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
Chronic stress induces altered energy metabolism and plays important roles in the etiology of depression, in which the glucocorticoid negative feedback is disrupted due to imbalanced glucocorticoid receptor (GR) functions. The mechanism underlying the dysregulation of GR by chronic stress remains elusive. In this study, we investigated the role of AMP-activated protein kinase (AMPK), the key enzyme regulating cellular energy metabolism, and related signaling pathways in chronic stress-induced GR dysregulation. In cultured rat cortical astrocytes, glucocorticoid treatment decreased the level, which was accompanied by the decreased expression of liver kinase B1 (LKB1) and reduced phosphorylation of AMPK. Glucocorticoid-induced effects were attenuated by glucocorticoid-inducible kinase 1 (SGK1) inhibitor GSK650394, which also inhibited glucocorticoid induced phosphorylation of Forkhead box O3a (FOXO3a). Furthermore, glucocorticoid-induced down-regulation of GR was mimicked by the inhibition of AMPK and abolished by the AMPK activators or the histone deacetylase 5 (HDAC5) inhibitors. In line with the role of AMPK in GR expression, AMPK activator metformin reversed glucocorticoid-induced reduction of AMPK phosphorylation and GR expression as well as behavioral alteration of rats. Taken together, these results suggest that chronic stress activates SGK1 and suppresses the expression of LKB1 via inhibitory phosphorylation of FOXO3a. Downregulated LKB1 contributes to reduced activation of AMPK, leading to the dephosphorylation of HDAC5 and the suppression of transcription of GR.
β-Catenin has been implicated in major depressive disorder (MDD), which is associated with synaptic plasticity and dendritic arborization. MicroRNAs (miRNA) are small noncoding RNAs containing about 22 nucleotides and involved in a variety of physiological and pathophysiological process, but their roles in MDD remain largely unknown. Here, we investigated the expression and function of miRNAs in the mouse model of chronic social defeat stress (CSDS). The regulation of β-catenin by selected miRNA was validated by silico prediction, target gene luciferase reporter assay, and transfection experiment in neurons. We demonstrated that the levels of miR-214-3p, which targets β-catenin transcripts were significantly increased in the medial prefrontal cortex (mPFC) of CSDS mice. Antagomir-214-3p, a neutralizing inhibitor of miR-214-3p, increased the levels of β-catenin and reversed the depressive-like behavior in CSDS mice. Meanwhile, antagomir-214-3p increased the amplitude of miniature excitatory postsynaptic current (mEPSC) and the number of dendritic spines in mPFC of CSDS mice, which may be related to the elevated expression of cldn1. Furthermore, intranasal administered antagomir-214-3p also significantly increased the level of β-catenin and reversed the depressive-like behaviors in CSDS mice. These results may represent a new therapeutic target for MDD.
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