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BACKGROUND: There is lack of studies on sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma (HCC). This study was to explore the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib failure in HCC patients. METHODS: This study was a retrospective, real-world study that included 50 HCC patients who received sequential regrafinib after sorafenib and lenvatinib failure. The safety and prognosis of two groups were compared. RESULTS: The incidence of all grade and III/IV adverse events were 68% and 24%. According to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and modified (m) RECIST standards, the objective response rates (ORRs) after receiving regorafenib were 14.0% and 22.0%, respectively. The disease control rates (DCRs) were 62.0% and 60.0%, respectively. Based on different first-line targeted drugs, 50 patients were divided into sorafenib (n=22) and lenvatinib group (n=28). There was no differences between two groups except age and bilirubin. And there was no differences in other treatments before or after regorafenib. The baseline between two groups was basically same and had good comparability. There was no difference in incidence of all grade and III/IV adverse events, ORR and DCR between two groups (P>0.05). On long-term prognosis, total overall survival (TOS) in sorafenib and lenvatinib group were 23.0 (95% CI: 15.1–30.9) vs. 29.7 (95% CI: 21.4–38.1) months. The difference was statistically significant (P=0.041). Besides, regorafenib overall survival (ROS) in sorafenib and lenvatinib group were 11.7 (95% CI: 7.1–16.3) vs. 15.9 (95% CI: 8.3–23.5) months. The difference was statistically significant ( P=0.045). The regorafenib progression-free survival (RPFS) was 5.6 (95% CI: 1.9–9.2) vs. 8.0 (95% CI: 5.1–10.9) months in sorafenib and lenvatinib group, respectively, and difference was not statistically significant (P=0.380). CONCLUSIONS: Regorafenib is an effective drug for second-line treatment of HCC, with fewer severe adverse events, ORR and DCR was 14–22% and 62–60%, respectively. Both TOS and ROS in lenvatinib group were better than those in sorafenib group. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after disease progresses.

e16125 Background: To explore the safety, efficacy and long-term prognosis of patients with unresectable hepatocellular carcinoma (HCC) treated with regorafenib after failure of first-line treatment. Methods: This retrospective single center study included 50 unresectable HCC patients who received regorafenib as a second line treatment in our hospital. Based on the difference of first-line targeted drugs, the 50 patients were divided into sorafenib group (n = 22) and lenvatinib group (n = 28). The adverse events, efficacy and long-term prognosis of sorafenib or lenvatinib followed by regorafenib were analyzed. Results: The median age of the 50 patients was 54.5 years. The patients had the following clinical characteristics: ECOG score 0-1, HbsAg positive, cirrhosis, BCLC stage B/C in 95.5%, 95.5%, 90.9% and 90.9% of all patients respectively. The baseline clinical characteristics between the sorafenib and lenvatinib groups were not statistically different (all p > 0.05), except for age and total bilirubin which were in favour of lenvatinib group. Regorafenib was administered oral 160 mg once daily during weeks 1–3 of each 4-week cycle. For 50 HCC patients, the incidence rate of adverse events after accepting regorafenib was 68%. The incidence rate of grade I/II and III/IV adverse events was 60% and 24%, respectively. According to the standards of RECIST 1.1 and mRSCIST, objective response rate (ORR) and disease control rate (DCR) after receiving regorafenib were 14.0%, 62.0% and 22.0%, 60.0%, respectively. There was no significant difference in incidence of all adverse events and grade III/IV adverse events, ORR and DCR between the two groups ( p > 0.05). In terms of long-term prognosis, total overall survival (TOS) and regorafenib overall survival (ROS) in sorafenib group and lenvatinib group were 23.0 months (95% confidence interval [CI]: 15.1-30.9) vs. 29.7 months (95CI: 21.4-38.1), and 11.7 months (95CI: 7.1-16.3) vs. 15.9 months (95CI: 8.3-23.5). The difference was statistically significant ( p= 0.041 and P = 0.045). The regorafenib progression-free survival (RPFS) was 5.6 months (95CI: 1.9-9.2) vs. 8.0 months (95CI: 5.1-10.9) in sorafenib group and lenvatinib group, respectively. The difference was not statistically significant ( P = 0.380). Conclusions: The data suggest that regorafenib is an effective drug for second-line treatment of HCC, with an acceptable toxicity level, an ORR of 14%-22% and a DCR of 62%-60%. Both TOS and ROS in lenvatinib group are better than those in sorafenib group. The possible mechanisms was that EGFR activation limits the response of HCC cells to lenvatinib. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after the disease progresses.

Background Density of tumor infiltrating lymphocytes (TIL) and expressions of certain immune-related genes have prognostic and predictive values in hepatocellular carcinoma (HCC); however, factors determining the immunophenotype of HCC patients are still unclear. In the current study, the transcript sequencing data of liver cancer were systematically analyzed to determine an immune gene marker for the prediction of clinical outcome of HCC. Methods RNASeq data and clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA), and the samples were assigned into high-stage and low-stage groups. Immune pathway-related genes were screened from the Molecular Signatures Database v4.0 (MsigDB) database. LASSO regression analysis was performed to identify robust immune-related biomarkers in predicting HCC clinical outcomes. Moreover, an immune gene-related prognostic model was established and validated by test sets and Gene Expression Omnibus (GEO) external validation sets. Results We obtained 319 immune genes from MsigDB, and the genes have different expression profiles in high-stage and low-stage of HCC. Univariate survival analysis found that 17 genes had a significant effect on HCC prognosis, among them, 13 (76.5%) genes were prognostically protective factors. Further lasso regression analysis identified seven potential prognostic markers (IL27, CD1D, NCOA6, CTSE, FCGRT, CFHR1, and APOA2) of robustness, most of which are related to tumor development. Cox regression analysis was further performed to establish a seven immune gene signature, which could stratify the risk of samples in training set, test set and external verification set (p Conclusion This study constructed a 7-immunogenic marker as novel prognostic markers for predicting survival of HCC patients.

Many in vitro studies support the general idea that vitamin D plays a protective role against cancer. Increased doses of vitamin D dietary supplements have been widely used for the potential anticancer benefits of vitamin D. However, despite substantial epidemiological research, there are no clear conclusive data to support the use of vitamin D as a cancer preventive or treatment agent. In the, herein, reported study, we checked the effects of 1,25-dihydroxyvitamin D3 concentrations on the expression level of the vitamin D receptor (VDR) and cell cycle-related proteins CDKN1A (p21) and CDK1 in pancreatic cells and Panc-1 pancreatic cancer (PC) cells. We found that VDR, CDKN1A, and CDK1 were upregulated by an increase in 1,25-dihydroxyvitamin D3 concentration in normal pancreatic cells but not in the advanced cancer cell line Panc-1 from poorly differentiated metastatic PC cells. A further increase in 1,25-dihydroxyvitamin D3 concentration above the physiological range significantly downregulated the expression of VDR, indicating that VDR is modulated by VDR levels to maintain normal functioning during dramatic variations in vitamin D concentration. By increasing the level of cell cycle inhibitory and promoting proteins p21 and CDK1, vitamin D theoretically has both preventive and promoting effects on pancreatic cell division.

A new method using polyphosphate kinase (PPK) probe was developed in this study to measure the ratio of denitrifying phosphate-accumulating organisms (DNPAOs) to bacteria. Advantages and disadvantages of this method and previously published methods were evaluated. Biochemical characteristics and metabolic mechanisms of the bacterial community in activated sludge were analyzed. The result indicated that PPK probe targeting at the gene of polyphosphate kinase in bacterial cells could marked more PAOs than traditional PAO probes. The ratio of DNPAOs/bacteria reached 60.30% in activated sludge. The whole bacterial community in activated sludge, at the end of A/A stage, presented significant non-fermentative characteristics although the activated sludge still contained some fermentative bacteria. Study on the metabolic mechanisms suggested that intracellular PHB served as the major carbon source and energy source of bacterial community in activated sludge.

Aim Hepatocellular carcinoma (HCC) is one of the most heterogeneous cancers worldwide, finding novel validate prognostic biomarker is the aim of this work. Main method Expression of AASS (aminoadipate-semialdehyde synthase) was assayed in three independent cohorts, and the diagnostic and prognostic values of this gene was also evaluated. Clinical indicators significantly associated with AASS were also analyzed. In vivo and in vitro studies were also performed to test the molecular functions of AASS. Finally, the pathways associated with AASS were identified. Key findings AASS was significantly down-regulated in tumor tissues compared to the corresponding normal tissues in three independent datasets, and AUROC (area under receiving operating characteristic curve) were 0.80, 0.87 and 0.77. In addition, the high expression of AASS predicts a better survival in these three datasets. Also, expression of AASS in the metastasis-incline HCC samples (MIH) is significantly lower than the metastasis-averse HCC samples (MAH). Clinical correlation analyses revealed differentiation level, primary tumor diameter and embolus presentation was significantly associated with AASS. Following knock down and overexpression of AASS, the migration and proliferation rate was significantly enhanced. Furthermore, Gene Set Enrichment Analysis (GSEA) revealed that AASS was significantly associated with metabolism pathways. Significance Our work identified a valuable biomarker, AASS, for both diagnosis and prognosis, and might be used as a target for HCC therapy.

Hepatic ischemia-reperfusion injury (IRI) is a very complex pathological process that is often associated with liver trauma and surgery, especially liver transplantation surgery. Although endoplasmic reticulum stress (ERS) plays a role in this process, the posttranscriptional regulators and the underlying mechanisms are still unclear. Here, we report that the lncRNA AK054386 was increased in hepatic IRI models. Furthermore, AK054386 can act as a “competing endogenous RNA (ceRNA)” and regulate ERS-related factors by binding and sequestering miR-199, which was shown to inhibit ERS in our previous report. Increased expression of AK054386, which might be mediated by activated NF-κB, resulted in sustained ERS and increased cell apoptosis and death in hepatic IRI mouse and cellular models. In contrast, AK054386 inhibition had protective effects on these models. Our data indicate that AK054386 and miR-199 are critical players in hepatic IRI, and we broadened the scope regarding ceRNA mechanisms. We hope that our results will improve the understanding of hepatic IRI and may provide potential therapeutic targets.

A newly designed pilot-scale system was developed to enrich denitrifying phosphate-accumulating organisms (DNPAOs) for nitrogen and phosphorus nutrient removal synchronously. A strain of DNPAOs was isolated and its biochemical characteristics and metabolic mechanisms of this bacterial strain were analyzed. The results showed that compared with previously reported system, this newly designed system has higher removal rates of nutrients. Removal efficiencies of NH3-N, TN, TP, and COD in actual wastewater were 82.64%, 79.62%, 87.22%, and 90.41%, respectively. Metabolic activity of DNPAOs after anoxic stage in this study even reached 94.64%. Pseudomonas aeruginosa is a strain of non-fermentative DNPAOs with strong nitrogen and phosphorus removal abilities. Study on the metabolic mechanisms suggested that intracellular PHB of P. aeruginosa plays dual roles, supplying energy for phosphorus accumulation and serving as a major carbon source for denitrification.

Autophagy is a highly conserved and lysosome-dependent degradation process which assists in cell survival and tissue homeostasis. Although previous reports have shown that deletion of the essential autophagy gene disturbs stem cell maintenance in some cell types such as hematopoietic and neural cells, it remains unclear how autophagy-deficiency influences hepatic progenitor cells (HPCs). Here we report that Atg5-deficiency in HPCs delays HPC-mediated rat liver regeneration in vivo. In vitro researches further demonstrate that loss of autophagy decreases the abilities of colony and spheroid formations, and disrupts the induction of hepatic differentiation in HPCs. Meanwhile, autophagy-deficiency increases the accumulations of damaged mitochondria and mitochondrial reactive oxygen species (mtROS) and suppresses homologous recombination (HR) pathway of DNA damage repair in HPCs. Moreover, in both diethylnitrosamine (DEN) and CCl4 models, autophagy-deficiency accelerates neoplastic transformation of HPCs. In conclusion, these findings demonstrate that autophagy contributes to stemness maintenance and reduces susceptibility to neoplastic transformation in HPCs.

Trandolapril is the pro-drug of trandolaprilat, a non-sulfhydryl angiotensin-converting enzyme inhibitor. This study was designed to assess the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of single and multiple doses of trandolapril in healthy Chinese subjects. Healthy subjects (six men and six women) were randomized into a single-dose, 3 × 3 crossover study (1–2–4 mg, 2–4–1 mg, and 4–1–2 mg), and a multiple-dose study (2 mg/day, 6 days). Serial blood and urine samples were collected after drug administration and analyzed using a validated LC–MS/MS method, and the trandolapril and trandolaprilat PK parameters were obtained. PD was evaluated by the changes in blood pressure and heart rates after dosing. Tolerability was assessed by monitoring adverse events, vital signs, ECGs, and changes in laboratory tests. In the single-dose study, trandolapril was absorbed rapidly, and peak plasma levels (C max, 1.57, 3.77, and 7.99 ng/mL) and AUCs (1.89, 3.46, and 6.47 ng/mL) were dose-dependent. The AUC0–∞ of trandolaprilat was dose-dependent, but in a non-linear fashion. The cumulative urine excretion of trandolapril and trandolaprilat was 5.51, 6.20, and 7.41 % for three doses, respectively. In the multiple-dose study, steady-state pharmacokinetics was observed; there was no trandolapril accumulation, but there was mild trandolaprilat accumulation (R = 1.67). Trandolapril was well tolerated. The most pronounced reductions in blood pressure were observed at 8 h after administration, which was later than T max. No orthostatic hypotension occurred. The pharmacokinetics and pharmacodynamics following single and multiple oral doses trandolapril in healthy Chinese subjects are similar to those observed in non-Chinese healthy subjects.

To investigate the characteristics and metabolic mechanism of short-cut denitrifying phosphorus-removing bacteria (SDPB) that are capable of enhanced biological phosphorus removal (EBPR) using nitrite as an electron acceptor, an aerobic/anoxic sequencing batch reactor was operated under three phases. An SDPB-strain YC was screened after the sludge enrichment and was identified by morphological, physiological, biochemical properties and 16S rDNA gene sequence analysis. Denitrifying phosphorus-removing experiments were conducted to study anaerobic and anoxic metabolic mechanisms by analyzing the changes of chemical oxygen demand (COD), phosphate, nitrite, poly-β-hydroxybutyrate (PHB), and glycogen. The results show that strain YC is a non-fermentative SDPB similar to Paracoccus denitrificans . As a kind of non-fermentative bacteria, the energy of strain YC was mainly generated from phosphorus release (96.2%) under anaerobic conditions with 0.32 mg P per mg synthesized PHB. Under anoxic conditions, strain YC accumulated 0.45 mg P per mg degraded PHB, which produced most of energy for phosphate accumulation (91.3%) and a little for glycogen synthesis (8.7%). This metabolic mechanism of strain YC is different from that of traditional phosphorus-accumulating organisms (PAOs). It is also found that PHB, a kind of intracellular polymer, plays a very important role in denitrifying and accumulating phosphorus by supplying sufficient energy for phosphorous accumulation and carbon sources for denitrification. Therefore, monitoring ΔP/ΔPHB and Δ-NO − 2 -N/ΔPHB is more necessary than monitoring ΔP/ΔCOD, ΔNO − 2 -N/ΔCOD, or ΔP/ΔNO − 2 -N.

This article describes the mechanism of energy management contract and the status of implementation of energy engineering projects in China's enterprises, takes the energy management contract projects as study object, and analyzes the risks of projects systematically. These risks include policy risk, financial risk, operational risk, efficiency risk and market risk. On this basis, this article discusses the risk evaluation index system of energy management contract project, proposes the analytic hierarchy process (AHP) and intuitionistic fuzzy sets to evaluate the risks of energy management contract project, then puts up with a quantitative method for the energy management contract companies.

Limaprost, a prostaglandin E1 analogue, is used to treat various symptoms in patients with ischemic diseases. The present study was designed to determine the pharmacokinetics and tolerability of single and multiple oral doses of limaprost 5 μg tablets in healthy Chinese subjects.Single and multiple doses of 5-μg limaprost were orally administered to 12 healthy Chinese subjects. There was a 2-week washout period between single and multiple dosing. Blood samples were collected at various times. Indomethacin and aspirin were added to the blood samples to inhibit the endogenous release of prostaglandins during the sample processing. Plasma limaprost was measured by a two-dimensional liquid chromatography-tandem mass spectrometry method.After single dosing, limaprost was rapidly absorbed (time to reach maximum plasma concentration [t max] = 22.50 min) and eliminated (elimination half-life [t ½] = 21.70 min), with the maximum plasma concentration (C max) being 2.56 pg/mL and area under the concentration-time curve (AUC) from time 0 to the last quantifiable time point (AUC0-t) being 70.68 pg·min/mL. There were significant inter-individual variations in the AUCs for both single- and multiple-dose regimens. The values of C max, AUC, t ½ and t max were not statistically different between single and multiple dosing. The accumulation factor R was 0.609 ± 0.432 (R1), indicating that there was no accumulation after multiple dosing. There were no statistically significant differences in pharmacokinetic parameters for both single and multiple dosing between female and male subjects. The drug was well tolerated, with no severe adverse events being observed.Limaprost is rapidly absorbed after oral administration and is rapidly eliminated, with no accumulation after multiple dosing. The drug is well tolerated and no serious adverse events occurred.

OBJECTIVE We compared the pharmacokinetic (PK) profiles of diethylstilbestrol orally dissolving film (DES ODF) and DES-capsule as well as assessing the safety, local tolerability, taste, and disintegration time of DES ODF. MATERIALS AND METHODS Twelve healthy male volunteers receiving a single administration of 2.0 mg of DES ODF or DES-capsule were included in the study. The tolerability, taste, and time to dissolution of DES ODF were assessed after dosing. Safety assessments included adverse events, hematology and biochemistry tests, urinalysis, vital signs, and electrocardiography. RESULTS The PK parameters of DES ODF were all greater than those of DEScapsule. The Cmax values were 5.64 ± 1.1 and 3.4 ± 1.93 ng/mL for DES ODF and DES-capsule, respectively. Assessment of bioequivalence was based on the 90% CIs of the treatment ratios of the log-transformed Cmax, AUC0-t, and AUC0-∞ (DES ODF to DES-capsule), with the mean values being 1.93 (141 - 264), 1.24 (98 - 156), and 1.59 (121 - 207), respectively, indicating that DES ODF had a significantly high bioavailability. The mean DES ODF disintegration time was 14 ± 5 minutes. DES ODF was well tolerated and no serious adverse events or clinically relevant changes were observed. CONCLUSIONS The DES ODF is well tolerated and better absorbed in comparison with DES-capsule.

Although HBV, liver function and tumor characteristics were proven as hepatocellular carcinoma (HCC) prognosis-related, no large-scale and long-term follow-up studies have ever given robust evidence about prognosis predictive effect and contribution to different stage of postoperation. In this study, we evaluated the influence of above index on overall survival (OS) and disease-free survival (DFS) and other clinical data in a rather large population and long-term follow-up. Our study consisted of 1,326 HCC patients who underwent radical resection from 1996 to 2010. Epidemiology, clinical and prognosis data were analyzed. Risk factors of OS and DFS were explored. Cumulative survival comparison between groups was performed with log-rank. Multivariate analysis for independent prognostic factors was determined by Cox proportional hazards model. HBsAg status was a universal factor of HCC recurrence, while preoperational albumin (ALB) and portal vein tumor thrombus (PVTT) affected survival during the whole lifetime. Early stage recurrence was associated with capsule intact [OR (95 %) = 1.54,1.12-2.12, p = 0.009], preoperational alpha-fetoprotein (AFP), TNM and BCLC stages were the most important prognosis factors of recurrence in the early 5 years and PVTT affected the rest time. Survival was mainly associated with tumor characteristic and ALB. Short-time survival was affected with age and AFP, while BCLC was related with the long-time survival. We confirmed that during different periods after resection, factors affecting prognosis did not remain unchanged. Liver function and tumor characteristic affected DFS and OS the whole time, especially the early recurrence. However, HBV infection situation was associated with later recurrence. PVTT showed an opposite effect between early and later recurrence.

Objective to discuss the effect of the early intervention to the patients with hearing loss by the hypoglycemic anti-deaf party. Methods 44 (56 ears) patients with diabetes and deafness treat by the hypoglycemic anti-deaf party, control group of 40 healthy persons Refuses to accept any drug and observe the same number of days with the treatment group. All patients were given the control diet, diabetes knowledge, education, sports and other treatment. Measured the two groups fasting blood glucose (FBG), 2 h postprandial blood glucose (2 hPBG), glycosylated hemoglobin (HbAIc), FINS, insulin (2 hINS), TCM syndromes and compared the before and the after. Results After treatment, FBG, 2 hPBG HbAIc decreased significantly than before treatment (P 0.05). After treatment FINS, 2 hINS than before treatment decreased significantly (P 0.05) the two groups’ BMI before and after treatment had no statistically significant (P > 0.05) Before and after treatment syndromes treatment group than the control group. Conclusion Hypoglycemic anti-deaf glue combined to control diet, diabetes knowledge, education, sports, and other patients with hearing loss early treatment of diabetes was significantly lower FBG, 2 hPBG, HbAIc, improve insulin secretion, control diabetes and development.

Objective To study the influence in bone mineral density of diabetes with deafness in different syndrome types by Prescriptions of hypoglycemic preventing deafness. Methods We treated 42 patients (84 ears) of diabetes with deafness in different syndrome type by prescriptions of hypoglycemic prevent deafness. Then determinate bone gla protein (BGP), calcitonin (HCT), parathyroid hormone (PTH) and bone metabolic index of these patients before treatment and after treatment. We also maesured the bone mineral density of lumbar spine, femoral, arm, heel of these patient in treatment group. There were 40 normal people in control group. Results We compared the bone metabolism of patients with different syndromes in group treatment before the treatment with the normal people. Results show that BGP, HCT of patients with Yin scorching has no obvious statistical significance (P > 0.05). PTH of patients had gawped higher (P 0.05). Patient in qi and Yin deficiency, deficiency of Yin and Yang have obvious changes (P 0.05). Conclusion Prescriptions of hypoglycemic preventing deafness can improve the bone metabolism and bone mineral density of diabetes patients with deafness in different syndrome types. It can provide basis for diabetes-kidney-bone-ear integration hypothesis.

Surgical resection is currently indicated for all potentially resectable intrahepatic cholangiocarcinoma (ICC), but the survival outcomes and the prognostic factors have not been well-documented due to its rarity. This study aims to assess these in a large, consecutive series of patients with ICC treated surgically. A retrospective study was conducted on 1,333 ICC patients undergoing surgery between January 2007 and December 2011. Surgical results and survival were evaluated and compared among different subgroups of patients. Univariate and multivariate analyses were performed to identify prognostic factors. R0, R1, R2 resection and exploratory laparotomy were obtained in 34.8, 44.9, 16.4, and 3.9 % of the patients, respectively. The overall 1-, 3-, and 5-year survival rates for the entire cohort were 58.2, 25.2, and 17.0 %, respectively, with corresponding rates of 79.1, 42.6, and 28.7 % for patients with R0 resection; 60.5, 20.1, and 13.9 % for patients with R1 resection; 20.5, 7.4, and 0 % for patients with R2 resection; and 3.8, 0, and 0 % for patients with an exploratory laparotomy. Independent factors for poor survival included positive resection margin, lymph node metastasis, multiple tumors, vascular invasion, and elevated CA19-9 and/or CEA, whereas hepatitis B virus infection and cirrhosis were independently favorable prognosis indicators. R0 resection offers the best possibility of long-term survival, but the chance of a R0 resection is low when surgery is performed for potential resectable ICC. Further randomized trials are warranted to refine indications for surgery in the management of ICC.

Background Lamivudine is used in the treatment of HIV and chronic hepatitis B (HBV) infections. Since 1999, at least 2 million Chinese HBV patients have been treated with lamivudine, but there are limited studies on the pharmacokinetics and safety of the drug in Chinese populations. Objective This study was designed to assess the bioequivalence of a newly developed lamivudine tablet (test drug) and a branded lamivudine tablet (reference drug) in healthy Chinese male volunteers. Methods A single-center, single-dose, randomized, open-label, 2-period crossover study was conducted in 28 healthy Chinese male volunteers. Blood samples were collected up to 24 hours after the administration of oral lamivudine 100 mg in each period. Plasma lamivudine concentrations were analyzed by a validated LC–MS/MS method. Pharmacokinetic and bioavailability parameters were calculated. Adverse events (AEs) were recorded. Results There were no significant differences in mean (SD) pharmacokinetic parameters between the test and reference drugs, including C max (1239 [328.9] ng/mL vs 1176 [341.5] ng/mL), AUC 0–t (4096 [599.1] ng · h/mL vs 4064 [678.2] ng · h/mL), and AUC 0–∞ (4200 [607.7] ng · h/mL vs 4162 [672.2] ng · h/mL). The geometric mean test/reference ratios (90% CI) calculated for the log-transformed parameters were C max , 1.06 (96.21–116.90); AUC 0–t , 1.01 (96.53–105.39); and AUC 0–∞ , 1.01 (96.81–105.16), all of which were within the acceptance limits for bioequivalence. No serious AEs were reported, and all mild AEs were recovered quickly without treatment. Conclusion These findings suggest that the test formulation of lamivudine 100 mg meets the FDA regulatory standards for bioequivalence with the reference formulation. Both formulations were well tolerated.

The significance of surgery in the treatment of hepatocellular carcinoma (HCC) extending into the inferior vena cava (IVC)/right atrium (RA) is currently unclear. We sought to clarify whether surgical treatment can improve survival in such patients.A retrospective review was undertaken of patients with HCC and IVC/RA tumor thrombus who were potential candidates for surgery but who were finally treated surgically and nonsurgically between September 2000 and October 2010. The patients were subdivided according to therapeutic modalities, and the results for each group were compared.A total of 56 patients were included in this study. They were divided into three groups. Twenty-five patients underwent hepatectomy plus thrombectomy (surgical group), with minor morbidity and no mortality; the patients in this group had 1-, 3-, and 5-year survival rates of 68.0, 22.5, and 13.5%, respectively, with a median survival of 19 months. Twenty patients were treated with transcatheter arterial chemoembolization, with 1- and 3-year survival rates of 15.0 and 5.0%, respectively (median survival 4.5 months). Eleven patients received symptomatic treatment only, and no one in this group survived longer than 1 year (median survival 5 months). The patients in surgical group survived significantly longer than the patients in the other two groups (p0.001).Although technically challenging, surgery for HCC with IVC/RA tumor thrombus can be safely performed and should be considered in patients with resectable primary tumor and sufficient hepatic reservoir because compared with transcatheter arterial chemoembolization or symptomatic treatment, it significantly improved patient survival.

Purposes: Local resection for hepatocellular carcinoma (HCC) has been traditionally performed non-anatomically. The purpose of this study is to evaluate the feasibility of precise local resection of HCC according to the anatomy of tumor-surrounding vessels revealed by three-dimensional (3D) analysis technique. Methods: The CT datasets of the livers of the patients with HCC were analyzed three-dimensionally. The tumor-bearing vessels were identified and virtually resected, and the depending parenchymal volume was calculated for definition of an optimal liver division plane. The actual local resections were then carried out according to the simulations. Results: Precise local resection based on tumor-surrounding vascular anatomy was performed in 13 HCC patients. Both resection margin and volume were significantly correlated with those predicted by preoperative simulations. After precise local resection, neither ischemia nor congestion was observed in the remnant livers. All patients obtained adequate resection margins, without recurrences in the resection sites after a median follow-up time of 18 months. Conclusions: Local resection for HCC can be carried out precisely according to the anatomy of tumor-surrounding vessels when guided by a 3D analysis. This precise procedure will enhance both the accuracy and safety of traditional local resection.

In economic era of information, the enterprises are facing complicated and changeable management environment, which has put forward higher requirement in adaptability to changes, innovation ability and management level to enterprises. The implementation of informatization projects is the important route, which improves the management level, strengthens the key competitiveness and realizes the management innovation. The characteristic of enterprise's informatization projects determines that there are greater risks in the implementation of the informationization. It is also the key to evalue the risk of informatization projects. This paper analysizes the risk influence factors of informatization projects,establishes risk factor index system and intuitiouistic fuzzy sets model. Finally, the model is proved feasible and effective by an example. This can provide reference value for Informatization project managers in measuring risk and preventiving measures.

In this paper, the integration evaluation index system of enterprises' informatization and industrialization is established, combining the characteristics of integration into maturity model, and presents effectively improved the DEA model that can effectively evaluate integrate maturity of information and industrialization. It plays a strong guide role for our country and enterprises to construct informatization and industrialization.

Nowadays, technological progress plays a more and more important role in the development of electric power industry. This paper collects data about the development of electric power industry in the past decade, and calculates the contribution degree of technology by using Solow method of remainder. Based on the analysis, the conclusion is drawn that at present China's power industry should seize the opportunities brought by the world new energy development and the intelligent electrical network construction, and realize electric economy's high-quality development relying on technological progress.

In power management load forecasting is important. Based on the advantage and deficiency of gray GM (1, 1) predict and Markov's chain this paper puts up with the the electric load models, that is gray - of Markov's chain predicts. Take power consumption of nearly ten years in Jiangxi Province as an example to prove this model.

Invasion and metastasis are key features of human hepatocellular carcinoma (HCC). Heparanase is an endoglycosidase that can degrade extracellular matrix by cleaving heparan sulfate chains of heparan sulfate proteoglycan, thus playing important roles in the invasion and metastasis of human cancers. Heparanase has been detected in various human cancers and regarded as a prospective target in human cancer treatments. However, the effects of inhibiting the expression of heparanase on human HCC have not been fully evaluated. In this article we show that downregulating the expression of heparanase either by antisense oligodeoxynucleotide or by RNA interferencing can significantly reduce the expression of heparanase in SMMC7721 human HCC cells, leading to inhibition of the invasiveness, metastasis, and angiogenesis of HCC cells both in vitro and in vivo. Our results suggest that genetic downregulation of the expression of heparanase may serve as an efficient cancer therapeutic for human HCC.

e15165 Background: In partial hepatectomy for primary liver cancer (PLC), portal triad clamping (PTC) is an efficient tool to minimize bleeding during parenchymal transection. Currently, most surge...

To evaluate the surgical techniques and feasibility for resecting the hepatic caudate lobe including the paracaval portion.Right posterior approach for right caudate lobectomy and left lateral approach for total caudate lobectomy were taken with or without some kinds of preparatory segmentectomies.Seven right and 6 total caudate lobectomies, all including paracaval portion, ware accomplished without operative death. The mean intraoperative blood loss was 896.15 (250 - 2 000) ml and the mean portal triad clamping time was 25.4 (10 - 83) min. The postoperative course was uneventful for all the cases, and the mean hospital stay was 12 (9 - 22) days.Although being complicated anatomically, resection of the hepatic caudate lobe including the paracaval portion is feasible with a high safety.