Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

Allicin as add-on therapy for Helicobacter pylori infection: A systematic review and meta-analysis

BACKGROUND Allicin(2-propene-1-sulfinothioic acid S-2-propenyl ester,diallyl thiosulfinate)extracted from garlic,has proven activity against Helicobacter pylori(H.Pylori)infection.In recent years,clinical trials have explored its utility as an add-on therapy with variable outcomes reported.AIM To perform a systemic review of allicin as an add-on treatment for H.Pylori infection and assess its efficacy in randomized controlled trials(RCTs).METHODS Electronic databases including MEDLINE,EMBASE,the Web of Science,the Cochrane Database,the China National Knowledge Infrastructure Database,Chinese VIP Information Databases,Chinese Medical Databases,and the Wan-Fang Database were searched for keywords including“allicin”,“Helicobacter pylori”,“randomized clinical trials”,and their synonyms.A meta-analysis was performed using the fixed-effects model for low heterogeneity and the randomeffects model for high heterogeneity with sensitivity analysis.Bias was evaluated using Egger’s tests.Trial sequential analysis(TSA)was used to evaluate information size and treatment benefits.The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to assess the level of quality,and studies were classed as“high quality”,“moderate quality”,“low quality”,and“very low quality”.RESULTS A total of eight RCTs consisting of 867 participants(435 from the allicin group and 432 from the control group)were included.Eradication rate in the allicin group(93.33%,406/435)was significantly higher than that of the control group(83.56%,361/432)[I2=0%,odds ratio(OR)=2.75,95%confidence interval(CI):1.74-4.35,P<0.001].The healing rate of ulcers following H.pylori therapy in the allicin group(86.17%,349/405)was significantly higher than that of the control group(75.87%,305/402)[I2=0%,OR=2.05,95%CI:1.39-3.03,P<0.001].The total remission rate of peptic ulcers across all allicin groups was 95.99%,which was significantly higher than that of controls[95.99%(359/374)vs 89.25%(332/372),I2=0,heterogeneity P=0.84,OR=3.13,95%CI:1.51-6.51,P=0.002].No significant differences in side effects were observed.TSA suggested that the trials were of sufficient standard to draw reliable conclusions.The quality of outcomes including eradication rates and side effects was graded as“very low”due to downgrades for“risk of bias”and“indirectness”.Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as"low"due to downgrades for“risk of bias”.CONCLUSION Allicin as an add-on therapy improves H.pylori eradication,healing of ulcers,and remission of symptoms.These results are suggested to be treated with caution due to limited quality.

Add-on therapy of herbal formulation rich in standardized fenugreek seed extract in type 2 diabetes mellitus patients with insulin therapy: An efficacy and safety study

Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract(IND-2) add-on therapy in type 2 diabetes mellitus(T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial.Methods: T2DM patients(n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar(FBS) level between 100-140 mg/dL received IND-2 capsules(700 mg, thrice a day) for 16 weeks.The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16.Secondary end-points include post-prandial blood sugar level, glycosylated Hb(HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks.Safety and adverse events(AEs) were also assessed during the study.Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after addon therapy of IND-2.However, add-on therapy of IND-2 significantly reduced(P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline.Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoproteincholesterol levels were significantly increased(P<0.01) after IND-2 add-on therapy.Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16.Additionally, add-on therapy of IND-2 did not produce any serious adverse events.Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia.Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM.

Follow-Up Study of a Multiple Myeloma Patient Successfully Treated with Clarithromycin (CAM), Low-Dose Lenalidomide and Low-Dose Dexamethasone: Significance and Possible Mechanism of Action of CAM as an Add-On Therapy

Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied;but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.

A follow-up study on newer anti-epileptic drugs as add-on and monotherapy for partial epilepsy in China

Background Recently,new anti-epileptic drugs （AEDs） have been more frequently selected to treat epilepsy.In the present study,we evaluated the dynamic changes of efficacy and safety of three newer AEDs for treating partial epilepsy in China.Methods Patients were collected sequentially and were divided into three groups which accepted oxcarbazepine （OXC）,lamotrigine （LTG） or topiramate （TPM） therapy.Each group included monotherapy and add-on therapy subgroups.We followed all patients for one year and recorded the indexes of efficacy and safety in detail.Results A total of 909 patients finished the follow-up observation.No significant difference was found in proportion of patients with 〉 or =50% reduction,〉 or =75% reduction and 100% seizure reduction in the LTG and OXC groups between the first and the second six months.In the TPM group there was a statistical difference between the first and the second six months in proportion of patients with 〉 or =50% reduction （P=-0.002）,〉 or =75% reduction （P 〈0.0001） and 100% seizure reduction （P=0.009） in the monotherapy subgroup,and about 〉 or =75% reduction and 100% seizure reduction in the add-on therapy subgroup （P 〈0.0001）.The efficacy between the add-on and monotherapy subgroups showed a statistical difference.The safety of the three newer AEDs was good.Conclusions The three newer AEDs all showed good efficacy and tolerability for partial epilepsy.And the efficacy can be maintained for at least one year.

网络游戏“私服”、“外挂”行为的民事法律责任研究

"私服"、"外挂"行为严重威胁和冲击着网络游戏产业的健康发展。界定了"私服"、"外挂"行为,指出了"私服"、"外挂"行为的危害性,并在此基础上进一步研究了"私服"、"外挂"行为构成要件内容的特殊性、承担民事责任的方式和损害赔偿数额的确定,最后提出了"私服"、"外挂"的立法建议。这有利于网络游戏产业的健康发展,净化网络文化环境,打击"私服"、"外挂"行为。

故宫太和殿山面扶柁木结构现状分析

主要对故宫太和殿山面扶柁木结构现状进行了静力分析,根据扶柁木卯榫节点连接特点,采用ANSYS仿真技术,研究了支顶前后的扶柁木结构力学和变形,详细分析了各项相关参数,得出了有效结论。供古建筑结构保护参考。

在Origin7.0中实现化合物红外光谱数据可视化

介绍如何利用数学软件Origin7.0及其插件对含有化合物红外光谱信息的数据文件进行可视化,并对视图予以编辑,以获得峰值标注选择性好、精确度高的可用于化合物结构解析的红外光谱图,以及实现化合物红外光谱数据可视化的一般过程与特点.

基于多变量加权一阶局域法多步预报模型的舰船摇荡预报

针对舰船各个自由度摇荡之间存在耦合的实际,提出了一种多变量加权一阶局域法多步预报模型(MAOLMM)。对Chen’s吸引子仿真数据及某型船真实海浪下航行的摇荡数据进行了预报分析,结果显示,多变量加权一阶局域法多步预报模型的预报精度高于单变量加权一阶局域法多步预报模型,提高了舰船摇荡预报的有效性。

Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets

Schizophrenia is a severe psychiatric disorder characterized by emotional,behavioral and cognitive disturbances, and the treatment of schizophrenia is oftencomplicated by noncompliance and pharmacoresistance. The search for thepathophysiological mechanisms underlying schizophrenia has resulted in theproposal of several hypotheses to explain the impacts of environmental, genetic,neurodevelopmental, immune and inflammatory factors on disease onset andprogression. This review discusses the newest insights into the pathophysiologyof and risk factors for schizophrenia and notes novel approaches in antipsychotictreatment and potential diagnostic and theranostic biomarkers. The currenthypotheses focusing on neuromediators (dopamine, glutamate, and serotonin),neuroinflammation, the cannabinoid hypothesis, the gut-brain axis model, andoxidative stress are summarized. Key genetic features, including small nucleotidepolymorphisms, copy number variations, microdeletions, mutations andepigenetic changes, are highlighted. Current pharmacotherapy of schizophreniarelies mostly on dopaminergic and serotonergic antagonists/partial agonists, butnew findings in the pathophysiology of schizophrenia have allowed theexpansion of novel approaches in pharmacotherapy and the establishment ofmore reliable biomarkers. Substances with promising results in preclinical andclinical studies include lumateperone, pimavanserin, xanomeline, roluperidone,agonists of trace amine-associated receptor 1, inhibitors of glycine transporters,AMPA allosteric modulators, mGLUR2-3 agonists, D-amino acid oxidase inhibitorsand cannabidiol. The use of anti-inflammatory agents as an add-on therapy ismentioned.

多功能称重配料仪表设计与应用

应用MCS-51设计一个多功能、多用途的称重配料显示仪表。以Atmel公司生产的AT89C52Flash单片机为核心,采用了Σ-Δ结构分辨率高达24位的AD7710芯片完成模数转换,通过8279芯片完成键盘及显示部分的控制,实现了RS-232接口与PC机之间的通讯,构成了可以完成自动配料的多功能仪表。通过软件设计,加强了配料精度的控制,实现了故障自动报警、信息自动保存、多种配料控制方式等功能。该称重配料仪表能实现4种原料的累加计量功能。

Effect of Second-generation Antiepileptic Drugs on Diplopia:A Metaanalysis of Placebo-controlled Studies

Different antiepileptic drugs(AEDs) may cause similar adverse effects,one of which is diplopia.However,the AEDs causing diplopia and the dose-response effect of each drug remains uncertain.In this study,we compared several second-generation AEDs to find out whether they would contribute to the risk of diplopia and their effect-causing dose.A meta-analysis was performed on 19 studies in agreement with our inclusion criteria.The results showed that eight commonly used second-generation AEDs(gabapentin,levetiracetam,oxcarbazepine,lamotrigine,pregabalin,topiramate,vigabatrin and zonisamide) could cause diplopia.The reported odds ratios(ORs) ranged from 1.406 to 7.996.Ranking risks from the highest to the lowest ORs of the eight AEDs of any dose resulted in the following order:use of oxcarbazepine(7.996),levetiracetam(7.472),lamotrigine(5.258),vigabatrin(3.562),pregabalin(3.048),topiramate(2.660),gabapentin(1.966),zonisamide(1.406).Taking into account the ORs above,we can conclude that second-generation AEDs of any dose may cause diplopia.However,the levetiracetam-caused diplopia needs to be further studied according to the data(OR,7.472;95% confidence interval,0.375-148.772).These findings ask for better concerns about patients’ quality of life when giving antiepileptic treatments.

烟台市对外贸易发展战略研究

在分析了烟台市对外贸易发展的现状特点和存在问题的基础上 。

利用加行加列法计算广义Vandermonde行列式

通过对广义Vandermonde行列式进行增加一行或一列的方法,把广义Vandermonde行列式转化为一般的Vandermonde行列式进行计算.

支持Agent软件与Web服务软件互操作的AWIA

针对当前Agent软件系统与Web服务软件系统之间无法互操作和集成问题,设计并实现了一个JADE插件AWIA,该插件在Agent软件与Web服务软件之间建立了一座桥梁,提供了一系列的软件开发接口,可有效实现Agent软件与Web服务软件之间的相互访问.AWIA充分利用JADE的扩展机制和XFire的可嵌入特点,将XFire模块包装后插入JADE系统,使用该平台开发者可方便地开发能够提供Web服务或访问Web服务的Agent,从而实现Agent软件与Web服务软件的集成.该方法相比以往的集成实现方法具有性能高、实现简单、部署灵活、支持并行等特点.本文详细介绍了AWIA的技术框架和实现的技术细节,并通过案例分析来验证技术和插件的可行性和有效性.

WEB信息发布的“自动采集”方案研究

目前多数网站在发布信息时采用类似“留言板”的形式 ,即 :由专门负责发布信息的人员在一个特定的WEB页面中 ,将要发布的信息输入一个录入窗口 ,然后提交给数据库 ,用以在网站上发布———信息只能逐条添加 ,效率低。笔者在这里提出用程序自动采集信息的构思 。

揭开MSN Messenger 5.0糖衣陷阱

随着MSN 8正式登场,Microsoft日前也继而推出MSN Messenger 5.0。或者一些MSN Messenger用户已经急不及待升级了MSN Messenger 5.0。相信用过MSN Messenger 5.0的人,评语就是觉得新版本外观不错,但新功能未见突出。不过,在这个美丽的外表背后,MSN Messenger 5.0原来隐藏了一些“玄机”,甚至会“不利”于用户,就让笔者亲自为大家解剖这套软件,好让大家考虑清楚才决定应否升级吧!

一种128位高精度浮点乘加部件的研究与实现

高性能高精度的浮点数值处理一直是科学计算追求的目标。为此,本文研究并实现了一种128位浮点乘加融合计算单元。在乘法模块中,使用分块乘法,复用57位乘法模块,减小了数据宽度。采用三输入前导1预期技术,简化了预编码,缩短了预测电路的延时并减小面积。该模块单元使用Verilog语言实现,用Design Compiler进行逻辑综合,在simc0.13μm工艺下频率达202MHz,关键路径延时为4.93μs,面积约为191000门。

浮点乘加部件中三操作数前导1预测算法的设计

提出了一种应用于高效浮点乘加部件的三操作数前导1预测算法。高效浮点乘加部件需要实现三个操作数的前导1预测(LOP)电路,传统的LOP算法不能直接处理三个操作数,通过间接方法实现又会增加关键路径延时并增大电路面积。三操作数LOP算法是针对传统LOP算法的这一局限提出的,可以有效缩短前导1预测电路的延时并减少面积,从而缩短整个乘加部件的延时。文章以龙芯2号通用CPU中浮点乘加部件的106位前导1预测电路为例,分别采用传统LOP算法和三操作数LOP算法实现了电路,实验结果表明,三操作数LOP算法比传统算法延时能降低约16.67%,总面积减少约19.63%。