To Investigate the Clinical Efficacy and Potential Mechanism of Tongxinluo Capsules in Preventing Coronary Restenosis Based on Meta-Analysis and Network Pharmacology Analysis.

Objective: The aim of this study is to evaluate the clinical efficacy of Tongxinluo capsules in preventing coronary restenosis based on meta-analysis and network pharmacology research methods and to preliminarily explore its intervention mechanism. Methods: First, through meta-analysis, we comprehensively searched databases such as CNKI, Wanfang, PubMed, the Cochrane Library, and Web of Science to find out the randomized controlled trials of Tongxinluo capsules in the treatment of coronary restenosis until February, 2022. According to the Cochrane Library, risk bias assessment tools were used to evaluate the included literature and Review Manager 5.2 software was used to conduct statistical analysis of the included studies. Then, based on network pharmacology, through TCMSP database and BATMAN-TCM database screening, the chemical components of Tongxinluo capsules and their related effects, symptom, and common targets were analyzed. String net was used to construct protein-protein interaction (PPI) network, and R3.6.1 software was used to carry out GO biological process enrichment analysis and KEGG signaling pathway enrichment analysis to clarify key pathways. Results: The meta-analysis finally included 10 RCTs with a total of 1318 subjects. Meta-analysis results showed that Tongxinluo capsules combined with conventional cardiovascular drugs could significantly improve the clinical efficacy of preventing in-stent restenosis and the clinical efficacy of preventing angina pectoris. There was no significant difference in the clinical efficacy of preventing myocardial infarction. Network pharmacology obtained a total of 101 chemical components and 149 targets through the online database. The results of network analysis showed that the targets were mainly involved in receptor ligand activity, carboxylic acid binding, steroid hormone receptor activity, and other related action pathways and were also involved in AGE-RAGE signaling pathway, cell senescence signaling pathway, and other related pathways. Conclusion: Tongxinluo capsules combined with conventional cardiovascular drugs can improve the clinical efficacy of preventing in-stent restenosis and angina pectoris and have a significant effect on reducing inflammatory factors. The comprehensive result of the effect is mainly through the participation of receptor ligand activity, carboxylic acid binding, steroid hormone receptor activity, and other ways to achieve the purpose of treating coronary restenosis.

The role of microRNA-4723-5p regulated by c-myc in triple-negative breast cancer.

The aim of this study was to investigate the expression of miRNA regulated by c-myc and its mechanism in three negative breast cancer (TNBC). We constructed MDA-MB-231 cell line with low expression of c-myc by lentivirus short hairpin RNA (shRNA), analyzed the miRNA expression profile of MDA-MB-231 cell line with different expression levels of c-myc by high-throughput sequencing technology, obtained differential miRNA by bioinformatics analysis and statistical analysis, and verified hsa-mir-4723-5p by Quantitative Real-time polymerase chain reaction(QRT-PCR). The target gene of hsa-mir-4723-5p was analyzed by miRDB and miRWalk database. The results showed that there were significant differences in 126 miRNAs in c-myc knockdown cell lines compared with the control group, of which 84 were significantly up-regulated and 42 were significantly down regulated. According to the results of miRNA sequencing, the miRNA closely related to the expression of c-myc was hsa-mir-4723-5p. QRT PCR showed that the expression of hsa-mir-4723-5p was down regulated in TNBC cell line MDA-MB-231 with low expression of c-myc, which was positively correlated with the expression. The target genes of hsa-mir-4723-5p were predicted according to mirdb and mirwalk database. A total of 112 target genes were obtained, and 107 target genes were related to hsa-mir-4723-5p. Through mirdb and mirwalk databases, it was found that the target gene TRAF4 of hsa-mir-4723-5p may be related to cancer pathway and affect tumor metastasis. In conclusion, the hsa-miR-4723-5p regulated by c-myc may be involved.

Thyroidectomy Using the Lateral Cervical Small Incision Approach for Early Thyroid Cancer.

Objective: Surgical resection is the main treatment for thyroid cancer, but while traditional open thyroidectomy improves prognosis, it also results in poor cosmetic outcomes. Therefore, we devised the lateral cervical small incision approach to thyroidectomy and will evaluate its efficacy. Methods: The clinicopathological data of 191 patients who underwent unilateral thyroidectomy and isthmusectomy for early thyroid cancer were collected retrospectively. Of these, 100 patients underwent a traditional thyroidectomy using the median cervical approach (control group), and 91 patients underwent a thyroidectomy using the lateral cervical small incision approach (experimental group). The differences in perioperative prognosis, postoperative complications, and cosmetic outcomes between the two groups were evaluated. Results: There was no significant difference in sex, age, tumor size, lymph node dissection, number of metastases, or postoperative complications between the experimental group and the control group (P > 0.05). There were significant differences in the duration of the operation; postoperative blood loss, drainage, and hospital stay; and scar color, blood circulation, hardness, and thickness between the groups (P < 0.05). The cosmetic outcomes of the incisions in the experimental group were more satisfactory than in the control group (P < 0.05). Conclusion: When compared with traditional open thyroidectomy, the lateral cervical small incision approach has a lower incidence of complications, a better perioperative prognosis, and an improved cosmetic outcome.

Association between Health-Related Physical Fitness and Risk of Dyslipidemia in University Staff: A Cross-Sectional Study and a ROC Curve Analysis.

BACKGROUND: This study aimed to assess the relationship between dyslipidemia (DL) risk and health-related physical fitness (HPF) and evaluated the prognostic value of HPF for risk of DL. METHODS: A total of 776 university staff members were recruited, of which 407 were females, and 369 males. Blood samples and HPF tests were collected from all participants after 12 h fasting. RESULTS: The prevalence of DL was 41.77% and 51.49% in female and male university staff members, respectively, and there was no significant difference between genders (χ2 = 2.687, p = 0.101). According to the logistic regression analysis, age, male sex, GLU, hypertension, BMI, BF, WHtR, and LAP were significant risk factors for DL (p < 0.05), VCI and, SAR were significant protective factors for DL (p < 0.05), and SMI, GS, and VG were not significantly associated with the risk of DL. The area under the receiver-operating characteristic (ROC) curve (AUC) analysis indicated that, LAP (AUC: 0.730, 95CI%: 0.697-0.762), WHtR (AUC: 0.626, 95CI%: 0.590-0.660), and BMI (AUC: 0.599, 95CI%: 0.563-0.634) are valid predictors of DL, and LAP and WHtR perform better than BMI (Z = 8.074, p < 0.001) in predicting DL in male and female university staff members. CONCLUSION: The risk of DL is significantly related to body composition, cardiorespiratory fitness, and flexibility. LAP and WHtR perform better than BMI in predicting risk of DL in male and female university staff members.

Adipose extracellular matrix promotes skin wound healing by inducing the differentiation of adipose­derived stem cells into fibroblasts.

Fibroblasts are the major effector cells of skin wound healing. Adipose­derived stem cells can differentiate into fibroblasts under certain conditions. In the present study, it was hypothesized that adipose­derived stem cells (ADSCs) could be induced by the adipose extracellular matrix (ECM) to differentiate into fibroblasts in order to promote skin wound healing. First, flow cytometry was used to detect the ratio of fibroblasts and relative expression of the fibroblast markers cytokeratin 19 (CK19) and vimentin in ADSCs. Then, the effect of the adipose ECM during the differentiation of ADSCs into fibroblasts was investigated by detecting the total amount of collagen fibers and degree of fibrosis, and the proliferation and cell cycle of differentiated fibroblasts, using the MTT assay and flow cytometry analysis respectively. Finally, a mouse skin wound model was established and treated with PBS, ADSC suspension or ECM + ADSCs to compare wound healing rate and expression of collagen I and collagen III by immunohistochemistry. Following induction of ADSCs with the adipose ECM, more fibroblasts were found, expression of CK19 and vimentin increased, and a greater degree of fibrosis occurred, which revealed the positive effect of the adipose ECM on the differentiation of ADSCs into fibroblasts. In addition, the induced fibroblasts had enhanced proliferation activity, with more cells in the S phase and fewer in the G2/M phase. The in vivo experiment indicated that the ECM produced by the ADSCs had a faster wound healing rate and increased expression of collagen I and collagen III compared with mice injected with PBS or ADSCs alone, which verified that ADSCs induced by the adipose ECM had a positive effect on skin wound healing. The present study demonstrated that the adipose ECM in combination with ADSCs may be a novel therapeutic target for the repair of skin injury, due to the ability of the adipose ECM to induce the differentiation of ADSCs into fibroblasts and to facilitate the wound healing process.

Long-term survival after partial hepatectomy for sub-stage patients with intermediate stage hepatocellular carcinoma.

BACKGROUND: The current study aimed to examine the long-term survival after partial hepatectomy for patients with BCLC intermediate stage hepatocellular carcinoma (HCC) stratified by the Bolondi's sub-staging model. MATERIALS AND METHODS: This cohort consisted of 360 patients with BCLC intermediate stage HCC who underwent partial hepatectomy between January 2008 and February 2010. Patients were stratified into 3 subgroups (B1-B3) based on the Bolondi's sub-staging model. The last follow-up was conducted at February 2014. RESULTS: Of these patients, 166, 171 and 23 patients had B1, B2, and B3 sub-stage HCC, respectively. The postoperative 5-year Overall survival (OS) rate for patients with these three sub-stages was 49.5%, 33.7% and 12.9%, respectively (P < 0.001). Compared with the reported survival outcomes from previous studies which used transarterial chemoembolization (TACE) as first-line treatment, hepatectomy had a better median survival than TACE in B1 and B2 patients. On multivariable analysis, presence of esophageal and gastric varices, higher NDR score, presence of microvascular invasion, differentiation grade III-IV, and patterns of AFP decreases after surgery were the independent risk factors of OS in the sub-stages B1 and B2 patients. A nomogram which integrated all these independent risk factors was developed, with a C-index of 0.71 for OS prediction. The calibration curve showed an optimal agreement between prediction by the nomogram and actual observation. CONCLUSIONS: The patients with intermediate stage HCC clarified as sub-stages B1 and B2 according to Bolondi's model had an optimal long-term survival following partial hepatectomy than TACE. Their postoperative prognosis could be accurately predicted by our proposed nomogram.

Targeting of AUF1 to vascular endothelial cells as a novel anti-aging therapy.

BACKGROUND: Inhibition of aging of vascular endothelial cells (VECs) may delay aging and prolong life. The goal of this study was to prepare anti-CD31 monoclonal antibody conjugated PEG-modified liposomes containing the AU-rich region connecting factor 1 (AUF1) gene (CD31-PILs-AUF1) and to explore the effects of targeting CD31-PILs-AUF1 to aging VECs. METHODS: The mean particle sizes of various PEGylated immunoliposomes (PILs) were measured using a Zetasizer Nano ZS. Gel retardation assay was used to confirm whether PILs had encapsulated the AUF1 plasmid successfully. Fluorescence microscopy and flow cytometry were used to quantify binding of CD31-PILs-AUF1 to target cells. Flow cytometry was also used to analyze the cell cycles of aging bEnd3 cells treated with CD31-PILs-AUF1. We also developed an aging mouse model by treating mice with D-galactose. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The malondialdehyde (MDA) and the superoxide dismutase (SOD) levels were detected by commercial kits. Hematoxylin-eosin (HE) staining was used to determine whether treatment with CD31-PILs-AUF1 was toxic to the mice. RESULTS: CD31-PILs-AUF1 specifically could targeted bEnd3 VECs and increased the percentage of cells in the S and G2/M phases of aging bEnd3 cells. ELISA showed that content of the IL-6 and TNF-α decreased in CD31-PILs-AUF1 group. The level of SOD increased, whereas MDA decreased in the CD31-PILs-AUF1 group. Additionally, CD31-PILs-AUF1 was not toxic to the mice. CONCLUSION: CD31-PILs-AUF1 targets VECs and may delay their senescence.