Silencing of long noncoding RNA XIST attenuated Alzheimer's disease-related BACE1 alteration through miR-124.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. However, its pathogenetic mechanism is still poorly understood. An increasing number of studies have evidenced the important role of long noncoding RNAs (lncRNAs) in AD. The aim of the current study was to investigate the effect and molecular mechanism of the lncRNA X-inactive specific transcript (XIST) in AD. Bilateral common carotid artery occlusion (2VO) was used to induce an AD model in mice. Hydrogen peroxide (H2 O2 ) was used to induce an AD model in N2a cells. The lncRNA XIST, miR-124, and BACE1 messenger RNA expression levels were detected by a real-time polymerase chain reaction. The BACE1 protein expression level was detected by western blot and immunofluorescence assay. The Aß1-42 expression level was detected using an enzyme-linked immunosorbent assay kit. The expression level of lncRNA XIST was significantly upregulated in AD models, both in vivo and in vitro. Silencing of lncRNA XIST negatively regulated miR-124 and positively regulated BACE1 expression in N2a cells, which is attenuated by cotransfection of anti-miR-124 oligodeoxyribonucleotide (AMO-124). Silencing of lncRNA XIST reversed the effect of H2 O2 on miR-124, BACE1, and Aß1-42 expression in N2a cells, which was reversed by cotransfection of AMO-124. Silencing of lncRNA XIST attenuated AD-related BACE1 alteration through miR-124. LncRNA XIST may be a new potential target for the treatment of AD.

Activating mGluR8 Attenuates Visceral Hypersensitivity in Neonatal Maternally Separated Rats / 胃肠病学

Activating metabolite glutamate receptor 8 (mGluR8) has anti-hyperpathia effect in central nervous system, however, studies of effects in gastrointestinal tract are rare. Visceral hypersensitivity is one of the pathogenesis factors of irritable bowel syndrome (IBS). Aims: To investigate the effect and potential mechanism of activating mGluR8 on visceral hypersensitivity in neonatal maternally separated (NMS) rats. Methods: Twenty-four male newborn SD rats were randomly divided into normal control (NC) group, NMS group and mGluR8 agonist (S)-3, 4-DCPG group (3, 10 mg/kg). Newborn rats were subjected to 3 hours daily maternal separation on postnatal day 2-14 to establish the NMS model; in (S)-3, 4-DCPG group, (S)-3, 4-DCPG (3 or 10 mg/kg) were administered 1 hour prior to the visceral sensitivity test in NMS rats. Abdominal withdrawal reflex (AWR) score and abdominal electromyography (EMG) activity were used to measure visceral sensitivity. mGluR8 mRNA and protein expressions in colon mucosa were measured by RT-PCR and Western blotting, respectively; TNF-α, IL-1β and IL-6 mRNA expressions in colon mucosa were measured by RT-PCR. The protein expression of myeloperoxidase (MPO) was measured by immunohistochemistry. Results: AWR score and EMG activity in NMS group were significantly higher than those in NC group under different colorectal distension (CRD) pressure. AWR score and EMG activity were significantly decreased in (S)-3, 4-DCPG group. mGluR8 mRNA and protein expressions in NMS group were significantly higher than those in NC group (P<0.05). Compared with NMS group, TNF-α mRNA expression was significantly decreased in 3 mg/kg (S)-3, 4-DCPG group (P<0.05), and MPO protein expression was significantly decreased in 10 mg/kg (S)-3, 4-DCPG group (P<0.05). Conclusions: Activating mGluR8 attenuates visceral hypersensitivity in NMS rats, the mechanism may be related to decrease of pro-inflammatory cytokine TNF-α.

Association of brain-derived neurotrophic factor valine to methionine polymorphism with sexual dysfunction following selective serotonin reuptake inhibitor treatment in female patients with major depressive disorder.

INTRODUCTION: The occurrence of female sexual dysfunction (FSD) in patients with major depressive disorder (MDD) receiving selective serotonin reuptake inhibitors (SSRIs) treatment gives negative impacts on patients' quality of life and causes treatment discontinuation. We aimed to investigate whether genetic polymorphism of identified candidate gene is associated with FSD in our study population. METHODS: This is a cross-sectional study. A total of 95 female patients with MDD who met the criteria of the study were recruited and were specifically assessed on the sexual function by trained psychiatrists. Patients' DNA was genotyped for BDNF Val66Met polymorphism using real-time polymerase chain reaction. RESULTS: The prevalence of FSD in this study is 31.6%. In the FSD group, patients with problematic marriage were significantly more frequent compared with patients who did not have problematic marriage (P = 0.009). Significant association was detected in the lubrication domain with BDNF Val66Met polymorphism (P = 0.030) using additive genetic model, with even stronger association when using the recessive model (P = 0.013). DISCUSSION: This study suggested that there was no significant association between BDNF Val66Met with FSD. However, this polymorphism is significantly associated with lubrication disorder in patients treated with SSRIs.

Content Changes of Eight Components in Tetrastigmatis Hemsleyani Radix of Different Months / 中国实验方剂学杂志

Objective:To establish a HPLC method for determination of chlorogenic acid,rutin,polydatin,kaempferol-3-O-rutinoside,astragalin,resveratrol,quercetin,kaempferol in Tetrastigmatis Hemsleyani Radix,in order to study the content changes of eight components of different months. Method:Zorbax SB C18column (4.6 mm×250 mm,5 μm)was adopted with mobile phase consisting of acetonitrile(A)and 0.1%phosphoric acid(B)in gradient elution(0-30 min,10%-30%A;30-40 min,30%-95%A;40-45 min,95%A;45-60 min,95%-10%A). The flow rate was 0.8 mL·min-1,the column was kept at 25℃,and the detection wavelength was 320 nm. Result:Chlorogenic acid,rutin,polydatin,kaempferol-3-O-rutinoside,astragalin,resveratrol,quercetin,kaempferol showed a good linearity within the range of 13.7-549 mg·L-1(r=0.999 0),12.6-253 mg·L-1(r=0.999 1),15.8-316 mg·L-1(r=0.999 0),14.7-147 mg·L-1(r=0.999 2),8.8-88 mg·L-1(r=0.999 1),7.9-79 mg·L-1(r=0.999 5),8.6-172 mg·L-1(r=0.999 1),8.9-89 mg·L-1(r=0.999 4). There were great differences in contents of the eight flavonoid active components in different growth phases. In July and August,the relative contents of chlorogenic acid,rutin,kaempferol 3-O-rutinoside and polydatin were the highest. The highest relative content of quercetin was observed in June. The relative contents of resveratrol and kaempferol in April and May was higher than those in other mouths. The relative content of astragalin in November was the highest. Conclusion:It could provide abundant information for the production and quality control of Tetrastigmatis Hemsleyani Radix.

Chemical components of flavonoids from leaves of Zelkova serrata / 中国药学杂志

OBJECTIVE: To study flavonoids from the leaves of Zelkova serrata. METHODS: The leaves were extracted with 70% ethanol by continuous thermal reflux. The extract was separated and purified by silica gel column chromatography, polyamide column chromatography, preparative TLC and other isolation techniques. Their structures were identified by their physical properties and spectroscopic data. RESULTS: Eight flavonoids were isolated and identified as myricetin (1), dihydromyricetin (2), quercetin (3), myricitrin(4), myricetin-3-O-β-D-xyloside(5), quercetin-3-O-β-D-xyloside(6), quercitrin(7), and rutin(8). CONCLUSION: All compounds were isolated from Schneider Zelkova leaves for the first time.

Effects of Notch-1 down-regulation on malignant behaviors of breast cancer stem cells / 华中科技大学学报（医学）（英德文版）

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.

Effects of Notch-1 down-regulation on malignant behaviors of breast cancer stem cells / 华中科技大学学报（医学）（英德文版）

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.

Discrepancy of blood pressure between the brachial artery and radial artery / 世界急诊医学杂志（英文）

@#BACKGROUND: In this study, we attempted to find the relations between blood pressure (BP) measured on the brachial artery (bBP) and BP assessed on the radial artery (rBP) in the right arm. METHODS: Three hundred and fifteen patients were enrolled in this study. Those who had peripheral vascular disease, wounds of arm skin or subcutaneous tissue infection were excluded. After a 15-minute equilibration and stabilization period after inducation of anesthesia, three bBP and rBP records were obtained sequentially using an oscillometric device with an adult cuff and infant cuff, respectively. Order for each BP was randomized. RESULTS: The bBP was significantly lower than the rBP (P<0.05). The difference between the two values varied from 13 to 18 mmHg in systolic BP (SBP), diastolic BP (DBP) and mean blood pressure (MAP) respectively. And the rBP was positively correlated with the bBP (r=0.872, 0.754, 0.765; P<0.001, <0.001, <0.001; SBP, DBP, MAP, respectively). CONCLUSION: The bBP value can be evaluated by the noninvasive measurements of rBP using an appropriate cuff in clinical practice.

Effects of Celastrol on growth inhibition of U937 leukemia cells through the regulation of the Notch1/NF-kappaB signaling pathway in vitro / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Leukemia is a malignant tumor highly dependent on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), which is relevant for the occurrence, metastasis, proliferation, apoptosis, and drug resistance of tumor cells. Research has confirmed that the NF-kappaB family is one of the target genes in the Notch signaling pathway. This study investigated the effects of Celastrol on the apoptosis of U937 cells and the expression levels of Notch1 and NF-kappaB in these cells.</p><p><b>METHODS</b>U937 cells were treated with various concentrations Celastrol (0.5-16.0) micromol/L for 12-60 h. MTT assay was performed to examine the effect of Celastrol on growth inhibition of U937 cells. Cell apoptosis was detected through both Annexin-V FITC/PI double-labeled cytometry and transmission electron microscopy (TEM). Cell cycle regulation was studied by propidium iodide. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) technologies were applied to assess the expression level of Notch1 in U937 cells. Subcellular distributions of NF-kappaB/p65 were detected through confocal microscopy.</p><p><b>RESULTS</b>Celastrol presented striking growth inhibition and apoptosis induction potency on U937 cells in vitro in a time- and dose-dependent manner. The IC50 value of Celastrol for 24 h was (6.21 +/- 0.242) micromol/L. Moreover, Celastrol induced apoptosis in U937 cells in a cell-cycle dependent manner, which means that Celastrol could arrest U937 cells in the G0/G1 phase. Through TEM, apoptotic bodies containing nuclear fragments were found in Celastrol-treated U937 cells. Overexpression of Notch1 was found in U937 cells, while Celastrol could downregulate it at both the protein and mRNA level in a dose-dependent manner, and expression of NF-kappaB decreased in nuclei and increased in the cytoplasm (P < 0.05).</p><p><b>CONCLUSIONS</b>Celastrol inhibited cell proliferation and induced apoptosis in U937 cells in a concentration-dependent manner. The possible mechanism might be involved in the regulation of a survival signaling pathway, such as Notch or NF-kappaB.</p>

Clinicopathologic features and prognosis of gastric cancer in young adults / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathologic features and prognosis of young patients with gastric cancer by comparing with older patients.</p><p><b>METHOD</b>The clinicopathologic data of 157 younger adults (age, </= 40 years) with gastric cancer and 1761 cases of elder gastric cancer patients (age, > 40 years) was analyzed and compared retrospectively. All of the 1918 patients were surgically treated between January 1980 and December 2000.</p><p><b>RESULTS</b>The rates of poorly differentiation, diffusive growth, Borrmann 4 type, whole-stomach invasion were significantly higher in younger cases than those in the elder counterparts (P < 0.05), especially in young female patients. The rate of early gastric cancer was significantly higher in young patients than that in older patients (P < 0.05), especially in young male patients. There was significant difference between the survival rate of younger male cases (median survival, 35 months) and younger female cases (median survival, 19 months) (P = 0.0219), but no significant difference was found between elder male and elder female (median survival, 26 vs. 30 months). TNM stage, operative curability, gross type were independent predictive factors of survival for younger patients.</p><p><b>CONCLUSIONS</b>Younger female gastric cancer patients tends to have worse prognosis than older patients, while younger male patients have better prognosis due to higher percentage of early gastric cancer when diagnosed. Pathologic staging and operative curability are the independent predictive factors of survival for younger patients.</p>

Assessment on different modes of lymphadenectomies in the treatment for early gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of different modes of lymphadenectomies in the surgical treatment for early gastric cancer (EGC) in order to provide evidence for reasonable selection of lymphadenectomy for the ECG.</p><p><b>METHODS</b>The clinicopathological data of 325 EGC patients were reviewed. The lymph node metastasis (LNM) rate of different levels and the efficiency of different modes of lymphadenectomies were analyzed, and the correlation between LNM and clinicopathological features were analyzed either.</p><p><b>RESULTS</b>The overall LNM rate in the EGC was 14.8%, and the overall LNM degree was 3.0%. In the ECG located in the lower third of the stomach, the rate of first level nodal involvement was 14.5%, which was detected in the No. 3, No. 4, No. 5, No. 6 station of draining lymph nodes for the stomach; and it was 6.9% in the second level lymph nodes which were seen in the No.7 and No. 8a station. There was rare metastasis in the No. 1, No. 9, No. 11p, No. 12a and No. 14v station. In the ECG located in the middle third of the stomach, the rate of first level nodal involvement was 13.8% , which was found in the No. 1, No. 3, No. 5 and No. 6 station, and it was 6.9% in the second level nodes only seen in the No. 7 and No. 8a station. The LNM rate was significantly higher in the lesion larger than 3.0 cm in diameter, or having submucosa invasion, or being poorly differentiated, or with lymphatic involvement than that of the lesion smaller than 3.0 cm in diameter, without mucosa invasion or lymphatic involvement, or being well differentiated (P < 0.05).</p><p><b>CONCLUSION</b>Based on our data, it is suggested that the D1 or D1 + lymphadenectomy of the No. 7 station of lymph node may be suitable for the lesion smaller than 1.0 cm in diameter or only located in the mucosa; the D1 + lymphadenectomy of the No. 7 and No. 8a station of lymph nodes may be suitable for the lesion larger than 1.0 cm in diameter, or being depressed type or with submucosa invasion in the middle and/or lower third of the stomach. For the lesion larger than 3.0 cm in diameter, the No. 1 and No. 9 station lymph node should be dissected. It is also suggested that regular D2/ D3 lymphadenectomy should be avoided in the surgical treatment for the early gastric cancer whenever the tumor situation is suitable.</p>

Retrospective analysis of extended gastrectomy and lymphadenectomy in early gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To objectively evaluate the practical significance of different extended surgeries in early gastric cancer(EGC) patients, and to choose reasonable gastrectomies and lymphadenectomies.</p><p><b>METHODS</b>A total of 217 EGC patients were investigated undergone normalized D2 or above extended surgery and their clinicopathological data were recorded in detail. The efficiency of the extended lymphadenectomies, complications and operation causes were analyzed, and the correlation between the group 2 lymph node metastasis (LNM) and clinicopathological factors were assessed, too.</p><p><b>RESULTS</b>There was no nodal involvement in the No.5 and No.6 lymph nodes among the total gastrectomy in the upper third of the stomach, neither was in the No.10, 11p and 11d lymph nodes among the combined splenectomy, and neither was in the No.15 lymph nodes among the combined transverse mesocolon resection in the lower third of the stomach. There was no distant nodal involvement in the EGC. Above all, most of them were mistaken for advanced gastric cancer preoperatively and intraoperatively, the operation time was longer and the blood loss was more during operation. Among the resected nodes of group 2 in the lower third of the stomach, metastasis was not found in the No.11p, 12a and 14v lymph nodes. The rate of the No.7 and 8a nodal involvement in the submucosa cancer was higher than that in the mucosa cancer(P<0.05) and so did the No.7 in the lymphatic penetration positive(P<0.001). The No.1 and No.13 nodal involvement were only seen in the high risk cases, such as submucosa cancer, the lesion diameter more than 3.0 cm, depressed type and lymphatic involvement.</p><p><b>CONCLUSION</b>It is not necessary to execute total gastrectomy in the upper third of the stomach, combined organ resection (such as splenectomy, transverse mesocolon resection), and distant lymph node dissection in the EGC. In the lower third of the stomach, the No.11p 12a and 14v lymph nodes shouldn't be dissected. With respect to the high risk nodal involvement cases in the lower third of the stomach, the No.1 lymph nodes should be dissected and so does the No.13 lymph nodes if it's tumefied. It is the key point of reasonable operation to exactly diagnose the EGC before and during the surgery.</p>

Study on lymph node metastasis in 292 patients with early gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the status of lymph node metastasis (LNM) and reasonable procedure in early gastric cancer (EGC).</p><p><b>METHODS</b>Two hundred and ninety-two patients with histologically proven mucosal or submucosal gastric cancer who underwent gastrectomy/lymphadenectomy were included in this study. The numbers of total dissected lymph node were all above 15 in all patients. The clinical characteristics, pathologic features, and LNM were assessed by univariate and multivariate analysis.</p><p><b>RESULTS</b>LNM were observed in 43 of 292 cases (14.7%), and 6.4% in mucosal lesions and 22.4% in submucosal lesions. The LNM was identified in 12.7% at the first level, 7.2% at the second level and 0.34% at the third level. The LNM frequency was found in the 6, 3, 4, 1, 5 lymph node (from high to low) consequently at the first level and the 7, 8a lymph node at the second level. The EGC with nodal involvement and the tumors < 2.0 cm in diameter were all depressed type. The diameter of elevated type with LNM was no less than 3.0 cm in this series. The depth of invasion and lymphatic vessel involvement were independent influencing factors in LNM on multivariate analysis (P<0.05).</p><p><b>CONCLUSIONS</b>Less extensive surgery might be considered for the elevated type EGC, and tumors <or= 2.0 cm in diameter and mucosal lesions. Gastrectomy with D1 plus No.7, 8a lymphadenectomy might be carried out in the depressed type/<or= 3.0 cm in diameter, or in the elevated type/> 3.0 cm in diameter. With respect to the depressed type EGC/tumors > 3.0 cm in diameter, gastrectomy with D2 lymphadenectomy is proper.</p>

Expression of survivin mRNA in peritoneal lavage fluid from patients with gastric carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Peritoneal dissemination is the most common pattern of metastasis in advanced gastric carcinoma with serosal invasion. In the present study, we reported the clinical relevance of a new diagnostic method involving RT-PCR, using survivin as the target gene, for the detection of free cancer cells in peritoneal washes.</p><p><b>METHODS</b>Intraoperative peritoneal washes were obtained from 48 patients who underwent surgery for gastric cancer. RT-PCR analysis with primers specific for survivin and conventional cytological examinations were both performed.</p><p><b>RESULTS</b>Survivin mRNA was not detected in any peritoneal wash samples from patients with benign disease, but was detected in 28 of 48 samples taken from patients with gastric cancer and in all metastatic nodules. Survivin expression in the peritoneal cavity significantly correlated with depth of cancer invasion, lymph node metastasis, and TNM stage. There were 92% of clinically evident peritoneal metastasis cases showed detectable survivin expression. The combination of survivin RT-PCR and cytological examination yielded positive results in 66.7% (32/48) of patients with gastric cancer, much higher than the results produced by cytological method alone.</p><p><b>CONCLUSIONS</b>Survivin mRNA detected in peritoneal lavage fluid might indicate the presence of free cancer cells in the peritoneal cavity. The high sensitivity of the RT-PCR-based survivin assay suggests that survivin serves as a molecular marker for detecting peritoneal micrometastasis. Its ubiquitous expression in peritoneal cancer cells and metastatic nodules also suggests a promising future therapeutic strategy based on survivin inhibition for cases of gastric cancer involving peritoneal metastasis.</p>

Study on Action of kangfuxin Solution on Experimental Gastric ulcer / 中成药

Objective: To study the action of kangfuxin solution on the experimental gastric ulcer.Methods: The rat gastric ulcer models induced by the ligated pylorus and burned acetic acid, the gastric moucosa injury model induced by the absolute ethyl alcohol were used.Results: Kanfuxin solution possessed the protective action on the rat gastric ulcer model induced by the ligated pylorus and rat gastic mucosa injury model induced by the absolute ethyl alcohol, but didn't affect the rat gastric ulcer model induced by burned acetic acid. Conclusion: Kangfuxin Solution also has the actions of inhibiting the output of gastric acid and pepsin.