Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Advances in diagnosis and treatment of acute suppurative cholecystitis in the elderly / 国际外科学杂志

Acute suppurative cholecystitis is a complex acute abdomen in general surgery, which usually occurs in middle-aged and elderly people. With the improvement of living standards and the aging of the population, the incidence of the disease is increasing year by year. Elderly patients have certain clinical particularities, and they are often combined with other underlying diseases such as cardiovascular and cerebrovascular diseases. Therefore, specific programs should be implemented for different situations during patient treatment, and a more complete risk assessment should be carried out. The preferred treatment for acute suppurative cholecystitis is surgery, but for patients with poor general conditions or intolerable surgery, percutaneous transhepatic gallbladder drainage may be a good alternative. This article reviews the clinical characteristics, diagnosis and treatment of acute suppurative cholecystitis in the elderly.

Safety and feasibility of fast track surgery in operations for gastric cancer: a meta analysis / 中华消化外科杂志

Objective To estimate the safety and feasibility of fast track surgery (FTS) in operations for gastric cancer.Methods The Cochrane library,PubMed,EMBASE,Chinese biomedical literature database,China journal full text database,Chinese scientific journals full text database were searched with the key words of gastric cancer,gastric carcinoma, FTS,fast track surgery, enhanced recovery after surgery,ERAS, 胃癌,and 快速康复外科.The search was finished in April,2011.Randomized controlled trials of FTS for patients with gastric cancer were included.Two reviewers evaluated the quality of the included studies and extracted the data independently.Meta analysis was performed by RevMan 5.1.2 software.Results Fourteen randomized controlled trials involving 1270 patients were included.The results of meta analysis showed that FTS could significantly shorten the first exhaust time (MD =-6.15,95 ％ confidence interval:-8.22- -4.07,P＜ 0.05) and hospital stay ( MD =- 2.68,95％ confidence interval:- 3.26- - 2.10,P ＜ 0.05 ),and reduced the hospital fees ( MD =- 0.39,95 ％ confidence interval:- 0.55- - 0.22,P ＜ 0.05 ).FTS could lighten the postoperative stress and relatively enhance the immunity.Conclusion Compared with conventional methods,FTS could speed up the rehabilitation for patients with gastric cancer postoperatively without increasing the adverse reactions.

Meta-analysis on treatment of non-small cell lung cancer with brucea javanica oil emulsion in combination with platinum-contained first-line chemotherapy / 中国中药杂志

<p><b>OBJECTIVE</b>To study the efficacy and safety of brucea javanica oil emulsion (BJOE) combining platinum-contained first-line chemotherapy in treating non small cell lung cancer (NSCLC).</p><p><b>METHOD</b>Cochrane library, PubMed, EMBASE, VIP, CBM and CNKI were searched through computers. The search was finished in February, 2011. Randomized controlled trials (RCTs) of BJOE combining platinum-contained first-line chemotherapy were included. Two researchers extracted data and assess literature quality separately,and made a meta-analyses by RevMan 5.1.2 software.</p><p><b>RESULT</b>Totally 22 RCTs involving 1512 patients were included. The Meta-analysis showed that compared with the pure application of platinum-contained first-line chemotherapy,the combination of BJOE and chemotherapy can enhance the near-term curative effect (RR = 1. 31, 95% CI: 1.18-1.45, P < 0. 000 01), improve the quality of life (RR = 1.78, 95% CI: 1.51-2. 09, P < 0.00001) and reduce the suppression of bone marrow (OR = 0.37, 95% CI: 0. 27-0. 51, P < 0.00001) and the gastrointestinal reactions (OR = 0.59, 95% CI: 0.44-0.80, P = 0.0007) ,with an improvement in organism immunity.</p><p><b>CONCLUSION</b>The current evidence indicates that BJOE can enhance the chemotherapeutic effect on NSCLC patients, improve the quality of life and reduce adverse effect of platinum-contained chemotherapeutics and thus it is worth referring in clinic.</p>

Detection of beta-lactamase, porin-coding genes and linkage of KPC-ISKpn6 of the carbapenems-resistant Klebsiella pneumoniae / 中华微生物学和免疫学杂志

Objective To investigate the resistance-mechanism of the carbapenems-resistant Klebsiella pneumoniae isolated from clinical.Methods The clinical isolates of carbapenems-resistant Klebsiella pneumoniae from top three comprehensive hospitals of Nanjing area were examined by 40 beta-lactamase,porin-coding genes and linkage of KPC-ISKpn6 using PCR method,the PCR positive results were picked out for sequencing and sequencing BLAST search for comparison analysis.Results Twenty-four strains of carbapenems-resistant Klebsiella pneumoniae were detected,the positive rate of A beta-lactamase TEM-1 and SHV was 100％ (24/24),KPC-2 and LAP-2 was 95.8％ (23/24),45.8％ (11/24) respectively,and C beta-lactamase DHA was 4.2％ (1/24).Meanwhile,the positive detection rates of KPC-ISKpn6 linkage was 95.8％ (23/24),and the mutation rate of porin-coding genes ompK35 and ompK36 were up to 95.8％ (23/24) and 100％ (24/24).Conclusion High incidence of beta-lactamase TEM-1,SHV,KPC-2 and LAP-2 was found in the group of Klebsiella pneumoniae isolates,and carbapenems-resistant of which was primarily due to the high carrying rate of KPC-2 and the high mutation rate of porin-coding genes ompK35 and ompK36.The Insertion sequence ISKpn6 may be involved in the KPC-2 gene mediated-expression.

Nosocomial Infection of Lower Respiratory Tract by Coagulase-negative Staphtylococci:Clinical Characteristics and Their Resistance to Common Antibiotics / 中华医院感染学杂志

OBJECTIVE To explore the clinical characteristics of nosocomial infection of lower respiratory tract by coagulase negative staphtylococci(CNS) and their drug resistance to common antibiotics.METHODS The clinical data and drug resistance of CNS of 37 nosocomial infection cases and 68 cases with colonization of lower respiratory tract by CNS were analyzed retrospectively,and the study mainly was focused on the risk factors and basic clinical features of nosocomial infection of lower respiratory tract by CNS.The resistance to common antibiotics of CNS was also summarized.RESULTS The risk factors were determined,which included long duration,age more than 65 years old,chronic obstructive pulmonary disease,the use of antibiotic suchs as carbapenems,the third generation cephalosporin,fluoroquinolones and concurrent infection of fungus.The mortality rate of infection was higher than after colonization.The clinical characteristics of nosocomial infection of lower respiratory tract by CNS included that the temperature of patients was focus on 37.5-38.5 ℃,peripheral blood routine of patients appearsed normal mostly and the lung imaging displayed the bilateral exudation changing near 50% the total.The 105 isolates of CNS were resistant to multi-antibiotics,the drug resistance rate to rifampicin and sodium fusidate was relatively low and resistant strains to vancomycin and teicoplanin were not detected.CONCLUSIONS The toxemia symptoms of nosocomial infection of lower respiratory tract by CNS are mild and the clinical manifestation is atypical.It is more likely to catch nosocomial infection of lower respiratory tract by CNS for the patients who are with low immunity and applied with broad spectrum antibiotic for long-term.

L-type Calcium Channel Modulates Proliferation and Differentiation of Neural Stem Cells From Rat Embryonic Hippocampus In vitro / 生物化学与生物物理进展

In order to identify whether functional L-type calcium channels are expressed in neural stem cells(NSCs) from rat embryonic hippocampus, and whether L-type calcium channels participate in the modulation of proliferation and differentiation of NSCs, the rat embryonic hippocampal tissue was dispersed into a single cell suspension, and the dissociated cells were cultured in serum-free DMEM/F12 medium containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), N-2 and B27 supplement. Immunofluorescent labeling showed an expression of nestin-positive cells. Following five-days culture in differentiation medium, neuron-like and astrocyte-like cells were observed, which expressed ?-tubulin Ⅲ(Tuj1) and Glial fibrillary acidic protein (GFAP), respectively. Western blot analysis showed an expression of Cav1.2?1C subunits in NSCs, but no Cav1.3?1D subunits. Moreover, L-type calcium channel currents were recorded in those cells by using whole-cell patch clamp techniques. It was found that activation of L-type calcium channels promotes proliferation and differentiation to neuronal type of NSCs. The results indicated that rat embryonic hippocampal NSCs express functional L-type calcium channels, L-type calcium channels modulate proliferation and differentiation of NSCs.

Nitric Oxide Inhibits Delayed Rectifier Potassium Currents in Cultured Hippocampal Neurons via S-Nitrosylation / 生物化学与生物物理进展

The modulating action and mechanism of endogenous nitric oxide (NO) on the delayed rectifier potassium currents in cultured hippocampal neurons were examined using whole-cell patch clamp techniques. L-arginine (L-Arg, 2 mmol/L), a substrate of NO synthases, significantly suppressed the delayed rectifier K+ currents in hippocampal neurons, while its isomer D-arginine (D-Arg, 2 mmol/L) exerted no effect. Moreover, pretreatment with NO synthase inhibitor L-NAME (0.5 mmol/L) completely blocked the suppressing effect by L-Arg, indicating that L-Arg exerted its modulation by producing NO but not by itself. No effect was found on the L-Arg-induced inhibition by 10 min pretreatment of 10 |?mol/L ODQ (a specific inhibitor of guanylate cyclase). In contrast, thiol-alkylating agent N-ethylmaleimide (1 mmol/L) completely precluded L-Arg-induced inhibition on the whole K+ currents. The results indicate that endogenous NO modulates the delayed rectifier K+ currents in cultured hippocampal neurons mostly through S-nitrosylation.

Verification on hypothesis for optimum ratio in various active constituents of Chinese materia medica with desired effects / 中草药

To propose the hypothesis of the requirement for optimum ratio of various active cons tituents of Chinese materia medica with desired effects, which suggests that both single drug and compound drug prescriptions have their own target effects corresponding to their main indications and their active constituents must be in optimum ratio This hypothesis was initially tested in an ischemic animal model The neuroprotection of Yushen Oral Liquor (YSOL, an oral liquor made of Chinese materia medica) on neuronal injury in CA1 region of rat hippocampus following transient forebrain ischemia was used as an index to evaluate the drug's effect By combination of HPLC and pharmacological method, the relationship of HPLC and pharmacodynamical results of each sample made of YSOL was studied to observe the chromatogram peaks representing the drug's neuro protective effects There are three peaks named as R1, R2, and R3 for YSOL, which closely correlate to the drug's neuronal protective effects and the relative weight but not the absolute quantity of those peaks plays a critical role in producing neuronal protective effects of YSOL on ischemia induced neuronal damage The results provide experimental data supporting our proposed hypothesis