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

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.

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.

Parkinson's disease (PD) is a degenerative disease of the central nervous system due to the loss or death of dopaminergic neurons in the substantia nigra. Clinically, levodopa is the most effective and commonly used drug for PD treatment. However, long-term levodopa therapy is prone to motor complications and other side effects caused by excessive peripheral dopamine production, which has become an urgent problem to be solved in PD treatment. Dopamine receptor (DR) agonists are similar to dopamine. They can directly stimulate postsynaptic dopamine receptors, produce the same effect as dopamine, delay the application of levodopa as much as possible, and reduce complications caused by long-term use of levodopa. Therefore, screening effective dopamine receptor agonists has become a key issue in the study and treatment of PD. In order to establish a rapid, stable and reliable method for dopamine receptor agonist screening, this study used the human dopamine receptor 2 (DRD2) gene fused with a circular permuted EGFP (cpEGFP) to construct a recombinant gene, packaged with lentiviral vector, and the vector replaced the parted inner transmembrane domain of the third intracellular loop (ICL3) of genetically-encoded GPCR-activation based (GRAB) sensors. The fluorescence of GPCR-fused cpEGFP is regulated by conformational changes mediated by the interaction of dopamine receptor agonists with GPCRs without altering GPCR activity. The HEK293T cells were infected with viral vector, screened by puromycin to select highly expressed cells. Dopamine receptor agonists (including dopamine, bromocriptine mesylate, cabergoline, pramipexole) were used as positive drugs to explore the best screening and detection conditions, establishing a stable model to evaluate the dopamine receptor agonist. The results showed that the optimal filter for the dopamine receptor agonist in this study was the cell seeding count of 7×10⁴, and the effective concentration of the positive drug was 1-100 µmol·L^-1. In addition, pretreated with 10 µmol·L^-1 dopamine receptor antagonists (including chlorprothixol hydrochloride, domperidone, and sulpiride), the positive fluorescence signal of overexpressed DRD2-cpEGFP HEK293T cells could not be detected when exposed to 10 µmol·L^-1 dopamine receptor agonists, which proved that dopamine receptor antagonists could block the activity of dopamine receptor agonists, so they cannot activate dopamine receptor allosteric, indicating that the model has good specificity and can also be used for the screening and detection of new dopamine receptor antagonists. In summary, the study constructs a stable dopamine sensor detection system, which can effectively screen potential dopamine receptor agonists. The operation procedures are simple and rapid. And it can be used for a large-scale screening providing a fundamental methodology for drug development and PD treatment targeted on DRD2.

Background Human paired box gene 6 (PAX6)encodes a transcriptional regulator.It is essential for eye and brain morphogenesis.Mutation of PAX6 gene isresponsible for many congenital ocular malformations,such as aniridia.Aniridia is a autosomal dominant inheritance mode.Objective In this study,PAX6 gene mutation was analyzed in three Chinese families with aniridia through polymerase chain reaction (PCR) and sequencing.Methods The blood specimens were collected from 5 suffers and normal individuals of 3 aniridia families to extract DNA.The sequences of extron 4-13 were designed based on PAX6 gene.The primer was amplified by PCR and sequenced and compared with the known PAX6 gene sequence.This study complied with Declaration of Helsinki and approved by ethic committee of Sichuan University.Written informed consent was obtained from each individual before any medial examination.ResultsThere were 5 suffers in the 3 families.A heterozygous mutation (c.718 C＞T) in PAX6 gene was identified in 2 patients of family A.This mutation caused an amino acid substitution of arginine to termination codon at position 240 ( p.Arg240X) of PAX6 protein.No similar change in the normal families.No any the alteration of PAX6 gene was detected in family B whatever suffers and normal individuals.In family C,a deletion mutation of c.331 delG ( p.Val111 SerfsX13 ) in PAX6 gene was found.The deletion of one base caused frame shift mutation of PAX6 protein,and no such mutation was seen in other families.Conclusions Mutation of PAX6 gene appeares to be causative mutations of the disease in family A and C.

Cannabinoid receptors are one of the most expressed G protein-coupled receptors in the central nervous system, which are potential drug targets for inflammation, pain and drug abuse. Cannabinoid receptors are composed of type 1 receptor (CB1R), type 2 receptor (CB2R) and other receptors, of which CB1R plays a vital role in regulating central memory, cognition, and motor function. Therefore, screening CB1R agonists has potential value in treating nervous system diseases. In this study, the intracellular loop 3 (ICL3) domain of CB1R was replaced with a circular-permutated enhanced green fluorescent protein (cpEGFP). After infecting HEK 293T cells with lentivirus particles, we obtained a stable cell line that was overexpressed human CB1R-cpEGFP after puromycin selection. The interaction between receptor agonists and CB1R led to the change of receptor conformation, resulting in de-protonation of the EGFP, and enhancing the fluorescence intensity. Therefore, active CB1R compounds could be verified by measuring the fluorescence intensity. Using CB1R agonist arachidonyl-2′-chloroethylamide (ACEA) as a positive control to evaluate the reliability of this model, studies have shown that ACEA could induce receptor activation and increase fluorescence intensity, while antagonist rimonabant inhibited receptor activation with unchanged fluorescence intensity. In conclusion, this study successfully constructed a fluorescent probe screening model for CB1R agonists.

Objective To investigate the current condition of Keshan disease(KD), and inner and outer environmental selenium (Se) levels in Shandong Province, in order to provide scientific evidence for the research, prevention and control work. Methods Inhabitants from 20 villages of 8 counties in KD endemic areas were selected as subjects undergoing general physical examination and electrocardiogram (ECG). Suspicious cases were followed up by chest X-ray radiographs. Meanwhile the Se contents in hair, wheat, corn and sweet potato were measured. Results Ninety one patients with KD, including 82 with latent KD and 9 with chronic KD, were screened out of 2613 inhabitants. The total incidence of KD was 3.48% (91/2613), while the incidence of latent and chronic KD was 3.14%(82/2613) and 0.34%(9/2613) respectively. No new cases of acute or sub-acute KD were found. A total of 368 abnormal ECCs were discovered and the rate of abnormal ECG detected among surveyed population was 14.08% (368/2613). Out of 113 suspects who took X-ray, 57 cases had cardiomagaly. In 217 samples of hair, 228 samples of wheat, 214 samples of corn and 190 samples of sweet potato that were collected, the Se contents were determined by fluorescence. The average Se content in hair, wheat,corn and sweet potato were (0.406±0.090), (0.026±0.009), (0.023±0.010), (0.024±0.006)mg/kg respectively. Conclusions Current condition of KD in Shandong Province remains relatively stable. Se content was increased in the hair, nearly achieving the level in normal areas, but remains low in food.

OBJECTIVETo explore the relationship between immunochemical level of salivary and caries in children aged 4-6 years old.

METHODSTwo groups were assorted as patients with caries and without caries. Every group included 45 people. Measurements of salivary secretory immunoglobulin A (SIgA)were performed by using radio-immunoassay and single agar diffusion assay. The levels of lysozyme (LZ), alkaline phosphatase (ALP) and lactic dehydrogenase (LDH) were studied with colorimetry and turbidimentry.

RESULTSThe levels of LDH, SigA, ALP, LZ had significant difference between the two groups (P < 0.05). The level of LDH between patients and peoples without caries had little difference (P > 0.05).

CONCLUSIONThe incidence of caries is associated with age, and it may have association with immunochemical levels of salivary.

Alkaline Phosphatase ; Child ; Dental Caries ; Female ; Humans ; Immunoglobulin A, Secretory ; Male ; Saliva

OBJECTIVETo compare and assess the effectiveness of leukocyte-filtered platelet and standard platelet concentrates transfusion in preventing platelet transfusion refractoriness (PTR) and human leukocyte antigen (HLA)-alloimmunization.

METHODSRandomized controlled trials (RCTs) or quasi-RCTs comparing leukocyte-filtered platelet with standard platelet concentrates transfusion (up to December 31, 2009) were searched and identified from Medline, EMBASE, The Cochrane Library, and CBM. A meta-analysis was conducted with Cochrane Collaboration's RevMan 5. 0.

RESULTSThe search identified 558 citations in total, in which 7 articles in English were finally included in the meta-analysis. The analysis showed that compared with standard platelet concentrates transfusion, leukocyte-filtered platelet transfusion significantly decreased PTR [ RR = 0. 59, 95% CI (0. 42, 0. 82) , P = 0. 002 ] and HLA-alloimmunization [ RR = 0. 49,95% CI (0. 33, 0. 74) , P =0. 0006]. Subgroup analysis showed that HLA-alloimmunization was significantly reduced by leukocyte-filtered platelet transfusion among the patients with acute myelocytic leukemia [ RR =0.42, 95% CI (0.32, 0.56), P <0. 00001], while no significant difference was detected in patients with acute lymphoblastic leukemia because of the limited sample size [ RR = 0. 50, 95% CI (0. 10, 2.41) , P =0. 39].

CONCLUSIONSThe current evidence shows that leukocyte-filtered platelet transfusion can prevent PTR and HLA-alloimmunization more effectively than standard platelet transfusion. Well-designed large-scale RCTs are still needed to further confirm this finding.

Filtration ; HLA Antigens ; immunology ; Humans ; Leukocytes ; immunology ; Platelet Transfusion ; methods ; Randomized Controlled Trials as Topic

OBJECTIVETo study the possible relationship between coronary artery lesions and fibrinogen Bbeta-148 C/T polymorphism in children with Kawasaki disease.

METHODSFast blood samples were taken from 36 children with Kawasaki disease (21 had coronary artery lesions) and 49 age- and gender-matched healthy children (control group). Plasma levels and molecular reactivity of fibrinogen were measured with Assist Plasma Fibrinogen Activity Assay System. Polymerize chain reaction and restriction enzyme digestion were used to detect the genotypes of fibrinogen Bbeta-148C/T gene polymorphism.

RESULTSThe plasma fibrinogen levels in patients with coronary artery lesions were significantly higher than those in patients without coronary artery lesions and in the control group. T allele frequency in patients with Kawasaki disease was significantly higher than that in the control group. The patients with coronary artery lesions had more increased T allele frequency compared with the patients without coronary artery lesions.

CONCLUSIONSPlasma fibrinogen levels and fibrinogen Bbeta-148C/T polymorphism are associated with coronary artery lesions in children with Kawasaki disease.

Child, Preschool ; Coronary Artery Disease ; etiology ; Female ; Fibrinogen ; analysis ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; genetics ; Polymorphism, Genetic