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Background Coronary microvascular disease (CMVD) is currently a research hotspot in the field of cardiovascular disease, traditional Chinese medicine (TCM) has unique advantages and significant efficacy in the treatment of CMVD, but there are problems in relevant clinical trials, such as inconsistencies in the diagnostic and efficacy criteria, exploring the core outcome set of TCM in the treatment of CMVD is conducive to the development of high-quality evidence in the future. Objective To analyze the application of outcomes measures in randomized controlled trials (RCTs) of CMVD treated with TCM, and propose corresponding questions and recommendations. Methods CNKI, SinoMed, VIP, Wanfang, PubMed, Embase and Cochrane Library were systematically searched for RCTs of CMVD treated with TCM from inception to February 09, 2023. The basic information, interventions and outcome measures in RCTs of CMVD treated with TCM were extracted, the Cochrane systematic review manual bias risk assessment tool was used to evaluate the bias risk of the included literature and the Excel software was used to statistically analyze the outcome measures. Results A total of 88 articles were included, involving 2 clinical trial registration protocols and 1 English literature. Cochrane systematic review manual bias risk assessment showed that the included literature were evaluated as unclear in terms of random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessors, and other bias; mostly low risk in terms of outcome data completeness and selective reporting. A total of 18 RCTs were analyzed for TCM syndromes of patients diagnosed with CMVD, involving 6 RCTs related to blood stasis due to qi deficiency, 3 RCTs related to intermingled phlegm and blood stasis. A total of 115 outcome measures were obtained by statistical analysis, the total frequency was 571 times, which can be divided into 7 categories, including clinical efficacy, physicochemical testing, signs and symptoms, TCM syndrome points, quality of life, long-term prognosis, and safety testing. The frequency of total clinical efficacy rate was the highest (46 times), 3 months was the most commonly used intervention node. and the highest frequency of composite outcome measures was the clinical efficacy combined with physicochemical testing. Conclusion It was found that the overall quality of RCTs of TCM in the treatment of CMVD was generally low, and there are some problems in the outcome measures, such as the lack of standardized TCM syndrome diagnosis criteria and efficacy criteria, and the lack of long-term prognosis monitoring. In the future, it is also necessary to conduct high-quality RCTs, combined with the characteristics of TCM treatment, to construct a standardized core outcome set of TCM in the treatment of CMVD.

The intestine is the principal digestive organ which is generally divided into three segments as the proximal intestine (PI), the mid intestine (MI), and the distal intestine (DI) in fish. In this study, the role of dietary vitamin D3 (VD3) in regulating the function and health of different intestinal segments was evaluated in grass carp (Ctenopharyngodon idella) fingerlings through the supplementation with the increasing levels of dietary VD3 (0, 500, 1000, 1500, 2000, and 2500 IU/kg). The results showed that VD3 supplementation (1000–2000 IU/kg) significantly enhanced the fish growth performance, and the correlation analysis suggested that this effect was positively correlated with intestinal somatic index (ISI) and intestinal length index (ILI) of MI and DI except PI. In support of this finding, dietary VD3 enhanced the activities of digestive and brush border enzymes in the fish mainly in MI and DI rather than PI. Furthermore, the intestinal microbiota analysis revealed that VD3 increased the abundance of intestinal flora at the genus level rather than the phylum level. Meanwhile, hematoxylin and eosin staining presented that VD3 supplementation reduced epithelial goblet cell hyperplasia and lamina propria edema compared with the VD3 deficiency group in the MI and DI. Further studies showed that feeding VD3 decreased malondialdehyde levels but increased total antioxidant capacity, glutathione levels, and total superoxidase activity in MI or DI but not PI, suggesting the antioxidant potential of VD3 in two intestinal segments. Moreover, in MI and DI but not PI, dietary VD3 suppressed pro-inflammatory cytokine (il1 β and tnf α ) but enhanced antimicrobial peptide (hepcidin and βdefensin) mRNA levels and increased the activities of immune-related enzymes (lysozyme and acid phosphatase), highlighting the ability to improve fish immunity. Corresponding to these effects, dietary VD3 was able to mediate NF-E2-related factor 2 (Nrf2) and NF-κB pathways in MI and DI. Finally, quadratic regression models based on weight gain (PWG), feed efficiency (PE), ISI, and ILI suggested that the appropriate VD3 requirements for grass carp fingerlings were 1233.70–1387.11 IU/kg. Taken together, our findings strengthened the potential of dietary VD3 in managing the functions and health of particular intestinal segments and provided valuable reference data for VD3 requirements of fingerling fish. [ABSTRACT FROM AUTHOR]

AIM: Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury (MIRI). METHODS: Firstly, the rat MIRI related dataset GSE122020, E-MEXP-2098, and E-GE0D-4105 were downloaded from the database. Secondly, differentially expressed genes (DEGs) were screened from each dataset using the linear models for microarray data (limma) package, and robust DEGs were filtered using the robust rank aggregation (RRA) method. In addition, the surrogate variable analysis (SVA) package was used to merge all datas-ets into one, and merged DEGs were screened using the limma package. The common DEGs were obtained by taking the intersection of the two channels of DEGs. Next, the protein-protein interaction (PPI) network of common DEGs was constructed, and the hub genes were identified using the density-maximizing neighborhood component (DMNC) algorithm. The receiver operating characteristic curve (ROC) was plotted to evaluate the diagnostic performance of the hub gene. Then, the mRNA and protein expression levels of hub genes were detected in the rat MIRI model, and the literature review analysis was carried out on the involvement of hub genes in MIRI. Finally, the gene set enrichment analysis (GSEA) was performed on hub gene to further reveal the possible mechanism in mediating MIRI. RESULTS: A total of 143 robust DEGs and 48 merged DEGs were identified. After taking the intersection of the two, 48 common DEGs were obtained. In the PPI network of common DEGs, 5 hub genes were screened out, namely MYC proto-oncogene bHLH transcription factor (MYC), prostaglandin-endoperoxide synthase 2 (PTGS2), heme oxygenase 1 (HMOX1), caspase-3 (CASP3), and plasminogen activator urokinase receptor (PLAUR). The ROC results showed that the area under the curve values for all hub genes were greater than 0. 8. MYC, PTGS2, CASP3, and PLAUR showed high mRNA and protein expression in rat MIRI, while there was no difference in mRNA and protein expression for HMOX1. The literature review revealed that among the 5 hub genes, only PLAUR has not been reported to be involved in MIRI. The GSEA results for PLAUR indicated that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway, P53 signaling pathway, Toll-like receptor signaling pathway, apoptosis, and fatty acid metabolism. CONCLUSION: MYC, PTGS2, CASP3, HMOX1, and PLAUR are involved in the pathological process of MIRI. PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling, P53 signaling, Toll like receptor signaling, cell apoptosis, and fatty acid metabolism. The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI. [ABSTRACT FROM AUTHOR]