Depression is a devastating mental disorder and major depressive disorder (MDD) that afflicts 16％ of the global population at some point in their lives. Currently available classical antide-pressants (SSRIs, SNRIs, TCAs and MOIs), require a minimum of 2–4 weeks of continuous treat-ment to elicit therapeutic relief in depressed patients and are associated with high rates of non-respon-siveness, and limited duration of efficacy. Therefore, faster-acting antidepressant therapies are need-ed,particularly for patients at risk for suicide for current therapies for depression.Although the molecu-lar mechanisms underlying the pathogenesis of depression are still largely unclear, previous studies have suggested that modulators of mammalian target of rapamycin complex 1 (mTORC1) signaling may have beneficial neuroprotective and antidepressant effects. Here, we review recent advances in understanding mTORC1 signaling in depression and potential therapeutic strategies resulting from modulation of the mTORC1 signaling network. We also highlight recent studies considered to support mTORC1 signaling modulation as a rapid-acting antidepressant therapy (e.g. ketamine, scopolamine, GLYX-13, (2R,6R)-HNK, Ro-256891 etc.) and discuss future research directions. Studies on prospec-tive next-generation rapid-acting antidepressant therapies should focus on developing more selective glutamate receptors(e.g.α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPARs) agonists or activators)that activate the mTORC1 signaling pathway free of ketamine's adverse effects.

Adolescent ; Adult ; Female ; Humans ; Male ; Manipulation, Orthopedic ; methods ; Middle Aged ; Shoulder Dislocation ; pathology ; therapy ; Shoulder Joint ; injuries ; pathology

Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Phytotherapy ; Severe Acute Respiratory Syndrome ; drug therapy ; prevention & control

Cerebrum ; pathology ; physiopathology ; Congenital Abnormalities ; physiopathology ; Humans ; Infant, Newborn ; Male ; Neonatology ; Osteopetrosis ; complications ; physiopathology ; Research Report ; Telencephalon ; abnormalities

Depression is one of the diseases with the highest disability rate in the world. A large number of studies have shown that the intake of unsaturated fatty acids can deal with depression while chronic overconsumption of saturated fatty acids is a risk factor for depression. It was suggested that the mechanism of saturated fatty acids inducing depression is related to the following four aspects: regulating the function which links to depression in whole brain and specific brain regions, including the hippocampus, the hypothalamic-pituitary-adrenal axis, the striatum, and the prefrontal cortex; stimulating the secretion of inflammatory factors; affecting the balance and function of metabolic regulatory hormones, including leptin, adiponectin, glucocorticoid, and insulin; inducing the disturbance of intestinal flora. This article reviews the relationship between dietary fatty acids and depression, and the possible mechanisms by which saturated fatty acids induce depression from the four aspects mentioned above.

Objective To study aminopeptidase N/CD13 expression in hepatocellular carcinoma and its relationship with clinical data and proguosis in patients with hepatocellular carcinoma.Methods The immunohistochemical SP method was used to detect the CD13 monoclonal antibody in 40 cases of hepatocellular carcinoma,10 cases of corresponding para-carcinoma and 10 cases of cavernous hemangioma.Results Forty cases ( 100％ ) hepatocellular carcinoma tissues were seen varying degrees of CD13 expression,3 (30％) corresponding para-carcinoma tissues were weakly positive,and 10 cases of cavernous hemangioma with no expression.The expression rate of CD13 was not significantly correlated with the patient gender,age,serum AFP value,HbsAg,differentiation,CHILD grade and TNM stage (P＞0.05).But the expression of CD13 was closely related with the patient serum AFP value,HbsAg,differentiation ( P ＜ 0.05 ).By the survival function graph we could find the expression rate was negativly correlated with survival in patients,but the expression was not significantly correlated with tumor relapse.Conclusion CD13 can be used as the surface marker of liver cancer stem cells,and it is expected to become an effective indicator of prognosis in patients with hepatocellular carcinoma.

Common Cold ; drug therapy ; epidemiology ; virology ; Humans ; Rhinovirus ; genetics ; isolation & purification

Objective To investigate the effect of low frequency electric deep brain stimulation on amygdale kindling in rats.Methods The amygdale kinkling model of rats was established by operation on the brain.The effects of low frequency deep brain electric stimulation used alone or in combination with anti-epilepsy drugs were ob- served in terms of severity of seizure attack reflected by Racine's scale and afterdischarge duration recorded in electro- encephalogram.Results Fifteen minutes of low frequency electric stimulation at 1 Hz and 100 to 350?A effective- ly inhibited amygdale kindling as demonstrated by a significant decrease of afterdischarge duration,and decreased the severity of seizure attack (P

Objective To establish the reference databases for bone mineral density(BMD)in multiple skeletal regions,which would be useful for diagnosis of osteoporosis(OP)and prediction of fracture risk in adult women in Qingdao.Methods BMD was measured by dual-energy X-ray absorptiometry at skeletal regions of lumbar spine,left hip(femoral neck,Ward's triangle and greater trochanter)in 868 healthy adult women aged 25- 83 years and 191 women with fractures.BMD of skeletal regions with age-related change was found to fit in 8 kinds of regression models.Best model equations of fitting were found and the reference database was established.BMD of women with fractures was compared with the reference databases to predict the risk of fracture.Results BMD in 6 skeletal regions changed with aging and a cubic regression model was better fitted with aged-related change as compared with other regression models.The coefficients of determination(R~2)of fitting curve were 0.21?0.09 (P＜0.01).The BMD reference databases of women in Qingdao were established by cubic regression equation, the peak BMD of lumbar spine and hip appeared at 25-29,and 40-44 years old groups respectively.Finally,the BMD in fracture group was significantly decreased by 1.6-2.5 s as compared with the peak BMD of health women. Conclusion The bone quantity is lost rapidly after 45 years old in women.If the BMD in women after 50 years old is decreased by 1.6-2.5 s compared with the peak BMD in the same area,the risk of fracture is increased.

Objective To determine the correlation between mouse maerophage metalloelastase (MME)and vascular endothelial growth factor(VEGF)expression involved in angiogenesis of colon cancer.Methods A eDNA fragment coding for domainsⅠandⅡof MME was transfected into murine CT-26 colon cancer cells that were MME deficient.The enzymatic activity of recombinant MME was confirmed by cleavage of native substrate in vitro.An orthotopic implantation model was established by using MME-transfected cells and control cells.Tumor samples were subjected to in situ hybridization (ISH)and immunohistochemical staining(IHC)to detect expressions of MME and VEGF.The microvessel counting was used to assess angiogenesis of murine colon tumors.Results It was demon- strated that the tumor growth was significantly inhibited in MME-transfected group compared with pcDNA3.1 transfected and nontransfected groups(P＜0.001).It was also found that,compared with pcDNA3.1-transfected and nontransfected groups,the microvessel formation in MME transfected group was significantly reduced(P＜0.001).The expression of VEGF mRNA and protein was significantly lower in MME-transfected group than those in the controls,as demonstrated by ISH(MME-transfected group versus pcDNAa.1-transfected group,P=0.028;and versus nontransfected group,P=0.003) and by IHC(MME-transfected group versus pcDNA3.1-transfected group,P=0.025;and versus non- transfected group,P=0.008).Conclusions The MME gene transfected into murine colon cancer cells can effectively suppress the growth of orthotopic tumors by inhibition of vaseularity.Both MME and VEGF gene expression is highly associated with the vascularity of tumors,which may depend on a hal- ance between MME and VEGF expression.