cord blood by Ficoll density gradient centrifugation, then induced into EOCs tnd expanded in vitro. The endothelial characteristics of EOCs were identified by immunostaining and fluorescent staining. The EOCs were pretreated with or without ryanodine ( 10 μmol/L) for 1 h, and then treated with or without rapamycin ( 10nmoL/L) for 24 h. Proliforation was evaluated by CCK8 and migration was measured by Transwell. The protein expression of EOCs was evaluated by immunobloting technique with total eNOS antibody and phosphoeNOS(Thr495) antibody. Results Compared with control group, the proliferation and migration capacities of EOCs were significantly reduced while the phosphorylation of eNOS ( Thr495 ) protein was significantly upregulated in rapamycin group( P ＜ 0. 05 ), expression of total eNOS was not affected by rapamycin ( P ＞0. 05). Compared with rapamycin group, the proliferation and migration capacities of EOCs were significantly increased and the phosphorylation of eNOS(Thr495) protein was significantly downregnlated in ryanodine + rapamycin group( P ＜0. 05). The proliferation and migration capacities, the phosphorylation of eNOS (Thr495) protein and the expression of total eNOS were not affected by ryanodine alone ( P ＞ 0. 05 ).ConclusionsRapamycin reduced proliferation and migration capacities while upregulated the phosphorylation of eNOS (Thr495) protein of EOCs and these effects could bepartly reversed by cotreatment with ryanodine.

OBJECTIVETo observe the effect of curcumin on nitric oxide (NO) in plasma of atherosclerotic rabbits, activity of constitutive nitric oxide synthase (cNOS) and asymmetric dimethylarginine (ADMA), and discuss curcumin's effect against AS and its correlation with ADMA.

METHODThirty-eight male Japanese white rabbits were randomly divided into four groups: the control group (eight rabbits fed with standard diets), the model group (ten rabbits fed with high-fat diets), the low dose curcumin group (ten rabbits fed with high-fat diets and 100 mg . kg-1 d -1 ) and the high dose curcumin group (ten rabbits fed with high-fat diets and 200 mg kg-1 d-1 curcumin). At the end of the 12th week, their plasmas were tested for TC, LDL-C, NO, endothelin (ET) , ADMA and activity of aortic cNOS. Aortic tissues were collected for histological examinations.

RESULTThe three groups fed with high-fat diets showed higher plasma ADMA and ET than the control group (P <0. 01) , but with decrease in plasma NO concentration and arterial cNOS activity (P <0. 01). Compared with the model group (P <0. 05) , the curcumin groups showed lower plasma ADMA and ET (P <0. 05), but higher plasma NO concentration and arterial cNOS activity than the model group (P <0. 01). There was no significant difference between the two curcumin groups.

CONCLUSIONCurcumin may play an important protective role in AS process by reducing plasma ADMA level. [Key words] atherosclerosis; asymmetric dimethylarginine; crucumin; nitric oxide; nitric oxide synthase

Animals ; Arginine ; analogs & derivatives ; blood ; Atherosclerosis ; blood ; drug therapy ; metabolism ; Curcumin ; therapeutic use ; Endothelium, Vascular ; drug effects ; Male ; Nitric Oxide Synthase ; metabolism ; Rabbits

Heterotypic cell-in-cell structures(heCICs)mediate unique non-autonomous cell death,which are widely involved in a variety of important pathological processes,such as tumorigenesis,pro-gression and clinical prognosis.Methylenetetrahydrofolata dehydrogenase 2(MTHFD2),one of the key enzymes of one-carbon metabolism,is highly expressed in a variety of tumor cells.In this study,in order to investigate the effect of MTHFD2 on the formation of heCICs,liver cancer cells and immune cells were first labeled separately by live cell dyes,and the heCIC model was established by using fluorescence mi-croscopy for cell imaging and analysis.After transiently knocking down MTHFD2 in cells by RNAi,we found that the ability of PLC/PRF/5 and Hep3B to form heCICs with immune cells was significantly in-creased(all P＜0.01).MTHFD2 recombinant expression plasmid was constructed by the homologous re-combination method,and MTHFD2 overexpression cell lines were further constructed.Then,the effect of MTHFD2 overexpression on the ability to form heCICs was detected by co-culturing the overexpression cell lines with immune cells.The results showed that the rate of heCIC formation was significantly re-duced after overexpression of MTHFD2(all P＜0.001).In conclusion,this study demonstrated that MTHFD2 is a negative regulator of heCIC formation,providing a research basis for targeting MTHFD2 to promote heCIC formation and enhance the in-cell killing of immune cells.