ObjectiveTo investigate the effect of protein arginine methyltransferase 5 （PRMT5） on the angiogenesis of colorectal cancer （CRC） through the Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway. MethodsThe expression and prognostic value of PRMT5 in CRC tissues were analyzed based on the cancer genome atlas （TCGA） and gene expression omnibus （GEO） databases. A total of 105 pairs of cancer tissues and matched adjacent non-tumor tissues were collected from CRC patients， and PRMT5 expression was detected by immunohistochemistry （IHC）； Western blot was used to detect the PRMT5 protein level in normal colonic epithelial cells （FHC） and CRC cell lines （including RKO， SW480）. SW48 and LoVo cells were divided into negative control （NC） group and PRMT5 knockdown interference group. After the stable knockdown cell models were successfully constructed， the effects of conditioned medium on the proliferation， cell cycle， migration and tube formation abilities of human umbilical vein endothelial cells （HUVECs） were detected； the correlation between PRMT5 and vascular endothelial growth factor A （VEGFA） was analyzed by real-time quantitative polymerase chain reaction （RT-qPCR） and enzyme-linked immunosorbent assay （ELISA）. Gene set enrichment analysis （GSEA） and cytoplasm-nucleus separation assay were performed to verify the regulatory pathway. ResultsPRMT5 was highly expressed in CRC tissues and cell lines， which was significantly correlated with poor prognosis and pathological characteristics of patients （all P<0.05）； PRMT5 knockdown could significantly inhibit the angiogenesis-related abilities of HUVECs （all P<0.05） and down-regulate the expression of VEGFA （all P<0.01）. GSEA results indicated that PRMT5 expression was significantly associated with the activation of JAK2/STAT3 signaling pathway （all P<0.001）. PRMT5 knockdown could inhibit the activation of JAK2/STAT3， the nuclear translocation of STAT3 and the protein level of phosphorylated STAT3 （p-STAT3） in the nucleus， thus inhibiting the expression of VEGFA. ConclusionPRMT5 is highly expressed in CRC tissues and indicates poor prognosis of patients. It promotes the nuclear translocation and transcriptional activity of STAT3 by activating the JAK2/STAT3 pathway and drives the expression of VEGFA to promote tumor angiogenesis.

The effect of Huanglian Jiedu Decoction on the intestinal flora of type 2 diabetes mellitus(T2DM) was investigated using 16S rRNA sequencing technology. Sixty rats were randomly divided into a normal group(10 rats) and a modeling group(50 rats). After one week of adaptive feeding, a high-fat diet + streptozotocin was given for modeling, and fasting blood glucose >16.7 mmol·L~(-1) was considered a sign of successful modeling. The modeling group was randomly divided into the model group, high-, medium-, and low-dose groups of Huanglian Jiedu Decoction, and metformin group. After seven days of intragastric treatment, the feces, colon, and pancreatic tissue of each group of rats were collected, and the pathological changes of the colon and pancreatic tissue of each group were observed by hematoxylin-eosin staining. The changes in the intestinal flora structure of each group were observed by the 16S rRNA sequencing method. The results showed that compared with the model group, the high-, medium-, and low-dose of Huanglian Jiedu Decoction reduced fasting blood glucose levels to different degrees and showed no significant changes in body weight. The number of islet cells increased, and intestinal mucosal damage attenuated. Alpha diversity analysis revealed that Huanglian Jiedu Decoction reduced the abundance and diversity of intestinal flora in rats with T2DM; at the phylum level, low-and mediam-dose of Huanglian Jiedu Decoction reduced the abundance of Bacteroidota, Proteobacteria, and Desulfobacterota and increased the abundance of Firmicute and Bacteroidota/Firmicutes, while the high-dose of Huanglian Jiedu Decoction increased the relative abundance of Proteobacteria and Bacteroidota/Firmicutes ratio, and decreaseal the relative; abundance of Firmicute; at the genus level, Huanglian Jiedu Decoction increased the relative abundance of Allobaculum, Blautia, and Lactobacillus; LEfse analysis revealed that the biomarker of low-and medium-dose groups of Huanglian Jiedu Decoction was Lactobacillus, and the structure of the intestinal flora of the low-dose group of Huanglian Jiedu Decoction was highly similar to that of the metformin group. PICRUSt2 function prediction revealed that Huanglian Jiedu Decoction mainly affected carbohydrate and amino acid metabolic pathways. It suggested that Huanglian Jiedu Decoction could reduce fasting blood glucose and increase the number of islet cells in rats with T2DM, and its mechanism of action may be related to increasing the abundance of short-chain fatty acid-producing strains and Lactobacillus and affecting carbohydrate and amino acid metabolic pathways.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Bacteria/drug effects* ; Blood Glucose/metabolism*

This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Apoptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Animals ; Rats ; Humans ; Molecular Docking Simulation ; Aging/metabolism* ; Protein Interaction Maps/drug effects* ; Heart/drug effects* ; Network Pharmacology

This study explores the role and underlying molecular mechanisms of fucoidan sulfate(FPS) in regulating heme oxygenase-1(Hmox1)-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy(DCM) through in vivo and in vitro experiments and network pharmacology analysis. In vivo, a DCM rat model was established using a combination of "high-fat diet feeding + two low-dose streptozotocin(STZ) intraperitoneal injections". The rats were randomly divided into four groups: normal, model, FPS, and dapagliflozin(Dapa) groups. In vitro, a cellular model was created by inducing rat cardiomyocytes(H9c2 cells) with high glucose(HG), using zinc protoporphyrin(ZnPP), an Hmox1 inhibitor, as the positive control. An automatic biochemical analyzer was used to measure blood glucose(BG), serum aspartate aminotransferase(AST), serum lactate dehydrogenase(LDH), and serum creatine kinase-MB(CK-MB) levels. Echocardiography was used to assess rat cardiac function, including ejection fraction(EF) and fractional shortening(FS). Pathological staining was performed to observe myocardial morphology and fibrotic characteristics. DCFH-DA fluorescence probe was used to detect reactive oxygen species(ROS) levels in myocardial tissue. Specific assay kits were used to measure serum brain natriuretic peptide(BNP), myocardial Fe~(2+), and malondialdehyde(MDA) levels. Western blot(WB) was used to detect the expression levels of myosin heavy chain 7B(MYH7B), natriuretic peptide A(NPPA), collagens type Ⅰ(Col-Ⅰ), α-smooth muscle actin(α-SMA), ferritin heavy chain 1(FTH1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), 4-hydroxy-2-nonenal(4-HNE), and Hmox1. Immunohistochemistry(IHC) was used to examine Hmox1 protein expression patterns. FerroOrange and Highly Sensitive DCFH-DA fluorescence probes were used to detect intracellular Fe~(2+) and ROS levels. Transmission electron microscopy was used to observe changes in mitochondrial morphology. In network pharmacology, FPS targets were identified through the PubChem database and PharmMapper platform. DCM-related targets were integrated from OMIM, GeneCards, and DisGeNET databases, while ferroptosis-related targets were obtained from the FerrDb database. A protein-protein interaction(PPI) network was constructed for the intersection of these targets using STRING 11.0, and core targets were screened with Cytoscape 3.9.0. Molecular docking analysis was conducted using AutoDock and PyMOL 2.5. In vivo results showed that FPS significantly reduced AST, LDH, CK-MB, and BNP levels in DCM model rats, improved cardiac function, decreased the expression of myocardial injury proteins(MYH7B, NPPA, Col-Ⅰ, and α-SMA), alleviated myocardial hypertrophy and fibrosis, and reduced Fe~(2+), ROS, and MDA levels in myocardial tissue. Furthermore, FPS regulated the expression of ferroptosis-related markers(Hmox1, FTH1, SLC7A11, GPX4, and 4-HNE) to varying degrees. Network pharmacology results revealed 313 potential targets for FPS, 1 125 targets for DCM, and 14 common targets among FPS, DCM, and FerrDb. Hmox1 was identified as a key target, with FPS showing high docking activity with Hmox1. In vitro results demonstrated that FPS restored the expression levels of ferroptosis-related proteins, reduced intracellular Fe~(2+) and ROS levels, and alleviated mitochondrial structural damage in cardiomyocytes. In conclusion, FPS improves myocardial injury in DCM, with its underlying mechanism potentially involving the regulation of Hmox1 to inhibit ferroptosis. This study provides pharmacological evidence supporting the therapeutic potential of FPS for DCM-induced myocardial injury.
Animals ; Ferroptosis/drug effects* ; Rats ; Diabetic Cardiomyopathies/physiopathology* ; Male ; Rats, Sprague-Dawley ; Polysaccharides/pharmacology* ; Heme Oxygenase-1/genetics* ; Myocytes, Cardiac/metabolism* ; Myocardium/pathology* ; Humans ; Cell Line ; Heme Oxygenase (Decyclizing)

Traditional Chinese medicine(TCM) decoction pieces are a core carrier for the inheritance and innovation of TCM, and their quality and safety are critical to public health and the sustainable development of the industry. Conventional quality control models, while having established a well-developed system through long-term practice, still face challenges such as relatively long inspection cycles, insufficient objectivity in characterizing complex traits, and urgent needs for improving the efficiency of integrating multidimensional quality information when confronted with the dual demands of large-scale production and precision quality control. With the rapid development of artificial intelligence, machine learning can deeply analyze multidimensional data of the morphology, spectroscopy, and chemical fingerprints of decoction pieces by constructing high-dimensional feature space analysis models, significantly improving the standardization level and decision-making efficiency of quality evaluation. This article reviews the research progress in the application of machine learning in the processing, production, and rapid quality evaluation of TCM decoction pieces. It further analyzes current challenges in technological implementation and proposes potential solutions, offering theoretical and technical references to advance the digital and intelligent transformation of the industry.
Machine Learning ; Drugs, Chinese Herbal/standards* ; Quality Control ; Medicine, Chinese Traditional/standards* ; Humans

Objective To study the tongue manifestation of patients with different syndromes in non-small cell lung cancer(NSCLC)and the correlation between tongue characteristics of different syndromes and tumor markers and coagulation indicators.Methods Totally 497 patients with NSCLC were grouped according to syndrome differentiation,and the differences in tongue characteristics of different syndromes were compared.Bivariate correlation analysis was used to study the correlation between tongue characteristics and serum tumor markers and coagulation indicators in patients with NSCLC of different syndromes.Results Compared with healthy people of different syndromes,in TB-a,yin deficiency and phlegm-heat syndrome>healthy group>qi-yin deficiency syndrome>spleen deficiency and phlegm-dampness syndrome>lung stagnation and phlegm-stasis syndrome(P<0.001).In TB-L,healthy group>spleen deficiency and phlegm-dampness syndrome>qi-yin deficiency syndrome>lung stagnation and phlegm-stasis syndrome>yin deficiency and phlegm-heat syndrome(P<0.001).In TB-b,yin deficiency and phlegm-heat syndrome>qi-yin deficiency syndrome>spleen deficiency and phlegm-dampness syndrome>healthy group>lung stagnation and phlegm-stasis syndrome(P<0.001).Yin deficiency and phlegm-heat syndrome had the highest TB-a and the lowest Per-all.Spleen deficiency and phlegm-dampness syndrome had the highest TB-L and Per-all.Lung stagnation and phlegm-stasis syndrome had lower TB-b and TC-b than other groups,lower TB-a than the healthy group,and a high Per-all index(P<0.05).In terms of tumor markers,Per-all in spleen deficiency and phlegm-dampness syndrome was positively correlated with Ca199,Ca50 and Ca242(P<0.05).In terms of coagulation indicators,the tongue texture index of lung stagnation and phlegm-stasis syndrome had a high correlation with the coagulation indicator Fg(P<0.01).Conclusion Different TCM syndromes of NSCLC have their own typical tongue characteristics.Tongue manifestations of different syndromes are correlated with tumor markers and coagulation indicators,respectively,which can reflect changes in clinical status.

Colorectal cancer(CRC)is a common malignancy of the digestive system,with increasing morbidity and mortality worldwide.The standard treatment for CRC has,in the past,been surgery,chemotherapy,and radiotherapy.However,these treatments have significant side effects and are particularly challenging for patients with advanced metastatic CRC(mCRC).Therefore,it is crucial to explore alternative and more effective treatments.In recent years,with the development of molecular technology,numerous biomarkers have been identified,and targeted therapy and immunotherapy have achieved surprisingly positive results in the treatment of mCRC.Patients receiving targeted ther-apy and immunotherapy have an improved prognosis and quality of life.On this basis,this article reviews the latest research progress in tar-geted therapy and immunotherapy for mCRC,providing a reference for precision treatment of mCRC.

Objective:To construct and evaluate a training program for health management specialist nurses.Methods:Mainly qualitative analysis, The training system of health management specialist nurses was preliminarily drawn up based on literature review and semi-structured interview. The Delphi expert consultation method was used to conduct a two-round expert letter inquiry with 17 experts in the professions such as health management medicine, health management nursing, nursing management, and nursing education; and the analytic hierarchy process was applied to determine the weights of the indicators.Results:The effective recall rates of the questionnaires for the 2 rounds of expert consultation was 94.44%(17/18) and 100%(17/17), with expert authority coefficients of 0.90 and 0.92 and Kendall harmony coefficients of 0.207 and 0.249, respectively (all P<0.001). The training system of health management specialist nurses included 4 parts: training objective, training content, training management, training assessment and evaluation. There were 8 indicators in the training objective part. There were 5 first-level indicators, 15 second-level and 67 third-level indicators in the training content part. There were 5 first-level indicators, 12 second-level indicators in the training management part. There were 3 first-level indicators, 10 second-level indicators in the training assessment and evaluation part. Conclusion:The training program for specialized nurses in health management developed in this study demonstrates high levels of expert enthusiasm, authority, and consensus, indicating its feasibility.

Objective To introduce a modified technique of right ventricular outflow tract (RVOT) reconstruction using a handmade bicuspid pulmonary valve crafted from expanded polytetrafluoroethylene (ePTFE) and to summarize the early single-center experience. Methods Patients with complex congenital heart diseases (CHD) who underwent RVOT reconstruction with a handmade ePTFE bicuspid pulmonary valve due to pulmonary regurgitation at Guangdong Provincial People’s Hospital from April 2021 to February 2022 were selected. Postoperative artificial valve function and right heart function indicators were evaluated. Results A total of 17 patients were included, comprising 10 males and 7 females, with a mean age of (18.18±12.14) years and a mean body weight of (40.94±19.45) kg. Sixteen patients underwent reconstruction with a handmade valved conduit, with conduit sizes ranging from 18 to 24 mm. No patients required mechanical circulatory support, and no in-hospital deaths occurred. During a mean follow-up period of 12.89 months, only one patient developed valve dysfunction, and no related complications or adverse events were observed. The degree of pulmonary regurgitation was significantly improved post-RVOT reconstruction and during follow-up compared to preoperative levels (P<0.001). Postoperative right atrial diameter, right ventricular diameter, and tricuspid regurgitation area were all significantly reduced compared to preoperative values (P<0.05). Conclusion The use of a 0.1 mm ePTFE handmade bicuspid pulmonary valve for RVOT reconstruction in complex CHD is a feasible, effective, and safe technique.