This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

This study systematically analyzed the global research landscape, technological composition, and core patents in the field of networks target and network pharmacology, and proposes further suggestions based on the IncoPat patent citation database and VOSviewer bibliometric network visualization tool. Using patent literature metrics and scientific knowledge mapping method, technological innovation pathways, research hotspots, and future directions in this field were further revealed. In particular, this field is moving towards data-driven, intelligent, and systematic approaches. Patent analysis indicated that most patent applications in this domain focused on traditional Chinese medicine(TCM), which have provided key engineering technical approaches to explore and solve complex problems of TCM. By integrating big data and artificial intelligence technologies, network targets and network pharmacology have conferred high-precision screening and quality control of key components and targets in herbal formulations and prescriptions, accelerating the clinical translation and industrialization of TCM-based new drugs and health products with medicine-food homology. Therefore, it is essential to optimize the patent protection system and establish integrated technology platforms in this field for ensuring the competitiveness of technological achievements in research and clinical application. These efforts will advance the widespread application and high-quality development of TCM modernization, precision medicine, and innovative drug discovery.
Bibliometrics ; Patents as Topic ; Humans ; Medicine, Chinese Traditional ; Network Pharmacology/trends* ; Drugs, Chinese Herbal/pharmacology*

Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

Objective To investigate the effect of liquid-liquid phase separation(LLPS)of YTH domain family protein 2(YTHDF2)on the sodium arsenite-induced malignant transformation of skin cells,providing a new intervention target for the prevention and control of sodium arsenite-induced carcinogenesis.Methods The HaCaT cell model of malignant transformation was constructed by continuous treatment with 1 μmol/L sodium arsenite for 22 weeks,including cells with normal YTHDF2 LLPS(YTHDF2-wt)and cells with inhibited YTHDF2 LLPS(YTHDF2-mut).Confocal microscopy was employed to observe and characterize the LLPS droplets formed by YTHDF2 during sodium arsenite-induced malignant transformation of skin cells.Cell proliferation,scratch healing,and colony formation assays were performed to detect malignant phenotypes.Western blotting,quantitative reverse transcription PCR,and immunofluorescence experiments were conducted to examine the effects of YTHDF2 LLPS on the mRNA and protein levels of phosphatase and tensin homolog deleted on chromosome ten(PTEN)during sodium arsenite-induced malignant transformation of skin cells.Results After 4 weeks of sodium arsenite treatment,LLPS droplets of YTHDF2 appeared in YTHDF2-wt cells,and the number of droplets gradually increased as the treatment time was prolonged(F=35.252,P<0.001),while no phase-separated droplets were observed in YTHDF2-mut cells.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed enhanced proliferation at the time points of 48 h(t=3.654,P=0.006)and 72 h(t=5.458,P<0.001)after 22 weeks of sodium arsenite treatment.The scratch healing rate of YTHDF2-wt cells was increased at the 8th(t=12.137,P<0.001)and 22th(t=4.484,P=0.011)weeks of sodium arsenite treatment.The number of colonies formed by YTHDF2-wt cells was higher at the 4th(t=3.365,P=0.027),8th(t=5.580,P=0.005),and 22th(t=3.328,P=0.029)weeks of sodium arsenite treatment.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed down-regulated protein(t=-3.119,P=0.036)and mRNA(t=4.051,P=0.015) levels of PTEN after 22 weeks of sodium arsenite treatment.Immunofluorescence results showed that after 4 weeks of sodium arsenite treatment,YTHDF2 LLPS droplets in YTHDF2-wt cells were localized to stress granules,translation-related membrane-less organelles.Conclusions During sodium arsenite-induced malignant transformation of skin cells,YTHDF2 undergoes LLPS and localizes to stress granules,translation-related membrane-less organelles.YTHDF2 LLPS participates in sodium arsenite-induced malignant transformation of skin cells by down-regulating the mRNA level of the key tumor suppressor PTEN.
Arsenites/toxicity* ; Sodium Compounds/toxicity* ; Humans ; Cell Transformation, Neoplastic/drug effects* ; PTEN Phosphohydrolase/metabolism* ; Cell Proliferation ; Skin/cytology* ; RNA-Binding Proteins ; Skin Neoplasms/chemically induced* ; Cell Line

Aortic regurgitation and mitral regurgitation are more common in elderly heart valve disease,and both may be present in some patients.Severe aortic regurgitation complicated with severe mitral regurgitation often requires surgical valve replacement,but in patients at high risk of surgery,the risk of perioperative mortality is significantly increased.Therefore,for such patients,minimally invasive interventions can significantly improve long-term patient outcomes while reducing surgical risk.This article report a case of transcatheter aortic valve replacement combined with transcatheter edge-to-edge repair in the treatment of severe aortic regurgitation combined with mitral valve prolapse,in order to explore new treatment ideas for similar cases.

AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P＜0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P＜0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P＜0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P＜0.05,P＜0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P＜0.05,P＜0.01);mitigated inflammation and collagen deposition(P＜0.05,P＜0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.05,P＜0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.

Objective:To compare the impact of different treatment strategies on the survival outcomes in rectal cancer patients with poor response to neoadjuvant therapy, and to explore the survival-related influencing factors.Methods:A retrospective cohort study was conducted. Between January 2018 and November 2022, the clinical, pathological, and follow-up data of 106 rectal cancer patients who received neoadjuvant therapy and were evaluated as grade 4 or 5 based on the Magnetic Resonance Tumor Regression Grade (mrTRG) from the rectal cancer database at Peking Union Medical College Hospital were retrospectively collected. Based on the post-neoadjuvant therapy assessment, patients were classified into three groups: the chemotherapy-radiotherapy group (23 patients), the consolidation therapy group (18 patients), and the standard treatment group (65 patients). General condition, pathological findings, selection of neoadjuvant therapy, comorbidities, as well as 3-year expected DMFS and OS were observed in the three groups.Results:All 106 patients were followed up, with a median follow-up time of 28 (21, 38) months. The overall 3-year DMFS rate was 60%, and the 3-year OS rate was 74%. The 3-year DMFS in the standard treatment and consolidation therapy groups were 74% and 72%, respectively; the 3-year OS were 84%, 81%, respectively. The Log-rank test showed that there was no significant difference in the 3-year expected DMFS and OS between the standard treatment group and the consolidation therapy group (both P>0.05), but both groups had better survival outcomes than the chemotherapy-radiotherapy group (10% and 39%, respectively; all P<0.001). Multivariate Cox regression analysis indicated that the chemotherapy-radiotherapy only regimen was an independent risk factor for DMFS (HR=12.425, 95% CI: 4.436–34.594, P<0.001), and the independent risk factors for OS were chemotherapy-radiotherapy only regimen (HR=8.991, 95%CI:2.220–36.403, P=0.002) and age≥65 years (HR=3.495, 95%CI: 1.017–12.009, P=0.047). Stratified analysis showed that chemotherapy-radiotherapy only regimen was the independent risk factors for DMFS and OS in patients with extramural vascular invasion (EMVI) positive ( n=66) and mesorectal fascial invasion (MRF) positive (n=56) (all P<0.05). Whether consolidation therapy was added to the standard neoadjuvant treatment regimen was not an independent factor affecting 3-year expected DMFS or OS in rectal cancer patients with poor response to neoadjuvant therapy. Further comparisons between the standard neoadjuvant treatment and consolidation therapy groups showed no statistically significant differences in spincter-preservation rate or postoperative complication rates (both P>0.05). However, the consolidation therapy group had a longer interval between the end of radiotherapy and surgery [80.1 (50.8, 109.4) days vs. 61.8 (48.8, 74.8) days, P<0.001], and a higher incidence of chemotherapy-related adverse effects ([10/18] vs. 26.2% [17/65], P=0.018). Conclusion:In rectal cancer patients with poor response to neoadjuvant therapy and clear adverse prognostic features before surgery (locally advanced stage, MRF positive or EMVI positive), the addition of short- or long-course chemotherapy-based systemic therapy does not provide short- or long-term survival benefits. Moreover, an extended chemotherapy duration increases the incidence of chemotherapy-related adverse effects.

Aortic regurgitation and mitral regurgitation are more common in elderly heart valve disease,and both may be present in some patients.Severe aortic regurgitation complicated with severe mitral regurgitation often requires surgical valve replacement,but in patients at high risk of surgery,the risk of perioperative mortality is significantly increased.Therefore,for such patients,minimally invasive interventions can significantly improve long-term patient outcomes while reducing surgical risk.This article report a case of transcatheter aortic valve replacement combined with transcatheter edge-to-edge repair in the treatment of severe aortic regurgitation combined with mitral valve prolapse,in order to explore new treatment ideas for similar cases.

Objective:To compare the impact of different treatment strategies on the survival outcomes in rectal cancer patients with poor response to neoadjuvant therapy, and to explore the survival-related influencing factors.Methods:A retrospective cohort study was conducted. Between January 2018 and November 2022, the clinical, pathological, and follow-up data of 106 rectal cancer patients who received neoadjuvant therapy and were evaluated as grade 4 or 5 based on the Magnetic Resonance Tumor Regression Grade (mrTRG) from the rectal cancer database at Peking Union Medical College Hospital were retrospectively collected. Based on the post-neoadjuvant therapy assessment, patients were classified into three groups: the chemotherapy-radiotherapy group (23 patients), the consolidation therapy group (18 patients), and the standard treatment group (65 patients). General condition, pathological findings, selection of neoadjuvant therapy, comorbidities, as well as 3-year expected DMFS and OS were observed in the three groups.Results:All 106 patients were followed up, with a median follow-up time of 28 (21, 38) months. The overall 3-year DMFS rate was 60%, and the 3-year OS rate was 74%. The 3-year DMFS in the standard treatment and consolidation therapy groups were 74% and 72%, respectively; the 3-year OS were 84%, 81%, respectively. The Log-rank test showed that there was no significant difference in the 3-year expected DMFS and OS between the standard treatment group and the consolidation therapy group (both P>0.05), but both groups had better survival outcomes than the chemotherapy-radiotherapy group (10% and 39%, respectively; all P<0.001). Multivariate Cox regression analysis indicated that the chemotherapy-radiotherapy only regimen was an independent risk factor for DMFS (HR=12.425, 95% CI: 4.436–34.594, P<0.001), and the independent risk factors for OS were chemotherapy-radiotherapy only regimen (HR=8.991, 95%CI:2.220–36.403, P=0.002) and age≥65 years (HR=3.495, 95%CI: 1.017–12.009, P=0.047). Stratified analysis showed that chemotherapy-radiotherapy only regimen was the independent risk factors for DMFS and OS in patients with extramural vascular invasion (EMVI) positive ( n=66) and mesorectal fascial invasion (MRF) positive (n=56) (all P<0.05). Whether consolidation therapy was added to the standard neoadjuvant treatment regimen was not an independent factor affecting 3-year expected DMFS or OS in rectal cancer patients with poor response to neoadjuvant therapy. Further comparisons between the standard neoadjuvant treatment and consolidation therapy groups showed no statistically significant differences in spincter-preservation rate or postoperative complication rates (both P>0.05). However, the consolidation therapy group had a longer interval between the end of radiotherapy and surgery [80.1 (50.8, 109.4) days vs. 61.8 (48.8, 74.8) days, P<0.001], and a higher incidence of chemotherapy-related adverse effects ([10/18] vs. 26.2% [17/65], P=0.018). Conclusion:In rectal cancer patients with poor response to neoadjuvant therapy and clear adverse prognostic features before surgery (locally advanced stage, MRF positive or EMVI positive), the addition of short- or long-course chemotherapy-based systemic therapy does not provide short- or long-term survival benefits. Moreover, an extended chemotherapy duration increases the incidence of chemotherapy-related adverse effects.

AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P＜0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P＜0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P＜0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P＜0.05,P＜0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P＜0.05,P＜0.01);mitigated inflammation and collagen deposition(P＜0.05,P＜0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.05,P＜0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.