Advance of research on endoplasmic reticulum stress and genetic epilepsy / 中华医学遗传学杂志

Epilepsies are a group of chronic neurological disorders characterized by spontaneous recurrent seizures caused by abnormal synchronous firing of neurons and transient brain dysfunction. The underlying mechanisms are complex and not yet fully understood. Endoplasmic reticulum (ER) stress, as a condition of excessive accumulation of unfolded and/or misfolded proteins in the ER lumen, has been considered as a pathophysiological mechanism of epilepsy in recent years. ER stress can enhance the protein processing capacity of the ER to restore protein homeostasis through unfolded protein response, which may inhibit protein translation and promote misfolded protein degradation through the ubiquitin-proteasome system. However, persistent ER stress can also cause neuronal apoptosis and loss, which may aggravate the brain damage and epilepsy. This review has summarized the role of ER stress in the pathogenesis of genetic epilepsy.

Alendronate combined with Lactobacillus rhamnosus to combat bone loss in ovariectomized mice / 中华创伤骨科杂志

Objective:To study the protective effect of alendronate combined with Lactobacillus rhamnosus on bone loss in ovariectomized mice.Methods:Fifty female C57BL/6 mice were divided into 5 equal groups ( n=10). Ovariotomy was performed in groups A, B, C and D while a sham operation was performed in group E. Group A was subjected to combined administration of alendronate and Lactobacillus rhamnosus, group B to administration of alendronate, group C to administration of Lactobacillus rhamnosus, and groups D and E to administration of physiological saline only. At 3 months after operation, all the mice were sacrificed to harvest their femurs. Micro CT scanning was performed to detect the bone mineral density (BMD), trabecular relative volume, bone surface area/bone volume, and trabecular thickness and number of trabecular bone. Three-point bending test was used to detect the maximum load, stiffness, ultimate load, Young＇s modulus, and fracture energy. Osteocalcin and alkaline phosphatase levels were measured using blood samples from the mice eyeballs. The 2 groups were compared in terms of all the above indexes. Results:The BMD [(669.87±67.87) mg/cm 3], maximum load [(14.35±0.75) N] and fracture energy [(1,497.43±38.29) J/m 2] in group A were significantly higher than those in group B [(520.07±9.01) mg/cm 3, (11.94±0.82) N and(1,277.61±35.12) J/m 2] and group C [(388.15±25.61) mg/cm 3, (11.10±0.93) N and (1,115.27±63.24) J/m 2] (all P<0.05). The osteocalcin level in group A [(22.25±1.78) ng/mL] was significantly higher than that in group B [(19.08±1.45) ng/mL] and group D [(19.33±1.66) ng/mL] (both P<0.05). The alkaline phosphatase level in group A [(83.21±9.69) ng/mL] was significantly lower than that in group C [(113.16±14.44) ng/mL] and group D [(137.96±14.01) g/mL] (both P<0.05). Conclusion:Alendronate combined with Lactobacillus rhamnosus may play a synergistic role in prevention of bone loss in ovariectomized mice, because combined administration of the two is more effective than administration of either of the two.

Nurse Led Smartphone Electrographic Monitoring for Atrial Fibrillation after Ischemic Stroke: SPOT-AF / 대한뇌졸중학회지

Background@#and Purpose Paroxysmal atrial fibrillation (PAF) underlying acute stroke frequently evades detection by standard practice, considered to be a combination of routine electrocardiogram (ECG) monitoring, and 24-hour Holter recordings. We hypothesized that nurse-led in-hospital intermittent monitoring approach would increase PAF detection rate. @*Methods@#We recruited patients hospitalised for stroke/transient ischemic attack, without history of atrial fibrillation (AF), in a prospective multi-centre observational study. Patients were monitored using a smartphone-enabled handheld ECG (iECG) during routine nursing observations, and underwent 24-hour Holter monitoring according to local practice. The primary outcome was comparison of AF detection by nurse-led iECG versus Holter monitoring in patients who received both tests: secondary outcome was oral anticoagulant commencement at 3-month following PAF detection. @*Results@#One thousand and seventy-nine patients underwent iECG monitoring: 294 had iECG and Holter monitoring. AF was detected in 25/294 (8.5%) by iECG, and 8/294 (2.8%) by 24-hour Holter recordings (P<0.001). Median duration from stroke onset to AF detection for iECG was 3 days (interquartile range [IQR], 2 to 6) compared with 7 days (IQR, 6 to 10) for Holter recordings (P=0.02). Of 25 patients with AF detected by iECG, 11 were commenced on oral anticoagulant, compared to 5/8 for Holter. AF was detected in 8.8% (69/785 patients) who underwent iECG recordings only (P=0.8 vs. those who had both iECG and 24-hour Holter). @*Conclusions@#Nurse-led in-hospital iECG surveillance after stroke is feasible and effective and detects more PAF earlier and more frequently than routine 24-hour Holter recordings. Screening with iECG could be incorporated into routine post-stroke nursing observations to increase diagnosis of PAF, and facilitate institution of guideline-recommended anticoagulation.

Value of lymph node ratio in prognosis of patients with intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective To determine the value of lymph node ratio (LNR) in prognosis of patients with intrahepatic cholangiocarcinoma (ICC).Methods The pathological and survival data of ICC patients were extracted from the Surveillance Epidemiology and End Result Database (SEER).The value of LNR in prognosis of patients with intrahepatic cholangiocarcinoma was evaluated by the Kaplan-Meier and Cox proportional hazard models.Results A total of 357 pathologically confirmed ICC patients were included in this study (158 males,199 females).The results showed that patients with lymph node metastasis had significantly shorter survival time than patients without metastasis [(41.6 ± 1.8) vs.(23.2 ± 2.2) months,P＜ 0.05].Multivariate analysis on survival showed that the status of lymph node metastasis was independent prognostic factor of survival,after adjusting for age,gender and tumor stage.Only a LNR ≥ 20％ was an independent risk factor of prognosis (HR=2.3,95％CI:1.4～3.8,P＜0.05).Conclusion A positive lymph node ratio was superior to lymph node metastasis in predicting survival in patients with intrahepatic cholangiocarcinoma.

Determining Osteogenic Differentiation Efficacy of Pluripotent Stem Cells by Telomerase Activity

BACKGROUND: Bone tissue engineering based on pluripotent stem cells (PSCs) is a new approach to deal with bone defects. Protocols have been developed to generate osteoblasts from PSCs. However, the low efficiency of this process is still an important issue that needs to be resolved. Many studies have aimed to improve efficiency, but developing accurate methods to determine efficacy is also critical. Studies using pluripotency to estimate efficacy are rare. Telomerase is highly associated with pluripotency. METHODS: We have described a quantitative method to measure telomerase activity, telomeric repeat elongation assay based on quartz crystal microbalance (QCM). To investigate whether this method could be used to determine the efficiency of in vitro osteogenic differentiation based on pluripotency, we measured the pluripotency pattern of cultures through stemness gene expression, proliferation ability and telomerase activity, measured by QCM. RESULTS: We showed that the pluripotency pattern determined by QCM was similar to the patterns of proliferation ability and gene expression, which showed a slight upregulation at the late stages, within the context of the general downregulation tendency during differentiation. Additionally, a comprehensive gene expression pattern covering nearly every stage of differentiation was identified. CONCLUSION: Therefore, this assay may be powerful tools for determining the efficiency of differentiation systems based on pluripotency. In this study, we not only introduce a new method for determining efficiency based on pluripotency, but also provide more information about the characteristics of osteogenic differentiation which help facilitate future development of more efficient protocols.

Human INO80/YY1 chromatin remodeling complex transcriptionally regulates the BRCA2- and CDKN1A-interacting protein (BCCIP) in cells

The BCCIP (BRCA2- and CDKN1A-interacting protein) is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCCIP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and colorectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCCIP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation (ChIP) experiments clarify the enrichment of INO80 and YY1 at +0.17 kb downstream of the BCCIP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCCIP promoter region. Our findings strongly indicate that BCCIP is a potential target gene of the INO80/YY1 complex.

Effect of Zhusha Anshen pill, cinnabar, HgS, HgCl2 and MeHg on gene expression of renal transporters in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of Zhusha Anshen pill, cinnabar, HgS, HgCl2 and MeHg on the gene expression of renal transporters in mice.</p><p><b>METHOD</b>Healthy male mice were given equivalent physiological saline, Zhusha Anshen pill (1.8 g · kg(-1), containing 0.17 g · kg(-1) of mercury), cinnabar (0.2 g · kg(-1), containing 1.7 g · kg(-1) of mercury), high dose cinnabar (2 g · kg(-1), containing 1.7 g · kg(-1) of mercury), HgS (0.2 g · kg(-1), containing 0.17 g · kg(-1) of mercury), HgCl2 (0.032 g · kg(-1), containing 0. 024 g · kg(-1) of mercury), MeHg (0.026 g · kg(-1), containing 0.024 g · kg(-1) of mercury), once daily, for 30 d, measuring body mass gain. 30 days later, the mice were sacrificed. The mercury accumulation in kidneys was detected with atomic fluorescence spectrometer. Expressions of Oat1, Oat2, Oat3, Mrp2, Mrp4, Urat1 were detected with RT-PCR.</p><p><b>RESULT</b>Compared with the normal control group, a significant accumulation of Hg in kidney in HgCl2 and MeHg groups was observed (P <0.05), but these changes were not found in other groups. Compared with normal control group, mRNA expressions of Oat1 and Oat2 were evidently lower in HgCl2 and MeHg groups, but mRNA expressions of Mrp2 were apparently higher in HgCl2 group (P <0.05), mRNA expression of Mrp4 was significant higher in HgCl2 and MeHg groups, and mRNA expression of Urat1 was apparently lower in MeHg group.</p><p><b>CONCLUSION</b>HgCl2 and MeHg groups show significant difference from the normal group in mercury accumulation in kidneys and gene expression of kidney transporters, but with no difference between other groups and the normal group. Compared with HgCl2 and MeHg, cinnabar and its compounds could cause lower renal toxicity to mice.</p>

ARIMA models to predict new-diagnosing cases of pneumoconiosis in Nanjing / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>The primary goal of our study was to evaluate and predict the epidemiological trend of pneumoconiosis.</p><p><b>METHODS</b>We established a new database on new-diagnosing cases of pneumoconiosis in Nanjing during 1955-2007. The database was analyzed by using SAS9.1.3 statistical software, Data sequence was stabilized by using the process of differencing. Goodness of Fit Test verified that the residual-error sequence was white noise sequence. We determined the Autoregressive Integrated Moving Average models (ARIMA models) as an appropriate model. By Taking advantage of back-substitution model, we predicted new cases of pneumoconiosis during 2008-2012. We then compared the predicted value with the actual value to test and verify the predicting function.</p><p><b>RESULTS</b>We finally had chosen out ARIMA (2, 1, 0) models to fit the original sequence, which led to the results that the observed values are basically comparable with the predicted values. The past 5-year predicted-value was similar to the actual value. We then built a new model by new cases during 1955-2012, predicting that the trend of pneumoconiosis in the next 5 years will tend to approach plateau with approximately 10∼13 new cases per year.</p><p><b>CONCLUSION</b>ARIMA models is suitable for fitting large sample series of new diagnosed pneumoconiosis over the years and for the predicting the incidence of pneumoconiosis.</p>

Synthesis and immunosuppressive activity of new artemisinin derivatives containing polyethylene glycol group / 药学学报

<p><b>AIM</b>To search for new artemisinin derivatives with higher immunosuppressive activity.</p><p><b>METHODS</b>Two kinds of new artemisinin derivatives containing polyethylene glycol group were synthesized from dihydroartemisinin via condensation and esterification. These compounds were assayed for their inhibitory activity on ConA-induced T cell proliferation and LPS-induced B cell proliferation.</p><p><b>RESULTS</b>Twenty three new compounds (2a - 2f, 3a - 3d, 4a - 4f, 6a, 6b and 7a - 7g) were synthesized and identified by 1H NMR and elemental analysis.</p><p><b>CONCLUSION</b>These compounds had immunosuppressive activity in vitro. Among them, the symmetrical substituted compound 2 and 6 had higher activity than mono-substituted compound 3, 4 and 7. Especially, compounds 2a - 2f remarkably exhibited higher inhibition in comparison with artemisinin and artesunate.</p>

Trans-meridional-point therapeutics and transdermal therapeutic system / 中国组织工程研究

AIM: To compare difference and similarity of transdermal therapeutics between traditional Chinese medicine(TCM) and Western Medicine, to investigate the merit and shortage of the trans-meridional-point therapeutics in TCM, and to find out the problems urgent to be resolved so as to expand external remedy of TCM.METHODS: A part of literatures of TCM about transdermal therapeutics were reviewed, and PubMed database and relevant articles in Chinese medical journals were retrieved to analyze the relevant information RESULTS: The trans-meridional-point therapeutics of TCM had a long his tory, with rich experience and definite effect. The key of it was the amplification and integrative effect produced during the process of absorption of drugs through meridional point. The research of transdermal therapeutics combined with transdermal therapeutic system(TTS) had been in a starting stage, but it was limited in the research of a disease and a prescription, being of shortage in evidence of effective mechanism and morphology. Now one of the hot points in effective mechanism of TTS was to resolve rate-limiting process for medicine transportation through the corneal layer so as to promote entering of enough medicine into the body.CONCLUSION: It is urgent to solve the essence of the morphological basis of acupoint structure, establish experimental animal mode of transdermal therapeutics, and popularize clinical application on the basis of a great deal of medicinal experiments on animals so as to bring new ideas for transdermal remedy of Chinese drug.

Additive effects of the variants in the beta(3)-adrenergic receptor and uncoupling protein-2 genes on obesity in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the additive effects of uncoupling protein 2 (UCP2) gene Ala55Val variation and ADR beta(3) gene Trp64Arg variation on the obesity in Chinese Han population.</p><p><b>METHODS</b>The UCP2 gene Ala55Val variation and ADR beta(3) gene Trp64Arg variation were examined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in 119 obese subject with mean BMI (27.9+/-2.98)kg/m(2) and in 177 control subjects with mean BMI(21.9+/-1.9)kg/m(2). The additive effects of the two gene mutations were analyzed.</p><p><b>RESULTS</b>(1) The frequency of ADR beta(3) gene Trp64Arg variation in obese subjects was not significantly different from that in control subjects. In control subjects, the Trp64Arg variation carriers had higher fasting glucose level and 2-hour-post-prandial glucose level than did non-carriers. (2) The frequency of homozygote of UCP2 gene Ala55Val variation in obese subjects was higher than that in the control subjects (OR=3.71, P=0.001). In control subjects the Ala55Val variation carriers had higher BMI. (3) When there was only UCP2 gene or ADR beta(3) gene mutation, the frequency of gene mutation in obese subjects was not significantly different from that in control subjects (P>0.05). But when there were simultaneously two gene mutations, the frequency of gene mutations was higher in obese subjects than in control subjects (OR=2.57, P=0.009). (4) The genotype carriers with Val/Val+ Trp/Arg were the greatest relation to obese obesity (OR=8.58, P=0.002).</p><p><b>CONCLUSION</b>The homozygote of UCP2 gene Ala55Val mutation increases the risk of obesity. Though the UCP2 gene mutation alone or the ADR beta(3) gene mutation alone is not associated with obesity, the possible additive effects of the two micro-genes increase the occurring of obesity.</p>

Determination of TanshinoneⅡ_A in Ganxinkang Capsules by HPLC / 中国药房

OBJECTIVE:To establish HPLC method for the determination of tanshinoneⅡ A in Ganxinkang capsules.ME_ THODS:The separation was carried out on C 18 column.The mobile phase was composed of methanol-water(80∶20)with a fl_ ow rate at0.8ml/min and detection wavelength at269nm.RESULTS:The linear range of tanshinoneⅡ A was0.16?g～0.80?g (r=0.9989)with average recovery at96.3%(RSD=1.21%).CONCLUSION:This method was convenient,accurate,rapid and reproducible,and suitable for the quality control of this preparation.