Discovery of β-nitrostyrene derivatives as potential quorum sensing inhibitors for biofilm inhibition and antivirulence factor therapeutics against Serratia marcescens

Quorum sensing(Qs)inhibition has emerged as a promising target for directed drug design,providing an appealing strategy for developing antimicrobials,particularly against infections caused by drug-resistant pathogens.In this study,we designed and synthesized a total of 33β-nitrostyrene derivatives using 1-nitro-2-phenylethane(NPe)as the lead compound,to target the facultative anaerobic bacterial pathogen Serratia marcescens.The QS-inhibitory effects of these compounds were evaluated using S.marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026.Among the 33 newβ-nitrostyrene derivatives,(E)-1-methyl-4-(2-nitrovinyl)benzene(m-NPe,compound 28)was proven to be a potent inhibitor that reduced biofilm formation of S.marcescens NJ01 by 79%.Scanning electron microscopy(SEM)and confocal laser scanning microscopy(CLSM)results revealed that treatment with m-NPe(50μg/ml)not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%.m-NPe(50μg/ml)decreased virulence factors in S.marcescens NJ01,reducing the activity of protease,prodigiosin,and extracellular polysaccharide(EPs)by 36%,72%,and 52%,respectively.In S.marcescens 4547,the activities of hemolysin and EPs were reduced by 28%and 40%,respectively,outperforming the positive control,vanillic acid(VAN).The study also found that the expression levels of QS-and biofilm-related genes(flhD,fimA,fimC,sodB,bsmB,pigA,pigC,and shlA)were downregulated by 1.21-to 2.32-fold.Molecular dynamics analysis showed that m-NPe could bind stably to SmaR,Rhll,RhiR,LasR,and CviR proteins in a 0.1 M sodium chloride solution.Importantly,a microscale thermophoresis(MST)test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor(QSl)against S.marcescens.Overall,this study highlights the efficacy of m-NPe in suppressing the virulence factors of S.marcescens,identifying it as a new potential Qsl and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.

Risk Factors for Geo-Helminthiasis in Children Aged 6 - 36 Months in a Rural Health District in Cameroon

Introduction and Objectives: Soil-Transmitted-Helminthiasis (STH) is a public health problem in Cameroon. The control strategies currently in place, particularly chemoprevention, has shortcomings linked to the target population, which are school-age children. The objective was to determine the prevalence and the risk factors associated with geo-helminthiasis in children aged 0 to 3 years in a rural health district. Method: From December 2020 to May 2021, a descriptive and analytical cross-sectional study of 376 children between 6 and 36 months was carried out in the Akonolinga health district. This was a cluster sampling in 4 health areas. Stool samples were collected and analysed using the mini-FLOTAC method. The results expressed as the number of eggs per gram of stool. A questionnaire on socio-demographic and lifestyle data was administered to the parents. The Chi-squared test was used to measure the association between geo-helminth infection and the data collected. A multivariate analysis using logistic regression was performed (p 0.05). Results: The prevalence of STH was 19.4% (Ascaris lumbricoides: 16% and Trichuris trichiura: 8%). Risk factors were: consumption of contaminated water (AOR = 1.93 [1.03 - 3.6];p = 0.040), early contact of the child with the ground (before age of 4 months) (AOR = 4.9 [2.1 - 11.37];p .001), habit of walking barefoot (AOR = 2.91 [1.1 - 7.97];p = 0.038), and living in a habitat with unpaved ground (AOR = 7.4 [1.55 - 35.7];p = 0.012). Conclusion: The prevalence of STHs in infants was high. Preventive chemotherapy should be extended to this age-group, and other measures intensified.

Factors Associated with Acute Respiratory Infections in Children Aged 0 - 5 Years in the Yénawa District of Cotonou (Benin) in 2023

Introduction: Acute respiratory infections remain one of the main causes of mortality in children aged 0 to 5. This work aimed to study the associated factors with the occurrence of acute respiratory infections in children 0 to 5 years old in Yénawa, Cotonou in 2023. Subjects and Method: It was an analytical cross-sectional study of children aged 0 - 5 years and their mothers in Yénawa, selected by four-degree random sampling. The sampling size, calculated using the Schwartz formula, was 126 children and 126 mothers. The dependent variable was the occurrence of acute respiratory infections. The independent variables were classified into four groups: socio-demographic and economic characteristics, behavioral factors, child-related factors, and environmental factors. Data collected by observation and questionnaire survey were analyzed using STATA version 15 software. Associated factors were investigated by bivariate analysis and multiple logistic regression, at the 5% significance level. Results: A total of 126 children aged 0 - 5 years and 126 mothers were surveyed, aged 23.5 (11 - 36) months and 30 (18 - 48) years respectively. The prevalence of acute respiratory infections was 74.60% (CI95% = 66.89 to 82.30). The associated factors were the mother’s age between 18 and 28 (OR = 10.77;CI95% = 1.89 to 61.27;p = 0.007), the use of charcoal/wood for cooking (OR = 7.36;IC = 1.99 to 27.10;p = 0.003)), children's poor personal hygiene (OR = 8.87;IC = 2.92 to 26.97;p 0.001)), and cohabitation with domestic animals (OR = 7.27;IC = 1.67 to 31.71;p = 0.015). Conclusion: Communicating with mothers about the factors identified will help reduce the prevalence of acute respiratory infections in children aged 0 to 5.

CRITICAL CONCENTRATIONS OF α(1→3)-D-GLUCAN FROM LENTINUS EDODES IN NaOH AQUEOUS SOLUTION

Critical concentrations of α-(1→3)-D-glucan L-FV-Ⅱ from Lentinus edodes were studied by viscometry andfluorescence probe techniques. The dependence of the reduced viscosity on concentration of the glucan in 0.5 mol/L NaOHaqueous solutions with or without urea showed two turning points corresponding to the dynamic contact concentration c_s andthe overlap concentration c~* of the polymer. The values of c_s and c~* were found to be 1×10^(-3) g cm^(-3) and 1.1×10^(-2) g cm^(-3),respectively, for L-FV-Ⅱ in 0.5 mol/L NaOH aqueous solutions. The two critical concentrations of L-FV-Ⅱ in 0.5 mol/LNaOH aqueous solutions were also found to be 1.2×10^(-3) g cm^(-3) fbr c_s and 9.2×10^(-3) g cm^(-3) for c~* from the concentrationdependence of phenanthrene fluorescence intensities. The overlap concentration c~* of L-FV-Ⅱ in 0.5 mol/L NaOH aqueoussolutions was lower than that of polystyrene with same molecular weight in benzene, owing to the fact that polysaccharidetends to undergo aggregation caused by intermolecular hydrogen bonding. A normal viscosity behavior of L-FV-Ⅱ in 0.5 mol/L urea/0.5 mol/L NaOH aqueous solutions can still be observed in an extremely low concentration range at 25℃.

基于CRITIC和改进Grey-TOPSIS的电能质量分级评估方法

为提高电能质量分级评估的客观性和准确性,提出了一种基于CRITIC和改进Grey-TOPSIS的电能质量分级评估方法。首先,基于压力-状态-响应模型中子系统间的逻辑关系,从压力、状态、响应多维度选取评价指标,建立科学的电能质量综合评估指标体系。由于指标间存在一定关联关系,综合指标间的差异因素,从两种信息角度采用CRITIC赋权法,保证指标赋权的客观性。然后,建立改进Grey-TOPSIS评估模型,引入灰色关联度改进单一的欧氏距离。将图形贴近度与空间位置融合,构建新距离测度,弥补原有判据的缺陷。同时,将电能质量等级矩阵加入评估矩阵中,通过计算实测和等级序列与正理想解间的贴近度,实现对电能质量等级客观的量化分级。最后,通过实际算例分析,验证了所提方法能够充分利用数据信息,降低主观因素影响,获得更准确、全面的电能质量分级评估结果。

改进CRITIC修正G2-TOPSIS的钻孔自燃预测模型及应用

针对瓦斯抽采钻孔自燃危险评价系统模型中指标权重难以确定的问题,提出一种改进的基于指标相关性权重确定法(CRITIC)的G2赋权法。首先引入欧式距离函数,建立优化决策模型,采用CRITIC的“差异驱动”型赋权法修正“功能驱动”型G2赋权法;其次获得各指标综合权重,评价影响钻孔自燃危险因素的主次关系;再次基于逼近理想解排序法(TOPSIS)“驱动功能”的G2赋权法,建立G2-TOPSIS钻孔自燃危险评判模型;然后分析贴近度,预测钻孔自燃危险等级;最后将该模型应用于晋牛煤矿1303工作面瓦斯抽采钻孔。结果表明:煤氧化还原燃点温差为诱发钻孔自燃危险的主导因素;钻孔自燃危险等级为III级,预测结果与实际情况相吻合。

MT_1-MMP和Factor Ⅷ在人脑胶质瘤中表达差异及其意义

目的探讨膜型基质金属蛋白酶-1(MT1-MMP)和FactorⅧ在人脑胶质瘤中的表达及两者之间的关系。方法用免疫组织化学SP法检测45例人脑胶质瘤组织和10例正常人脑组织中MT1-MMP和FactorⅧ的表达。结果正常人脑组织中无MT1-MMP表达,高级别脑胶质瘤组织(Ⅲ、Ⅳ)中MT1-MMP和FactorⅧ的阳性表达率显著高于低级别胶质瘤组织(Ⅰ、Ⅱ),并且两者的表达呈显著正相关性。结论MT1-MMP在高级别脑胶质瘤组织中高表达,其表达与脑胶质瘤的进展和侵袭密切相关,可作为脑胶质瘤恶性表型的有用指标。MT1-MMP可能在脑胶质瘤的血管生成中发挥重要的调控作用。

基于CRITIC法计算权重系数的星点设计-效应面法优化雷公降压颗粒成型工艺的研究

目的:优选雷公降压颗粒的最佳成型工艺。方法:以辅料配比(糊精-甘露醇)、辅料用量、乙醇体积分数为考察因素,以成型率、休止角、溶化时间、吸湿率、脆碎度作为考察指标,CRITIC法分配各指标权重系数,采用星点设计-效应面法优化雷公降压颗粒成型工艺。结果:CRITIC法得出成型率、休止角、溶化时间、吸湿率、脆碎度的权重系数分别为0.1943、0.2065、0.2089、0.1797、0.2106,最佳成型工艺为辅料配比3∶1,辅料用量4倍,乙醇体积分数80%。结论:优选的成型工艺稳定可行,重复性好,可为雷公降压颗粒的生产提供参考。

Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

基于组合赋权-TOPSIS法的受灾点救援需求紧迫度研究

为了更合理高效地在灾害发生时对不同受灾点进行应急救援,提出了一种基于组合赋权的优劣解距离法(technique for order preference by similarity to an ideal solution,TOPSIS)模型,对受灾点救援需求紧迫度进行分级研究。首先,分析受灾点救援需求紧迫度的影响因素,构建受灾点救援需求紧迫度评价指标体系;其次,综合运用客观权重赋值法(criteria importance though intercrieria correlation,CRITIC)和熵权法对各指标进行组合赋权;然后,运用组合赋权-TOPSIS法对受灾点救援需求紧迫度量化分级;最后,以汶川地震为背景进行算例分析,结果表明:组合赋权所得权值相比单一赋权能够得到更加客观合理的结果,有利于灾害发生情况下应急管理部门更加及时、准确、有序地进行应急救援。

基于博弈论-云模型的地下室防水工程质量潜在缺陷风险评价

地下室防水工程质量是保障建筑工程使用功能的关键一环,对其工程质量潜在缺陷进行风险评价具有重要意义。本文首先将地下室防水工程划分为勘察设计、施工、竣工验收、复查四个工程阶段,识别出21个风险点以构建其风险指标体系;其次,运用G1法和改进CRITIC法分别求出各指标的主、客观权重,并利用博弈论确定综合权重;最后,基于云模型建立地下室防水工程质量潜在缺陷风险评价模型并应用于实际工程案例,风险评价结果与模糊综合评价结果和实际情况一致。研究结果表明:基于博弈论-云模型的风险评价模型综合考虑主、客观因素对地下室防水工程质量风险等级的影响,评价结果合理可靠,可为TIS机构有效评价地下室防水工程质量风险等级提供技术支持。

Determination of velocity correction factors for real-time air velocity monitoring in underground mines

When there are installations of air velocity sensors in the mining industry for real-time airflow monitoring, a problem exists with how the monitored air velocity at a fixed location corresponds to the average air velocity, which is used to determine the volume flow rate of air in an entry with the cross-sectional area. Correction factors have been practically employed to convert a measured centerline air velocity to the average air velocity. However, studies on the recommended correction factors of the sensor-measured air velocity to the average air velocity at cross sections are still lacking. A comprehensive airflow measurement was made at the Safety Research Coal Mine, Bruceton, PA, using three measuring methods including single-point reading, moving traverse, and fixed-point traverse. The air velocity distribution at each measuring station was analyzed using an air velocity contour map generated with Surfer~. The correction factors at each measuring station for both the centerline and the sensor location were calculated and are discussed.

Influencing factors on as-cast and heat treated 400-18 ductile iron grade characteristics

As-cast and heat-treated 400-18 ductile iron （DI） grade was obtained in different foundry conditions, as metallic charge, Mg-treatment alloy and inoculation. It was found that the Pearlitic Influence Factor （P） and Anti- nodulizing Complex Factor （K1） have an important influence on property of DI, depending on the Mn and P level, the metallurgical quality of iron melt, rare earth （RE） and inoculation. It was also found that the influence of Mn is depended on the phosphorus and residual elements level in ductile iron. Less than 0.03%P and 0.2%Mn and P〈2.0 are the basic conditions to obtain as-cast ferritic structure. At the same lower level of Mn and P, the increasing of residual elements （P〉2.0） determines presence of pearlite in as-cast structure, while ferrite structure is obtained after a short annealing heat treatment. Lower level of phosphorus （P〈0.025%） and residual elements （Px〈2.0） allow to use relative high Mn content （0.32%-0.38%）, in condition of ferritic structure, including in as-cast state. High P （0.04%- 0.045%） and Mn （0.25%-0.35%） content stabilized peadite, especially at lower level of residual elements （P 〈2.0）. Antinodulizing action of elements was counteracted up to K1=2.0 level, by RE included in Mg-treatment alloy, which are beneficial for K1〈1.2 and compulsory for K1〉1.2. Si has a significant influence on the mechanical properties of heat treated ductile irons： an important decreasing of elongation level and a moderate increasing of yield and tensile strength and their ratio in 150-170 HB typical hardness field. A typical final chemical composition for as-cast 400-18 ductile iron could include 3.5%-3.7%C, 2.4%-2.5%Si, max.0.18%Mn, max.0.025%P, max.0.01%S, 0.04%-0.05%Mg for Px〈1.5 and K1〈1.1. High purity pig iron, RE-bearing FeSiMg and powerful inoculant are also recommended.

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett's esophagus to adenocarcinoma

AIM： To investigate the expression of cyclooxygenase-2 （COX-2） and epithelial growth factor receptor （EGFR） throughout the progression of Barrett＇s esophagus （BE）. METHODS： COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined. Areas of COX-2 and EGFR expression were quantified by using computer Imaging System. RESULTS： The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma （EAC）. A positive correlation was found between COX-2 expression and EGFR expression. CONCLUSION： COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.

Inhibitory effect of interferon-α-2b on expression of cyclooxygenase-2 and vascular endothelial growth factor in human hepatocellular carcinoma inoculated in nude mice

AIM： To evaluate the effects of interferon-α-2b （IFN- α-2b） on expression of cyclooxygenase-2 （COX-2） and vascular endothelial growth factor （VEGF） in human hepatocellular carcinoma （HCC） inoculated in nude mice and to study the underlying mechanism of IFN-α- 2b against HCC growth. METHODS： Thirb/-two nude mice bearing human HCC were randomly divided into four groups （n = 8）. On the 10th day after implantation of HCC cells, the mice in test groups （groups A, B and C） received IFN-α- 2b at a serial dose （10000 IU for group A, 20000 IU for group B, 40000 IU for group C sc daily） for 35 d. The mice in control group received normal saline （NS）. The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and Western blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b. RESULTS： Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group （P 〈 0.01）, and the tumor growth inhibition rate in groups A, B and C was 27.78%, 65.22% and 49.64%, respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group （P 〈 0.01）. The apoptosis index （AI） of tumor cells in the IFN-α-2b treatment groups was markedly higher than that in the control group （P 〈 0.01）. Group B had a higher inhibition rate of tumor growth, a lower expression level of COX-2 and VEGF and a higher AI than groups A and C （P 〈 0.05）, but there was no significant difference between groups A and C. CONCLUSION： The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20 000 IU/d.

Intrastriatal glial cell line-derived neurotrophic factors for protecting dopaminergic neurons in the substantia nigra of mice with Parkinson disease

BACKGROUND： Substantia nigra is deep in position and limited in range, the glial cell line-derived neurotrophic factor （GDNF） injection directly into substantia nigra has relatively greater damages with higher difficulty. GDNF injection into striatum, the target area of dopaminergic neuron, may protect the dopaminergic neurons in the compact part of substantia nigra through retrograde transport. OBJECTIVE： To investigate the protective effect of intrastriatal GDNF on dopaminergic neurons in the substantia nigra of mice with Parkinson disease （PD）, and analyze the action pathway. DESIGN： A controlled observation. SETTING： Neurobiological Laboratory of Xuzhou Medical College. MATERIALS： Twenty-four male Kunming mice of 7 - 8 weeks old were used. GDNF, 1-methy1-4-pheny1-1,2,3,6-tetrahydropyridine （MPTP） were purchased from Sigma Company （USA）; LEICAQWin image processing and analytical system. METHODS： The experiments were carded out in the Neurobiological Laboratory of Xuzhou Medical College from September 2005 to October 2006. The PD models were established in adult KunMing mice by intraperitoneal injection of MPTP. The model mice were were randomly divided into four groups with 6 mice in each group： GDNF 4-day group, phosphate buffer solution （PSB） 4-day group, GDNF 6-day group and PSB 6-day group. Mice in the GDNF 4 and 6-day groups were administrated with 1 μ L GDNF solution （20 μ g/L, dispensed with 0.01 mol/L PBS） injected into right striatum at 4 and 6 days after model establishment. Mice in the PSB 4 and 6-day groups were administrated with 0.01 mol/L PBS of the same volume to the same injection at corresponding time points. ② On the 12^th day after model establishment, the midbrain tissue section of each mice was divided into 3 areas from rostral to caudal sides. The positive neurons of tyroxine hydroxylase （TH） and calcium binding protein （CB） with obvious nucleolus and clear outline were randomly selected for the measurement, and the number of positive neurons in unit area was counted. MAIN OUTCOME MEASURES： Number of positive neurons of TH and CB in midbrain substantia nigra of mice in each group. RESULTS： All the 24 mice were involved in the analysis of results. The numbers of TH^＋ and CB^＋ neurons in the GDNF 4-day group （54.33±6.92, 46.33±5.54） were obviously more than those in the PBS 4-day group （27.67±5.01, 21.50±5.96, P 〈 0.01）. The numbers of TH^＋ and CB^＋ neurons in the GDNF 6-day group （75.67±5.39, 69.67±8.69） were obviously more than those in the PBS 6-day group （27.17±4.50, 21.33 ±5.72, P 〈 0.01） and those in the GDNF 4-day group （P 〈 0.01 ）. CONCLUSION： Intrastriatal GDNF can protect dopaminergic neurons in substantia nigra of PD mice, and it may be related to the increase of CB expression.

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.

Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia

AIM： To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia （DH）-mediated liver regeneration. METHODS： Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bisr2-（3,5-dichloropyridyloxy）] benzene （TCPOBOP）, a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 （D0： prior to injection）, 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR （fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢβ , plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF）. The corresponding plasma levels of coagulation factors （fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢ, and VWF） were also analyzed and compared with their mRNA levels. RESULTS： Gavage administration of TCPOBOP （3 mg/kg body weight） resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the DO （control） ratios. At the peak of liver regeneration （D1 and D2）, the gene expression levels for most of the coagulationrelated factors （fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ,Ⅺ, Ⅻ, ⅩⅢβ, plasminogen, antithrombin, protein C, ADAMTS13, VWF） were found to be downregulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors （prothrombin, factors Ⅷ, Ⅸ, Ⅺ, and Ⅻ） demonstrated a significant decrease （P 〈 0.05） during the regeneration phase compared with DO. Among these 5 factors, factor Ⅸ and factor Ⅺ showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels, and these reductions in plasma activity for both factors were consistent with our RT-PCR findings. In contrast, the plasma activities of the other coagulation factors （fibrinogen, factors Ⅴ, Ⅶ, ⅩⅢ, and VWF） were not significantly reduced, despite the reduction in the liver mRNA levels. Unlike the other factors, FX showed a temporal increase in its plasma activity, with significant increases （P 〈 0.05） detected at DI. CONCLUSION： Investigating the coagulation cascade protein profiles during liver regeneration by DH may help to better understand the basic biology of the liver under normal and pathological conditions.

A comparative study on crash-influencing factors by facility types on urban expressway

This study aims at identifying crash-influencing factors by facility type of Nagoya Urban Expressway, considering the interaction of geometry, traffic flow, and ambient conditions. Crash rate （CR） model is firstly developed separately at four facility types： basic, merge, and diverge segments and sharp curve. Traffic flows are thereby categorized, and based on the traffic categories, the significances of factors affecting crashes are analyzed by principal component analysis. The results reveal that, the CR at merge segment is significantly higher than those at basic and diverge segments in uncongested flow, while the value is not significantly different at the three facility types in congested flow. In both un- and congested flows, sharp curve has the worst safety performance in view of its highest CR. Regarding influencing factors, geometric design and traffic flow are most significant in un- and congested flows, respectively. As mainline flow increases, the effect of merging ratio affecting crash is on the rise at basic and merge segments as opposed to the decreasing significance of diverging ratio at diverge segment. Mean- while, longer acceleration and deceleration lanes are adverse to safety in uncongested flow, while shorter acceleration and deceleration lanes are adverse in congested flow. Due to its special geometric design, crashes at sharp curve are highly associated with the large centrifugal force and heavy restricted visibility.

Effects of L-3-n-butylphthalide on caspase-3 and nuclear factor kappa-B expression in primary basal forebrain and hippocampal cultures after beta-amyloid peptide 1-42 treatment

BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP on caspase-3 and nuclear factor kappa-B （NF- K B） expression in a rat model of Alzheimer＇s disease. DESIGN, TIME AND SETTING： A cell experiment was performed at the Central Laboratory of Provincial Hospital affiliated to Shandong University between January 2008 and August 2008. MATERIALS： L-NBP （purity 〉 98%） was provided by Shijiazhuang Pharma Group NBP Pharmaceutical Company Limited. Aβ1-42, 3-[4,5-dimethylthiazolo-2]-2,5 iphenyltetrazolium bromide （MTT）, and rabbit anti-Caspase-3 polyclonal antibody were provided by Cell Signaling, USA; goat anti-choactase and rabbit anti-NF- kB antibodies were provided by Santa Cruz, USA. METHODS： Primary cultures were generated from rat basal forebrain and hippocampal neurons at 17 or 19 days of gestation. The cells were assigned into five groups： the control group, the Aβ1-42 group （2 μmol/L）, the Aβ1-42 ＋ 0.1 μmol/L L-NBP group, the Aβ1-42 ＋ 1 μ mol/L L-NBP group, and the Aβ1-42 ＋ 10μmol/L L-NBP group. The neurons were treated with Aβ1-42 （2 μmol/L） alone or in combination with L-NBP （0.1, 1, 10 μmol/L） for 48 hours. Cells in the control group were incubated in PBS. MAIN OUTCOME MEASURES： Morphologic changes were evaluated using inverted microscopy, viability using the M-I-I- method, and the changes in caspase-3 and NF- k B expression using Western blot. RESULTS： Induction with Aβ1-42 for 48 hours caused cell death and soma atrophy, and increased caspase-3 and NF- K B expression （P 〈 0.05）. L-NBP blocked these changes in cell morphology, decreased caspase-3 and NF- k B expression （P 〈 0.05）, and improved cell viability, especially at the high dose （P 〈 0.05）. CONCLUSION： AI3^-42 is toxic to basal forebrain and hippocampal primary neurons; L-NBP protects against this toxicity and inhibits the induction of caspase-3 and NF- K B expression.