OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Abstract: Objective To investigate the dynamic changes and clinical significance of specific antibodies in patients with coronavirus disease 2019 (COVID-19). Methods A retrospective study was conducted to collect 141 adult COVID-19 survivors who were followed up in the Eighth Hospital affiliated to Guangzhou Medical University from February 6, 2020, to March 24, 2021. The patients were divided into severe group (severe and critical) and non-severe group (light and ordinary) according to the diagnosis at discharge. The antibody changes of the two groups were compared and analyzed at 1 week, 2 weeks, 1 month, 3 months, 6 months and 1 year after discharge. Results After discharge from hospital, the positive rate of IgG in the severe group was 95.00% after 1 week and 100.00% in the following year, in the positive rate of IgG in the non-severe group was 59.50% after 1 week, 90.08% in 6 months and 76.03% in one year. The level of serum IgG in the severe group was significantly higher than that in non-severe group (Z=-2.441, P=0.015). One-year follow-up: the serum IgG in the severe group was significantly higher than that in the non-severe group (Z=-3.410, P=0.001). The serum IgM level of the severe group after one year follow-up was lower than that of the six months follow-up, the difference was statistically significant (Z=-2.259, P=0.024). The serum IgG and IgM level of the non-severe group after one year follow-up was lower than that of the six months follow-up, the difference was statistically significant (Z=-7.37, P<0.01; Z=3.850, P<0.01). Conclusion The level of serum protective antibody in COVID-19 patients remained high within 6 months after discharge, and remained stable within 1 year after discharge. The antibody titers in the severe group were significantly higher than those in the non-severe group and lasted for at least one year. COVID-19 survivors receive 1 year of natural immune protection, and patients with critical conditions receive immunity for longer periods of time.

Most of the active ingredients of herbs are secondary metabolites of plants. Cytochrome P450s (P450s) are hemoglobin-containing monooxygenases encoded by a super-gene family, which play important roles in the metabolic network of plants. This review focuses on the role of P450s on biosynthesis of secondary metabolites such as terpenoids, alkaloids, flavonoids and phenylpropanoids. This will provide references for biosynthesis and regulation of secondary metabolites in medicinal plants.

Tanshinones are abietane-type norditerpenoid quinones that make up the main bioactive ingredients of traditional Chinese medicine Salvia miltiorrhiza. Cytochrome CYP450 plays an important role in the post-structural modification of tanshinone biosynthesis pathway. Long non-coding RNA( lncRNA) have been defined as transcripts longer than 200 nucleotides,which have been functionally characterized in regulating the growth and development,secondary metabolism and stress of medicinal plants. In this study,we perform a comprehensive identification of lncRNAs in response to tanshinone metabolism induced by yeast extract( YE) and Ag~+ S. miltiorrhiza hairy roots. Deep RNA sequencing was used to identify a set of different 8 942 lncRNAs,of which 6 755 were intergenic lncRNAs. We predicted a total of 1 115 814 lncRNA-coding gene pairs,including 122 lncRNA-coding gene as cis pairs. The correlation analysis between lncRNA and CYP450 related to tanshinone biosynthesis was carried out and a total of 16 249 lncRNA-CYP450 target gene pairs were identified. Further analysis with functional known CYP76 AH1,CYP76 AH3 and CYP76 AK1 involved in tanshinone biosynthesis,we also identified a set of 216 target genes. These candidate genes will be the important target in the downstream regulation mechanism analysis of the tanshinone biosynthesis pathway.
Cytochrome P-450 Enzyme System ; genetics ; Diterpenes, Abietane ; biosynthesis ; Gene Expression Regulation, Plant ; Plant Roots ; RNA, Long Noncoding ; genetics ; RNA, Plant ; genetics ; Salvia miltiorrhiza ; genetics

Objective:To observe the effect of electroacupuncture (EA) on the expressions of acetylcholine (ACh) and mucin 5AC (MUC5AC) in the lungs of rats with chronic obstructive pulmonary disease (COPD),and explore the mechanism of EA in treating COPD.Methods:Thirty Sprague-Dawley (SD) rats were randomly divided into a control group,a COPD group,and an EA group,with 10 rats in each group.The control group was a group of normal rats.The COPD rat model was induced by cigarette smoke combined with lipopolysaccharide (LPS).The COPD rats were treated with EA at bilateral Feishu (BL 13) and Zusanli (ST 36) in the EA group,30 min each time,once a day,successively for 14 d.The lung function was tested.The contents of ACh and MUC5AC in lungs and bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA).Pearson method was used to analyze the correlation between pulmonary function and the content of MUC5AC in lungs.The mRNA and protein expressions of MUC5AC in lung tissues were detected by real-time polymerase chain reaction (RT-PCR) and Western blot (WB),respectively.The immune response of MUC5AC was observed by immunohistochemistry.Results:Eight rats were left in each group,and the other two died.Compared with the control group,the total airway resistance (Raw) increased significantly and dynamic compliance (Cdyn) decreased significantly in the COPD group (P＜0.01);compared with the COPD group,the Raw level declined significantly and Cdyn increased significantly in the EA group (P＜0.01).The contents of ACh and MUC5AC in the lungs and BALF were remarkably higher in the COPD group compared with those in the control group (P＜0.01,P＜0.001);compared with the COPD group,the contents of ACh and MUC5AC were significantly lower in the EA group (P＜0.05,P＜0.001).There was a negative correlation between MUC5AC content and lung function (P＜0.001).The mRNA and protein expressions of MUC5AC in the lungs were significantly higher in the COPD group than in the control group (P＜0.001);compared with the COPD group,the expressions were significantly lower in the EA group (P＜0.01).Compared with the control group,the immune response of MUC5AC in the airway epithelium significantly increased in the COPD group (P＜0.001);the immune response of MUC5AC was significantly lower in the EA group compared with that in the COPD group (P＜0.001).Conclusion:EA treatment can improve the lung function of COPD rats,which may be related to its effect in the down-regulation of ACh and MUC5AC contents in the lungs as well as the inhibition of mucus hypersecretion.

The aim of this study is to apply 3D printing technology to hospital drug dosing operations, and explore its feasibility and scalability. Drugs often dosed in hospitals are selected as models. The commercially available drug was ground into powder, diluted with medicinal excipients and then mixed with 75% ethanol and binder to prepare a paste for 3D printing. The dose and physicochemical properties of divided tablets were controlled by setting print parameters and printing models in computer software. Different 3D printers were employed to evaluate the impact of the device on the dosing tablet. Two drugs were dosed in this study to explore the scalability of 3D printing technology between different drugs. The drug content of the three divided dose tablets (warfarin sodium 1 mg, 2 mg, hydrochlorothiazide 5 mg) was 1.02±0.03, 1.96±0.01, 5.19±0.06 mg. The content uniformity was 1.0, 5.3, 2.6, respectively. The drug dissolution rate was (99.3±1.2)%, (101.5±0.3)%, (98.1±0.8)% in 45, 45 and 30 min. The mechanical properties of the three sub-doses and the stability within 30 days were in line with the Chinese Pharmacopoeia (2015) requirements. At the same time, it was found that the printing parameters and prescriptions can affect the properties of the divided dose tablets. By controlling the dilution ratio of commercial drug and printing parameters, the drug release rate can be customized to achieve individualized treatment. Both different modes of 3D printers can produce qualified sub-doses, and 3D print dispensing technology was also versatile between the two drugs. 3D printing can prepare small-volume, high-precision, high-repetition dosing tablets, with all properties in compliance with pharmacopoeia regulations. Thus, this method can be used as a new and scalable sub-dosing method.

Objective: To explore the relationship between plasma levels of soluble ST2 (sST2), galectin-3 (Gal-3) and clinical prognosis of ventricular septal myectomy in patients with obstructive hypertrophic cardiomyopathy (HOCM). Methods: A total of 200 consecutive HOCM patients received modified Morrow surgery in our hospital from 2011-03 to 2016-02 were studied. According to plasma levels of sST2, patients were divided into 3 groups: Low sST2 group (sST2<9.05 ng/ml), Middle sST2 group (sST2 9.05-16.74 ng/ml) and High sST2 group (sST2>16.74 ng/ml); based on plasma levels of Gal-3, patients were divided into another 3 groups: Low Gal-3 group (Gal-3<6.19 ng/ml), Middle group (Gal-3 6.19-8.22 ng/ml) and High Gal-3 group (Gal-3>8.22 ng/ml); in addition, Control group, n=42 volunteers without heart disease. Plasma levels of sST2 and Gal-3 were measured by ELISA, compared between Control group and HOCM group (n=42 patients with matched gender and age to Control group). The predictive value of sST2 and Gal-3 on major endpoint events including all cause death or cardiovascular hospitalization were assessed by Cox regression analysis.Results: Compared with Control group, plasma levels of sST2 and Gal-3 were increased in HOCM patients, P<0.01. The patients were followed-up for the average of 26 months, Kaplan-meier survival analysis showed that the incidences of composite endpoint event were similar at different levels of sST2 and Gal-3 (log-rank P=0.06 and P=0.68). Cox regression analysis indicated that either sST2 or Gal-3 could not independently predict the endpoint events, both P>0.05, while age was an independent risk factor for composite endpoint event occurrence (HR=1.06, 95% CI 1.02-1.11, P<0.01). Conclusion: Plasma levels of sST2 and Gal-3 were not related to clinical prognosis of ventricular septal myectomy in HOCM patients even they had increased sST2 and Gal-3; while advanced age was the independent predictor for endpoint event occurrence.

OBJECTIVE To study the methodology of achieving stable co-expression of drug-metab?olizing enzymes in the HepG2 cells by the piggyBac (PB) transposon system. METHODS N-terminal attachment of enhanced green fluorscent protein plasmid (pEGFP- N2) and 2A peptide linked recombinant PB transposon plasmid containing dual-genes encoding drug metabolizing enzymes cyto?chrome P450 3A4 (CYP3A4) and CYP2C19 (pPB-CYP3A4-2A-2C19) were transfected into HepG2 cells respectively by Lipofectamine?LTX reagent, GenJetTM (Ver.Ⅱ) reagent and Neon?Transfection System reagent, which were widely used for large-sized DNA fragments transfection. 48 h later, the transfection efficiency and cell toxicity were detected and compared between the three methods so as to find a method with relatively high efficiency and low toxicity for later transfection.Then,three groups of recombinant PB transposons-single-gene transposon (PB-CYP3A4), 2A peptide linked dual-gene transposon (PB-CYP3A4-2A-2C19) and multiple single-gene transposon mixture〔PB-CYP3A4, PB-CYP2C8, PB-CYP2A6, organic anion transporting polypeptide 1B1 PB transposon (PB-OATP1B1)〕-were transfected into HepG2 cells respectively with the above established method.The puromycin (Puro)-resistant and GFP positive cell clones were picked up and further cultured. The mRNA, protein and metabolic levels of drug-metabolizing enzymes in monoclonal cell lines were detected by quantitative real-time PCR,Western blotting and high performance liquid chromatography-tandem mass spectrometry respectively after screening by Puro and green fluorescence. Comparisons of different groups were made using statistical analysis. RESULTS The comparison of three different transfection methods indi?cated that the transfection efficiency of GenJetTMwas up to(94.2±2.5)% and (89.3±3.3)%,significantly higher than those of the other two methods (P<0.01), along with lower cytotoxicity. Then GenJetTMwas chosen for later transfection. In the Puro-resistant monoclonal cell lines of single transposon PB-CYP3A4,PB-CYP3A4-2A-2C19 groups,the mRNA,protein and enzyme activity levels of drug-metabo?lizing enzymes were significantly increased respectively.The recombinant transposon (PB-CYP3A4-2A-2C19) containing 2A peptide could achieve stable and efficient co-expression of two metabolizing enzymes CYP3A4 and CYP2C19,while the expression of drug-metabolizing enzymes remained unbal?anced and random in those of multiple single-gene transposon mixture group (PB-CYP3A4, PB-CYP2C8,PB-CYP2A6,PB-OATP 1B1)(CYP3A4 was expressed in some cell clones only).CONCLUSION GenJetTM could be an effective method for the PB recombinant transposon transfection into HepG2 cells, by which the PB transposon could mediate stable expression of drug-metabolizing enzymes. In terms of multi-gene expression,a low and unbalanced expression is found by multiple transposons co-transfection method,which is different from that by virus mediated method.In contrast,mono-PB trans?poson linked by 2A peptide can achieve stable expression of multi-genes.

Based on standard carotid endarterectomy, we performed modified carotid endarterectomy in two cases of carotid artery stenosis by changing the direction of the carotid artery incision to avoid restenosis of the internal carotid artery without using a patch. The two patients recovered smoothly without any complications. Compared with eversion or patch endarterectomy, this modified carotid endarterectomy avoids restenosis of the carotid artery and shortens operation time.