CONSORT extension for Traditional Chinese Medicine Formula 2017: recommendations, explanation and elaboration

Chinese herbal medicine (CHM) formulas are the major components of traditional Chinese medicine (TCM) interventions. The general reporting quality of randomized clinical trials (RCTs) of CHM formulas is disappointing although there are CONSORT (Consolidated Standards of Reporting Trials) Statement extensions for herbal medicinal interventions and acupuncture interventions. A group of TCM clinical experts, methodologists, epidemiologists and editors has developed CONSORT–CHM Formulas through a comprehensive process including publication of the CONSORT–CHM Formulas (Draft), solicitation of comments, revision and finalization. The CONSORT 2010 Statement was extended by introducing the idea of TCM Pattern and the features of CHM formulas. One new checklist sub-item, Keywords was added to facilitate the indexation and data searching. Seven of the 25 CONSORT checklist items, namely Title and Abstract, Background and Objectives, Participants, Interventions, Outcomes, Generalizability and Interpretation, are now elaborated upon and the explanation of Harms of CHM formulas is revised. Illustrative examples and explanations are also provided. We hope that CONSORT–CHM Formulas 2017 can improve the reporting quality of RCTs of CHM formulas

FGFR3, HRAS, KRAS, NRAS and PIK3CA Mutations in Bladder Cancer and Their Potential as Biomarkers for Surveillance and Therapy

Background: Fifty percent of patients with muscle-invasive bladder cancer (MI-BC) die from their disease and current chemotherapy treatment only marginally increases survival. Novel therapies targeting receptor tyrosine kinases or activated oncogenes may improve outcome. Hence, it is necessary to stratify patients based on mutations in relevant oncogenes. Patients with non-muscle-invasive bladder cancer (NMI-BC) have excellent survival, however two-thirds develop recurrences. Tumor specific mutations can be used to detect recurrences in urine assays, presenting a more patient-friendly diagnostic procedure than cystoscopy. Methodology/Principal Findings: To address these issues, we developed a mutation assay for the simultaneous detection of 19 possible mutations in the HRAS, KRAS, and NRAS genes. With this assay and mutation assays for the FGFR3 and PIK3CA oncogenes, we screened primary bladder tumors of 257 patients and 184 recurrences from 54 patients. Additionally, in primary tumors p53 expression was obtained by immunohistochemistry. Of primary tumors 64% were mutant for FGFR3, 11% for RAS, 24% for PIK3CA, and 26% for p53. FGFR3 mutations were mutually exclusive with RAS mutations (p = 0.001) and co-occurred with PIK3CA mutations (p = 0.016). P53 overexpression was mutually exclusive with PIK3CA and FGFR3 mutations (p≤0.029). Mutations in the RAS and PIK3CA genes were not predictors for recurrence-free, progression-free and disease-specific survival. In patients presenting with NMI-BC grade 3 and MI-BC, 33 and 36% of the primary tumors were mutant. In patients with low-grade NMI-BC, 88% of the primary tumors carried a mutation and 88% of the recurrences were mutant. Conclusions/Significance: The mutation assays present a companion diagnostic to define patients for targeted therapies. In addition, the assays are a potential biomarker to detect recurrences during surveillance. We showed that 88% of patients presenting with low-grade NMI-BC are eligible for such a follow-up. This may contribute to a reduction in the number of cystoscopical examinations

Elevation of the Yields of Very Long Chain Polyunsaturated Fatty Acids via Minimal Codon Optimization of Two Key Biosynthetic Enzymes

Eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17) and Docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19) are nutritionally beneficial to human health. Transgenic production of EPA and DHA in oilseed crops by transferring genes originating from lower eukaryotes, such as microalgae and fungi, has been attempted in recent years. However, the low yield of EPA and DHA produced in these transgenic crops is a major hurdle for the commercialization of these transgenics. Many factors can negatively affect transgene expression, leading to a low level of converted fatty acid products. Among these the codon bias between the transgene donor and the host crop is one of the major contributing factors. Therefore, we carried out codon optimization of a fatty acid delta-6 desaturase gene PinD6 from the fungus Phytophthora infestans, and a delta-9 elongase gene, IgASE1 from the microalga Isochrysis galbana for expression in Saccharomyces cerevisiae and Arabidopsis respectively. These are the two key genes encoding enzymes for driving the first catalytic steps in the Δ6 desaturation/ Δ6 elongation and the Δ9 elongation/Δ8 desaturation pathways for EPA/DHA biosynthesis. Hence expression levels of these two genes are important in determining the final yield of EPA/DHA. Via PCR-based mutagenesis we optimized the least preferred codons within the first 16 codons at their N-termini, as well as the most biased CGC codons (coding for arginine) within the entire sequences of both genes. An expression study showed that transgenic Arabidopsis plants harbouring the codon-optimized IgASE1 contained 64% more elongated fatty acid products than plants expressing the native IgASE1 sequence, whilst Saccharomyces cerevisiae expressing the codon optimized PinD6 yielded 20 times more desaturated products than yeast expressing wild-type (WT) PinD6. Thus the codon optimization strategy we developed here offers a simple, effective and low-cost alternative to whole gene synthesis for high expression of foreign genes in yeast and Arabidopsis

CONSORT extension for Traditional Chinese Medicine Formula 2017: recommendations, explanation and elaboration

Chinese herbal medicine (CHM) formulas are the major components of traditional Chinese medicine (TCM) interventions. The general reporting quality of randomized clinical trials (RCTs) of CHM formulas is disappointing although there are CONSORT (Consolidated Standards of Reporting Trials) Statement extensions for herbal medicinal interventions and acupuncture interventions. A group of TCM clinical experts, methodologists, epidemiologists and editors has developed CONSORT–CHM Formulas through a comprehensive process including publication of the CONSORT–CHM Formulas (Draft), solicitation of comments, revision and finalization. The CONSORT 2010 Statement was extended by introducing the idea of TCM Pattern and the features of CHM formulas. One new checklist sub-item, Keywords was added to facilitate the indexation and data searching. Seven of the 25 CONSORT checklist items, namely Title and Abstract, Background and Objectives, Participants, Interventions, Outcomes, Generalizability and Interpretation, are now elaborated upon and the explanation of Harms of CHM formulas is revised. Illustrative examples and explanations are also provided. We hope that CONSORT–CHM Formulas 2017 can improve the reporting quality of RCTs of CHM formulas

CONSORT extension for Traditional Chinese Medicine Formula 2017: recommendations, explanation and elaboration

Chinese herbal medicine (CHM) formulas are the major components of traditional Chinese medicine (TCM) interventions. The general reporting quality of randomized clinical trials (RCTs) of CHM formulas is disappointing although there are CONSORT (Consolidated Standards of Reporting Trials) Statement extensions for herbal medicinal interventions and acupuncture interventions. A group of TCM clinical experts, methodologists, epidemiologists and editors has developed CONSORT–CHM Formulas through a comprehensive process including publication of the CONSORT–CHM Formulas (Draft), solicitation of comments, revision and finalization. The CONSORT 2010 Statement was extended by introducing the idea of TCM Pattern and the features of CHM formulas. One new checklist sub-item, Keywords was added to facilitate the indexation and data searching. Seven of the 25 CONSORT checklist items, namely Title and Abstract, Background and Objectives, Participants, Interventions, Outcomes, Generalizability and Interpretation, are now elaborated upon and the explanation of Harms of CHM formulas is revised. Illustrative examples and explanations are also provided. We hope that CONSORT–CHM Formulas 2017 can improve the reporting quality of RCTs of CHM formulas