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.

Preoperative serum carbohydrate antigen 19-9 levels predict early recurrence after the resection of early-stage pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a serious disease with a poor prognosis.Only a minority of patients undergo surgery due to the advanced stage of the disease,and patients with early-stage disease,who are expected to have a better prognosis,often experience recurrence.Thus,it is important to identify the risk factors for early recurrence and to develop an adequate treatment plan.AIM To evaluate the predictive factors associated with the early recurrence of earlystage PDAC.METHODS This study enrolled 407 patients with stage I PDAC undergoing upfront surgical resection between January 2000 and April 2016.Early recurrence was defined as a diagnosis of recurrence within 6 mo of surgery.The optimal cutoff values were determined by receiver operating characteristic(ROC)analyses.Univariate and multivariate analyses were performed to identify the risk factors for early recurrence.RESULTS Of the 407 patients,98 patients(24.1%)experienced early disease recurrence:26(26.5%)local and 72(73.5%)distant sites.In total,253(62.2%)patients received adjuvant chemotherapy.On ROC curve analysis,the optimal cutoff values for early recurrence were 70 U/mL and 2.85 cm for carbohydrate antigen 19-9(CA 19-9)levels and tumor size,respectively.Of the 181 patients with CA 19-9 level>70 U/mL,59(32.6%)had early recurrence,compared to 39(17.4%)of 226 patients with CA 19-9 level≤70 U/mL(P<0.001).Multivariate analysis revealed that CA 19-9 level>70 U/mL(P=0.006),tumor size>2.85 cm(P=0.004),poor differentiation(P=0.008),and non-adjuvant chemotherapy(P=0.025)were significant risk factors for early recurrence in early-stage PDAC.CONCLUSION Elevated CA 19-9 level(cutoff value>70 U/mL)can be a reliable predictive factor for early recurrence in early-stage PDAC.As adjuvant chemotherapy can prevent early recurrence,it should be recommended for patients susceptible to early recurrence.

THE RELATIONSHIP BETWEEN EGYPT AND PALESTINE IN THE EARLY BRONZE AGE(ca.3400-2000 BCE)

The relationship between Egypt and Palestine can be traced back to theChalcolithic Age thanks to the evidence of current excavations in the Nile Deltaand Sinal.Palestinian pottery and cast metal objects from the Delta sites of Maadi,Minshat Abu Omar,and elsewhere have proved contacts with Palestine inProtodynastic(Nagada Ⅱ-Ⅲ)times.The Egyptian Protodynastic Period andDynasty 1 were contemporary with the Palestinian EB Ⅰ and EB Ⅲ,and

Usefulness of CA 19–9 for pancreatic cancer screening in patients with new-onset diabetes

Background： Generally, carbohydrate antigen 19–9 （CA 19–9） is not useful for screening pancreatic cancerin the asymptomatic general population. This study aimed to evaluate the utility of CA 19–9 level as a screening indicator of pancreatic cancer in asymptomatic patients with new-onset diabetes.

Variation in seed and seedling traits and their relations to geo-climatic factors among populations in Yunnan Pine(Pinus yunnanensis)

Differences in seed germination and seedling growth among populations of Pinus yunnanensis Franch. were quantified to provide information for use in the regeneration, reforestation, and improvement of this species. Seed germination and seedling growth traits at the nursery stage were investigated at the population level. We evaluated relationships between pairs of measured traits as well as the association between measured traits and geo- climatic variables including longitude, latitude, elevation, temperature and precipitation. Seedling growth showed significant differences although a low magnitude of variation was found in the seed germination traits among the populations. Some populations with strong and stable growth （e.g., the Baoshan population） may be selected as superior seed sources for regeneration and reforestation. Germination percentage was negatively correlated with elevation, and positively with precipitation. In addition, germination index, vigor index and seedling height were positively correlated with precipitation. Seed germination index, cotyledon number and length, and seedling diameter were significantly and positively correlated with seed weight. Strong correlations between pairs of traits will be helpful in early evaluations for the selection of certain prominent traits.

Comparison of two earthquake early warning location methods

According to earthquake catalog records of Fujian Seismic Network, the Tnow method and the fourstation continuous location method put forward by Jin Xing are inspected by using P-wave arrival information of the first four stations in each earthquake. It shows that the fourstation continuous location method can locate more seismic events than the Tnow method. By analyzing the results, it is concluded that the reason for this is that the Tnow method makes use of information from stations without being triggered, while some stations failed to be reflected in earthquake catalog because of discontinuous records or unclear records of seismic phases. For seismic events whose location results can be given, there is no obvious difference in location results of the two methods and positioning deviation of most seismic events is also not significant. For earthquakes outside the network, the positioning deviation may amplify as the epicentral distance enlarges, which may relate to the situation that the seismic stations are centered on one side of epicenter and the opening angle between seismic stations used for location and epicenter is small.

Chronoframe of Archaean in Anshan-Benxi Area,Liaoning Province,China

The Anshan- Benxi area is one of the important places of the Precambrian in the North China craton, in which a lot of old geological bodies were found, including the Baijiafen mylontized granitic gneiss of 3.8 Ga ,the Chentaigou gneissic granite of 33 Ga and the supracrustal rocks and associated granites of relatively younger ages .Based on the age data and other geological information obtained in recent yeais, mis paper establishes fourfold-divison scheme of the Archaean in the Anshan-Benxi area .The time boundaries are 2.5,2.8,3.2 and 3.6 Ga, corresponding to those recommended by the International Sub-commission on Precambrian Stratigraphy . This paper also discusses some questions related to the crustal evolution of the early history, and indicates that it is possible to find out more residual crustal materials of older than 2.8 Ga.

史氏鲟人工催产技术及低温早繁对策

对史氏鲟繁殖生物学作了分析，其中最小的繁殖个体体重3．5kg，体长54cm，认为自然产卵群体当前呈趋小现象。人工催产采用17нα-羟基-20β双羟孕酮等诱导史氏鲟在低温下（8．5－13℃）产卵，获得产卵率100％和受精率92．3％的理想效果。

Can Biomarkers Help the Early Diagnosis of Parkinson's Disease?

Parkinson＇s disease （PD） is a complex neurode- generative disease with progressive loss of dopamine neurons. PD patients usually manifest a series of motor and non-motor symptoms. In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients, there is an urgent need to identify sensitive and specific biomarkers. Biomarkers can be divided into four categories： clinical, imaging, biochemical, and genetic. Ideal biomarkers not only improve our under- standing of PD pathogenesis and progression, but also provide benefits for early risk evaluation and clinical diagnosis of PD. Although many efforts have been made and several biomarkers have been extensively investigated, few if any have been found useful for early diagnosis. Here, we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.

NIR-Ⅱ fluorescence/photoacoustic imaging of ovarian cancer and peritoneal metastasis

Ovarian cancer is a global problem,and is typically diagnosed in the middle or late stages,with a mysterious abdominal mass or atypical abdominal metastases due to the lack of specific initial diagnostic methods.Dual-modal near-infrared Ⅱ(NIR-Ⅱ,1,000–1,700 nm)fluorescence/photoacoustic imaging has great potential in early ovarian cancer diagnosis and image-guided surgery due to its high sensitivity and deep penetration.Herein,we report a novel organic NIR-Ⅱ dye(H10)with excellent aggregation-induced-emission(AIE)characteristics(I/I0>1.6)utilizing a selenadiazolo-[3,4-f]benzo[c][1,2,5]thiadiazole(ST)-based building block.Then,water-soluble and biocompatible H10@follicle-stimulating hormone(H10@FSH)dots with superior optical/photoacoustic properties and a tenfold increase in ovarian-specific targeting ability were synthesized.Finally,for the first time,in vivo dual-mode NIR-Ⅱ fluorescent/photoacoustic(PA)imaging and image-guided surgery of patient-derived tumor xenograft(PDTX)and micro-metastatic abdominal ovarian cancer lesions were investigated.This novel strategy will establish a new method for early detection of ovarian cancer and significantly improve the prognosis of ovarian cancer patients.

国产水痘减毒活疫苗株即刻早期基因ORF62的特征

目的：通过比较国产水痘减毒活疫苗株（ vOka ）与其父系株（ pOka ）即刻早期基因（ IE） ORF62启动子区序列及其启动活力、编码区序列及其反式激活力差别，探讨vOka株ORF62突变在其减毒机制中的可能作用。方法分别构建pOka株、长春百克生物科技股份公司vOka-BK株、上海生物制品研究所vOka-SH株和葛兰素史克公司vOka-GSK株（对照） ORF62启动子-报告子质粒和ORF62编码区表达质粒，通过测序分析ORF62启动子区和编码区序列差异，再应用基因转染瞬时表达技术分析3株vOka与pOka株ORF62启动子活力及ORF62编码IE62对即刻早期基因ORF4、早期基因ORF28和晚期基因ORF67启动子的反式激活力差异。结果与pOka株比较，3株vOka 一致存在ORF62启动子区110050位点T缺失突变，该突变未导致启动子区的转录因子结合基序改变，但3株vOka ORF62启动子的启动活力显著低于pOka株；3株vOka ORF62编码区存在一致的碱基置换突变并分别产生SmaⅠ、NaeⅠ和BssHⅡ新酶切位点；除vOka-SH株IE62在CV-1细胞中对ORF4启动子的反式激活力显著低于pOka株外，3株vOka IE62在CV-1和MeWo细胞中对ORF4、ORF28、ORF67启动子的反式激活力均显著高于pOka株。结论3株vOka ORF62启动子区110050位点T缺失突变可能是启动子活力降低和IE62反式激活力改变的原因之一，vOka与pOka株ORF62启动子活力和IE62反式激活力差异与转染细胞类型关系不大。