Demonstration of safety characteristics and effects on gut microbiota of Lactobacillus gasseri HMV18

Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human flora.In this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether L.gasseri HMV18 can colonize in the gut or modulate the gut microbiota after oral administration.The results suggest that L.gasseri HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's organs.L.gasseri HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for L.gasseri to cause infection is relatively low.Therefore,this work provides a basis for the foods or drugs application of L.gasseri HMV18 and gives a map of experiments for the safety assessment of probiotics.

Study on Quality Markers of Poria cocos Based on UPLC-Q-TOF-MS and Network Pharmacology Technology

[Objectives]To analyze the main chemical components of traditional Chinese medicine(TCM)Poria cocos by liquid chromatography-mass spectrometry,and explore the active components for P.cocos in the treatment of primary dysmenorrhea(PD)by network pharmacology to predict its quality markers(Q-marker).[Methods]Ultra performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry(UPLC-Q-TOF-MS)in positive and negative ion mode was used to collect high quality MS and MS/MS data of Poria cocos,and qualitative characterization of the components in Poria cocos was performed using Analyst TF 1.7.1 and PeakView 2.2 software with reference to internal databases and literature.Taking the above identified chemical components as the research object,we used network pharmacology to discover the potential effective components and their key targets of PD,and metabolic pathway enrichment analysis of the core targets was performed to screen the Q-marker of P.cocos based on the five principles of Q-marker of TCM.[Results]UPLC-Q-TOF-MS technique was used to identify 41 chemical components of P.cocos,including 3 amino acids,26 triterpenoids,4 lactones,7 organic acids and 1 adenosine.It was more likely to lose H 2O and CO 2 during cleavage and break at the carbonyl group.The triterpenoids were mainly in the form of[M-H]-peaks in negative ion mode,which was easy to lose some structural fragments such as H 2O,CH 3COOH,CH 4,CO 2,etc.Further network pharmacological analysis showed that 302 targets of chemical components of P.cocos,518 targets of PD,28 common targets of component and disease,and 27 core targets such as PTGS2,ESR1,TNF,IL1B were observed by PPI interactions network analysis.451 biological processes such as hormone response and inflammatory response regulation were obtained by GO enrichment analysis.KEGG enrichment analysis showed that 89 pathways including PI3K/Akt signaling pathway,IL-17 signaling pathway and TNF signaling pathway were obtained.The connectivity value of components was analyzed.The core components with the connectivity value greater than 10,including poricoic acid A,polyporenic acid,polyporenic acid C,and 25-hydroxy-3-epidehydrotumoric acid were selected,while the key targets with the connectivity value greater than 15 included TNF,PTGS2,IL1B and CASP3.Molecular docking between core components and key targets was performed,and most of the docking energy was less than-5 kcal/mol,indicating that the binding between the active components and target proteins of P.cocos was relatively stable,so 23 active components of P.cocos were determined.Following the five principles of Q-marker,four possible Q-markers of P.cocos were predicted,including poricoic acid A,pachymic acid,polyporenic acid C,and 25-hydroxy-3-epidehydrotumoric acid.[Conclusions]P.cocos was mainly composed of triterpenoids,its effect on the treatment of PD may be achieved mainly by poricoic acid A,pachymic acid,polyporenic acid C,and 25-hydroxy-3-epi-dehydrotumoric acid acting on PTGS2,ESR1,TNF,IL1B and other targets to regulate PI3K/Akt signaling pathway,IL-17 signaling pathway,TNF signaling pathway,etc.Based on these active components,poricoic acid A,pachymic acid,polyporenic acid C,and 25-hydroxy-3-epi-dehydrotumoric acid could be taken as Q-markers of P.cocos,which provided a solid basis for further improving the quality standard of P.cocos.

Study on Clinical Thinking of Traditional Chinese Medicine Based on Wang Yongyan＇s MedicalRecord Information System

运用医案信息系统工程技术将王永炎教授医案设定为总系统,并将其中的病、证、治、验分次建模,根据医家经验按照“问题一解”的程序将其组合,以此来研究王教授的治疗经验及其临床思维.

Lifestyle improvement and the reduced risk of cardiovascular disease:the China-PAR project

BACKGROUND The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease(CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project(Prediction for Atherosclerotic Cardiovascular Disease Risk in China).METHODS A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors(LFs)(smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios(HRs) and corresponding 95% confidence intervals(CIs). The risk advancement periods(RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage(PAR%) were also calculated.RESULTS A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1healthy LFs, maintaining 3–4 healthy LFs was associated with a 40% risk reduction of incident CVD(HR = 0.60, 95% CI: 0.45–0.79)and delayed CVD risk by 6.31 years(RAP:-6.31 [-9.92,-2.70] years). The PAR% of maintaining 3–4 unhealthy LFs was 22.0%compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2to 3–4 was associated with a 23% lower risk of CVD(HR = 0.77, 95% CI: 0.60–0.98).CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Foods that fight off cancer through anti-inflammation

Background Since the middle of the 19th century,German pathologist Rudolf Virchow proposed that tumors originate from chronic inflammation[1].At present,the medical community has determined that inflammation is closely related to the occurrence,development and efficacy of anti-cancer treatment[2].Recently,an“anti-inflammatory diet”that claims to have functions such as cancer prevention has attracted much attention.To unveil the magic of the“anti-inflammatory diet”,let’s start with the concept of inflammation,which is the core of the“anti-inflammatory diet”.

Research progress of ketogenic diet and colorectal cancer

tract,ranking second among the causes of cancer deaths worldwide,and nearly one million people die of CRC every year,which is a serious threat to human health[1].With the development of the economy and the improvement of living conditions,people's dietary structure is also quietly changing,and factors such as population aging,obesity,smoking,etc.all increase the risk of CRC[2],CRC morbidity and mortality under the influence of these conditions are showing a rising trend,and gradually younger[3].According to statistics,the incidence of CRC in men is second only to lung cancer and stomach cancer,while in women it is third only to breast cancer and cervical cancer[4–6].At present,there is still no special treatment plan for CRC,and surgery,radiotherapy,chemotherapy,and targeted therapy have long been used as the main treatment modalities.However,patients with malignant tumors often suffer from a variety of underlying diseases,low immunity or even malignant disease,and long-term radiotherapy will kill tumor cells while damaging normal cells,which is therefore difficult for patients to tolerate,and the quality of life of end-stage CRC patients is even more difficult.Therefore,it is often difficult for patients to tolerate it,and the quality of life of end-stage CRC patients is even more difficult to be guaranteed[7].

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles(2023 edition)

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization,led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles,research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles,Professional Committee on Extracellular Vesicle Research and Application,Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles.Based on the collation of relevant literature,we have adopted the Delphi method,the consensus meeting method combined with the nominal group method to form a discussion draft of“Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles(2023)”.The first draft was discussed in online and offline meetings on October 12,14,November 2,2022 and April and May 2023 on the current status of research,nomenclature,isolation methods,quality standards and research applications of extracellular vesicles of Chinese herbal medicines,and 13 consensus opinions were finally formed.At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles,held on May 26,2023,Kewei Zhao,convenor of the consensus,presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles.The consensus highlights the characteristics and advantages of Chinese medicine,inherits the essence,and keeps the righteousness and innovation,aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad,decode the mystery behind Chinese herbal vesicles together,establish a safe,effective and controllable accurate Chinese herbal vesicle prevention and treatment system,and build a bridge for Chinese medicine to the world.

Cytokine-induced killer (ClK) cells:from basic research to clinical translation

The accumulation of basic researches and clinical studies related to cytokine-induced killer(CIK) cells has confirmed their safety and feasibility in treating malignant diseases.This review summarizes the available published literature related to the biological characteristics and clinical applications of CIK cells in recent years.A number of clinical trials with CIK cells have been implemented during the progressive phases of cancer,presenting potential widespread applications of CIK cells for the future.Furthermore,this review briefly compares clinical applications of CIK cells with those of other adoptive immunotherapeutic cells.However,at present,there are no uniform criteria or large-scale preparations of CIK cells.The overall clinical response is difficult to evaluate because of the use of autologous CIK cells.Based on these observations,several suggestions regarding uniform criteria and universal sources for CIK cell preparations and the use of CIK cells either combined with chemotherapy or alone as a primary strategy are briefly proposed in this review.Large-scale,controlled,grouped,and multi-center clinical trials on CIK cell-based immunotherapy should be conducted under strict supervision.These interventions might help to improve future clinical applications and increase the clinical curative effects of CIK cells for a broad range of malignancies in the future.

Virologic characteristics of hepatitis B virus in patients infected via maternal-fetal transmission

AIM: To determine whether HBV with the same characteristics causes dissimilar mutations in different hosts. METHODS: Full-length HBV genome was amplified and linked with pMD T18 vector. Positive clones were selected by double-restriction endonuclease digestion (EcoRⅠ and HindⅢ) and PCR. Twenty seven clones were randomly selected from an asymptomatic mother [at two time points: 602 (1 d) and 6022 (6 mo)] and her son [602 (S)], and the phylogenetic and mutational analysis was performed using BioEditor, Clustal X and MEGA software. Potential immune epitopes were determined by the Stabilized Matrix Method (SMM), SMM-Align Method and Emini Surface Accessibility Prediction. RESULTS: All of the 27 sequences were genotype C, the divergence between the mother and son was 0%-0.8%. Compared with another 50 complete sequences of genotype C, the mother and her son each had 13 specific nucleotides that differed from the other genotype C isolates. AA 1-11 deletion in preS1 was the dominant mutation in the mother (14/18). The 1762T/1764A double mutation existed in all clones of the mother, 3 of them were also coupled with G1896A mutation, but none were found in the son.17 bp deletion starting at nucleotide 2330 was the major mutation (5/9) in the son, which caused seven potential HLA class Ⅰ epitopes and one B cell epitope deletion, and produced a presumptive new start codon, downstream from the original one of the P gene. CONCLUSION: The HBV strain in the son came from his mother, and discrepant mutation occurred in the mother and her son during infection.

Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin

LRP16 以前在乳癌房间作为导致雌激素的基因被识别。到在子宫内膜的癌症(EC ) 的雌激素和它的功能的效果的 LRP16 的应答的海角房间仍然是不清楚的。这里，我们证明 LRP16 基因的信使 rna 水平和倡导者活动被 17beta-estradiol (E2 ) 显著地在雌激素受体高山增加哈(嗯高山哈)-positiveIshikawa 人 EC 房间。尽管 Ishikawa 细胞的生长率没被 LRP16 的宫外的表示显然影响， Transwell 试金的结果显示出 LRP16-overexpressing 细胞的侵略能力的近似 one-thirdincrease。由于分子的屏蔽，我们观察到 E-cadherin 的表示，与肿瘤转移联系的一个必要粘附分子，被 LRP16 镇压。进一步的倡导者分析以一种剂量依赖者方式表明了那 LRP16 inhibitedE-cadherin transactivation。然而，抑制被雌激素剥夺废除，显示由 LRP16requires 的 E-cadherin 抄写的 down 规定嗯高山哈调停。染色质免疫降水分析表明到 E-cadherin 倡导者的 ERalpha 的绑定被 LRP16 反对，建议那 LRP16 能防碍嗯调停 alpha 的抄写。这些结果建议起来由雌激素的 LRP16 的规定能被在人的 EC 调整 E-cadherin 的 down 涉及侵略生长。

Polymorphism of CYPIAl and GSTMl genes associated with susceptibility of gastric cancer in Shandong Province of China

AIM: To explore whether polymorphisms of the CYPIA1 and GSTM1 genes are associated with susceptibility of stomach cancer.METHODS: A total of 102 stomach cancer cases and 62 healthy persons were diagnosed by pathology in 1998-2000 in the Qilu Hospital of Shandong University. Gene polymorphisms were detected by the PCR using sequence-specific primers. Data analysis of the case-control study was carried out using the unconditional logistic method.RESULTS: After adjustment for age, sex, educational levels, and occupation, the risk factors for stomach cancer were shown to be smoking, Helicobacter pylori(H pylori),and presence of the CYPIM G/G and GSTM1 O/O genotypes.Interaction was observed between the combined genotypes of either CYPIA1 G/G and GSTM1 O/O or H pylori infection,or GSTM1 O/O and H pylori infection or smoking.CONCLUSION: Polymorphisms of the CYPIA1 and GSTM1 genes, H pylori infection and smoking are related to susceptibility to stomach cancer.

Therapeutic effect of nerve growth factor on cerebral infarction in dogs using the hemisphere anomalous volume ratio of diffusion-weighted magnetic resonance imaging

A model of focal cerebral ischemic infarction was established in dogs through middle cerebral artery occlusion of the right side.Thirty minutes after occlusion,models were injected with nerve growth factor adjacent to the infarct locus.The therapeutic effect of nerve growth factor against cerebral infarction was assessed using the hemisphere anomalous volume ratio,a quantitative index of diffusion-weighted MRI.At 6 hours,24 hours,7 days and 3 months after modeling,the hemisphere anomalous volume ratio was significantly reduced after treatment with nerve growth factor. Hematoxylin-eosin staining,immunohistochemistry,electron microscopy and neurological function scores showed that infarct defects were slightly reduced and neurological function significantly improved after nerve growth factor treatment.This result was consistent with diffusion-weighted MRI measurements.Experimental findings indicate that nerve growth factor can protect against cerebral infarction,and that the hemisphere anomalous volume ratio of diffusion-weighted MRI can be used to evaluate the therapeutic effect.

Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma

AIM:To study the relationship between the cyclooxy-genase(COX)-2 gene and the proliferation and apopto-sis of esophageal squamous carcinoma EC109 cells.METHODS:The techniques of RNA interference(RNAi)and cell transfection,as well as the levels of oncogenic-ity in nude mice,were used to study the role of COX-2 in the esophageal squamous carcinoma cell(ESCC)line EC109.Following RNAi and transfection,Western blot-ting analysis was used to determine the expression of the COX-2 protein.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide(MTT)reduction assay was used to evaluate cell growth,and flow cytometry was used to detect cell apoptosis.RESULTS:Western blotting analysis demonstrated that COX-2 expression was significantly reduced in EC109 cells treated with COX-2-specif ic short interfering RNA(siRNA)but was increased in EC109 cells transfected with COX-2.Furthermore,COX-2 siRNA treatment in-hibited cell proliferation(P < 0.01)and induced apop-tosis in EC109 cells,as determined by an MTT assay and by flow cytometry,respectively.In contrast,trans-fected COX-2 led to increased cell proliferation(P < 0.05)and decreased apoptosis in EC109 cells.In addition,combination treatment of cells with COX-2 siRNA and aspirin had a synergistic effect(P < 0.01).For experi-ments measuring tumorigenicity,xenograft tumors of a greater volume and weight were found in the COX-2 group compared with other groups(P < 0.05).A large dose of aspirin inhibited tumor growth in nude mice ef-fectively(P < 0.05),and the rate of tumor suppression was 51.8% in the high-dose aspirin group.CONCLUSION:COX-2 plays a very critical role in ESCC carcinogenesis,and COX-2 siRNA combined with aspirin has the potential to be an anticancer therapy for the treatment of ESCC.

Effects of Fujian tablet on Nogo-A mRNA expression and plasticity of the corticospinal tract in a rat model of focal cerebral ischemia

The present study investigated the effects of Fujian tablet, a Chinese medicine compound that can nourish liver and kidney, on corticospinal tract plasticity and cervical cord microenvironment in rats with focal cerebral ischemia. Results showed that motor function of rats with right proximal middle cerebral artery occlusion was significantly improved following treatment with Fujian tablet, 9 g crude drug/kg. Anterograde tracing revealed significantly increased biotinylated dextran amine expression in the denervated (left) side of the cervical cord (C4-6) following Fujian tablet treatment, and significantly decreased Nogo-A mRNA expression was detected in the denervated side of the cervical cord (C4-6) using in situ hybridization. Pearson's correlation analysis showed a negative correlation between biotinylated dextran amine and Nogo-A mRNA expression (r = -0.943, P < 0.01). Results demonstrated that Fujian tablet can promote corticospinal tract plasticity possibly through the inhibitory effect on Nogo-A mRNA expression in the cervical spinal cord, thereby improving motor dysfunction.

Expression profile of polyunsaturated fatty acids in colorectal cancer

AIM:To investigate the relationship between the metabolism of polyunsaturated fatty acids(PUFAs)andtumor-associated factors for predicting the outcome of colorectal carcinoma(CRC)in Chinese patients.METHODS:Fresh-frozen malignant and normal tissues from 82 Chinese patients with CRC were analyzed for PUFA composition using gas-liquid chromatography.The levels of vascular endothelial growth factor(VEGF),cyclooxygenase-2(COX-2),prostaglandin E2 and platelet-derived growth factor(PDGF)were measured by enzyme-linked immunosorbent assay,and the levels of VEGF,p53 and Ki-67 were measured by immunohistochemistry.RESULTS:In malignant tissue,compared with normal tissue,the levels of totalω-6 PUFAs(24.64%±3.41%vs 26.77%±3.37%,P=0.00)and linoleic acid(LA)(15.46%±3.51%vs 18.30%±2.83%,P<0.01)were lower,whereas the levels of totalω-3 PUFAs(1.58%±0.74%vs 1.35%±0.60%,P<0.01)and dihomo-gamma-linolenic acid(DGLA)(1.32%±0.69%vs 0.85%±0.29%,P<0.01)were significantly higher.The ratios of arachidonic acid(AA)/LA(0.53±0.22 vs0.42±0.19,P<0.01)and AA/totalω-6 PUFAs(0.31±0.09 vs 0.27±0.10,P<0.01)were also significantly higher in malignant tissue.The levels of PDGF(353.10±148.85 pg/m L vs 286.09±104.91 pg/m L,P<0.01),COX-2(125.21±70.29 ng/m L vs 67.06±42.22 ng/m L,P<0.01)and VEGF(357.11±128.76 pg/m L vs211.38±99.47 pg/m L,P<0.01)were also higher in malignant tissue compared to normal tissue.COX-2was inversely correlated with LA(R=-0.3244,P<0.05)and positively correlated with AA/totalω-6 PUFAs(R=0.3083,P<0.05)and AA/LA(R=0.3001,P<0.05).The tissue level of LA was highest in poorly differentiated tumors(19.9%±6.3%,P<0.05),while the ratio of AA/ω-3 PUFAs was lowest in these tumors(10.8±2.6,P<0.05).In VEGF-positive tumors,the level of LA was higher(16.2%±3.7%vs 13.9%±2.7%,P<0.01),while the AA/ω-3PUFA,AA/ω-6 PUFA,and AA/LA ratios were lower than in VEGF-negativetumors(5.0±1.8 vs 6.7±3.3,0.30±0.09 vs 0.34±0.09,0.50±0.21 vs 0.61±0.21,P<0.01).CONCLUSION:The metabolism of PUFAs may playan important role in the evolution of inflammationdriven tumorigenesis in CRC and may be considered apotential marker for prognosis.

Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program

AIM To determine the association of p53, carcinoembryonic antigen(CEA) and CA19-9 protein expression with esophageal carcinogenesis.METHODS An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia(BCH), 247 with low-grade dysplasia(LGD), 51 with high-grade dysplasia(HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROCcurve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions.RESULTS The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH.CONCLUSION p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.

Beneficial effects of moderate to vigorous physical activity on cardiovascular disease among Chinese adults

Background In China,lack of evidence remains a significant challenge for the national initiative to promote physical activity(PA).We aimed to quantify the beneficial effects of meeting or maintaining the recommended PA level[150 minutes per week(min/wk)of moderate PA or 75 min/wk of vigorous PA or an equivalent combination]on incident cardiovascular disease(CVD)among Chinese population.Methods We included 100,560 participants without history of CVD from three cohorts in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR)project.Cox proportional hazards models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)for CVD events and its subtypes,including stroke,coronary heart disease,heart failure,and CVD death.Results During a median follow-up of 7.3 years(range:6–15 years),777,163 person-years and 4693 incident CVD events were observed.Compared with participants who were inactive at baseline,the multivariable adjusted HR(95%CI)of developing CVD was 0.74(0.69–0.79)for those who met recommended moderate to vigorous physical activity(MVPA)level at baseline.Furthermore,the risk of CVD incidence was reduced with increment of MVPA(Ptrend<0.001),and the HR(95%CI)of highly-active versus inactive category was 0.62(0.56–0.68).Compared with individuals who were inactive both at the baseline and follow-up,those keeping active over the period of follow-up had a substantial lower risk of incident CVD with the HR(95%CI)of 0.57(0.43–0.77).Conclusions The findings demonstrated that meeting and maintaining the recommended MVPA level could reduce the cardiovascular risk.Wider adoption of the PA recommendations would have considerable health impacts to the Chinese population.

Urotensin Ⅱ inhibits electrical activity of hippocampal CA1 neurons by potentiating the GABA_A receptor-mediated Cl^- current

Objective To examine the effects of urotensin Ⅱ (UII) on the discharges of neurons in CA1 area of hipp-ocampal slices by using extracellular recording technique. Results (1)In response to the application of UII (0.3 , 3.0, 30.0, 300.0 nmol/L, n=77) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 63/77 (81.8%) neurons were significantly decreased in a dose-dependent manner. (2)Pretreatment with bicuculline(BIC,100μmol/L) , a specific GABAA receptor antagonist, led to a marked increase in the SDR of 6/7 (85.71% ) neurons in an epileptiform pattern. The increased discharges were not significantly changed after UII (30.0 nmol/L) was applied into the perfusate for 2 min. (3) Pretreatment with picrotoxin (PIC, 50μmol/L) , a selective blocker of Cl- channel, led to an increase in the SDR of all 8/8(100% ) neurons. The increased discharges were not influenced by the UII (30.0 nmol/L) applied. (4)Application of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50μmol/L) into the perfusate for 2 min also significantly augmented the SDR of 14/16 (87.5% ) neurons , then UII (30. 0 nmol/L) applied into the perfusate reduced the increased the SDR of all 14/14 ( 100% ) neurons. Conclusion These results suggest that UII may decrease neuronal activity by potentiating GABAA receptor-mediated Cl- current in hippocampal CA1 neurons, and involved with the mediation of nitric oxide.

FHL2 Interacts with and Acts as a Functional Repressor of Id2 in Human Neuroblastoma Cells

Objective:Id2 is a natural inhibitor of the basic helix-loop-helix(bHLH) transcription factors.Although it is well known that active Id2 prevents differentiation and promotes cell cycle progression and tumorigenesis,the molecular events that regulate Id2 activity remain to be investigated.Methods:Yeast two-hybrid,mammalian two-hybrid,GST-pulldown and immunoprecipitation(CoIP) assays were used to screen and identify novel Id2 interactors.Luciferase assays were used to detect E47-mediated transcription activity.Colony formation and BrdU incorporation assays were used to determine cellular proliferation abilities.Northorn blot,western blot and quantitative PCR methods were used to measure gene expression levels.Electrophoretic mobility shift assays(EMSAs) were performed to investigate protein/DNA binding.Results:The LIM-only protein FHL2(four-and-a-half-LIM-only protein 2) was identified to be a novel Id2 interactor.The HLH domain within Id2 is not required for its interaction with FHL2.FHL2 antagonizes the inhibitory effect of Id2 on the basic helix-loop-helix protein E47-mediated transcription.FHL2 prevents the formation of Id2-E47 heterdimer,thus releasing E47 to its target DNA and restoring its transcriptional activity.FHL2 expression was remarkably up-regulated during retinoic acid-induced differentiation of neuroblastoma cells,during which the expression of Id2 is opposite to that.Ectopic FHL2 expression in neuroblastoma cells markedly reduces the transcriptional and cell-cycle promoting functions of Id2.Conclusion:These results indicate that FHL2 is an important repressor of the oncogenic activity of Id2 in neuroblastoma cells.

Association of genetic polymorphisms of aldehyde dehydrogenase-2 with esophageal squamous cell dysplasia

AIM:To demonstrate the possible associations between genetic polymorphisms of aldehyde dehydrogenase-2(ALDH2) and esophageal squamous cell dysplasia(ESCD).METHODS:All participants came from an area of high incidence of esophageal cancer and underwent an endoscopic staining examination;biopsies were taken from a non-staining area of the mucosa and diagnosed by histopathology.Based on the examinations,the subjects were divided into the control group with normal esophageal squamous epithelial cells and the ESCD group.ALDH2 genotypes of 396 cases were determined including 184 ESCD cases and 212 controls.The odds ratio(OR) and 95% confidence intervals(95% CI) were calculated by binary logistic regression models.RESULTS:The distribution of ALDH2 genotypes showed significant differences between the two groups.The adjustment factors were gender and age in the logistic regression models.Compared with 2*2/2*2 genotype,2*1/2*1 genotype was found to be a risk factor for ESCD,and the OR(95% CI) was 4.50(2.21-9.19).There were significant correlations between ALDH2 genotypes and alcohol drinking/smoking/history of esophageal cancer.CONCLUSION:The ALDH2 polymorphism is significantly associated with ESCD.