AIM: To investigate the relationship between increases in expression time of ABCG2 mRNA driven by cisplatin and efficacy of platinum-containing chemotherapy for gastric cancer.
METHODS: Tumor specimens and normal control tissues were collected from 78 patients with gastric cancer treated from January 2008 to December 2011. Fresh tumor tissue obtained from the surgically resected specimens was tested within 6 h. Polymerase chain reaction products were run on 2% agarose gels and analyzed under ultraviolet light after ethidium bromide staining. Increases in ABCG2 mRNA expression time were assessed after cancer cells were incubated with cisplatin, and were divided into terciles and compared in relation to clinical outcomes.
RESULTS: Among groups classified by expression time of ABCG2 mRNA, no significant differences in baseline clinical characteristics and pathological findings were detected. The median overall time was 14.2 (95%CI: 9.7-18.6), 11.4 (95%CI: 6.3-16.5) and 8.1 (95%CI: 5.4-10.8) in patients with low, intermediate and high increases in ABCG2 mRNA expression times (P < 0.05), respectively. Median survival associated with performance status and tumor node metastasis (TNM) stage showed a similar trend, with longer survival and higher risk for mortality associated with lower performance status score and TNM stage. In a multivariate analysis for survival with Cox proportional-hazards model, increased ABCG2 mRNA expression time was an independent predictor for overall survival. Overall survival was longer with increased ABCG2 mRNA expression times ≤ 0.71 than increased ABCG2 mRNA expression times > 0.71, with a hazard ratio for death of 0.855 (95%CI: 0.615-0.962, P = 0.038).
CONCLUSION: Increased ABCG2 mRNA expression time driven by cisplatin is associated with survival of gastric cancer patients, and this may help modify the therapeutic strategies.
Gastric cancer; ABCG2 mRNA expression; Cisplatin; Overall survival
Cretaceous represents one of the hottest greenhouse periods in the Earth's history, but some recent studies suggest that small ice caps might be present in non-polar regions during certain periods in the Early Cretaceous. Here we report extremely negative δ18O values of −18.12‰ to −13.19‰ for early Aptian hydrothermal zircon from an A-type granite at Baerzhe in northeastern China. Given that A-type granite is anhydrous and that magmatic zircon of the Baerzhe granite has δ18O value close to mantle values, the extremely negative δ18O values for hydrothermal zircon are attributed to addition of meteoric water with extremely low δ18O, mostly likely transported by glaciers. Considering the paleoaltitude of the region, continental glaciation is suggested to occur in the early Aptian, indicating much larger temperature fluctuations than previously thought during the supergreenhouse Cretaceous. This may have impact on the evolution of major organism in the Jehol Group during this period.
Despite the recent realization of Interleukin (IL)-35 in tumorigenesis, its exact impact on colorectal cancer (CRC) progression and prognosis, however, is yet to be elucidated clearly. We thus in the present report conducted comparative analysis of IL-35 levels between CRC patients and matched control subjects. IL-35 is highly expressed in all CRC tissues, which can be detected in vast majority of colorectal cancer cells. IL-35 levels in CRC lysates and serum samples are highly correlated to the severity of malignancy and the clinical stage of tumor. Particularly, a significant reduction for serum IL-35 was noted in patients after surgical resection, indicating that IL-35 promotes CRC progression associated with poor prognosis. Mechanistic study demonstrated a significant correlation between serum IL-35 levels and the number of peripheral regulatory T (Treg) cells in CRC patients, suggesting that IL-35 implicates in CRC pathogenesis probably by inducing Treg cells, while cancer cell-derived IL-35 may also recruit Treg cells into the tumor microenvironment in favor of tumor growth. Together, our data support that IL-35 could be a valuable biomarker for assessing CRC progression and prognosis in clinical settings.
Interleukin-35; colorectal cancer; regulatory T cell; EBI3; IL-12p35
AIM: To investigate whether tumor necrosis factor-α (TNF-α) mediates ischemia-reperfusion (I/R)-induced intestinal mucosal injury through c-Jun N-terminal kinase (JNK) activation.
METHODS: In this study, intestinal I/R was induced by 60-min occlusion of the superior mesenteric artery in rats followed by 60-min reperfusion, and the rats were pretreated with a TNF-α inhibitor, pentoxifylline, or the TNF-α antibody infliximab. After surgery, part of the intestine was collected for histological analysis. The mucosal layer was harvested for RNA and protein extraction, which were used for further real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blotting analyses. The TNF-α expression, intestinal mucosal injury, cell apoptosis, activation of apoptotic protein and JNK signaling pathway were analyzed.
RESULTS: I/R significantly enhanced expression of mucosal TNF-α at both the mRNA and protein levels, induced severe mucosal injury and cell apoptosis, activated caspase-9/caspase-3, and activated the JNK signaling pathway. Pretreatment with pentoxifylline markedly downregulated TNF-α at both the mRNA and protein levels, whereas infliximab pretreatment did not affect the expression of TNF-α induced by I/R. However, pretreatment with pentoxifylline or infliximab dramatically suppressed I/R-induced mucosal injury and cell apoptosis and significantly inhibited the activation of caspase-9/3 and JNK signaling.
CONCLUSION: The results indicate there was a TNF-α-mediated JNK activation response to intestinal I/R injury.
Tumor necrosis factor-α; Intestine; Mucosa; Apoptosis; c-Jun N-terminal kinase
Many epidemiological studies have found a positive association between periodontal disease (PD) and the risk of preeclampsia, but the magnitude of this association varies and independent studies have reported conflicting findings. We performed a meta-analysis to ascertain the relationship between PD and preeclampsia.
The PubMed database was searched up to January 12, 2013, for relevant observational studies on an association between PD and the risk of preeclampsia. Data were extracted and analyzed independently by two authors. The meta-analysis was performed using comprehensive meta-analysis software.
Thirteen observational case-control studies and two cohort studies, involving 1089 preeclampsia patients, were identified. Based on a random-effects meta-analysis, a significant association between PD and preeclampsia was identified (odds ratio = 2.79, 95% confidence interval CI, 2.01–3.01, P<0.0001).
Although the causality remains unclear, the association between PD and preeclampsia may reflect the induction of PD by the preeclamptic state, or it may be part of an overall exaggerated inflammatory response to pregnancy. Larger randomized controlled trials with preeclampsia as the primary outcome and pathophysiological studies are required to explore causality and to dissect the biological mechanisms involved.
Angioimmunoblastic T-cell lymphoma (AITL) is a unique type of peripheral T-cell lymphoma with a constellation of clinical symptoms and signs, including weight loss, fever, chills, anemia, skin rash, hepatosplenomegaly, lymphadenopathy, thrombocytopenia and polyclonal hypergammaglobulinemia. The histological features of AITL are also distinctive. Pure red cell aplasia is a bone marrow failure characterized by progressive normocytic anemia and reticulocytopenia without leucopenia or thrombocytopenia. However, AITL with abdominal pain and pure red cell aplasia has rarely been reported. Here, we report a rare case of AITL-associated pure red cell aplasia with abdominal pain. The diagnosis was verified by a biopsy of the enlarged abdominal lymph nodes with immunohistochemical staining.
Angioimmunoblastic T-cell lymphoma; Anemia; Pure red cell aplasia; Abdominal pain
A severe disease in humans caused by a novel avian-origin influenza A (H7N9) virus emerged in China recently, which has caused at least 128 cases and 26 deaths. Rapid detection of the novel H7N9 virus is urgently needed to differentiate the disease from other infections, and to facilitate infection control as well as epidemiologic investigations. In this study, a reverse transcription loop-mediated isothermal amplification combined with a lateral flow device (RT-LAMP-LFD) assay to rapidly detect H7N9 virus was developed and evaluated. The RT-LAMP primers were designed to target the haemagglutinin (HA) and neuraminidase (NA) genes of H7N9 virus. Results of 10-fold dilution series assays showed that analysis of RT-LAMP products by the LFD method was as sensitive as real-time turbidity detection, and that the analytic sensitivities of the HA and NA RT-LAMP assays were both 10 copies of synthetic RNA. Furthermore, both the assays showed 100% clinical specificity for identification of H7N9 virus. The performance characteristics of the RT-LAMP-LFD assay were evaluated with 80 clinical specimens collected from suspected H7N9 patients. The NA RT-LAMP-LFD assay was more sensitive than real time RT-PCR assay. Compared with a combination of virus culture and real-time RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value of the RT-LAMP-LFD assay were all 100%. Overall, The RT-LAMP-LFD assay established in this study can be used as a reliable method for early diagnosis of the avian-origin influenza A (H7N9) virus infection.
Two new sesquiterpenes, 1β,5α,6α,14-tetraacetoxy-9α-benzoyloxy-7βH-eudesman-2β,11-diol (1) and 4α,5α-diacetoxy-9α-benzoyloxy-7βH-eudesman-1β,2β,11,14-tetraol (2), were produced as stress metabolites in the cultured mycelia of Pestalotiopsis sp. Z233 isolated from the algae Sargassum horneri in response to abiotic stress elicitation by CuCl2. Their structures were established by spectroscopic means. New compounds 1 and 2 showed tyrosinase inhibitory activities with IC50 value of 14.8 µM and 22.3 µM.
sesquiterpenes; Pestalotiopsis sp.; abiotic stress; tyrosinase inhibitory activities
Depression is one of the most frequent neuropsychiatric comorbidities associated with opiate addiction. Mitogen activated protein kinase (MAPK) and MAPK phosphatase (MKP) are involved in drug addiction and depression. However, the potential role of MAPK and MKP in depression caused by morphine withdrawal remains unclear. We utilized a mouse model of repeated morphine administration to examine the molecular mechanisms that contribute to prolonged withdrawal induced depressive-like behaviors. Depressive-like behaviors were significant at 1 week after withdrawal and worsened over time. Phospho-ERK (extracellular signal-regulated protein kinase) was decreased and MKP-1 was elevated in the hippocampus, and JNK (c-Jun N-terminal protein kinase), p38 (p38 protein kinase) and MKP-3 were unaffected. A pharmacological blockade of MKP-1 by intra-hippocampal sanguinarine (SA) infusion prevented the development of depressive-like behaviors and resulted in relatively normal levels of MKP-1 and phospho-ERK after withdrawal. Our findings support the association between hippocampal MAPK phosphorylation and prolonged morphine withdrawal-induced depression, and emphasize the MKP-1 as an negative regulator of the ERK phosphorylation that contributes to depression.
A virus known as severe fever with thrombocytopenia syndrome virus (SFTSV) was recently identified as the etiological agent of severe fever with thrombocytopenia syndrome (SFTS) in China. Reliable laboratory detection and identification of this virus are likely to become clinically and epidemiologically desirable. We developed a nearly instrument-free, simple molecular method which incorporates reverse transcription–cross-priming amplification (RT-CPA) coupled with a vertical flow (VF) visualization strip for rapid detection of SFTSV. The RT-CPA-VF assay targets a conserved region of the M segment of the SFTSV genome and has a limit of detection of 100 copies per reaction, with no cross-reaction with other vector-borne bunyaviruses and bacterial pathogens. The performance of the RT-CPA-VF assay was determined with 175 human plasma specimens collected from 89 clinically suspected SFTS patients and 86 healthy donors. The sensitivity and specificity of the assay were 94.1% and 100.0%, respectively, compared with a combination of virus culture and real-time RT-PCR. The entire procedure, from specimen processing to result reporting, can be completed within 2 h. The simplicity and nearly instrument-free platform of the RT-CPA-VF assay make it practical for point-of-care testing.
Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens presented by most, if not all, of the HLAs. Here, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24+ population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11+ and HLA-A24+ donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30). The cross-allele antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the major histocompatibility complex (MHC)-peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11+ population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidate the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.
To adapt and assess the validity and reliability of LupusQoL for use in Chinese patients with systemic lupus erythematosus (SLE).
Debriefing interviews of subjects with SLE guided the language modifications of the tool. The process of adaptation proceeded according to the guideline and pre-testing results of LupusQoL-China. 220 SLE patients completed LupusQoL-China and a generic preference-based measurement of health EuroQoL scale (EQ-5D), and 20 patients repeated them after 2 weeks. Internal consistency (ICR) and test-retest (TRT) reliability, convergent and discriminant validity were examined. Factor analysis and Rasch analysis were performed.
The mean (SD) age of the 208 subjects with SLE was 33.93 (±9.19) years. ICR and TRT of the eight domains ranged from 0.811 to 0.965 and 0.836 to 0.974, respectively. The LupusQoL-China domains demonstrated substantial evidence of construct validity when compared with equivalent domains on the EQ-5D (physical health and usual activities r = −0.63, pain and pain/discomfort r = −0.778, emotional health and anxiety/depression r = −0.761, planning and usual activities r = −0.560). Most LupusQoL-China domains could discriminate patients with varied disease activities and end-organ damage (according to SELENA-SLEDAI and SLICC-DI). The principal component analysis revealed six factors, and confirmatory factor analysis result of which is similar to eight factors model.
These results provide evidence that the LupusQoL-China is valid as a disease-specific HRQoL assessment tool for Chinese patients with SLE.
The reconstruction of large bone defects, including rib defects, remains a challenge for surgeons. In this study, we used biodegradable polydioxanone (PDO) cages to tissue engineer ribs for the reconstruction of 4cm-long costal defects.
PDO sutures were used to weave 6cm long and 1cm diameter cages. Demineralized bone matrix (DBM) which is a xenograft was molded into cuboids and seeded with second passage bone marrow mesenchymal stem cells (BMSCs) that had been osteogenically induced. Two DBM cuboids seeded with BMSCs were put into the PDO cage and used to reconstruct the costal defects. Radiographic examination including 3D reconstruction, histologic examination and mechanical test was performed after 24 postoperative weeks.
All the experimental subjects survived. In all groups, the PDO cage had completely degraded after 24 weeks and been replaced by fibrous tissue. Better shape and radian were achieved in PDO cages filled with DBM and BMSCs than in the other two groups (cages alone, or cages filled with acellular DBM cuboids). When the repaired ribs were subjected to an outer force, the ribs in the PDO cage/DBMs/BMSCs group kept their original shape while ribs in the other two groups deformed. In the PDO cage/DBMs/BMSCs groups, we also observed bony union at all the construct interfaces while there was no bony union observed in the other two groups. This result was also confirmed by radiographic and histologic examination.
This study demonstrates that biodegradable PDO cage in combination with two short BMSCs/DBM cuboids can repair large rib defects. The satisfactory repair rate suggests that this might be a feasible approach for large bone repair.
Tissue engineering; Rib reconstruction; PDO; Long defect of bone
HopPmaL is a member of the HopAB family of type 3 effectors present in the phytopathogen Pseudomonas syringae. Using both X-ray crystallography and solution NMR, we demonstrate that HopPmaL contains two structurally homologous yet functionally distinct domains. The N-terminal domain corresponds to the previously-described Pto-binding domain, while the previously uncharacterised C-terminal domain spans residues 308 to 385. While structurally similar these domains do not share significant sequence similarity and most importantly demonstrate significant differences in key residues involved in host protein recognition suggesting that each of them targets a different host protein.
Fitness is the central concept in evolutionary theory. It measures a phenotype's ability to survive and reproduce. There are different ways to represent this measure: Malthusian fitness and Wrightian fitness. One can go back and forth between the two, but when we characterize model properties or interpret data, it can be important to distinguish between them. Here, we discuss a recent experiment to show how the interpretation changes if an alternative definition is used.
Concept of fitness; natural selection
The protocols currently used for protein structure determination by NMR depend on the determination of a large number of upper distance limits for proton-proton pairs. Typically, this task is performed manually by an experienced researcher rather than automatically by using a specific computer program. To assess whether it is indeed possible to generate in a fully automated manner NMR structures adequate for deposition in the Protein Data Bank, we gathered ten experimental datasets with unassigned NOESY peak lists for various proteins of unknown structure, computed structures for each of them using different, fully automatic programs, and compared the results to each other and to the manually solved reference structures that were not available at the time the data were provided. This constitutes a stringent “blind” assessment similar to the CASP and CAPRI initiatives. This study demonstrates the feasibility of routine, fully automated protein structure determination by NMR.
As quality of work-life (QWL) among nurses affects both patient care and institutional standards, assessment regarding QWL for the profession is important. Work-related Quality of Life Scale (WRQOLS) is a reliable QWL assessment tool for the nursing profession. To develop a Chinese version of the WRQOLS-2 and to examine its psychometric properties as an instrument to assess QWL for the nursing profession in China.
Forward and back translating procedures were used to develop the Chinese version of WRQOLS-2. Six nursing experts participated in content validity evaluation and 352 registered nurses (RNs) participated in the tests. After a two-week interval, 70 of the RNs were retested. Structural validity was examined by principal components analysis and the Cronbach's alphas calculated. The respective independent sample t-test and intra-class correlation coefficient were used to analyze known-group validity and test-retest reliability.
One item was rephrased for adaptation to Chinese organizational cultures. The content validity index of the scale was 0.98. Principal components analysis resulted in a seven-factor model, accounting for 62% of total variance, with Cronbach's alphas for subscales ranging from 0.71 to 0.88. Known-group validity was established in the assessment results of the participants in permanent employment vs. contract employment (t = 2.895, p < 0.01). Good test-retest reliability was observed (r = 0.88, p < 0.01).
The translated Chinese version of the WRQOLS-2 has sufficient validity and reliability so that it can be used to evaluate the QWL among nurses in mainland China.
Quality of work life; Nurses; Validity and reliability; Work-Related Quality of Life Scale-2; Chinese version
Although the temperature response of soil respiration (Rs) has been studied extensively, several issues remain unresolved, including hysteresis in the Rs–temperature relationship and differences in the long- vs. short-term Rs sensitivity to temperature. Progress on these issues will contribute to reduced uncertainties in carbon cycle modeling. We monitored soil CO2 efflux with an automated chamber system in a Pinus tabulaeformis plantation near Beijing throughout 2011. Soil temperature at 10-cm depth (Ts) exerted a strong control over Rs, with the annual temperature sensitivity (Q10) and basal rate at 10°C (Rs10) being 2.76 and 1.40 µmol m−2 s−1, respectively. Both Rs and short-term (i.e., daily) estimates of Rs10 showed pronounced seasonal hysteresis with respect to Ts, with the efflux in the second half of the year being larger than that early in the season for a given temperature. The hysteresis may be associated with the confounding effects of microbial population dynamics and/or litter input. As a result, all of the applied regression models failed to yield unbiased estimates of Rs over the entire annual cycle. Lags between Rs and Ts were observed at the diel scale in the early and late growing season, but not in summer. The seasonality in these lags may be due to the use of a single Ts measurement depth, which failed to represent seasonal changes in the depth of CO2 production. Daily estimates of Q10 averaged 2.04, smaller than the value obtained from the seasonal relationship. In addition, daily Q10 decreased with increasing Ts, which may contribute feedback to the climate system under global warming scenarios. The use of a fixed, universal Q10 is considered adequate when modeling annual carbon budgets across large spatial extents. In contrast, a seasonally-varying, environmentally-controlled Q10 should be used when short-term accuracy is required.
Ligands targeting telomeric G-quadruplexs are considered good candidates for anticancer drugs. However, current studies on G-quadruplex ligands focus exclusively on the interactions of ligands and monomeric G-quadruplexes under dilute conditions. Living cells are crowded with biomacromolecules, and the ∼200-nucleotide G-rich single-stranded overhang of human telomeric DNA has the potential to fold into multimeric G-quadruplex structures containing several G-quadruplex units. Studies on interactions between ligands and multimeric G-quadruplexes under molecular crowding conditions could provide a new route for screening specific telomeric G-quadruplex-targeting ligands. Herein, TMPipEOPP, a cationic porphyrin derivative designed by us, was demonstrated as a promising multimeric telomeric G-quadruplex ligand under molecular crowding conditions. It could highly specifically recognize G-quadruplexes. It could also promote the formation of G-quadruplexes and stabilize them. Detailed studies showed that TMPipEOPP interacted with monomeric G-quadruplexes in sandwich-like end-stacking mode of quadruplex/TMPipEOPP/quadruplex and interacted with multimeric human telomeric G-quadruplexes by intercalating into the pocket between two adjacent G-quadruplex units. The pocket size greatly affected TMPipEOPP binding. A larger pocket was advantageous for the intercalation of TMPipEOPP. This work provides new insights into the ligand-binding properties of multimeric G-quadruplexes under molecular crowding conditions and introduces a new route for screening anticancer drugs targeting telomeric G-quadruplexes.
The 2009 influenza pandemic had a tremendous social and economic impact. To study the genetic diversity and evolution of the 2009 H1N1 virus, a mutation network for the non-structural (NS) gene of the virus was constructed. Strains of the 2009 H1N1 pandemic influenza A virus could be divided into two categories based on the V123I mutation in the NS1 gene: G1 (characterized as 123 Val) and G2 (characterized as 123 Ile). Sequence homology analysis indicated that one type of NS sequence, primarily isolated from Mexico, was likely the original type in this pandemic. The two genotypes of the virus presented distinctive clustering features in their geographic distributions. These results provide additional insight into the genetics and evolution of human pandemic influenza H1N1.
Sorting nexins (SNXs) are phosphoinositide-binding proteins implicated in the sorting of various membrane proteins in vitro, but the in vivo functions of them remain largely unknown. We reported previously that SNX10 is a unique member of the SNX family genes in that it has vacuolation activity in cells. We investigate the biological function of SNX10 by loss-of-function assay in this study and demonstrate that SNX10 is required for the formation of primary cilia in cultured cells. In zebrafish, SNX10 is involved in ciliogenesis in the Kupffer's vesicle and essential for left-right patterning of visceral organs. Mechanistically, SNX10 interacts with V-ATPase complex and targets it to the centrosome where ciliogenesis is initiated. Like SNX10, V-ATPase regulates ciliogenesis in vitro and in vivo and does so synergistically with SNX10. We further discover that SNX10 and V-ATPase regulate the ciliary trafficking of Rab8a, which is a critical regulator of ciliary membrane extension. These results identify an SNX10/V-ATPase-regulated vesicular trafficking pathway that is crucial for ciliogenesis, and reveal that SNX10/V-ATPase, through the regulation of cilia formation in various organs, play an essential role during early embryonic development.
SNX10; V-ATPase; ciliogenesis; zebrafish
Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear.
A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated.
After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results.
These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.
Gefitinib maintenance treatment; EGFR mutation; Cost-effectiveness; Non-small cell lung cancer
Pasteurella multocida is an important etiological agent that can cause many economically important diseases in a wide range of mammals and birds. Here, we report the complete genome sequence of P. multocida HN06, a toxigenic serogroup D strain isolated from a diseased pig in China.
Several rescue therapies have been used in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB); however, the economic outcome of these therapies is unclear. The object of the current analysis was to evaluate the lifetime cost-effectiveness of rescue therapies among patients with LAM-resistant CHB.
A Markov model was developed to simulate the clinical course of patients with LAM-resistant CHB. From the perspective of Chinese health care, a lifetime cost-utility analysis was performedfor 4 rescue strategies: adefovir (ADV), entecavir (ETV) or tenofovir (TDF) monotherapy and combination therapy using LAM and ADV. A hypothetical cohort of 45-year-old patients with genotypic or clinical LAM-resistant CHB entered the model, and the beginning health state was LAM-resistant CHB without other complications. The transition probabilities, efficacy and resistance data for each rescue therapy as well as the costs and utility data were estimated from the literature. The discount rate (3%) utilized for costs and benefits. Sensitivity analyses were used to explore the impact of uncertainty on the results.
In LAM-resistant HBeAg-positive and HBeAg-negative CHB cohorts, TDF monotherapy and combination therapy were on the efficiency frontier for both positive and negative populations. Compared with no treatment, the use of combination therapy cost an additional $6,531.7 to gain 1 additional quality-adjusted life year (QALY) for HBeAg-positive patients and $4,571.7 to gain 1 additional QALY for HBeAg-negative patients. TDF monotherapy for HBeAg-positive patients, shows greater increase in QALYs but higher incremental cost-effectiveness ratio (ICER) in comparison with combination therapy. In probabilistic sensitivity analyses, combination therapy was the preferred option for health care systems with limited health resources, such as Chinese health care system.
In Chinese patients with LAM-resistant CHB, combination therapy is a more cost-effective option than the competing rescue therapies.
Hepatitis B; Lamivudine resistance; Rescue therapy; Cost-effectiveness