This study aims to optimize the most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549 using the orthogonal design method, and to investigate its effects of the component formula on cell proliferation, apoptosis and cytoskeleton in lung cancer A549 cells. The orthogonal design method was introduced to optimize the most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549 cells. CCK-8 assay and Real-time cell analysis were adapted to analyze the effect of component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on A549 cells viability at different time and dose. Cell apoptosis was measured by Annexin V- FITC/PI double staining and flow cytometry. Cell skeleton protein F-actin was detected by high content screening (HCS). The optimizing component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma for total salvianolic acid, total saponins of panax ginseng and ginseng polysaccharide doses were 5, 10, 5 mg L(-1). CCK-8 assay and real-time cell analysis demonstrated that the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma treatment could significantly decrease the A549 cell viability in both dose- and time-dependent manner compared with control group (P < 0.01). Moreover, the increase of cell apoptosis was detected by Annexin V-FITC/PI double staining and flow cytometry when cells treated with the component formula, which indicating that the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma could induce A549 cell apoptosis in a time-dependent manner compared with control group (P < 0.01). Furthermore, compared with control group, a significant decrease in A549 cell skeleton area was found in the component formula-exposed cells in the dose-dependent manner (P < 0.01). In summary, the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma inhibits A549 cell proliferation by inducing cell apoptosis and decreasing cell microfilament formation. All of these results will be helpful to reveal antitumor mechanism of the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma, which provides a basis for the exploration of antitumor mechanism of the component formula on lung cancer.
Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Lung Neoplasms ; drug therapy ; Panax ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; Plant Roots ; chemistry ; Rhizome ; chemistry ; Salvia miltiorrhiza ; chemistry

Objective To investigate a feasibility of using dose constraint template (DCT) to increase conformity index (CI) of planning target volume (PTV) and improve intensity modulated radiation therapy (IMRT) planning efficiency for early stage nasopharyngeal carcinoma. Methods Ten patients with pathological diagnosed and treated by IMRT were selected for this study. Target volumes were delineated with Corvus 6.3 of treatment planning system, two dose limiting regions(DLR) around PIN were added by extending from PIN,each DLR was 1 cm thick. We created three plans:Plan0,Planl and Plan2. PianO was without DLR and DCT, Planl without DLR but with DCT, Plan2 with both condition;but to compare dose distribution in PLTV and normal tissue using three plans. Results Three plans could fill equal request of dose distribution in PLTV and normal tissue, and their difference was not statistical significant. CI of Plan2 was increased and planning time was decreased significantly compared with Piano and Planl. Conclusloa Usage of DCT together with DLR can increase CI of PTV and improve IMRT planning efficiency for early stage nasopharyngeal carcinoma, planning time is shortened significantly.

BACKGROUNDTarget-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model (NONMEM), and to investigate the influence of relevant factors in adult patients.

METHODSFourteen ASA I-II patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration (Cpt) was 2.0 µg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T₁ scale was blocked by 90% - 95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The population pharmacokinetics analysis was performed using NONMEM program.

RESULTSThe pharmacokinetics of TCI rocuronium in adult patients was best described by a three-compartment model. Pharmacokinetic parameters were clearance (CL)₁ = 0.205 L/min, CL₂ = 0.324 L/min, CL₃ = 0.0292 L/min, volumes of distribution (V)₁ = 4.00 L, V₂ = 2.28 L, V₃ = 4.26 L, Vdss = 10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V₁ and CL₁ were negatively correlated with patient age. CL₁ was positively correlated with weight.

CONCLUSIONSNo pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Androstanols ; administration & dosage ; pharmacokinetics ; Female ; Humans ; Infusion Pumps ; Male ; Middle Aged ; Young Adult

Objective To investigate the anti-apoptotic effect of gene A20 in treatment of trau-matic brain injury (TBI). Methods Thirty-five Sprague-Dawley rats were made severe TBI models and assigned randomly to experimental group and control group (35 rats in each group). After severe TBI, the rats in experimental group were injected with liposome-pcDNA3.1-A20 and those in control group injected with liposome pcDNA3.1-A20 at 30 minutes after severe TBI. The animals in both groups were sacrificed to remove the brain of five rats from each group at 12, 24, 48, 72 and 168 hours for sec-tioning. The expression of A20 and neurocyte apoptosis were defined by immunohistological method and TUNEL accordingly. The other ten rats were testified for neurological function at 1,2, 3 and 4 weeks af-ter TBI. Results The expression of A20 in experimental group was higher than that in control group, with statistical differences (P < 0. 01). The peak neurocyte apoptosis was found at 72 hours after TBI. The number of apoptosis cells in experimental group was lower than that in control group at 12, 24, 48 and 72 hours afte TBI (P < 0.01 or 0.05). At the 4th week after TBI, the neurological function in exper-imental group was better than that in control group (P < 0.05). Conclusion Gene therapy with A20 may have anti-apoptosis effect and exert neuroprotective effect on severe TBI.

The HIV-1 Rev protein facilitates nuclear export of unspliced and singly spliced viral transcripts containing RRE RNA through the CRM1 export pathway. Inhibition of Rev-mediated RNA nuclear export can arrest HIV-1 transcriptional process, which clearly, reveals a target for anti-HIV drug development. In this work, a cell-based assay has been established for screening anti-HIV compounds targeting the Rev-mediated RNA nuclear export. This assay utilized a codon-optimized green fluorescent protein (GFP) as reporter gene, which expression is in a Rev-dependent manner. Any compound that inhibits the Rev-mediated RNA nuclear export is identified by reducing emission of GFP. The Z' score of this model is 0.8220. Three thousands compounds were screened and the positive rate was 9.3% with a cutoff at 50% inhibition. IMB7C7, one of the positive compounds, efficiently inhibits viral production from HIV-1 infected cells.

Objective To observe the effects and security of rapamycin drug-eluting stents implanting in eld-eay patients with coronary heart disease(CHD).Methods 107 patients with CHD treated with Firebird rapamycin drug-eluting stents,the immediate angiographic outcome,complication in hospitalization.six months'follow-up results were assessed.Results 175 Firebird stents implanted successfully,the successful stenting procedure achieved in 98.9% patients,1 patient(0.9%) died of thrombosis instent during hospitalization.there were no myocardial infarction occurred during six months'follow-up,angina recrudesced in 6 patients,and the ratio of instent restenosis was 2.6%,the MACE rate during 6 months follow-up was 2.8%.Conclusion Firebird rapamycin drug-eluting stents implanta-tion in CHD in elderly was safe and effective.

BACKGROUNDMost HCC patients with decompensation of liver function lost the chance of surgical and/or interventional treatment. The aim of this study was to evaluate feasibility and outcome of radiofrequency ablation (RFA) in treating hepatocellular carcinoma (HCC) patients with poor liver function (Child-Pugh class C), who are not suitable for surgery or hepatic artery chemo-embolization.

METHODSThirteen HCC patients (the number of tumors was 17) with liver function of Child-Pugh C (scores: 10.2 +/- 0.4) were included in the study. Among the patients, 8 were male and 5 were female with the average age of (61.6 +/- 10.9) years old. The average size of HCC was (3.8 +/- 1.0) cm. Two patients were recurrent HCC and 30.8% of the patients had multiple tumors (2 - 3 tumors). All the patients were treated with RFA.

RESULTSThere were 22 RFA sessions (1 - 4 sessions per patient) in all, average ablations per tumor at first session was 3.1. One week after RFA, the liver enzymes elevated in 9 patients (69.2%), in 7 of them, the liver enzyme returned to pre-RFA level in 1 - 3 months. One month after RFA, the Child-Pugh grading was 10.3 +/- 0.8 (Child-Pugh C), while that of pre-RFA was 10.2 +/- 0.4 (Child-Pugh C), with no significant difference. Computer tomography (CT) one month after RFA showed that the tumor necrosis rate was 88.2% (15/17). Five patients had 2 - 4 repeated RFA due to HCC recurrence. During the follow-up of 2- 69 months in this group, survival rate of one year was 53.8%, two years was 30.8%, and three year was 15.4%. The incidence of RFA-related complications was 13.6% (3/22 sessions), including 1 case of GI hemorrhage and 1 sub-capsular hemorrhage of the liver. One patient with HCC over 5 cm who had fever and liver abscess after RFA, and was dead 2 months later due to liver function failure.

CONCLUSIONSMinimal invasive RFA provides possible treatment modality for HCC patients with poor liver function, who are not candidates for surgical and/or interventional therapy. For large HCC, due to the required extended treatment region, special attention should be paid to the possibility of acute liver failure.

Adult ; Aged ; Carcinoma, Hepatocellular ; therapy ; Catheter Ablation ; methods ; Female ; Humans ; Liver Cirrhosis ; therapy ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Treatment Outcome

BACKGROUNDRecently, the combination of sevoflurane and remifentanil has been widely used in general anesthesia. In this study, we investigated the sevoflurane-remifentanil pharmacodynamic interactions at clinical concentrations using the observer's assessment of alertness/sedation (OAA/S) and the bispectral index (BIS) by response surface analysis.

METHODSTotally 65 American Society of Anesthesiologists (ASA) I patients age 20 to 50 years old were included in this study. Patients were randomly assigned to be anesthetized with different target end-tidal sevoflurane concentrations that ranged from 0.2% to 3.4% in increments of 0.2%. The end-tidal sevoflurane concentration was maintained constant throughout the study. Remifentanil was infused with a target controlled infusion (TCI) system at increasing step-wise concentrations from 1 ng/ml to 10 ng/ml. The values of OAA/S and BIS at different sevoflurane-remifentanil concentration combinations were measured. The pharmacodynamic interactions between sevoflurane and remifentanil were analyzed by a response surface method. The three-dimensional response surfaces were constructed with Minitab Software. Model parameters were estimated with NONMEM program.

RESULTSSevoflurane and remifentanil acted synergistically on OAA/S. Sevoflurane alone could produce OAA/S ≤ 1 at a minimal alveolar concentration (MAC) of 0.93%. When used in combination with remifentanil at 1, 3, 6, and 10 ng/ml, the corresponding sevoflurane MACs were reduced to 0.79%, 0.58%, 0.48%, and 0.38%, with reductions of 17.2%, 37.6%, 48.4%, and 62.0% from baseline, respectively. In patients administered remifentanil alone, the OAA/S score was ≥ 3 even when the remifentanil concentration reached 10 ng/ml. BIS was closely associated with the sevoflurane concentration and the remifentanil concentration did not noticeably influence the relationship between the sevoflurane concentration and BIS. A sevoflurane concentration of (1.04 ± 0.19)% to (1.81 ± 0.21)% could maintain a BIS between 60 and 40.

CONCLUSIONSThe response surface method can analyze the pharmacodynamic interactions between remifentanil and sevoflurane qualitatively and quantitatively. Within the range of our study (remifentanil ≤ 10 ng/ml, sevoflurane ≤ 3.4%), the two drugs produced synergistic effects on OAA/S but had no interactive effect on BIS. A guideline of BIS between 40 and 60 may cause excessive anesthesia when opioids are used to maintain anesthesia.

Adult ; Anesthesia ; methods ; Consciousness ; drug effects ; Female ; Humans ; Male ; Methyl Ethers ; pharmacokinetics ; pharmacology ; Middle Aged ; Piperidines ; pharmacokinetics ; pharmacology ; Young Adult

OBJECTIVETo develop a draft questionnaire (China Musculoskeletal Questionnaire, CMQ) for evaluating of musculoskeletal workload and associated potential hazardous working conditions as well as musculoskeletal symptoms of workers in Sitting Posture.

METHODSMulti-methods, which include the reviewing references, the summarizing results of preliminary studies, the reviewing ergonomic tools, the consulting experts and occupational health workers and the interviewing or discussing with individual workers in sitting posture, were used in developing item pool. The experts and epidemiologists of occupational health scored the importance of every single item in the item pool, and then the survey and sampling were carried out in 325 workers of sitting posture who completed the questionnaire. On the basis of these data, the methods including experts scoring, item analysis, Cronbach's α analysis and factor analysis were synthetically used to select the reliable items which consisted of the formal questionnaire.

RESULTSThe standard of the CMQ, which consists of 34 items on musculoskeletal workload and associated potentially hazardous working conditions, can be divided into nine indices (dynamic loads, static loads, repetitive loads, forces-exertion, prolong time, climatic factors, vibration, position and ergonomic environmental factors).

CONCLUSIONThe CMQ possesses good content validity, and the items of CMQ are divergent, reliable and typical. However, the reliability and validity of CMQ should be validated.

China ; Ergonomics ; Humans ; Musculoskeletal System ; Occupational Health ; Posture ; Surveys and Questionnaires ; Workload

As a novel and effective approach, response surface model is used in the study of drug-drug interactions. When two drugs are used simultaneously, this model can be applied to estimate the key characters of the response surface, to find the desired response region by optimal drugs combination, to explore the mechanism of drug-drug interactions, and thus to guide sound clinical application and reduce the risk and cost. In this article, the model's basic mathematical and pharmacological concepts are introduced, and its research progresses are reviewed.
Alfentanil ; pharmacology ; Anesthetics ; pharmacology ; Computer Simulation ; Drug Interactions ; Drug Synergism ; Humans ; Midazolam ; pharmacology ; Models, Statistical ; Propofol ; pharmacology