Objective To investigate the effect of tetramethylpyrazine(TMP), a traditional Chinese herbal medicine, on the neural injury caused by spinal cord ischemia and reperfusion in rabbit.Methods Twenty-two male New Zealand white rabbits were anesthetized with isoflurane. Spinal cord ischemia was induced by 20min by infra-renal aortic occlusion. Animals were randomly allocated to 3 groups. Group C received no pharmacologic intervention. Group P and T received 30 mg?kg -1 TMP infused iv at a constant rate over 30min before aortic crossclamping(prevention) and after reperfusion(therapeutic) respectively. Neurologic deficit was assessed at 4, 8, 12, 24 and 48h after reperfusion using neurologic dificit score(NDS 4 = normal, 0 = paraplegia) . The animals were sacrificed at 48h after reperfusion and spinal cords (L 5-7) were removed immediately for histopathologic study.Results All animals survived the experiment. The NDSs at each observation interval were significantly higher in group P and T than those in group C (P

OBJECTIVETo investigate the reversal effect of dihydromyricetin(DMY) on drug resistance of K562/A02 cells to adriamycin and explore its possible mechanism.

METHODSK562 and K562/A02 cells were treated with DMY (5, 10, 20, 40, 60, 80 and 100 mg/L) and ADM (100-0.05 mg/L) for 48 h. The viability of K562 cells and K562/A02 cells was tested and the reversal effect of DMY on drug resistance of K562/A02 cells to adriamycin was analyzed by MTT. The relative concentration of ADM in cells was measured by flow cytometry. Protein expressions of drug resistance related genes including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), glutathione transferase π (GSTπ) and BCL-2 were measured by Western Blot.

RESULTSThe proliferation of K562 and K562/A02 cells was significantly decreased by DMY in dose-dependent manner as compared with control group (r1=0.37, r2=0.38). The ICof ADM on K562 and K562/A02 cells were 71.23±6.51 and 72.88±5.49 mg/L respectively. DMY (5, 10 and 20 mg/L) was low cytotoxicity. DMY (5, 10 and 20 mg/L) enhanced the sensitivity of K562/A02 cells to ADM in dose-dependent manner (r1=-0.62, r2=-0.71) and the reversal multiples was from 1.38 to 28.591. The relative concentrations of ADM in K562/A02 of DMY (5, 10 and 20 mg/L) group cells were significantly increased in dose-dependent manner compared with the control group (r=0.34). Compared with the control group, the expressions of drug resistance related protein P-gp, MRP1, GSTπ and BCL-2 were significantly decreased in dose-dependent manner in DMY (5, 10 and 20 mg/L) group (r1=-0.41, r2=-0.37, r3=-0.58, r=-0.46). Compared with the ADM group, the protein expressions of drug resistance related genes P-gp, MRP1, GSTπ and BCL-2 in DMY (5, 10 and 20 mg/L)+ADM group were significantly decreased in dose-dependent manner (r1=-0.55, r2=-0.41, r3 =-0.38, r4=-0.44).

CONCLUSIONDMY enhances the sensitivity of K562/A02 cells to ADM, its mechanism may be related with decrease of P-gp, MRP1, GSTπ and BCL-2 expressions.

Objective To investigate the influence of renal failure on the area under curve (AUC) and adverse reactions of docetaxel in breast cancer patients, and provide evidence for the dosage of docetaxel in renal failure patients. Methods A retrospective study was conducted on 24 patients with breast cancer who had undergone radical mastectomy and received AC-T adjuvant chemotherapy in our hospital from January 2019 to November 2021. According to renal function cases, the patients were divided into two groups: renal failure group (n=5) and normal renal function group (n=19). The clinical characteristics such as gender, age, body weight and body surface area of patients in two groups, docetaxel dose, blood concentration, area under the curve, liver and kidney function, white blood cell count and absolute value of neutrophil before chemotherapy were collected. Single factor linear regression was used to analyze the influencing factors of the AUC of docetaxel. Adverse reactions after chemotherapy with docetaxel including nausea and vomiting, bone marrow suppression, constipation and liver function injury were collected. CTCAE 4.0 evaluation standard was used to evaluate adverse reactions. Results The clinical characteristics of creatinine [908.0 (819.0, 1018.0) μmol/L vs 54.8 (52.0, 65.0) μmol/L] and creatinine clearance rate [4.9 (4.3, 5.4) ml /min vs 86.3 (59.3, 92.5) ml/min] of the renal failure group and the normal renal function group have significant difference (P<0.001), while no significant difference (P>0.05) were found in the body surface area [1.4 (1.4, 1.5) m² vs 1. 6 (1.5, 1.6) m²], docetaxel dose [70.4 (69.4, 73.0) mg/m² vs 74.4 (72.3, 91.2) mg/m²], body weight [(51.4±3.8) kg vs (51.5±5.5) kg]. Liver function, white blood cells and neutrophils were within the normal range before chemotherapy with docetaxel. There was no significant difference in AUC value [(1.6±0.6) mg·h/L vs (1.8±0.8) mg·h/L] between the two groups after chemotherapy with docetaxel (P>0.05). Linear univariate regression analysis indicated that the blood concentration at the end of docetaxel infusion was significantly associated with AUC of docetaxel (P<0.001), while the body surface area, dose of docetaxel, body weight, liver and kidney function were not correlated with AUC of docetaxel (P>0.05). After chemotherapy with docetaxel, adverse reactions of patients in the two groups: nausea and vomiting (grade I incidence: 40% vs. 57.9%, grade II incidence: 60% vs. 42.1%), myelosuppression (grade I incidence: 60% vs. 84.2%, grade II incidence: 20% vs 15.8%) and constipation (all mild constipation) had no significant difference (P>0.05). Conclusion Renal failure did not affect the exposure of docetaxel and the adverse reactions after chemotherapy with docetaxel in breast cancer patients.

Objective To evaluate the individualized fluid therapy in the elderly patients with coronary heart disease undergoing gastrointestinal surgery.Methods From January 2009 to December 2012,80 cases of coronary heart disease patients (aged 65-80 years) undergoing gastrointestinal surgery were divided into test group and control group by random digits table with 40 cases each.Traditional fluid therapy was used in control group in the intraoperative and postoperative period.Individualized fluid therapy was used in test group in the intraoperative and postoperative transferred to the intensive care unit (ICU) during the period of 24 h:in cardiac index (CI),stroke output index,stroke variation degree,under the guidance of indicators such as capacity titration type treatment.Hemodynamic index,fluid intake,incidence of cardiac adverse events and recovery of gastrointestinal function were compared in two groups into the operating room (T1),after anesthesia induction (T2),the operation started (T3),intraoperative 1 h (T4),the end of surgery (T5),transferred to the ICU 6 h (T6),transferred to the ICU 12 h (T7) and transferred to the ICU 24 h (T8).Results Compared with T1,two groups of patients with mean arterial pressure (MAP),central venous pressure (CVP),CI and stroke volume (SV) were lower than those at T2 [test group:(68.1 ±6.1) mm Hg(1 mm Hg =0.133 kPa) vs.(84.4 ±5.2) mm Hg,(5.5 ±0.8) cm H2O(1 cm H2O =0.098 kPa) vs.(6.2 ± 1.0) cm H2O,(2.8 ± 1.6) L/(min·m2) vs.(3.3 ± 0.8) L/(min·m2),(65.7 ± 4.5) ml vs.(74.3 ± 7.5) ml;control group:(65.4 ± 7.3) mm Hg vs.(85.1 ± 6.6) mm Hg,(4.6 ± 0.8) cm H2O vs.(6.4± 1.1) cm H2O,(2.7 ±0.7) L/(min·m2) vs.(3.3 ±0.6) L/(min·m2),(60.6 ± 7.6) ml vs.(73.8 ±7.5)ml],stroke variation degree (SVV) was significantly increased [test group:(15.9 ±5.1)％ vs.(12.1 ±5.9)％; control group:(15.8 ± 9.4)％ vs.(12.6 ± 8.4)％],there was significant difference (P ＜ 0.05).Compared with the same time of control group,MAP was higher at T3,CI was higher at T4 and T5,SV was higher at T2-T7,there was significant difference (P＜ 0.05).The total transfusion amount,crystal usage and urine in intraoperative and transferred to the ICU 24 h in test group were less than those in control group,while colloid usage was more than that in control group,there was significant difference (P ＜ 0.05).The incidence of cardiac adverse events between two groups had no significant difference (P =0.232).The postoperative ICU stay time,exhaust time,defecation time,into the liquid diets time and hospital stay in test group were less than those in control group [(37 ± 13) h vs.(55 ± 25) h,(72 ± 12) h vs.(99 ± 13) h,(92 ± 16) h vs.(113 ± 16) h,(4.0 ±0.8) d vs.(4.9 ± 1.9) d,(17 ±4) d vs.(27 ±5) d],there was significant difference (P ＜ 0.05 or ＜ 0.01).Conclusion In the elderly patients with coronary heart disease undergoing gastrointestinal surgery,individualized fluid therapy can effectively decrease adverse cardiac events,improve postoperative gastrointestinal function,and reduce length of hospital stay.

0.05).In comparison with pre-treatment,WOMAC scores,pain index,and physiological integral scores in treatment and control groups after the first and the last treatment decreased significantly(P

Objective: To investigate the protective effects of Polygonatum odoratum polysaccharides (POP) on alcohol-induced injury of HepG2 cells and its potential molecular mechanisms. Methods: After screening the appropriate concentration of alcohol-treated HepG2 cells and the intervention concentration of POP by MTT method, HepG2 cells were divided into three groups according to different intervention concentrations (200 μg/L, 400 μg/L and 600 μg/L) of POP, and the blank group without POP. After pretreated for 1 h, HepG2 cells were treated with 4% alcohol for 24 h. The activities of intracellular alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the levels of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF- α) were measured. The protein expressions of Kelch-like epichlorohydrin-associated protein-1 (Keap1), phosphorylated nuclear factor E2-related factor 2 (p-Nrf2), phosphoamide adenine dinucleotide quinone oxidoreductase -1 (NQO1), B lymphocyte tumor-2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase 3 were detected. Results: Compared with the HepG2 cells treated with 4% alcohol, POP at the various concentrations could effectively down-regulate the activities of ALT and AST in HepG2 cells induced by alcohol (P＜0.05). The levels of IL-1β and TNF-α in the 200 μg/L POP treated group were decreased significantly (P＜0.05), while the level of GSH was increased significantly (P＜0.01). The levels of ROS, MDA, IL-1β and TNF-α in the 400 μg/L and 600 μg/L POP treated groups were decreased significantly (P＜0.05 or P＜0.01), while the GSH level was increased significantly (P＜0.01). POP effectively up-regulated the expressions of p-Nrf2 and NQO1 protein in HepG2 cells induced by alcohol, and also down-regulated the Bax/Bcl-2 index (P＜0.05), and inhibited the protein expressions of Keap1 and cleaved-caspase-3 (P＜0.05). Conclusion: POP can improve alcohol-induced oxidative stress injury in HepG2 cells by regulating the Nrf2/Keap1 pathway, thereby reducing the inflammatory index and apoptosis level of HepG2 cells. Among them, 400 μg/L and 600 μg/L POP have better intervention effects.
Ethanol ; Hep G2 Cells ; Humans ; Kelch-Like ECH-Associated Protein 1/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Polygonatum/metabolism* ; Polysaccharides/pharmacology* ; Reactive Oxygen Species/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism*

Objective To investigate the effect of methylene blue(MB)on liver ischemia-reperfusion (I/R) injury in rabbits.Methods Twenty-four healthy New Zealand white rabbits of both sexes welshins 2.0-2.3 kg were randomly divided into 3 groups (n=8 each):group Ⅰ sham operation(group s);group Ⅱ I/R and group Ⅲ methylene blue (group MB).The animals were anesthetized with intravenous 2% pentobarbital 30 mg/kg.Liver I/R was produced by occlusion of hepatic blood flow for 40 min followed by 60 min repeffusion.In group MB methylene blue 5 mg/kg was injected iv at 20 min before liver ischemia.Femoral artery was carmulated for MAP monitoring and blood sampling.MAP and HR were recorded immediately before(T1,baseline)and at 20 and 40 min of ischemia (T2,3) and 1,5,30,60 min(T4-7)of repedusion.Blood samples were collected at T1,T5,T6 and T7 for measurement of seruln TNF-α and IL-6 concentrations.Plasma AST and ALT activities were measured at T1,T6 and T7.Liver specimens were obtained at the end of experiment for determination of SOD activity and MDA content.Results In group I/R MAP was significantly decreased at T4-7 during reperfusion and HR at T7 as compared with the baseline at T1;while in group MB no significant change in MAP and HR Was observed during ischemia and reperfusion as compared with the baseline.The gerum TNF-α and IL-6 concentrations and the plasma ALT and AST activities were significantly increased during reperfusion as compared with the baseline immediately before ischemia in group I/R and MB and were significantly lower in group MB than in group. I/R. The SOD activity was significantly higher while MDA content was significantly lower in group MB than in group I/R. Microscopic examination showed that liver damage was less severe in group MB than in group I/R. Conclusion The administration of MB can maintain hemodynamic stability and attenuate liver I/R injury in rabbits.

ObjectlveTo evaluate the role of cannabinoid receptor 2 (CB2 receptor) in microglial injury induced by glutamate.MethodsMicroglia cells were randomly divided into 4 grups:control group (group C),microglial injury group ( group Ⅰ),specific CB2 receptor agonist AM 1241 group ( group AM1241 ) and specific CB2 receptor antagonist AM630 group (group AM630).In group C,the cells were cultured routinely for 26 h.In group Ⅰ,the cells were incubated in the culture medium containing glutamate 10 mmol/L for 24 h.In group AM1241,the cells were incubated in the culture medium containing AM1241 2 μmol/L for 2 h,and then in the culture medium containing glutamate 10 mmol/L for 24 h.In group AM630,the cells were incubated in the culture medium containing AM630 2 μmol/L for 2 h,and then in the culture medium containing glutamate 10 mmol/L for 24 h.The cell viability and release of LDH were measured.Microglial morphology was observed under microscope.Results Compared with group C,the cell viability was significantly decreased,and the release of LDH was significantly increased in groups Ⅰ,AM1241 and AM630 (P ＜ 0.05).Compared with group Ⅰ,the cell viability was significantly increased,and the release of LDH was significantly decreased in group AM1241 ( P ＜ 0.05).There was no significant difference in the cell viability and the release of LDH between groups 1 and AM630 ( P ＞ 0.05).Conclusion Glutamate induces microglial injury through inhibiting the function of CB2 receptor.

Objective To investigate the effects of propofol on intracellular free Ca2+ concentration and nitric oxide synthase (NOS) activity in PC12 cells exposed to bupivacaine. Methods The PC12 cells were provided by Shanghai Cell Biology Research Institute, Chinese Academy of Sciences and cultured in DMEM liquid culture medium. The cultured PC12 cells were seeded in 36 well plates and randomly assigned to one of 4 groups (n=9 wells each): group Ⅰ control (C);group Ⅱ propofol (P);group Ⅲ bupivacaine (B) and group Ⅳ propofol + bupivacaine (PB). In control group D-Hank solution was added. The cells were exposed to propofol 2 mmol/L and bupivacaine 0.09 mmol/L in group P and B respectively. In group PB the cells were incubated with propofol 2 mmol/L and bupivacaine 0.09 mmol/L simultaneously. After being incubated for 6 and 24 h the apoptosis in BC12 cells was assessed by flow cytometry. Apoptotic rate was calculated. NOS activity and intracellular free Ca2+ coneentration in PC12 cells were determined. Results Bupivacaine significantly increased the apoptotic rate of PC12 cells, the intracellular free Ca2+ concentration and NOS activity in PC12 cells in group B as compared with control group. Propofol significantly decreased the toxic effects of bupivacaine on PC12 cells in group PB compared with group B. Conclusion Bupivacaine is toxic to PC12 cells by increasing apoptosis, intracellular Ca+ concentration and NOS activity in the cells. The toxic effects can be prevented to some extent by concomitant administration of propofol.

Objective To investigate the distribution characteristics and risk factors of intracranial atherosclerotic stenosis ischemic stroke. Methods We retrospectively collected 342 consecutive patients with first-ever ischemic stroke. Clinical data was collected including demographics, the presence of risk factors,MRI with MRA and other routine admis?sion laboratory tests. Results Intracranial atherosclerotic stenosis (ICAS) was located most frequently in MCA (47.0%), Extracranial internal carotid artery was the most common affected artery (65.0%) among extracranial atherosclerotic steno? sis (ECAS). MetS (OR=1.586,95%CI:1.232~2.268), ApoB/ApoA1 ratio (OR=1.926,95%CI:1.051~4.288), were as?sociated with ICAS (vs ECAS), whereas hypertension (OR=3.603,95%CI:1.675~12.485), MetS (OR=2.268,95%CI:1.274~6.103), HbA1c (OR=2.015,95%CI:1.182~5.613) and ApoB/ ApoA I ratio (OR=1.948,95%CI:1.157~4.285) were related to ICAS (vs NCAS). Hypertension (OR=2.437,95%CI:1.492~3.505,P=0.005), Hcy (OR=2.437,95%CI:1.492~3.505,P=0.005) and HbA1c (OR=1.769,95%CI:1.034~3.121, P=0.005) were the independent risk factors re?lated to posterior circulation strokes (vs anterior circulation strokes ) in ICAS strokes. Conclusions The occurrence of ICAS may be more frequent than that of ECAS in ischemic stroke. Posterior circulation ICAS strokes seems to be close?ly associated with metabolic derangement.