Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.

An explicit illustration of pulmonary delivery processes (PDPs) was a prerequisite for the formulation design and optimization of carrier-based DPIs. However, the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately, or the approaches merely used a simplified and idealized model. In the present study, a novel modular modified Sympatec HELOS (MMSH) was developed to fully investigate the mechanism of each PDP separately in real-time. An inhaler device, artificial throat and pre-separator were separately integrated with a Sympatec HELOS. The dispersion and fluidization, transportation, detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates. Moreover, time-sliced measurements were used to monitor the PDPs in real-time. The Next Generation Impactor (NGI) was applied to determine the aerosolization performance of the model DPIs. The release profiles of the drug particles, drug aggregations and carriers were obtained by MMSH in real-time. Each PDP of the DPIs was analyzed in detail. Moreover, a positive correlation was established between the total release amount of drug particles and the fine particle fraction (FPF) values ( = 0.9898). The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs, providing a theoretical basis for the design and optimization of carrier-based DPIs.

Objective To evaluate the effects of turmeric volatile oil (TVO) combined with cisplatin on the proliferation and apoptosis of a human cutaneous squamous cell carcinoma cell line A431,and to explore their mechanisms.Methods Some cultured A431 cells at exponential growth phase were divided into several groups to be treated with 5,10,20,40 and 80 mg/L TVO,as well as high-glucose Dulbecco's modified Eagle's medium (DMEM) containing 1％ dimethyl sulfoxide (DMSO,control group),respectively.After 24-hour treatment,cell counting kit 8 (CCK8) assay was performed to estimate the proliferative activity of A431 cells in the above groups.Some other A431 cells were divided into 4 groups:control group treated with high-glucose DMEM containing 1％ DMSO,TVO group treated with 40 mg/LTVO,cisplatin group treated with 10 mg/L cisplatin,and TVO + cisplatin group treated with 40 mg/L TVO and 10 mg/L cisplatin.After 24-hour treatment,CCK8 assay was performed to estimate the cellular proliferative activity,inverted microscopy to observe changes in cell morphology,fluorescence microscopy to detect cell apoptosis after acridine orange (AO)/ethidium bromide (EB) double-staining,colorimetry to evaluate the activity of Caspase-3 and Caspase-9,and Western blot analysis to determine the protein expression of Caspase-3 and p-glycoprotein.Results After 24-hour treatment with 5,10,20,40 and 80 mg/L TVO,the cell proliferation rates were inhibited by (12.83 ± 6.4)％,(16.27 ± 11.4)％,(21.61 ± 9.1)％,(33.11 ± 2.0)％ and (46.00 ± 3.3)％ respectively,and the inhibition rates were all significantly higher in these groups than in the control group (4.03％ ± 1.4％,all P ＜ 0.05).The 50％ inhibitory concentration (IC50) of TVO at 24 hours was (61.66 ± 1.03) mg/L.Compared with the control group,the proliferation inhibition rates significantly increased in the TVO group,cisplatin group and TVO + cisplatin group (all P ＜ 0.05),suggesting that the combination of TVO and cisplatin showed synergistic inhibitory effects with a combination index of 1.366.Moreover,A431 cells turned round to different extents and became apoptotic in the TVO group and cisplatin group,and the TVO + cisplatin group showed obviously decreased number of cells and a large number of cell debris.The TVO + cisplatin group also showed significantly increased activity of Caspase-3 (1.520 ± 0.115) and Caspase-9 (2.760 ± 0.297) as well as protein expression of Caspase-3 (1.482 ± 0.016) compared with the TVO group (Caspase-3 activity:1.117 ± 0.095;Caspase-9 activity:1.259 ± 0.059;Caspase-3 protein expression:1.156 ± 0.006,all P ＜ 0.01) and cisplatin group (Caspase-3 activity:1.381 ± 0.089;Caspase-9 activity:1.829 ± 0.171;Caspase-3 protein expression:1.296 ± 0.021,all P ＜ 0.01),but significantly decreased p-glycoprotein expression (0.528 ± 0.014) compared with the TVO group (1.311 ± 0.011,P ＜ 0.01) and cisplatin group (1.169 ± 0.012,P ＜ 0.01).Conclusion TVO combined with cisplatin can synergistically inhibit the proliferation of A431 cells and induce cell apoptosis,which may be associated with activation of the caspase system and decreased expression of pglycoprotein.

Dry powder inhalers (DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance. The purpose of this review is to summarize and illuminate how these factors affect drug-carrier interaction and influence the performance of DPIs.

Objectives To investigate the effect of proliferation and invasiveness by turmeri cvolatile oil on human neuroblastoma cell line SH-SY5Y. Methods Cells were incubated with different concentrations of TVO in vitro. Then cell survival rate was measured by MTT assay. The effect of 160 mg/L TVO on cell migration was assessed by cell scuffing test. Invasive ability of cell was detected by Transwell test. Apoptosis of cells was detected observed by flow cytometry assay. Results Survival rate of SH-SY5Y cells decreased and apoptisis rate was abated with elevated TVO concentration and prolonged cultivation time. Level of cell migration was lower than that in control group after being cultured with 160 mg/L TVO solution for 12 , 24 and 48h. With the in-crease of TVO concentration , the invasion ability of cells gradually decreased , and the invasive force and cis-platin had no obvious difference when the concentration of drug reached 160 mg/L. Conclusion The prolifera-tion of cells can be inhibited by inhibiting the proliferation and invasiveness ability with TVO.

Objective To investigate the effects of an ar?turmerone derivative(ATD)on the proliferation and apoptosis of A375 human melanoma cells. Methods Both A375 cells and human skin fibroblasts (HSFs) were cultured with different concentrations(5, 10, 20, 40 and 80μmol/L)of ATD, vincristine and ar?turmerone, separately, for 48 hours in vitro. Subsequently, cell counting kit?8 (CCK?8) was used to evaluate cell proliferation, inverted microscopy to observe cell morphology after acridine orange/ethidium bromide (AO/EB) staining, and a colorimetric method to estimate caspase?3 activity. DNA fragmentation assay and flow cytometry were performed to assess cell apoptosis, and flow cytometry was conducted to analyze cell cycle. Results ATD, vincristine and Ar?turmerone all inhibited the proliferation of A375 cells in a dose?dependent manner(ATD:R2=0.99, F=340.96, P<0.05;vincristine:R2=0.99, F=349.19, P<0.05;ar?turmerone:R2=0.89, F=25.41, P<0.05). The fifty percent inhibitory concentra?tions(IC50s)of ATD, vincristine and ar?turmerone against A375 cells were 15.96 ± 0.02μmol/L, 77.00 ± 0.04μmol/L and 356.95 ± 0.01μmol/L respectively. When the drug concentrations were 5 and 10μmol/L, the proliferation of HSFs was inhibited by 8%± 0.06%and 25%± 0.02%respectively by ATD, by 49%± 0.09%and 34%± 0.07%respectively by ar?turmerone, and by 33%± 0.04%and 29%± 0.08%respectively by vincristine, and the proliferation of A375 cells was inhibited by 26%± 0.06%and 39%± 0.02%respectively by ATD, by 6%± 0.09%and 10%± 0.07%respectively by ar?turmerone, and by 8% ± 0.04% and 17% ± 0.08% respectively by vincristine, with the inhibitory effects of the three drugs being significantly different from that of dimethyl sulfoxide(all P<0.05). ATD showed stronger inhibitory effects on the proliferation of A375 cells, but weaker cytotoxic effects on HSFs compared with ar?turmerone and vincristine(all P<0.05). Meanwhile, ATD, vincristine and ar?turmerone all induced the apoptosis of A375 cells(P<0.05), and caspase?3 activity increased with the increase in drug concentrations(ATD:R2=0.98, F=162.30, P<0.05;vincristine:R2=0.96, F=94.39, P<0.05;ar?turmerone:R2=0.95, F=57.35, P<0.05). The effect of ATD on caspase?3 activity was strongest, followed by that of vincristine and ar?turmerone. As flow cytometry showed, all the three drugs induced cell apoptosis to different degrees, and ATD showed a relatively strong effect on cell apoptosis, especially late apoptosis, compared with the other two drugs. In the ATD group, the number of A375 cells in G1 phase gradually increased, while that in G2 phase and S phase significantly decreased with the increase in drug concentrations. Conclusions ATD exhibited proliferation?inhibiting and apoptosis?inducing effects on A375 cells, and the effects were stronger than those of vincristine and ar?turmerone. It is quite possible that ATD affects cell proliferation and differentiation by activating caspase?3 and arresting cell cycle in the G1 phase.

OBJECTIVE: To determine the combined cytotoxic effect and the molecular basis of triptolide and sodium cantharidinate on hepatoma cell line 7721.
 METHODS: After treating the hepatoma cell line 7721 with triptolide(9, 18, or 36 μg/mL) and/or sodium cantharidinate (2, 5, or 10 μg/mL), cell viability assay and apoptosis were examined by MTT and flocytometry, respectively. The protein levels of caspase 3 and nuclear factor κB were analyzed by Western blot.
 RESULTS: Viability of hepatoma cell line 7721 was inhibited by either the therapy of triptolide and/or sodium cantharidinate (P<0.05) in a time- and dose-dependent manner. The combined effects of both drugs were better than those of the single drug (P<0.05). The combined therapy down-regulated the expression of NF-κB p65 (P<0.05) while up-regulated the expression of caspase-3 (P<0.05).
 CONCLUSION Triptolide and sodium cantharidinate exert a synergistic toxic effect on hepatoma cell line 7721, which is related to increasing capase-3 activity and suppression of NF- κB.
Apoptosis ; drug effects ; Cantharidin ; pharmacology ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; Caspase 3 ; drug effects ; Cell Line, Tumor ; Diterpenes ; pharmacology ; therapeutic use ; Down-Regulation ; Drug Therapy, Combination ; Epoxy Compounds ; pharmacology ; therapeutic use ; Humans ; Liver Neoplasms ; drug therapy ; NF-kappa B ; drug effects ; Phenanthrenes ; pharmacology ; therapeutic use ; Transcription Factor RelA

Objective To examine the existing Framingham Risk Score (FRS) and Chinese Risk Score (CRS) in predicting the development of ischemic cardiovascular diseases (ICVD),and determine potential added value of novel risk factors.Methods The China Multi-Provincial Cohort Study (CMCS) was a population-based prospective cohort study in 11 provinces of China.An annual follow up was conducted in 840 men aged 35 to 64 years in Shanghai cohort,who were without coronary heart disease and stroke at baseline examination in 1992,to collect the incidence data of ICVD events (coronary death,myocardial infarction,and ischemic stroke).The detection of novel risk factors were conducted for the cohort in 2007.The basic Framingham and Chinese prediction scores power were assessed by using C-statistic of ICVD events associated with risk scores,then the novel risk factors were evaluated by adding them independently to the basic Chinese models.The area under the curve (AUC),net reclassification improvement (NRI),and integrated discrimination improvement (IDI) were calculated to determine if each of the novel risk factors improved risk prediction.Results By the end of December 2014,24 cases of coronary heart disease (myocardial infarction or/and coronary death),45 cases of ischemic stroke had occurred in 840 subjects in Shanghai cohort with a follow-up of 22.3 years averagely.Both the FRS and CRS had predicting power for ICVD,the AUCs were 0.657 6 (95％ CI:0.594 2-0.724 0) and 0.726 5 (95％ CI:0.664 3-0.788 7),respectively.The incremental AUC was 0.068 9 (95％ CI:0.019 6-0.117 1) (P=0.006).None of the novel risk factors significantly improved the AUC.High-sensitive-CRP (hs-CRP) was the only novel risk factor resulting in a significant increase of NRI.CRS in 2007 significantly improved the IDI,but net changes were small.Conclusions CRS had high power in the 20-year risk prediction for ICVD in middle-aged men in Shanghai.The inclusion of hs-CRP could make some improvement in risk prediction,but is unlikely to be meaningful when reclassification or new discrimination strategy are made which can change the clinical risk.

In recent years, the number of outpatients in stomatological hospital is in increasing year by year and being accompanied by the corresponding medical risks. One of the risks which may endanger the patient life is medical emergency which need emergency treatment by the dentists in dental clinical practice. The most common emergency type is syncope, followed by hyperventilation, drug overdose, adrenaline reaction and hypertension, etc. Unexpected events mainly occurred at the end of the treatment and before leaving the dental clinic, during or immediately after the local anesthesia, in the treatment process. Tooth extraction related emergency is the most frequently occurring emergency, followed by the local anesthesia related ones. It's strongly suggested that dentists should pay more attention to outpatient clinical emergency treatment, and related knowledge and skills training should be offered to improve the ability to handle medical emergencies.
Dental Care ; Dental Clinics ; Dentists ; Emergencies ; Emergency Treatment ; Humans

In?recent?years,?the?number?of?outpatients?in?stomatological?hospital?is?in?increasing?year?by?year?and?being?accompanied?by?the?corresponding?medical?risks.?One?of?the?risks?which?may?endanger?the?patient?life?is?medical?emergency?which?need?emergency?treatment?by?the?dentists?in?dental?clinical?practice.?The?most?common?emergency?type?is?syncope,?followed?by?hyperventilation,?drug?overdose,?adrenaline?reaction?and?hypertension,?etc.?Unexpected?events?mainly?occurred?at?the?end?of?the?treatment?and?before?leaving?the?dental?clinic,?during?or?immediately?after?the?local?anesthesia,?in?the?treat-ment?process.?Tooth?extraction?related?emergency?is?the?most?frequently?occurring?emergency,?followed?by?the?local?anes-thesia?related?ones.?It’s?strongly?suggested?that?dentists?should?pay?more?attention?to?outpatient?clinical?emergency?treatment,?and?related?knowledge?and?skills?training?should?be?offered?to?improve?the?ability?to?handle?medical?emergencies.