Intra-nucleus accumbens shell injection of baclofen blocks the reconsolidation of conditioned place preference in morphine-addicted mice / 生理学报

Preclinical studies suggest that the GABA receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABA receptor agonist, is the only specific GABA receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABA receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 μL/side or 0.12 nmol/0.2 μL/side), rather than vehicle or BLF (0.01 nmol/0.2 μL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABA receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.

Effect of combination of dexmedetomidine and droperidol on emergence agitation of sevoflurane general anesthesia in the elderly undergoing thoracotomy / 临床麻醉学杂志

Objective To evaluate the treatment effect of combination of dexmedetomidine and droperidol on emergence agitation during general anesthesia recovery period in the elderly undergoing thoracotomy. Methods Sixty patients with severe emergence agitation during general anesthesia recovery period undergoing thoracotomy for esophageal cancer or pulmonary lobectomy, aged 66-75 years, falling into ASA physical status Ⅱ or Ⅲ, were divided into three groups, 20 patients in each according to table of random number: group droperidol (group F) and group dexmedetomidine (group D) and group dexmedetomidine combining droperidol (group DF). In group F, 0.06 mg/kg droperidol was administrated via central vein. In group D, 1 μg/kg dexmedetomidine was pumped via central vein in 10 min, followed by continuous infusion of dexmedetomidine in 0.2 μg·kg-1·h-1 for 1 h. While in group DF, 0.03 mg/kg droperidol was administrated via central vein and 0.5 μg/kg dexmedetomidine was pumped via central vein in 10 min, then followed by continuous infusion of dexmedetomidine in 0.2 μg·kg-1·h-1 for 1 h. The agitation scores and the Ramsay scores were collected after the beginning of anti-agitation. Arterial blood partial pressure of carbon dioxide was tested. Postoperative complications including nausea and vomiting were recorded. Results Compared with group D, the agitation scores at 5, 10, 15 and 20 min in group DF were lower (P ＜ 0.05). Comparing with group F, the agitation scores at 60, 90 and 120 min in group DF were lower (P ＜ 0.05). The incidence of over-sedation in group DF and in group D was less than that in group F (P ＜ 0.05). PaCO2 was unaltered in all the groups after treatment. The incidence of nausea, vomiting, bradycardia, hypertension, hypotension and respiration depression and long QT interval between the groups were comparable. Conclusion Combination of dexmedetomidine and droperidol is effective and safe in the treatment of agitation during sevoflurane general anesthesia recovery period in the elderly undergoing thoracotomy.

miR-124-1 promotes neural differentiation of rat bone marrow mesenchymal stem cells / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of miR-124-1 on neuronal differentiation of rat bone marrow mesenchymal stem cells (MSCs).</p><p><b>METHODS</b>MSCs cells were assigned into three groups: control (uninfected and untransfected), miR-124-1+ (infected with miR-124-1), and miR-124-1- (transfected with Anti-rno-miR-124* Inhibitor). MSCs were induced by β-mercaptoethanol (β-ME) to differentiate into neurons. The fluorescence expressed by infected MSCs was observed under an inverted fluorescence microscope. MTT method was used to measure cell survival rate after transfection or infection. Immunocytochemistry, RT-PCR and Western blot methods were used to detect the expression of β3 tubulin, MAP-2 and GFAP 6 days after β-ME induction.</p><p><b>RESULTS</b>The expression of miR-124-1 in the miR-124-1+ group was significantly higher 2 days after infection of lentivirus vector compared with the control group (P<0.01). In the miR-124-1- group, the cell survival rate and the miR-124-1 expression level decreased significantly 24 hrs after transfection of anti-rno-miR-124* inhibitor (P<0.01). After 6 days of β-ME induction, the protein and mRNA expression levels of β3 tubulin and MAP-2 in the miR-124-1+ group were much higher than the other two groups (P<0.01); while the expression levels of β3 tubulin and MAP-2 in the miR-124-1-group were lower than the control group (P<0.01). The expression of GFAP in the three groups was weak (<1%).</p><p><b>CONCLUSIONS</b>miR-124 might promote neuronal differentiation of rat MSCs.</p>

Inhibition of PDK1 gene expression in esophageal cancer EC9706 cells by RNA interference and its effect on their malignant biological behavior / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the silencing effects of RNA interference on the expression of 3-phosphoinositide-dependent protein kinase 1 (PDK1) gene, and the effects on malignant phenotypes of esophageal carcinoma EC9706 cells.</p><p><b>METHODS</b>PDK1 siRNAs was transfected into the EC9706 cells. The expression of PDK1 mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). At the same time, expressions of PDK1, Akt and phosphorylated Akt proteins were detected by Western blot. Methyl thiazolyl tetrazolium assay (MTT) was used to examine the cell proliferation after transfection. Flow cytometry was used to determine the percentage of apoptosis cells, and Transwell chambers were used to detect the invasion ability of the cells. Tumor formation in nude mice was used to assess the tumorigenic characteristics in vivo.</p><p><b>RESULTS</b>Compared with the non-transfected group, PDK1 siRNA effectively inhibited the expression of PDK1 mRNA in EC9706 cells, with an inhibition rate of (28.5 ± 4.2)% at 24 h, (51.1 ± 5.7)% at 48 h and (60.6 ± 4.1)% at 72 h after transfection. The expressions of PDK1 and phosphorylated Akt protein were also knocked down by PDK1 siRNA (P < 0.05). PDK1 siRNA significantly inhibited the cell proliferation and invasion, promoted the cell apoptosis, and inhibited the EC9706 cells proliferation in vivo and the expression of PDK1 protein in the transplanted tumors (P < 0.05).</p><p><b>CONCLUSION</b>PDK1 may play an important role in esophageal cancer cell proliferation, invasion and apoptosis, and may serve as an effective target for cancer gene therapy.</p>

Splenic sarcoidosis: a case report and review of literature / 中华内科杂志

Objective To describe the clinical features and imaging characteristics of nodular splenic sarcoidosis. Methods We describe a patient with splenic sarcoidosis and review the related medical literature, the etiology, symptomatology, pathology, diagnosis, differential diagnosis, management and prognosis of splenic sarcoidosis. Results The etiology of this rare disease remains unknown. Symptoms are scanty and usually mild; computed tomography usually reveals splenomegaly or the presence of multiple nodules, confusing with metastatic tumor in spleen. On histopathologic examination, sarcoid produces noncaseating granulomas. Sarcoid is typically treated only when symptomatic. Oral corticosteroids is the most important method of treatment in patients with progressive loss of organ functions. Prognosis has closed relationship with early clinical manifestation. Conclusion Splenic sarcoidosis is rare and often misdiagnosis as other diseases.

Expression of nucleostemin mRNA and protein in the esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the mRNA and protein expression of nucleostemin (NS) in human esophageal squamous cell carcinoma.</p><p><b>METHODS</b>The mRNA and protein expression of NS were detected in 31 mucosal atypical hyperplasia specimens, 62 esophageal squamous cell carcinoma specimens and the matched normal esophageal mucosa samples by RT-PCR and immunohistochemistry method, respectively.</p><p><b>RESULTS</b>The positive expression rate of NS protein in normal esophageal mucosa, atypical hyperplasia and esophageal squamous cell carcinoma was 17.7% (11/62), 41.9% (13/31) and 69.4% (43/62), respectively. There was a significant difference among the above three groups (chi2 = 33.676, P < 0.01). The expression levels of NS mRNA in esophageal squamous cell carcinoma (0.971 +/- 0.121) was significantly higher than that in the atypical hyperplasia (0.913 +/- 0.085) and also in the normal esophageal mucosa (0.866 +/- 0.103; F = 14.829, P < 0.01). The expression level of both NS protein and mRNA was positively correlated with histological grade, infiltration depth, and lymph node metastasis (P < 0.05), but not with age, gender or pathological type (P > 0.05).</p><p><b>CONCLUSION</b>Our results indicate that nucleostemin mRNA and protein are over-expressed in human esophageal squamous cell carcinoma, and it may be related with its oncogenesis.</p>

Construction and identification of matrix metalloproteinase inhibitor-1 siRNA eukaryotic expression vectors / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To construct TIMP-1 siRNA eukaryotic expression vectors and evaluate their effect on TIMP-1 mRNA expression in hepatic stellate cells.</p><p><b>METHODS</b>The combinant lone DNA with cutting sites of BamH I and Xho I enzyme according to the sequences of 447-465, 552-540 TIMP-1 of rats and nonspecific sequence were selected and cloned to pGEM-T vector and sub-cloned to pRNAT-U6.2. They were then identified by double enzyme digestion analysis and DNA sequencing. Three plasmids were transfected into T6 separately through an oligofectamine package. TIMP-1 mRNA expression was evaluated by RT-PCR.</p><p><b>RESULTS</b>Targeting sequences of TIMP-1 siRNA eukaryotic expression vectors were correct. TIMP-1 mRNA expression was significantly reduced by transfecting them into the T6.</p><p><b>CONCLUSION</b>We successfully constructed two TIMP-1 siRNA eukaryotic expression vectors and the transfected cells can significantly suppress the TIMP-1 expression.</p>

Inhibitory effects of transfected Bcl-XL antisense oligodeoxynucleotide on proliferation of esophageal cancer cells and growth of human esophageal carcinoma in nude mice / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the biologic effects of Bcl-XL antisense oligodeoxynucleotide (ASODN) transfected into cultured esophageal carcinoma cells and human esophageal carcinoma xenograft in nude mice.</p><p><b>METHODS</b>Cationic liposome-mediated ASODN was used to transfect esophageal carcinoma cells. RT-PCR, Western blot, MTT assay, flow cytometry and in-situ apoptosis cells detection (TUNEL detection) were used to systematically study the biological effects of the transfected cells in vitro and in vivo.</p><p><b>RESULTS</b>MTT assay showed that the proliferation of esophageal carcinoma cells in the ASODN group decreased significantly as compared with control (P < 0.05), along with a 57.3% inhibitory rate of Bcl-XL mRNA, a significant decrease of Bcl-XL protein and the apoptosis rates of (31.1 +/- 5.8)% and 35.0% by flow cytometry and TUNEL assay, respectively (P < 0.01, as compared with controls). The growth of human esophageal carcinoma in nude mice was also significantly inhibited in the ASODN group (P < 0.05), along with a significant decrease of Bcl-XL mRNA and protein expression, and also an enhanced apoptosis of the tumor cells in nude mice.</p><p><b>CONCLUSIONS</b>Bcl-XL ASODN can effectively inhibit the proliferation of esophageal carcinoma cells in vitro and the growth of the tumor in vivo. The suppression of Bcl-XL expression by ASODN may offer both a therapeutic approach and an important theoretic foundation for gene therapy against esophageal carcinoma.</p>