Development of Evidence-Based Chinese Medicine Clinical Service Recommendations for Cancer Palliative Care Using Delphi Approach Based on the Evidence to Decision Framework.

Objectives: Existing evidence supports the use of certain Chinese medicine (CM) interventions for symptom management among palliative cancer patients. However, evidence-based service recommendations tailored to the local context are needed for CM planning and implementation. In response, we aimed to establish consensus on CM clinical service recommendations for cancer palliative care among Hong Kong experts. Methods: Seven CM interventions showing statistically significant favorable results in existing systematic reviews (SRs) and overviews of SRs were subjected to a GRADE-ADOLOPMENT-based 2-round Delphi survey. Twelve Hong Kong experts in cancer palliative care, including conventionally trained physicians, CM practitioners, and nurses (n = 4 from each category), were invited to participate. Use of the Evidence to Decision framework within the GRADE-ADOLOPMENT approach enabled experts to consider aspects of problem priority, benefits, harms, equity, acceptability, and feasibility when making CM recommendations in cancer palliative care. Results: Three evidence-based CM interventions reached positive consensus as service recommendations, namely: (1) acupuncture for reducing fatigue among palliative cancer patients; (2) acupressure for reducing fatigue among palliative cancer patients; and (3) moxibustion for reducing nausea and vomiting among patients receiving chemotherapy. Median rating of recommendation ranged from 2.5 to 3.0 (interquartile range = 0.00-1.00) on a 4-point Likert-type scale, and the percentage agreement ranged from 83.4% to 91.7%. Conclusions: The GRADE-ADOLOPMENT approach facilitates a consensus-based process of reaching 3 evidence-based CM recommendations for cancer palliative care. Future studies may develop tailored strategies to implement these recommendations in the Hong Kong health system

Chinese herbal medicine for functional dyspepsia: systematic review of systematic reviews

© The Author(s), 2018. Background: Pharmacotherapy, including prokinetics and proton pump inhibitors for functional dyspepsia (FD) have limited effectiveness, and their safety has been recently questioned. Chinese herbal medicine (CHM) could be considered as an alternative. A systematic review (SR) of SRs was performed to evaluate the potential effectiveness and safety of CHM. Method: We conducted a comprehensive literature search for SRs with meta-analyses in eight international and Chinese databases. Pooled effect estimation from each meta-analysis was extracted. The AMSTAR instrument was used to assess the methodological quality of the included SRs. Results: A total of 14 SRs of mediocre quality assessing various CHMs, alone or in combination with conventional pharmacotherapy, were included. Meta-analyses showed that CHM was more effective than prokinetic agents for the alleviation of global dyspeptic symptoms. Three specific CHM formulae appeared to show superior results in the alleviation of global dyspeptic symptoms, including Si Ni San, modified Xiao Yao San and Xiang Sha Liu Jun Zi decoction. No significant difference in the occurrence of adverse events in using CHM or pharmacotherapy was reported. Conclusion: CHM can be considered as an alternative for the treatment of FD symptoms when prokinetic agents and proton pump inhibitors are contraindicated. Future trial design should focus on measuring changes in individual dyspeptic symptoms and differentiate the effectiveness of different CHM for postprandial distress syndrome and epigastric pain syndrome. A network meta-analysis approach should be used to explore the most promising CHM formula for FD treatment in the future

Granulin-epithelin precursor is an oncofetal protein defining hepatic cancer stem cells

Background and Aims: Increasing evidence has suggested that hepatocellular carcinoma (HCC) might originate from a distinct subpopulation called cancer stem cells (CSCs), which are responsible for the limited efficacy of conventional therapies. We have previously demonstrated that granulin-epithelin precursor (GEP), a pluripotent growth factor, is upregulated in HCC but not in the adjacent non-tumor, and that GEP is a potential therapeutic target for HCC. Here, we characterized its expression pattern and stem cell properties in fetal and cancerous livers. Methods: Protein expression of GEP in fetal and adult livers was examined in human and mouse models by immunohistochemical staining and flow cytometry. Liver cancer cell lines, isolated based on their GEP and/or ATP-dependent binding cassette (ABC) drug transporter ABCB5 expression, were evaluated for hepatic CSC properties in terms of colony formation, chemoresistance and tumorigenicity. Results: We demonstrated that GEP was a hepatic oncofetal protein that expressed in the fetal livers, but not in the normal adult livers. Importantly, GEP+ fetal liver cells co-expressed the embryonic stem (ES) cell-related signaling molecules including β-catenin, Oct4, Nanog, Sox2 and DLK1, and also hepatic CSC-markers CD133, EpCAM and ABCB5. Phenotypic characterization in HCC clinical specimens and cell lines revealed that GEP+ cancer cells co-expressed these stem cell markers similarly as the GEP+ fetal liver cells. Furthermore, GEP was shown to regulate the expression of ES cell-related signaling molecules β-catenin, Oct4, Nanog, and Sox2. Isolated GEP high cancer cells showed enhanced colony formation ability and chemoresistance when compared with the GEP low counterparts. Co-expression of GEP and ABCB5 better defined the CSC populations with enhanced tumorigenic ability in immunocompromised mice. Conclusions: Our findings demonstrate that GEP is a hepatic oncofetal protein regulating ES cell-related signaling molecules. Co-expression of GEP and ABCB5 further enriches a subpopulation with enhanced CSC properties. The current data provide new insight into the therapeutic strategy. © 2011 Cheung et al.published_or_final_versio

Acupuncture and related therapies for treating irritable bowel syndrome: overview of systematic reviews and network meta-analysis

© The Author(s), 2019. Background: An overview of systematic reviews (SRs) and a network meta-analysis (NMA) were conducted to evaluate the comparative effectiveness of acupuncture and related therapies used either alone, or as an add-on to other irritable bowel syndrome (IBS) treatments. Methods: A total of eight international and Chinese databases were searched for SRs of randomized controlled trials (RCTs). The methodological quality of SRs was appraised using the AMSTAR instrument. From the included SRs, data from RCTs were extracted for the random-effect pairwise meta-analyses. An NMA was used to evaluate the comparative effectiveness of different treatment options. The risk of bias among included RCTs was assessed using the Cochrane risk of bias tool. Results: From 15 SRs of mediocre quality, 27 eligible RCTs (n = 2141) were included but none performed proper blinding. Results from pairwise meta-analysis showed that both needle acupuncture and electroacupuncture were superior in improving global IBS symptoms when compared with pinaverium bromide. NMA results showed needle acupuncture plus Geshanxiaoyao formula had the highest probability of being the best option for improving global IBS symptoms among 14 included treatment options, but a slight inconsistency exists. Conclusion: The risk of bias and NMA inconsistency among included trials limited the trustworthiness of the conclusion. Patients who did not respond well to first-line conventional therapies or antidepressants may consider acupuncture as an alternative. Future trials should investigate the potential of (1) acupuncture as an add-on to antidepressants and (2) the combined effect of Chinese herbs and acupuncture, which is the norm of routine Chinese medicine practice

Reduced RET expression in gut tissue of individuals carrying risk alleles of Hirschsprung's disease

Receptor tyrosine kinase (RET) single nucleotide polymorphisms (SNPs) are associated with the Hirschsprung's disease (HSCR). We investigated whether the amount of RET expressed in the ganglionic gut of human was dependent on the genotype of three regulatory SNPs (-5G>A rs10900296 and -1A>C rs10900297 in the promoter, and C>T rs2435357 in intron 1). We examined the effects of three regulatory SNPs on the RET gene expression in 67 human ganglionic gut tissues using quantitative real-time PCR. Also, 315 Chinese HSCR patients and 325 ethnically matched controls were genotyped for the three SNPs by polymerase chain reaction (PCR) and direct sequencing. The expression of RET mRNA in human gut tissue did indeed correlate with the genotypes of the individuals. The lowest RET expression was found for those individuals homozygous for the three risk alleles (A-C-T/A-C-T), and the highest for those homozygous for the 'wild-type' counterpart (G-A-C/G-A-C), with expression values ranging from 218.32±125.69 (mean ± SE) in tissues from individuals carrying G-A-C/G-A-C to 31.42±8.42 for individuals carrying A-C-T/A-C-T (P 5 0.018). As expected, alleles -5A, -1C and intron 1 T were associated with HSCR (P 5 5.94 × 10-31, 3.12 3 10-24 and 5.94 × 10-37, respectively) as was the haplotype encompassing the three associated alleles (A-C-T) when compared with the wild-type counterpart G-A-C (χ2 5 155.29, P « 0.0001). To our knowledge, this is the first RET expression genotype-phenotype correlation study conducted on human subjects to indicate common genetic variants in the regulatory region of RET may play a role in mediating susceptibility to HSCR, by conferring a significant reduction of the RET expression. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

Stage specific requirement of platelet-derived growth factor receptor-α in embryonic development

published_or_final_versio

Role of RET and PHOX2B gene polymorphisms in risk of Hirschsprung's disease in Chinese population [9]

published_or_final_versio

Chinese herbal medicine for symptom management in cancer palliative care systematic review and meta-analysis

© 2016 Wolters Kluwer Health, Inc. All rights reserved. Use of Chinese herbal medicines (CHM) in symptom management for cancer palliative care is very common in Chinese populations but clinical evidence on their effectiveness is yet to be synthesized. To conduct a systematic review with meta-analysis to summarize results from CHM randomized controlled trials (RCTs) focusing on symptoms that are undertreated in conventional cancer palliative care. Five international and 3 Chinese databases were searched. RCTs evaluating CHM, either in combination with conventional treatments or used alone, in managing cancer-related symptoms were considered eligible. Effectiveness was quantified by using weighted mean difference (WMD) using random effect model meta-analysis. Fourteen RCTs were included. Compared with conventional intervention alone, meta-analysis showed that combined CHM and conventional treatment significantly reduced pain (3 studies, pooled WMD:-0.90, 95% CI:-1.69 to-0.11). Six trials comparing CHM with conventional medications demonstrated similar effect in reducing constipation. One RCT showed significant positive effect of CHM plus chemotherapy for managing fatigue, but not in the remaining 3 RCTs. The additional use of CHM to chemotherapy does not improve anorexia when compared to chemotherapy alone, but the result was concluded from 2 small trials only. Adverse events were infrequent and mild. CHM may be considered as an add-on to conventional care in the management of pain in cancer patients. CHM could also be considered as an alternative to conventional care for reducing constipation. Evidence on the use of CHM for treating anorexia and fatigue in cancer patients is uncertain, warranting further research

Acupuncture and related therapies for symptom management in palliative cancer care: Systematic review and meta-analysis

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Available systematic reviews showed uncertainty on the effectiveness of using acupuncture and related therapies for palliative cancer care. The aim of this systematic review and meta-analysis was to summarize current best evidence on acupuncture and related therapies for palliative cancer care. Five international and 3 Chinese databases were searched. Randomized controlled trials (RCTs) comparing acupuncture and related therapies with conventional or sham treatments were considered. Primary outcomes included fatigue, paresthesia and dysesthesias, chronic pain, anorexia, insomnia, limb edema, constipation, and health-related quality of life, of which effective conventional interventions are limited. Thirteen RCTs were included. Compared with conventional interventions, meta-analysis demonstrated that acupuncture and related therapies significantly reduced pain (2 studies, n=175, pooled weighted mean difference: -0.76, 95% confidence interval: -0.14 to -0.39) among patients with liver or gastric cancer. Combined use of acupuncture and related therapies and Chinese herbal medicine improved quality of life in patients with gastrointestinal cancer (2 studies, n=111, pooled standard mean difference: 0.75, 95% confidence interval: 0.36-1.13). Acupressure showed significant efficacy in reducing fatigue in lung cancer patients when compared with sham acupressure. Adverse events for acupuncture and related therapies were infrequent and mild. Acupuncture and related therapies are effective in reducing pain, fatigue, and in improving quality of life when compared with conventional intervention alone among cancer patients. Limitations on current evidence body imply that they should be used as a complement, rather than an alternative, to conventional care. Effectiveness of acupuncture and related therapies for managing anorexia, reducing constipation, paresthesia and dysesthesia, insomnia, and limb edema in cancer patients is uncertain, warranting future RCTs in these areas

Hedgehog/notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans

Hirschsprung (HSCR) disease is a complex genetic disorder attributed to a failure of the enteric neural crest cells (ENCCs) to form ganglia in the hindgut. Hedgehog and Notch are implicated in mediating proliferation and differentiation of ENCCs. Nevertheless, how these signaling molecules may interact to mediate gut colonization by ENCCs and contribute to a primary etiology for HSCR are not known. Here, we report our pathway- based epistasis analysis of data generated by a genome-wide association study on HSCR disease, which indicates that specific genotype constellations of Patched (PTCH1) (which encodes a receptor for Hedgehog) and delta-like 3 (DLL3) (which encodes a receptor for Notch) SNPs confer higher risk to HSCR. Importantly, deletion of Ptch1 in mouse ENCCs induced robust Dll1 expression and activation of the Notch pathway, leading to premature gliogenesis and reduction of ENCC progenitors in mutant bowels. Dll1 integrated Hedgehog and Notch pathways to coordinate neuronal and glial cell differentiation during enteric nervous system development. In addition, Hedgehog-mediated gliogenesis was found to be highly conserved, such that Hedgehog was consistently able to promote gliogenesis of human neural crest-related precursors. Collectively, we defined PTCH1 and DLL3 as HSCR susceptibility genes and suggest that Hedgehog/Notch-induced premature gliogenesis may represent a new disease mechanism for HSCR.published_or_final_versio