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Objective. To systematically review whether the Kangai injection (KAI), which is commonly used traditional Chinese medicine, can improve the clinical efficacy of chemotherapy and relieve adverse reactions of chemotherapy in advanced colorectal cancer (CRC) patients. Methods. A comprehensive literature search was performed in three English and three Chinese electronic databases until March 2019. The literature was screened by EndNote X8 and data were analysed by RevMan5 and Stata12.0. Results. This meta-analysis consisted of twenty-eight studies, of which 2310 cases were reported. Among the 2310 cases, 1207 cases were treated with KAI combined with chemotherapy and 1103 cases were treated with chemotherapy alone. The results showed that KAI combined with chemotherapy significantly improved tumor response (Risk Ratio (RR) =1.32; 95% confidence interval (CI): 1.22-1.43; p p p p p p p p = 0.0004); increased immune function (CD3+: MD=6.34; 95% CI: 5.52-7.16; p < 0.00001, CD4+: MD=-5.99; 95% CI: 5.20-6.78; p < 0.00001; and CD4+/CD8+: MD=0.34; 95% CI: 0.14-0.54; p < 0.0009), and prolonged survival time (OR =1.77; 95% CI: 1.25-2.50; p = 0.001). Renal dysfunction caused by chemotherapy was not affected by KAI treatment (Odds Ratio (OR) =0.53; 95%IC: 0.25-1.12; p = 0.10). Conclusion. KAI can increase clinical effectiveness, improve quality of life, alleviate ADRs, and prolong survival time in advanced colorectal (CRC) patients receiving chemotherapy.

Objective. To systematically evaluate the efficacy of Xihuang pill (XHP) in breast cancer patients receiving chemotherapy. Methods. Three English and four Chinese databases were searched. Literature was screened using EndNote X7 and data were analyzed by Review Manager. Results. This review included 13 randomized clinical studies of 1272 patients. The results showed that XHP increased the tumor response [risk ratio (RR) = 2.91; 95% confidence interval (CI): 1.98-4.26] and improved Karnofsky performance score (KPS) for breast cancer patients receiving chemotherapy [RR = 4.96; 95% CI = 2.07-11.86]. In addition, XHP treatment significantly reduced chemotherapy-induced adverse events, including nausea and vomiting [RR = 0.50; 95% CI = 0.33-0.74], WBC reduction [RR = 0.71; 95% CI = 0.47-1.06], platelet reduction [RR = 0.53; 95% CI = 0.19-1.44], hemoglobin reduction [RR = 0.31; 95% CI = 0.19-0.52], and hepatic function damage [RR = 0.63; 95% CI = 0.35-1.11]. Conclusion. XHP combined with chemotherapy in comparison with chemotherapy alone could significantly enhance the tumor response, improve KPS, and alleviate toxicity induced by chemotherapy in breast cancer patients.

Colorectal cancer (CRC) is a commonly occurring tumour with poor prognosis. Autophagy-related long non-coding RNAs (lncRNAs) have received much attention as biomarkers for cancer prognosis and diagnosis. However, few studies have focused on their prognostic predictive value specifically in CRC. This research aimed to construct a robust autophagy-related lncRNA prognostic signature for CRC. Autophagy-related lncRNAs from The Cancer Genome Atlas database were screened using univariate Cox, LASSO, and multivariate Cox regression analyses, and the resulting key lncRNAs were used to establish a prognostic risk score model. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression of several lncRNAs in cancer tissues from CRC patients and in normal tissues adjacent to the cancer tissues. A prognostic signature comprising lncRNAs AC125603.2, LINC00909, AC016876.1, MIR210HG, AC009237.14, and LINC01063 was identified in patients with CRC. A graphical nomogram based on the autophagy-related lncRNA signature was developed to predict CRC patients' 1-, 3-, and 5-year survival. Overall survival in patients with low risk scores was significantly better than in those with high risk scores (P < 0.0001); a similar result was obtained in an internal validation sample. The nomogram was shown to be suitable for clinical use and gave correct predictions. The 1- and 3-year values of the area under the receiver operating characteristic curve were 0.797 and 0.771 in the model sample, and 0.656 and 0.642 in the internal validation sample, respectively. The C-index values for the verification samples and training samples were 0.756 (95% CI = 0.668-0.762) and 0.715 (95% CI = 0.683-0.829), respectively. Gene set enrichment analysis showed that the six autophagy-related lncRNAs were greatly enriched in CRC-related signalling pathways, including p53 and VEGF signalling. The qRT-PCR results showed that the expression of lncRNAs in CRC was higher than that in adjacent tissues, consistent with the expression trends of lncRNAs in the CRC data set. In summary, we established a signature of six autophagy-related lncRNAs that could effectively guide clinical prediction of prognosis in patients with CRC. This lncRNA signature has significant clinical implications for improving the prediction of outcomes and, with further prospective validation, could be used to guide tailored therapy for CRC patients.

Ethnopharmacological relevance Traditional Chinese medicine has been utilized for the treatment of cancer. Jianpi Jiedu decoction (JPJD), a traditional Chinese medicine formula, has been used for the treatment of colorectal cancer for decades. However, the underlying molecular mechanistic basis for the effect of JPJD on colorectal cancer is poorly understood. Aim of the study The aim of this study was to identify the effects of JPJD on human colon cancer cells in vitro as well as in vivo and to investigate the mechanistic basis for the anticancer effect of JPJD. Materials and methods The in vitro antitumor activity of JPJD was assessed by MTT assay, flow cytometric analysis, wound-healing assay, transwell assays, and tube formation assays in order to assess cell activity, apoptosis, migration, invasion, and angiogenesis, respectively. The anticancer properties of JPJD in vivo were assessed by immunohistochemistry in a nude mouse xenograft model of HCT116 cells. In addition, the level of mTOR/HIF-1α/VEGF signaling pathway proteins in HCT116 cells and tumor tissue was evaluated by immunoblotting. Results In vitro, JPJD significantly inhibited colorectal cancer cell lines viability and proliferation. Flow cytometry analysis demonstrated JPJD to induce HCT116 cell apoptosis. Additionally, JPJD effectively suppressed tumor cell migration, invasion, and angiogenesis by inhibiting the mTOR/HIF-1α/VEGF signaling pathway. In vivo, JPJD significantly inhibited HCT116 tumor growth in athymic nude mice, decreased the levels of CD34 as well as VEGF, and downregulated the mTOR/HIF-1α/VEGF pathway. Conclusions JPJD treatment produced anti-colorectal tumor effects by inhibiting tumorigenesis, metastasis, as well as angiogenesis through the mTOR/HIF-1α/VEGF pathway. Thus, these results provide a strong rationale for the therapeutic use of JPJD in cancer treatment. Further studies are required to investigate the mechanisms underlying anti-CRC effect of JPJD.

Objective. To systematically review the effect of invigorating Pi and detoxification (Jianpi Jiedu, (JPJD)) herbs in advanced colorectal cancer (CRC) patients receiving chemotherapy. Methods. Three English and four Chinese databases were searched. Literature was screened by EndNote X7 and data were analyzed by RevMan 5.2. Results. This review comprised 12 randomized clinical studies of 701 patients. The results showed that JPJD herbs improved the therapeutic effect on Chinese medicine symptoms [risk ratio (RR) = 1.59; 95% confidence interval (CI): 1.35~1.88] and Karnofsky performance score [RR = 2.07; 95% CI: 1.52~2.82] for advanced CRC patients receiving chemotherapy, lowered the Chinese medicine symptoms’ score [weighted mean difference = −2.44; 95% CI: −3.23~−1.64], reduced the incidence of nausea and vomiting [RR = 0.23; 95% CI: 0.11~0.49], improved platelet at toxicity grades III-IV [odds ratio = 0.29; 95% CI: 0.12~0.74] and I–IV [RR = 0.65; 95% CI: 0.51~0.82], and improved white blood cell at toxicity grades III-IV [RR = 0.37; 95% CI: 0.23~0.58] and I–IV [RR = 0.69; 95% CI: 0.60~0.79]. However, the results showed no significant effect on tumor response. Conclusion. JPJD herbs can improve quality of life, relieve symptoms, and reduce adverse events of advanced CRC patients receiving chemotherapy.

Several studies have previously reported that endothelial cells contributed to pathological fibrosis in proliferative diabetic retinopathy (PDR) through endothelial-mesenchymal transition (EndMT); however, the precise mechanism of this interaction has not been completely elucidated. The present study investigated the expression of microRNA (miR)-29a/b cluster in human retinal microvascular endothelial cells (HRMECs) and examined its functional role in high glucose (HG)-induced EndMT. HRMECs were exposed to glucose at concentrations of 5, 15, 30 and 50 mM for 7 days and reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were conducted to determine the expression of genes associated with miR-29a/b and EndMT. A luciferase reporter gene assay was also performed to confirm the association between miR-29a/b and neurogenic locus notch homolog protein 2 (Notch2). The expression levels of miR-29a/b, and endothelial markers vascular endothelial cadherin and cluster of differentiation 31 were decreased, whereas the expression levels of Notch2 and mesenchymal markers, including α-smooth muscle actin, fibroblast-specific protein 1 (also named S100 calcium binding protein A4, S100A4), fibronectin and SNAI1 were increased in HRMECs under HG (30 nM) conditions. In addition, Notch2 was identified as a target of miR-29a and miR-29b. Overexpression of miR-29a/b downregulated the expression of Notch2 and subsequently suppressed HG-induced EndMT. Taken together, the results of the present study revealed that the miR-29/Notch2 signaling pathway may participate in the regulation of HG-induced EndMT, and may serve as a potential molecular target during fibrosis in PDR.

Objective: To validate a visual ability instrument for school-aged children with visual impairment in China by translating, culturally adopting and Rasch scaling the Cardiff Visual Ability Questionnaire for Children (CVAQC). Methods: The 25-item CVAQC was translated into Mandarin using a standard protocol. The translated version (CVAQC-CN) was subjected to cognitive testing to ensure a proper cultural adaptation of its content. Then, the CVAQC-CN was interviewer-administered to 114 school-aged children and young people with visual impairment. Rasch analysis was carried out to assess its psychometric properties. The correlation between the CVAQC-CN visual ability scores and clinical measure of vision (visual acuity; VA and contrast sensitivity, CS) were assessed using Spearman's r. Results: Based on cultural adaptation exercise, cognitive testing, missing data and Rasch metrics-based iterative item removal, three items were removed from the original 25. The 22-item CVAQC-CN demonstrated excellent measurement precision (person separation index, 3.08), content validity (item separation, 10.09) and item reliability (0.99). Moreover, the CVAQC-CN was unidimensional and had no item bias. The person–item map indicated good targeting of item difficulty to person ability. The CVAQC-CN had moderate correlations between CS (−0.53, p

(-)-Epigallocatechin-3-gallate (EGCG) is the main bioactive component in tea (Camellia sinensis) catechins, and exhibits potential antitumor activity against colorectal cancer (CRC). However, the underlying mechanisms are largely unclear. We investigated the effects of EGCG on activities of CRC cells and the exact molecular mechanism. We used human colon cancer cells (HT-29) and exposed them to EGCG at various concentrations. The MTT assay, flow cytometry, and TUNEL staining were used to study the underlying mechanisms of EGCG (proliferation, apoptosis, autophagy). Western blotting was used to measure expression of marker proteins of the cell cycle, apoptosis, and autophagy. Using a combined microarray-based transcriptomic and ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomic approach, we investigated the perturbed pathways induced by EGCG treatment at transcript and metabolite levels. Transcriptomic analyses showed that 486 genes were differentially expressed between untreated and EGCG-treated cells. Also, 88 differentially expressed metabolites were identified between untreated and EGCG-treated cells. The altered metabolites were involved in the metabolism of glutathione, glycerophospholipids, starch, sucrose, amino sugars, and nucleotide sugars. There was substantial agreement between the results of transcriptomics and metabolomics analyses. Our data indicate that the anticancer activity of EGCG against HT-29 cells is mediated by induction of cell-cycle arrest, apoptosis, and autophagy. EGCG modulates cancer-cell metabolic pathways. These results provide a platform for future molecular mechanistic studies of EGCG.

BACKGROUND Zuojinwan (ZJW) is a traditional Chinese prescription normally used for gastritis. Several studies indicated that it could fight against gastric cancer. This study was designed to determine the potential pharmacological mechanism of ZJW in the treatment of gastric cancer. MATERIAL AND METHODS Bioactive compounds and potential targets of ZJW and related genes of gastric cancer were retrieved from public databases. Pharmacological mechanisms including crucial ingredients, potential targets, and signaling pathways were determined using protein-protein interaction (PPI) and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Virtual docking was performed to validate the findings. RESULTS Network analysis identified 47 active ZJW compounds, and 48 potential ZJW target genes linked to gastric cancer. Quercetin, beta-sitosterol, isorhamnetin, wogonin, and baicalein were identified as potential candidate agents. Our PPI analysis results combined with previously published results indicated that matrix metalloproteinases family members MMP9, MMP1, and MMP3 may play key roles in the anti-gastric cancer effect of ZJW. Molecular docking analysis showed that these crucial targets had good affinity for the representative components in ZJW. GO and KEGG enrichment analysis showed that ZJW target genes functioned in multiple pathways for treating gastric cancer, including interleukin-17 signaling and platinum drug resistance. CONCLUSIONS Our results illuminate the active ingredients, associated targets, biological processes, and signaling pathways of ZJW in the treatment of gastric cancer. This study enhances our understanding of the potential effects of ZJW in gastric cancer and demonstrates a feasible method for discovering potential drugs from Chinese medicinal formulas.

PURPOSE: To assess psychometric properties of the Hong Kong Quality of Life Questionnaire (HKQ) using Rasch analysis and use it to assess cataract surgery outcomes. METHODS: The HKQ was interviewer administered to participants at baseline (preoperative) and 12 months of follow-up (postoperative). Rasch analysis was used to assess and improve psychometric properties of the HKQ using the preoperative data. The responsiveness of the HKQ was assessed on the stacked preoperative and postoperative data, reported with the effect size. RESULTS: One hundred ninety-nine participants (median age: 72 years; interquartile range: 65 to 78 years) with cataract completed the HKQ at the preoperative assessment. There were more women (58%) and most of the participants had bilateral cataract (83.9%). Nearly half of the participants had undergone surgery in one eye (45.2%) followed by bilateral surgery (38.7%). Psychometric assessment guided by Rasch analysis resulted into a 15-item HKQ with promising psychometric properties including adequate measurement precision (2.09), no misfitting items, near perfect targeting (−0.05), unidimensionality, and with no evidence of item bias. For those who completed the HKQ (n = 82, 41.2%) at the 12-month follow-up visit, all groups demonstrated statistically significant gains in the HKQ scores, with the highest gain in participants who had undergone bilateral surgery (effect size: 2.61). CONCLUSIONS: The 15-item HKQ was valid and psychometrically sound and might be a highly responsive instrument to measure cataract surgery outcomes in China. This study demonstrated that cataract surgery significantly improves quality of life in the Chinese population. [ J Refract Surg. 2018;34(6):413–418.]

Muller cells-derived proinflammatory cytokines exert important roles in the development of DR, while the molecular mechanisms of its release were not fully elucidated. Present study aims to investigate the mechanism underlying the regulation of c-myc on the release of Muller Cells-derived proinflammatory cytokines. Streptozotocin was utilized to induce diabetes mellitus (DM) rat and glucose was used to stimulate Muller cells. The interaction between c-myc, lncRNA MIAT and TXNIP was determined by the luciferase reporter, CHIP, RNA pull-down, RIP and ubiquitylation assays. Increased c-myc protein level and concentrations of IL-1β, TNF-α and IL-6 were found in DM rats and high glucose stimulated Muller cells. After glucose stimulation, c-myc promoted the releases of IL-1β, TNF-α and IL-6. The up-regulation of MIAT under glucose treatment was mediated by c-myc binding to its promoter. MIAT interacted with TXNIP and increased TXNIP protein level by inhibiting its ubiquitination degradation. C-myc regulated TXNIP expression through MIAT in glucose induced Muller cells. Under glucose treatment, c-myc facilitated the release of Muller cells-derived IL-1β, TNF-α and IL-6 by regulating MIAT/TXNIP pathway. The in vivo study further indicated that c-myc knockdown attenuated DR progression in vivo. Our results suggested a mechanism by which c-myc facilitates the release of Muller Cells-derived proinflammatory cytokines by regulating MIAT/TXNIP pathway.

Purpose: to assess cataract surgery outcome using the Rasch scaled Chinese version of the Catquest short-form. Methods: the Chinese translated and culturally adapted version of the Catquest-9SF was interviewer-administered to patients, pre and post cataract surgery. Rasch analysis was performed on the baseline data to revise the Catquest. For the surgical outcome assessment, we stacked pre- and post-surgical Catquest data to demonstrate improvement in visual function scores and responsiveness of the instrument to cataract surgery. Results: a total of 247 cataract patients (median age, 70 yrs; male 51.0%) completed the Catquest 9SF at baseline.The Catquest-9SF possessed adequate measurement precision of 2.15. No disordering of response categories were observed and all the items perfectly fit to the Rasch model except item 7 (outfit >1.5). A slight reduction in precision was observed after removing misfitting item 7 (Catquest-8SF-CN), but the precision value was well above the acceptable value of 2.00. Notably, the instrument was well targeted (mean person location 0.30), demonstrated no evidence of multidimensionality and DIF. At 12 months post-surgery, 74 (30%) patients came for follow-up and completed the Catquest. There was a significant improvement in the Catquest scores post cataract surgery with a considerably large effect size. Conclusion: the Catquest-8SF-CN demonstrated promising Rasch based psychometric properties and was highly responsive to cataract surgery. Refereed/Peer-reviewed

// Salman B. Hosain 1 , Sachin K. Khiste 1 , Mohammad B. Uddin 1 , Vindya Vorubindi 1 , Catherine Ingram 1 , Sifang Zhang 2 , Ronald A. Hill 1 , Xin Gu 3 , Yong-Yu Liu 1 1 Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe, Monroe, LA 71201, USA 2 Department of Integrated Chinese and Western Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China 3 Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA Correspondence to: Yong-Yu Liu, email: yliu@ulm.edu Keywords: tumor suppressor p53, epithelial-mesenchymal transition, cancer stem cells, glucosylceramide synthase, missense mutation Received: December 10, 2015 Accepted: July 26, 2016 Published: August 10, 2016 ABSTRACT Missense mutation of tumor suppressor p53, which exhibits oncogenic gain-of-function (GOF), not only promotes tumor progression, but also diminishes therapeutic efficacies of cancer treatments. However, it remains unclear how a p53 missense mutant contributes to induced pluripotency of cancer stem cells (CSCs) in tumors exposed to chemotherapeutic agents. More importantly, it may be possible to abrogate the GOF by restoring wild-type p53 activity, thereby overcoming the deleterious effects resulting from heterotetramer formation, which often compromises the efficacies of current approaches being used to reactivate p53 function. Herewith, we report that p53 R273H missense mutant urges cancer cells to spawn CSCs. SW48/TP53 cells, which heterozygously carry the p53 R273H hot-spot mutant (R273H/ + , introduced by a CRISPR/Casp9 system), were subchronically exposed to doxorubicin in cell culture and in tumor-bearing mice. We found that p53-R273H (TP53-Dox) cells were drug-resistant and exhibited epithelial-mesenchymal transition (EMT) and increased numbers of CSCs (CD44v6 + /CD133 + ), which resulted in enhanced wound healing and tumor formation. Inhibition of glucosylceramide synthase with d-threo -1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) sensitized p53-R273H cancer cells and tumor xenografts to doxorubicin treatments. Intriguingly, PDMP treatments restored wild-type p53 expression in heterozygous R273H mutant cells and in tumors, decreasing CSCs and sensitizing cells and tumors to treatments. This study demonstrated that p53-R273H promotes EMT and induced pluripotency of CSCs in cancer cells exposed to doxorubicin, mainly through Zeb1 and β-catenin transcription factors. Our results further indicate that restoration of p53 through inhibition of ceramide glycosylation might be an effective treatment approach for targeting cancers heterozygously harboring TP53 missense mutations.