In appropriate prescribing is a global problem. It is especially salient in China, where drug sales constitute a major portion of health care providers' incomes, price distortions are rampant, and oversight is lax. However, few data exist on the prevalence of inappropriate prescribing in China. This study, the first of its kind in China, examined 230,800 prescriptions written between 2007 and 2009 by 784 community health institutions in 28 cities across China. The data show substantial overprescribing, including twice as many prescriptions for antibiotics as recommended by the World Health Organization and rates of injection that are three times higher than in similar countries. These findings point to the need to integrate rational prescribing into China's ongoing health care reform. M arket-oriented reforms in the past three decades have brought unprecedented economic prosperity to China. At the same time, they dismantled the structure of China's equitable, albeit rudimentary, health care system. Today, with the Chinese Ministry of Health setting very low prices for physician consultation, hospitalization, and services, drug "markups" have become the major source of revenue for health care providers.Unlike the United States and many other countries, China does not have a widespread retail pharmacy system. Patients typically fill their prescriptions at the same hospital or clinic that they visit for care. These health care providers don't receive a dispensing fee but rather earn the difference between wholesale and retail price. Because these drug-related revenues are a major source of financial support for health care providers, one of the detrimental consequences is inappropriate or irrational prescribing. 1The irrational prescribing is further exacerbated by runaway manufacturer prices and lax oversight. This environment poses a serious risk for patients' health and sources of health care. 2Recognizing the ever-worsening problems in basic health care coverage, disease-induced poverty, disparities, and the resulting social instability, the Chinese government has launched a multitude of reforms. Central to the reforms has been the reconstruction of affordable and convenient community health service networks that provide basic disease prevention, medical treatment, rehabilitation, health education, and family planning services within designated urban communities. These networks are composed of health centers, each providing about 50 beds and serving 30,000 to 50,000 residents, and satellite health stations, each serving about 3,000 residents. 4 Most of these institutions are owned or subsidized by municipal governments; the rest are owned by private practitioners, trade organizations, and other nonprofit entities.5 By the end of 2008, 98 percent of the cities in all of China's thirty-one provinces had developed community health service networks. 6 In 2010 China's minister of health, Zhu Chen, Reform In China

Melatonin exhibits anti-inflammatory and anticancer effects and could be a chemopreventive and chemotherapeutic agent against cancers, but the precise mechanisms involved remain largely unresolved. In this study, we evaluated the mechanism of action of melatonin in human MDA-MB-361 breast cancer cells. Melatonin at pharmacological concentrations (10(-3)  m) significantly suppressed cell proliferation and induced apoptosis in a dose-dependent manner. The observed suppression of proliferation was accompanied by the melatonin-mediated inhibition of COX-2, p300, and NF-κB signaling. Melatonin significantly inhibited COX-2 expression and prostaglandin E(2) (PGE2) production, abrogated p300 histone acetyltransferase activity and p300-mediated NF-κB acetylation, thereby blocking NF-κB binding and p300 recruitment to COX-2 promoter. Pretreatment with a COX-2- or p300-selective inhibitor abrogated the melatonin-induced inhibition of cell proliferation, whereas PGE2 treatment or COX-2 transfection reversed the inhibition by melatonin. Moreover, melatonin markedly inhibited phosphorylation of PI3K, Akt, PRAS40, and GSK-3 proteins, thereby inactivating the PI3K/Akt signaling pathway. Pretreatment with a PI3K- or an Akt-selective inhibitor or an Akt-specific siRNA blocked the melatonin-mediated inhibition of cell proliferation. Conversely, gene delivery of a constitutively active Akt effectively reversed the inhibition by melatonin. Furthermore, melatonin induced Apaf-1 expression, triggered cytochrome C release, and stimulated caspase-3 and caspase-9 activities and cleavage, leading to an activation of the Apaf-1-dependent apoptotic pathway. Pretreatment with an Apaf-1-specific siRNA effectively attenuated the melatonin-induced apoptosis. These results therefore indicate that melatonin inhibits cell proliferation and induces apoptosis in MDA-MB-361 breast cancer cells in vitro by simultaneously suppressing the COX-2/PGE2, p300/NF-κB, and PI3K/Akt/signaling and activating the Apaf-1/caspase-dependent apoptotic pathway.

Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT) activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers.

7521wileyonlinelibrary.com in realistic point of view owing to their low cost, non-involving of poor reproducibility of the optimum doping level, and concise control in device fabrication required for metal-complexed phosphorescent materials. [ 4 ] In principle, red fl uorescent emission comes from a narrow bandgap. To date, fl uorophores with narrow bandgap either have extended π conjugation or possess polar donor-acceptor (D-A) architectures. [ 5 ] The latter one has been proved to be a very promising way to effectively extend the emission to long wavelength. In addition, D-A system is also benefi cial to the recombination of carriers because the modifi cation of low highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels will effectively lower the injection barriers for electrons and holes in OLEDs. [ 6 ] More importantly, the electron fl ip can take place since the charge transfer (CT) excitons formed between the donor and acceptor is a weak Coulomb hole-electron pair, which would facilitate a large fraction of singlet excitons formation under electrical charge injection. [ 7 ] However, a major shortcoming of D-A compound is that the spatially separated HOMO-LUMO orbitals always result in the forbidden electronic transition, which usually leads to the low photoluminescence quantum effi ciency. [ 1d , 5 ] In contrast, the fl uorophores with local excited (LE) states are generally reported to acquire high photoluminescence quantum effi ciency; however, such fl uorophores generally exhibit low singlet exciton yields originated from the forbidden spin fl ip from triplet state to singlet state and their electroluminescent internal quantum effi ciencies are limited to ≈25%. [ 8 ] Recently, materials based on new principle, such as hybridized local and charge transfer (HLCT) with excitons that undergo a reverse intersystem crossing process (RISC) along the high-lying CT channel, has emerged to reach a compromise of LE and CT states to break through the 25% upper limit of η s . [ 9 ] Unlike many D-A compounds suffering from the low efficiency originated from CT effects, these materials benefi t from the large dipole moment of the CT state and a certain degree of orbital overlap of the LE state, which is a promising way to endow the material with a high photoluminescence quantum effi ciency as well as a large singlet exciton yield. Highly Effi cient Solid-State Near-Infrared Emitting Material Based on Triphenylamine and Diphenylfumaronitrile with an EQE of 2.58% in Nondoped Organic Light-Emitting DiodeXiao Han , Qing Bai , Liang Yao , Haichao Liu , Yu Gao , Jinyu Li , Liqun Liu , Yulong Liu , Xiaoxiao Li , Ping Lu , * and Bing Yang The development of effi cient near-infrared (NIR) emitting material is of current focus. Donor-acceptor (D-A) architecture has been proved to be an effective strategy to obtain narrow energy gap. Herein, a D-A-type NIR fl uorescent compound 2,3-bis(4′-(diphenylamino)-[1,1′-biphenyl]-4-yl) fumaronitrile (TPATCN) is synthesized and full...

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