Publications by authors named "Zulian Liu"

20 Publications

  • Page 1 of 1

Gtsf1 is essential for proper female sex determination and transposon silencing in the silkworm, Bombyx mori.

PLoS Genet 2020 11 2;16(11):e1009194. Epub 2020 Nov 2.

Key Laboratory of Insect Developmental and Evolutionary Biology, Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

Sex determination pathways are astoundingly diverse in insects. For instance, the silk moth Bombyx mori uniquely use various components of the piRNA pathway to produce the Fem signal for specification of the female fate. In this study, we identified BmGTSF1 as a novel piRNA factor which participates in B. mori sex determination. We found that BmGtsf1 has a distinct expression pattern compared to Drosophila and mouse. CRISPR/Cas9 induced mutation in BmGtsf1 resulted in partial sex reversal in genotypically female animals by shifting expression of the downstream targets BmMasc and Bmdsx to the male pattern. As levels of Fem piRNAs were substantially reduced in female mutants, we concluded that BmGtsf1 plays a critical role in the biogenesis of the feminizing signal. We also demonstrated that BmGTSF1 physically interacted with BmSIWI, a protein previously reported to be involved in female sex determination, indicating BmGTSF1 function as the cofactor of BmSIWI. BmGtsf1 mutation resulted in piRNA pathway dysregulation, including piRNA biogenesis defects and transposon derepression, suggesting BmGtsf1 is also a piRNA factor in the silkworm. Furthermore, we found that BmGtsf1 mutation leads to gametogenesis defects in both male and female. Our data suggested that BmGtsf1 is a new component involved in the sex determination pathway in B. mori.
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http://dx.doi.org/10.1371/journal.pgen.1009194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660909PMC
November 2020

Dysfunction of dimorphic sperm impairs male fertility in the silkworm.

Cell Discov 2020 8;6:60. Epub 2020 Sep 8.

Key Laboratory of Insect Developmental and Evolutionary Biology, Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, 200032 Shanghai, China.

Sperm, which have a vital role in sexual reproduction in the animal kingdom, can display heteromorphism in some species. The regulation of sperm dichotomy remains a longstanding puzzle even though the phenomenon has been widely documented for over a century. Here we use as a model to study a form of sperm dimorphism (eupyrene and apyrene sperm), which is nearly universal among Lepidoptera. We demonstrate that () is crucial for apyrene sperm development, and that () is required for eupyrene sperm development. BmSXL is distributed in the nuclei and cytoplasm of somatic cyst cells in a mesh-like pattern and in the cytoplasm of germ cells enclosed in spermatocysts and sperm bundles. Cytological analyses of dimorphic sperm in mutants (∆) showed deficient apyrene sperm with abnormal nuclei, as well as loss of motility associated with malformed mitochondrial derivatives. We define the crucial function of apyrene sperm in the process of fertilization as assisting the migration of eupyrene spermatozoa from bursa copulatrix to spermatheca. By contrast, deficiency (∆) caused eupyrene sperm abnormalities and impaired the release of eupyrene sperm bundles during spermiation. Although apyrene or eupyrene sperm defects impaired fertility of the mutated males, double copulation of a wild-type female with ∆ and ∆ males could rescue the sterility phenotypes induced by single copulation with either gene-deficient male. Our findings demonstrate the crucial functions of and in the development of sperm dimorphism and the indispensable roles of nonfertile apyrene sperm in fertilization.
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http://dx.doi.org/10.1038/s41421-020-00194-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477584PMC
September 2020

Regulation of olfactory-based sex behaviors in the silkworm by genes in the sex-determination cascade.

PLoS Genet 2020 06 10;16(6):e1008622. Epub 2020 Jun 10.

Key Laboratory of Insect Developmental and Evolutionary Biology, Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

Insect courtship and mating depend on integration of olfactory, visual, and tactile cues. Compared to other insects, Bombyx mori, the domesticated silkworm, has relatively simple sexual behaviors as it cannot fly. Here by using CRISPR/Cas9 and electrophysiological techniques we found that courtship and mating behaviors are regulated in male silk moths by mutating genes in the sex determination cascade belonging to two conserved pathways. Loss of Bmdsx gene expression significantly reduced the peripheral perception of the major pheromone component bombykol by reducing expression of the product of the BmOR1 gene which completely blocked courtship in adult males. Interestingly, we found that mating behavior was regulated independently by another sexual differentiation gene, Bmfru. Loss of Bmfru completely blocked mating, but males displayed normal courtship behavior. Lack of Bmfru expression significantly reduced the perception of the minor pheromone component bombykal due to the down regulation of BmOR3 expression; further, functional analysis revealed that loss of the product of BmOR3 played a key role in terminating male mating behavior. Our results suggest that Bmdsx and Bmfru are at the base of the two primary pathways that regulate olfactory-based sexual behavior.
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http://dx.doi.org/10.1371/journal.pgen.1008622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307793PMC
June 2020

miR-34 regulates larval growth and wing morphogenesis by directly modulating ecdysone signalling and cuticle protein in .

RNA Biol 2020 09 25;17(9):1342-1351. Epub 2020 May 25.

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, CAS , Shanghai, China.

microRNAs (miRNA) are small non-coding RNAs that modulate the myriad biological activities by targeting genes, and many studies showed that miRNAs played a pivotal role in insect development. Here, we find that Bm-miRNA (miR-34) controls larval growth and wing morphology by targeting and . Overexpression of miR-34 in the whole body caused a smaller body size, partially displays deformed wings and venation defects in adults. Ablation of miR-34 by transgenic CRISPR/Cas9 technology resulted in a severe developmental delay during the larval stage. Moreover, we confirmed that miR-34 directly targeted and by using a dual luciferase reporter assay in HEK293T cells. Remarkably, loss-of-function of caused wing defects, which was similar to the phenotype of miR-34 overexpression in animals. In addition, our analysis revealed that ecdysone strongly inhibited miR-34 expression in . Taken together, our study identifies miR-34 as a modulator that regulates larval growth and wing morphogenesis by directly modulating ecdysone signalling and cuticle protein in .
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http://dx.doi.org/10.1080/15476286.2020.1767953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549633PMC
September 2020

Disruption of the ovarian serine protease (Osp) gene causes female sterility in Bombyx mori and Spodoptera litura.

Pest Manag Sci 2020 Apr 20;76(4):1245-1255. Epub 2019 Nov 20.

Key Laboratory of Insect Developmental and Evolutionary Biology, Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

Background: Precise regulation of oogenesis is crucial to female reproduction. Seventy percent of pests belong to lepidopteran species, so it would be interesting to explore the highly conserved genes involved in oogenesis that do not affect growth and development in the lepidopteran model, Bombyx mori. This can provide potential target genes for pest control and promote the development of insect sterility technology.

Results: In lepidopteran species, ovarian serine protease (Osp), which encodes a member of the serine protease family, is essential for oogenesis. In this study, we used transgenic CRISPR/Cas9 technology to obtain Osp mutants in the model lepidopteran insect Bombyx mori and in the lepidopteran agricultural pest Spodoptera litura. Sequence analysis of mutants revealed an array of deletions in Osp loci in both species. We found that the deletion of Osp resulted in female sterility, whereas male fertility was not affected. Although B. mori and S. litura mutant females mated normally, they laid fewer eggs than wild-type females and eggs did not hatch.

Conclusion: Osp is crucial for female reproductive success in two species of Lepidoptera. As the Osp gene is highly conserved in insect species, this gene is a potential molecular target for genetic-based pest management. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5634DOI Listing
April 2020

Mutation of the seminal protease gene, serine protease 2, results in male sterility in diverse lepidopterans.

Insect Biochem Mol Biol 2020 01 18;116:103243. Epub 2019 Sep 18.

Key Laboratory of Insect Developmental and Evolutionary Biology, Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, 200032, Shanghai, China. Electronic address:

Sterile insect technology (SIT) is an environmentally friendly method for pest control. As part of our efforts to develop a strategy that results in engineered male-sterile strains with minimum effects on viability and mating competition, we used CRISPR/Cas9 technology to disrupt Ser2, which encodes a seminal fluid protein, in the model lepidopteran insect, Bombyx mori, and an important agricultural pest, Plutella xylostella. Disruption of Ser2 resulted in dominant heritable male sterility. Wild-type females mated with Ser2-deficient males laid eggs normally, but the eggs did not hatch. We detected no differences in other reproductive behaviors in the mutant males. These results support the conclusion that Ser2 gene is necessary for male reproductive success in diverse lepidopterans. Targeting Ser2 gene has the potential to form the basis for a new strategy for pest control.
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http://dx.doi.org/10.1016/j.ibmb.2019.103243DOI Listing
January 2020

Mutation of doublesex induces sex-specific sterility of the diamondback moth Plutella xylostella.

Insect Biochem Mol Biol 2019 09 3;112:103180. Epub 2019 Jul 3.

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai, 200032, China. Electronic address:

DOUBLESEX (DSX): the downstream gene in the insect sex determination pathway, plays a critical role in sexual differentiation and development. The functions of dsx have been characterized in several model insect species. However, the molecular mechanism and functions of sex determination of dsx in Plutella xylostella, an agricultural pest, are still unknown. In present study, we identified a male-specific and three female-specific Pxdsx transcripts in P. xylostella. Phylogenetic analyses and multiple sequence alignment revealed that Pxdsx is highly conserved in lepidopterans. The CRISPR/Cas9 technology was used to induce mutations in the male-specific isoform, the female-specific isoform, and common regions of Pxdsx. Disruptions of Pxdsx sex-specific isoforms caused sex-specific defects in external genitals and partial sexual reversal. In addition, we found that female specific transcripts were detected in Pxdsx male mutants and male-specific transcripts were detected in Pxdsx female mutants. Mutations also caused changes in expression of several sex-biased genes and induced sex-specific sterility. This study demonstrates that Pxdsx plays a key role in sex determination of P. xylostella and suggests novel genetic control approaches for the management of P. xylostella.
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http://dx.doi.org/10.1016/j.ibmb.2019.103180DOI Listing
September 2019

Maelstrom regulates spermatogenesis of the silkworm, Bombyx mori.

Insect Biochem Mol Biol 2019 06 7;109:43-51. Epub 2019 Apr 7.

Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, China. Electronic address:

The spermatogenesis of animal is essential for the reproduction and a very large number of genes participate in this procession. The Maelstrom (Mael) is identified essential for spermatogenesis in both Drosophila and mouse, though the mechanisms appear to differ. It was initially found that Mael gene is necessary for axis specification of oocytes in Drosophila, and recent studies suggested that Mael participates in the piRNA pathway. In this study, we obtained Bombyx mori Mael mutants by using a binary transgenic CRISPR/Cas9 system and analyzed the function of Mael in B. mori, a model lepidopteran insect. The results showed that BmMael is not necessary for piRNA pathway in the ovary of silkworm, whereas it might be essential for transposon elements (TEs) repression in testis. The BmMael mutation resulted in male sterility, and further analysis established that BmMael was essential for spermatogenesis. The spermatogenesis defects occurred in the elongation stage and resulted in nuclei concentration arrest. RNA-seq and qRT-PCR analyses demonstrated that spermatogenesis defects were associated with tight junctions and apoptosis. We also found that BmMael was not involved in the silkworm sex determination pathway. Our data provide insights into the biological function of BmMael in male spermatogenesis and might be useful for developing novel methods to control lepidopteron pests.
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http://dx.doi.org/10.1016/j.ibmb.2019.03.012DOI Listing
June 2019

Transcatheter aortic valve implantation for aortic stenosis in high surgical risk patients: A systematic review and meta-analysis.

PLoS One 2018 10;13(5):e0196877. Epub 2018 May 10.

Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, United Kingdom.

Background: Symptomatic aortic stenosis has a poor prognosis. Many patients are considered inoperable or at high surgical risk for surgical aortic valve replacement (SAVR), reflecting their age, comorbidities and frailty. The clinical effectiveness and safety of TAVI have not been reviewed systematically for these high levels of surgical risk. This systematic review compares mortality and other important clinical outcomes up to 5 years post treatment following TAVI or other treatment in these risk groups.

Methods: A systematic review protocol was registered on the PROSPERO database (CRD42016048396). The Cochrane Library, Centre for Reviews and Dissemination Databases, MEDLINE, EMBASE, and ZETOC were searched from January 2002 to August 2016. Clinical trials or matched studies comparing TAVI with other treatments for AS in patients surgically inoperable or operable at a high risk were included. Data extraction and quality assessment were conducted by two reviewers. Data were pooled using random-effects meta-analysis. The main outcomes were all-cause mortality, efficacy and major complications.

Results: Three good quality randomised controlled trials (RCTs) were included. Patients' mean age ranged from 83-85 years, around half were female and New York Heart Association (NYHA) functional class III or IV ranged from 83.8% to 94.2% with frequent comorbidities. In 358 surgically inoperable patients from one RCT, TAVI was superior to medical therapy for all-cause mortality at 1 year (hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.36-0.92), 2 years (HR 0.50, 95% CI 0.39-0.65), 3 years (HR 0.53, 95% CI 0.41to 0.68) and 5 years (HR 0.50, 95% CI 0.39-0.65), and NYHA class III or IV at 2 years (TAVI 16.8% (16/95), medical therapy 57.5% (23/40), p<0.001), quality of life and re-hospitalisation. TAVI had higher risks of major bleeding up to 1 year, of stroke up to 3 years (at one year 11.2% versus 5.5%, p = .06; HR at 2 years 2.79, 95% CI 1.25-6.22; HR at 3 years 2.81; 95% CI 1.26-6.26) and of major vascular complication at 3 years (HR 8.27, 95% CI 2.92-23.44). Using the GRADE tool, this evidence was considered to be of moderate quality. In a meta-analysis including 1,494 high risk surgically operable patients from two non-inferiority RCTs TAVI showed no significant differences from SAVR in all-cause mortality at two years (HR 1.03, 95% CI 0.82-1.29) and up to 5 years (HR 0.83, 95% CI 0.83-1.12). There were no statistically significant differences in major vascular complications and myocardial infarction at any time point, discrepant results for major bleeding on variable definitions and no differences in stroke rate at any time point. Using the GRADE tool, this evidence was considered of low quality.

Conclusions: Symptomatic aortic stenosis can be lethal without intervention but surgical resection is contraindicated for some patients and high risk for others. We found that all-cause mortality up to 5 years of follow-up did not differ significantly between TAVI and SAVR in patients surgically operable at a high risk, but favoured TAVI over medical therapy in patients surgically inoperable. TAVI is a viable life-extending treatment option in these surgical high risk groups.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196877PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944928PMC
August 2018

MicroRNA-14 regulates larval development time in Bombyx mori.

Insect Biochem Mol Biol 2018 02 27;93:57-65. Epub 2017 Dec 27.

Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address:

MicroRNAs (miRNA) regulate multiple physiological processes including development and metamorphosis in insects. In the current study, we demonstrate that a conserved invertebrate miRNA-14 (miR-14) plays an important role in ecdysteroid regulated development in the silkworm Bombyx mori, a lepidopteran model insect. Ubiquitous transgenic overexpression of miR-14 using the GAL4/UAS system resulted in delayed silkworm larval development and smaller body size of larva and pupa with decrease in ecdysteriod titers. On the contrary, miR-14 disruption using the transgenic CRISPR/Cas9 system led to a precocious wandering stage with increase in ecdysteriod titers. We identified that the hormone receptor E75 (E75) and the ecdysone receptor isoform B (ECR-B), which both serve as essential mediators in the ecdysone signaling pathway, as putative target genes of miR-14 by in silico target prediction. Dual-luciferase reporter assays confirmed the binding of miR-14 to the 3'UTRs of E75 and ECR-B in a mammalian HEK293T cell line. Furthermore, transcription levels of E75 and ECR-B were significantly affected in both miR-14 overexpression and knockout transgenic animals. Taken together, our data suggested that the canonical invertebrate miR-14 is a general regulator in maintaining ecdysone homeostasis for normal development and metamorphosis in B. mori.
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http://dx.doi.org/10.1016/j.ibmb.2017.12.009DOI Listing
February 2018

Psychological interventions for coronary heart disease: Cochrane systematic review and meta-analysis.

Eur J Prev Cardiol 2018 02 7;25(3):247-259. Epub 2017 Dec 7.

3 Institute of Health Research, University of Exeter Medical School, Exeter, UK.

Background Although psychological interventions are recommended for the management of coronary heart disease (CHD), there remains considerable uncertainty regarding their effectiveness. Design Systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for CHD. Methods The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and PsycINFO were searched to April 2016. Retrieved papers, systematic reviews and trial registries were hand-searched. We included RCTs with at least 6 months of follow-up, comparing the direct effects of psychological interventions to usual care for patients following myocardial infarction or revascularisation or with a diagnosis of angina pectoris or CHD defined by angiography. Two authors screened titles for inclusion, extracted data and assessed risk of bias. Studies were pooled using random effects meta-analysis and meta-regression was used to explore study-level predictors. Results Thirty-five studies with 10,703 participants (median follow-up 12 months) were included. Psychological interventions led to a reduction in cardiovascular mortality (rfcelative risk 0.79, 95% confidence interval [CI] 0.63 to 0.98), although no effects were observed for total mortality, myocardial infarction or revascularisation. Psychological interventions improved depressive symptoms (standardised mean difference [SMD] -0.27, 95% CI -0.39 to -0.15), anxiety (SMD -0.24, 95% CI -0.38 to -0.09) and stress (SMD -0.56, 95% CI -0.88 to -0.24) compared with controls. Conclusions We found that psychological intervention improved psychological symptoms and reduced cardiac mortality for people with CHD. However, there remains considerable uncertainty regarding the magnitude of these effects and the specific techniques most likely to benefit people with different presentations of CHD.
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http://dx.doi.org/10.1177/2047487317739978DOI Listing
February 2018

Psychological interventions for coronary heart disease.

Cochrane Database Syst Rev 2017 04 28;4:CD002902. Epub 2017 Apr 28.

Institute of Health Research, University of Exeter Medical School, Veysey Building, Salmon Pool Lane, Exeter, UK, EX2 4SG.

Background: Coronary heart disease (CHD) is the most common cause of death globally, although mortality rates are falling. Psychological symptoms are prevalent for people with CHD, and many psychological treatments are offered following cardiac events or procedures with the aim of improving health and outcomes. This is an update of a Cochrane systematic review previously published in 2011.

Objectives: To assess the effectiveness of psychological interventions (alone or with cardiac rehabilitation) compared with usual care (including cardiac rehabilitation where available) for people with CHD on total mortality and cardiac mortality; cardiac morbidity; and participant-reported psychological outcomes of levels of depression, anxiety, and stress; and to explore potential study-level predictors of the effectiveness of psychological interventions in this population.

Search Methods: We updated the previous Cochrane Review searches by searching the following databases on 27 April 2016: CENTRAL in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO).

Selection Criteria: We included randomised controlled trials (RCTs) of psychological interventions compared to usual care, administered by trained staff, and delivered to adults with a specific diagnosis of CHD. We selected only studies estimating the independent effect of the psychological component, and with a minimum follow-up of six months. The study population comprised of adults after: a myocardial infarction (MI), a revascularisation procedure (coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI)), and adults with angina or angiographically defined coronary artery disease (CAD). RCTs had to report at least one of the following outcomes: mortality (total- or cardiac-related); cardiac morbidity (MI, revascularisation procedures); or participant-reported levels of depression, anxiety, or stress.

Data Collection And Analysis: Two review authors independently screened titles and abstracts of all references for eligibility. A lead review author extracted study data, which a second review author checked. We contacted study authors to obtain missing information.

Main Results: This review included 35 studies which randomised 10,703 people with CHD (14 trials and 2577 participants added to this update). The population included mainly men (median 77.0%) and people post-MI (mean 65.7%) or after undergoing a revascularisation procedure (mean 27.4%). The mean age of participants within trials ranged from 53 to 67 years. Overall trial reporting was poor, with around a half omitting descriptions of randomisation sequence generation, allocation concealment procedures, or the blinding of outcome assessments. The length of follow-up ranged from six months to 10.7 years (median 12 months). Most studies (23/35) evaluated multifactorial interventions, which included therapies with multiple therapeutic components. Ten studies examined psychological interventions targeted at people with a confirmed psychopathology at baseline and two trials recruited people with a psychopathology or another selecting criterion (or both). Of the remaining 23 trials, nine studies recruited unselected participants from cardiac populations reporting some level of psychopathology (3.8% to 53% with depressive symptoms, 32% to 53% with anxiety), 10 studies did not report these characteristics, and only three studies excluded people with psychopathology.Moderate quality evidence showed no risk reduction for total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.77 to 1.05; participants = 7776; studies = 23) or revascularisation procedures (RR 0.94, 95% CI 0.81 to 1.11) with psychological therapies compared to usual care. Low quality evidence found no risk reduction for non-fatal MI (RR 0.82, 95% CI 0.64 to 1.05), although there was a 21% reduction in cardiac mortality (RR 0.79, 95% CI 0.63 to 0.98). There was also low or very low quality evidence that psychological interventions improved participant-reported levels of depressive symptoms (standardised mean difference (SMD) -0.27, 95% CI -0.39 to -0.15; GRADE = low), anxiety (SMD -0.24, 95% CI -0.38 to -0.09; GRADE = low), and stress (SMD -0.56, 95% CI -0.88 to -0.24; GRADE = very low).There was substantial statistical heterogeneity for all psychological outcomes but not clinical outcomes, and there was evidence of small-study bias for one clinical outcome (cardiac mortality: Egger test P = 0.04) and one psychological outcome (anxiety: Egger test P = 0.012). Meta-regression exploring a limited number of intervention characteristics found no significant predictors of intervention effects for total mortality and cardiac mortality. For depression, psychological interventions combined with adjunct pharmacology (where deemed appropriate) for an underlying psychological disorder appeared to be more effective than interventions that did not (β = -0.51, P = 0.003). For anxiety, interventions recruiting participants with an underlying psychological disorder appeared more effective than those delivered to unselected populations (β = -0.28, P = 0.03).

Authors' Conclusions: This updated Cochrane Review found that for people with CHD, there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non-fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects. Considerable uncertainty also remains regarding the people who would benefit most from treatment (i.e. people with or without psychological disorders at baseline) and the specific components of successful interventions. Future large-scale trials testing the effectiveness of psychological therapies are required due to the uncertainty within the evidence. Future trials would benefit from testing the impact of specific (rather than multifactorial) psychological interventions for participants with CHD, and testing the targeting of interventions on different populations (i.e. people with CHD, with or without psychopathologies).
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http://dx.doi.org/10.1002/14651858.CD002902.pub4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478177PMC
April 2017

Adverse effects of extracorporeal carbon dioxide removal (ECCO2R) for acute respiratory failure: a systematic review protocol.

Syst Rev 2016 Jun 7;5:98. Epub 2016 Jun 7.

Murray Learning Centre, Institute of Applied Health Research, University of Birmingham, Room 137, B15 2TT, Birmingham, UK.

Background: The extracorporeal membrane carbon dioxide removal (ECCO2R) system is primarily designed for the purpose of removing CO2 from the body for patients with potentially reversible severe acute hypercapnic respiratory failure or being considered for lung transplantation. Systematic reviews have focused on the effectiveness of ECCO2R. To the author's best knowledge, this is the first systematic review to focus on the adverse effects of this procedure.

Methods: We will conduct a systematic review of procedure-related adverse effects of ECCO2R systems. A high sensitivity search strategy will be employed in Cochrane Library, MEDLINE, EMBASE, Web of Science and product regulatory databases and ongoing trial registers to identify citations. Reference lists of relevant studies and grey literature will also be searched. Screening of the results will be performed by two reviewers independently using pre-defined inclusion and exclusion criteria. Clinical trials and observational studies will be included. Data will be extracted using a purposefully developed extraction form. Appropriateness for statistical pooling of the results will be determined and carried out if heterogeneity is low to moderate. The GRADE framework will be employed to grade the overall quality of the evidence.

Discussion: In the UK, the current access to the use of ECCO2R is possible only with special arrangements for clinical governance, consent and for audit or research. Current evidence on ECCO2R suggests that there are a number of well-recognised complications which vary greatly across studies. This systematic review will consolidate the existing knowledge on adverse effects resulting from the use of ECCO2R.

Systematic Review Registration: PROSPERO CRD42015023503 .
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http://dx.doi.org/10.1186/s13643-016-0270-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897878PMC
June 2016

A review of Psyra Walker, 1860 (Lepidoptera, Geometridae, Ennominae) from China, with description of one new species.

Zootaxa 2013 ;3682:459-74

The genus Psyra Walker, 1860 in China is reviewed. Thirteen species are recognized, of which, P. breviprotrusa sp. nov. is described as new to science, and P. moderata Inoue, 1982, P. gracilis Yazaki, 1992 and P. boarmiata (Graeser, 1892) are recorded for the first time from China. P. cuneata szetschwana Wehrli, 1953 and P. cuneata dsagara Wehrli, 1953 are upgraded to specific level, i.e. P. szetschwana stat. nov. and P. dsagara stat. nov., and a lectotype is designated for P. dsagara. One new synonym is established: P. szetschwana Wehrli, 1953 = P. cuneata lidjangica Wehrli, 1953 syn. nov. The diagnoses for all species are given. Illustrations of external features and genitalia are presented.
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http://dx.doi.org/10.11646/zootaxa.3682.3.7DOI Listing
October 2014

Cost-effectiveness of dasatinib and nilotinib for imatinib-resistant or -intolerant chronic phase chronic myeloid leukemia.

Value Health 2011 Dec 12;14(8):1057-67. Epub 2011 Oct 12.

Peninsular College of Medicine and Dentistry, University of Exeter, Exeter, United Kingdom.

Objectives: To estimate the cost-effectiveness of dasatinib and nilotinib compared with high-dose imatinib for people with chronic phase chronic myeloid leukemia, which are resistant to normal-dose imatinib and compared with interferon-α for people intolerant to imatinib, from the perspective of the UK National Health Service.

Methods: An an area under the curve partitioned survival model was developed to estimate the cost-effectiveness of dasatinib and nilotinib. Clinical effectiveness evidence was taken mostly from single-arm trials.

Results: Both progression-free survival and overall survival are highly uncertain. In the base case, patients take nilotinib for much less time than dasatinib. Nilotinib is expected to dominate high-dose imatinib, yielding slightly more (0.32) quality-adjusted life years (QALYs) at slightly less cost (£11,100 [pound sterling]) per person. Dasatinib is predicted to provide slightly more (0.53) QALYs at substantially greater cost (£48,900), yielding a very high incremental cost-effectiveness ratio of £91,500 QALY against high-dose imatinib. Cost-effectiveness, however, changes radically under the plausible assumption that the drugs are taken for the same time. For people intolerant to imatinib, nilotinib is expected to yield an incremental cost-effectiveness ratio of £104,700/QALY, and dasatinib £82,600/QALY compared with interferon-α. Further, both drugs represent poor value for money for a range of plausible structural assumptions.

Conclusions: The model should be viewed as an exploratory analysis of the cost-effectiveness of dasatinib and nilotinib because it relies on many assumptions. Whilst clinical data remains immature, the cost-effectiveness of dasatinib and nilotinib for imatinib-resistant people is highly uncertain. Both nilotinib and dasatinib are highly unlikely to be cost-effective versus interferon-α for people intolerant to imatinib.
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http://dx.doi.org/10.1016/j.jval.2011.07.006DOI Listing
December 2011

Psychological interventions for coronary heart disease.

Cochrane Database Syst Rev 2011 Aug 10(8):CD002902. Epub 2011 Aug 10.

Centre for Multilevel Modelling, Graduate School of Education, University of Bristol, 2 Priory Road, Bristol, UK, BS8 1TX.

Background: Psychological symptoms are strongly associated with coronary heart disease (CHD), and many psychological treatments are offered following cardiac events or procedures.

Objectives: Update the existing Cochrane review to (1) determine the independent effects of psychological interventions in patients with CHD (principal outcome measures included total or cardiac-related mortality, cardiac morbidity, depression, and anxiety) and (2) explore study-level predictors of the impact of these interventions.

Search Strategy: The original review searched Cochrane Controleed Trials Register (CCTR, Issue 4, 2001), MEDLINE, EMBASE, PsycINFO, and CINAHL to December 2001. This was updated by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, PsycINFO and CINAHL from 2001 to January 2009. In addition, we searched reference lists of papers, and expert advice was sought for the original and update review.

Selection Criteria: Randomised controlled trials of psychological interventions compared to usual care, administered by trained staff. Only studies estimating the independent effect of the psychological component with a minimum follow-up of six months. Adults with specific diagnosis of CHD.

Data Collection And Analysis: Titles and abstracts of all references screened for eligibility by two reviewers independently; data extracted by the lead author and checked by a second reviewer. Authors contacted where possible to obtain missing information.

Main Results: There was no strong evidence that psychological intervention reduced total deaths, risk of revascularisation, or non-fatal infarction. Amongst a smaller group of studies reporting cardiac mortality there was a modest positive effect of psychological intervention (relative risk: 0.80 (95% CI 0.64 to 1.00)). Furthermore, psychological intervention did result in small/moderate improvements in depression, standardised mean difference (SMD): -0.21 (95% CI -0.35, -0.08) and anxiety, SMD: -0.25 (95% CI -0.48 to -0.03). Results for mortality indicated some evidence of small-study bias, though results for other outcomes did not. Meta regression analyses revealed four significant predictors of intervention effects on depression were found: (1) an aim to treat type-A behaviours (ß = -0.32, p = 0.03) were more effective than other interventions. In contrast, interventions which (2) aimed to educate patients about cardiac risk factors (ß = 0.23, p = 0.03), (3) included client-led discussion and emotional support as core therapeutic components (ß = 0.31, p < 0.01), or (4) included family members in the treatment process (ß = 0.26, p < 0.01) were significantly less effective.

Authors' Conclusions: Psychological treatments appear effective in treating psychological symptoms of CHD patients. Uncertainly remains regarding the subgroups of patients who would benefit most from treatment and the characteristics of successful interventions.
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http://dx.doi.org/10.1002/14651858.CD002902.pub3DOI Listing
August 2011

Cost-effectiveness of sorafenib for second-line treatment of advanced renal cell carcinoma.

Value Health 2010 Jan-Feb;13(1):55-60. Epub 2009 Sep 25.

Peninsula Medical School, University of Plymouth, Plymouth, UK.

Objectives: To estimate the cost-effectiveness of sorafenib (Nexavar, Bayer, Leverkusen, Germany) versus best supportive care (BSC) for second-line treatment of advanced renal cell carcinoma from the perspective of the UK National Health Service.

Methods: A decision analytic model was developed to estimate the cost-effectiveness of sorafenib. The clinical effectiveness of sorafenib versus BSC was taken from a recent randomized phase III trial. Utility values were taken from a phase II trial of sunitinib, using EQ-5D tariffs. Cost data were obtained from published literature and were based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses.

Results: Compared to BSC, sorafenib treatment resulted in an incremental cost per quality-adjusted life year (QALY) gained of pound75,398, based on an estimated mean gain of 0.27 QALYs per patient, at a mean additional cost of pound20,063 (inflated to 2007/2008). The probability that sorafenib is cost-effective compared to BSC at a willingness to pay threshold of pound30,000 per QALY is 0.0%. In sensitivity analysis, estimates of cost per QALY were sensitive to changes in the clinical effectiveness parameters, and to health state utilities and drug costs.

Conclusions: Sorafenib has been shown to be clinically effective compared to BSC, offering additional health benefits; however, with a cost per QALY in excess of pound70,000, it may not be regarded as a cost-effective use of resources in some health-care settings.
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http://dx.doi.org/10.1111/j.1524-4733.2009.00616.xDOI Listing
September 2010

Cost-effectiveness of temsirolimus for first line treatment of advanced renal cell carcinoma.

Value Health 2010 Jan-Feb;13(1):61-8. Epub 2009 Sep 25.

Peninsula Medical School, University of Plymouth, Plymouth, UK.

Objectives: To estimate the cost-effectiveness of temsirolimus compared to interferon-alpha for first line treatment of patients with advanced, poor prognosis renal cell carcinoma, from the perspective of the UK National Health Service.

Methods: A decision-analytic model was developed to estimate the cost-effectiveness of temsirolimus. The clinical effectiveness of temsirolimus compared with interferon-alpha and the utility values (using EQ-5D tariffs) were taken from a recent phase III randomized clinical trial. Cost data were obtained from published literature and based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses.

Results: Compared to interferon-alpha, temsirolimus treatment resulted in an incremental cost per QALY gained of pound94,632; based on an estimated mean gain of 0.24 quality-adjusted life years (QALYs) per patient, at a mean additional cost of pound22,331 (inflated to 2007/8). The cost per QALY for patient subgroups ranged from pound74,369 to pound154,752. The probability that temsirolimus is cost-effective compared to interferon-alpha at a willingness to pay threshold of pound30,000 per QALY for all patient groups is expected to be close to zero. The cost per QALY was sensitive to the clinical effectiveness parameters, health state utilities, drug costs and the cost of administration of temsirolimus.

Conclusions: Temsirolimus has been shown to be clinically effective compared to interferon-alpha offering additional health benefits, however, with a cost per QALY in excess of pound90,000, it may not be regarded as a cost-effective use of resources in some health care settings.
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http://dx.doi.org/10.1111/j.1524-4733.2009.00617.xDOI Listing
September 2010

Clinical effectiveness of treatment with hyperbaric oxygen for neonatal hypoxic-ischaemic encephalopathy: systematic review of Chinese literature.

BMJ 2006 Aug 11;333(7564):374. Epub 2006 May 11.

Department of Public Health and Epidemiology, University of Birmingham, Birmingham B15 2TT.

Objectives: To investigate the clinical effectiveness of treatment with hyperbaric oxygen for neonates with hypoxic-ischaemic encephalopathy. This treatment is frequently used in China but much less often in the West.

Data Sources: Western (Cochrane controlled trials register and database of systematic reviews, Medline, Embase, CINAHL, and HealthSTAR) and Chinese (China Hospital Digital Library, Chinese Medical Journal Network) databases and hand search of Chinese journals. No language restrictions.

Review Methods: Randomised or quasi-randomised controlled trials of treatment with hyperbaric oxygen compared with "usual care" in term neonates with hypoxic-ischaemic encephalopathy. Outcomes included mortality and long term neurological sequelae. Standardised forms were used to extract and compare data. Criteria of York Centre for Reviews and Dissemination were used to assess quality. Analysis was mainly qualitative but included meta-analysis.

Results: 20 trials were found, mainly from Chinese sources. The reporting quality of trials was poor by Western (CONSORT) standards. Treatment with hyperbaric oxygen had better outcomes than the comparator in almost all trials. The odds ratios of the meta-analyses were 0.26 (95% confidence interval 0.14 to 0.46) for mortality and 0.41 (0.27 to 0.61) for neurological sequelae.

Conclusion: Treatment with hyperbaric oxygen possibly reduces mortality and neurological sequelae in term neonates with hypoxic-ischaemic encephalopathy. Because of the poor quality of reporting in all trials and the possibility of publication bias, an adequately powered, high quality randomised controlled trial is needed to investigate these findings. The Chinese medical literature may be a rich source of evidence to inform clinical practice and other systematic reviews.
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http://dx.doi.org/10.1136/bmj.38776.731655.2FDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550437PMC
August 2006