Plant-derived exosomes are natural nanovesicles rich in bioactive compounds and show promise for tissue regeneration. However, their clinical use is limited by poor stability and low targeting accuracy. To overcome these issues, we developed an engineered approach to enhance the targeted delivery of plant exosomes, focusing on chronic inflammation—a key driver of heart failure—evaluating their therapeutic potential in myocardial infarction. By optimizing isolation methods and fusing exosomes with synthetic liposomes, we created collagen-targeted hybrid nanovesicles (GEP-NPs). In a mouse model of myocardial infarction, GEP-NPs efficiently accumulated in damaged heart tissue. Compared to non-engineered vesicles, GEP-NPs more effectively reduced fibrosis, suppressed ventricular remodeling, and modulated chronic post-infarction inflammation, thereby preventing progression from acute injury to chronic heart failure. Mechanistic studies showed that GEP-NPs may inhibit the overactive PI3K-AKT-mTOR pathway, which regulates inflammation, cell survival, and metabolism. The bioactive components from plant exosomes likely act effectively within the engineered vesicles to suppress this pathway, reducing persistent inflammation and promoting tissue repair. This work provides a scalable, reproducible method for engineering plant exosomes, improving both delivery precision and stability, and offering a promising strategy for treating chronic cardiac inflammation and preventing heart failure.

AIMS:High plasma fibrinogen and systemic inflammation response index (F-SIRI) has been proposed as a novel prognostic factor in resectable gastric cancer. However, available data on the prognostic value of F-SIRI in chronic heart failure (CHF) patients is limited. We aimed to conduct a retrospective cohort study exploring the correlation between F-SIRI and prognosis in CHF individuals. METHODS:We consecutively enrolled 1589 hospitalized patients (aged 66 ± 8 years, 32.9% women) with CHF from January 1, 2019 to August 31, 2022 in this single-center retrospective study. SIRI was calculated with the formula (monocyte count*neutrophil count/lymphocyte count). The primary endpoints encompassed all-cause death, the major adverse cardiac and cerebral events (MACCEs) and cardiovascular death. The association between F-SIRI and the risk of developing adverse outcomes were explored using four multivariate-adjusted Cox proportional hazard models. RESULTS:During a median follow-up of 687 days, 207 all-cause deaths, 462 MACCEs and 136 cardiovascular deaths were recorded. After adjusting for potential confounding factors, only risk of all-cause death remained significantly associated with higher levels of F-SIRI. The hazard ratios (HRs) for the highest F-SIRI group (F-SIRI = 2) versus the lowest F-SIRI group (F-SIRI = 0) were 2.37 (95% confidence interval [CI], 1.46-3.83; p < 0.001) for all-cause death. The addition of F-SIRI could increase the prognostic ability for all-cause death on the basis of traditional risk factors. CONCLUSIONS:F-SIRI is a significant predictor of all-cause death but has limited predictive value for MACCEs and cardiovascular death in CHF patients.

Ferroptosis is a new type of controlled cell death. It is distinguished by its reliance on iron and the production of lipid peroxidation. The role of ferroptosis in stroke has attracted a lot of attention recently. The purpose of this review is to clarify the connection between ferroptosis and stroke and to investigate the potential contribution of natural products to the clinical management of stroke and the discovery of novel medications. In this review, we summarize in detail the mechanism of ferroptosis after stroke, especially the relevant targets of ferroptosis after stroke. Furthermore, we summarize the natural products and herbal medicine currently employed in ferroptosis along with their mechanisms of action, highlighting the potential and challenges of clinical translation. We included 55 articles and classified them. After systematic screening, We think that ginkgolide B, kellerin, loureirin C, quercetin, icariside II, salvianolic acid A, berberine, Dl-3-n-butylphthalide is an effective candidate drug for the treatment of stroke.

One of the main pathological features of airway inflammatory diseases is hypersecretion of airway mucus, which is manifested by goblet cell hyperplasia and mucociliary clearance dysfunction. In recent years, it has been found that the molecular structure of calcium activated chloride ion channels, transmenbrane protein 16A（TMEM16A）, is closely related to airway mucus hypersecretion.TMEM16A not only mediates ion transepithelial transport and hydration, but also participates in the regulation of mucin secretion. TMEM16A is highly expressed in airway epithelium of a variety of inflammatory diseases of upper and lower airway, such as asthma, cystic fibrosis, allergic rhinitis, chronic sinusitis and so on. Understanding the expression level and regulation mechanism of TMEM16A in different airway diseases and revealing its physiological function and pathological mechanism is critical for targeted disease treatment. This paper summarizes the research status of the discovery process, structural characteristics and regulatory mechanism of TMEM16A, and then summarizes the expression level of TMEM16A in asthma, cystic fibrosis, allergic rhinitis and chronic sinusitis ant related pathological mechanisms, clarifies the potential value of TMEM16A as a therapeutic target for the above four diseases, in order to guide treatment of airway inflammatory diseases.

BackgroundSeptic cardiomyopathy is a frequent complication in patients with sepsis and is associated with a high mortality rate. Given its clinical significance, understanding the precise underlying mechanism is of great value.Methods and resultsOur results unveiled that Z-DNA binding protein 1 (ZBP1) is upregulated in myocardial tissues of lipopolysaccharide (LPS)-treated mice. Single-cell mRNA sequencing (scRNA-seq) and single-nucleus mRNA sequencing (snRNA-seq) indicated that Zbp1 mRNA in endothelial cells, fibroblasts and macrophages appeared to be elevated by LPS, which is partially consistent with the results of immunofluorescence. Through echocardiography, we identified that global deletion of ZBP1 improves cardiac dysfunction and the survival rate of LPS-treated mice. Mechanistically, snRNA-seq showed that ZBP1 is mainly expressed in macrophages and deletion of ZBP1 promotes the macrophage polarisation towards M2-subtype, which reduces inflammatory cell infiltration. Notably, myeloid-specific deficiency of ZBP1 also promotes M2 macrophage polarisation and improves cardiac dysfunction, validating the role of macrophage-derived ZBP1 in septic myocardial dysfunction. Finally, we revealed that LPS increases the transcription and expression of ZBP1 through signal transducer and activator of transcription 1 (STAT1). Fludarabine, the inhibitor of STAT1, could also promote M2 macrophage polarisation and improve cardiac dysfunction of LPS-treated mice.ConclusionsOur study provides evidence of a novel STAT1-ZBP1 axis in macrophage promoting septic cardiomyopathy, and underscores the potential of macrophage-derived ZBP1 as a therapeutic target for septic cardiomyopathy.Key points Macrophage-derivedZBP1 exacerbates LPS-induced myocardial dysfunction and inflammatory cellinfiltration. Deletionof ZBP1 promotes macrophage polarisation from M1 to M2. STAT1-ZBP1axis promotes septic cardiomyopathy. ZBP1has emerged as a potential therapeutic target for inflammationand septic cardiomyopathy.

Compared with stem cells, exosomes as a kind of nanoscale carriers intrinsically loaded with diverse bioactive molecules, which had the advantages of high safety, small size, and ethical considerations in the treatment of myocardial infarction, but there are still problems such as impaired stability and rapid dissipation. Here, we introduce a bioengineered injectable hyaluronic acid hydrogel designed to optimize local delivery efficiency of trophoblast stem cells derived-exosomes. Its hyaluronan components adeptly emulates the composition and modulus of pericardial fluid, meanwhile preserving the bioactivity of nanoscale exosomes. Additionally, a meticulously designed hyperbranched polymeric cross-linker facilitates a gentle cross-linking process among hyaluronic acid molecules, with disulfide bonds in its molecular framework enhancing biodegradability and conferring a unique controlled release capability. This innovative hydrogel offers the added advantage of minimal invasiveness during administration into the pericardial space, greatly extending the retention of exosomes within the myocardial region. In vivo, this hydrogel has consistently demonstrated its efficacy in promoting cardiac recovery, inducing anti-fibrotic, anti-inflammatory, angiogenic, and anti-remodeling effects, ultimately leading to a substantial improvement in cardiac function. Furthermore, the implementation of single-cell RNA sequencing has elucidated that the pivotal mechanism underlying enhanced cardiac function primarily results from the promoted clearance of apoptotic cells by myocardial fibroblasts.

Among heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox. The study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints. In MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95

Radix Astragali (RA) has been recognized for its therapeutic potential in allergic rhinitis (AR), yet its potential pharmacological mechanisms remain elusive. This study systematically investigated the physicochemical properties and biological activities of RA’s phytochemicals, aiming to elucidate their targets and mechanisms in AR treatment. We identified 775 potential targets of RA’s key phytochemicals and intersected these with 29,544 AR-related disease targets, pinpointing 747 shared therapeutic targets. A protein-protein interaction network analysis categorized these targets into five subclusters, with TNF, NFKB1, IKBKB, NFKBIA, and CHUK emerging as central nodes. Enrichment analysis revealed their roles in inflammatory and immune responses, particularly through the NF-κB, TNF, IL-17, Toll-like receptor, and NOD-like receptor signaling pathways. Molecular docking and dynamics simulations confirmed the strong binding affinity and stability of RA’s phytochemicals to these targets. In vivo, RA intervention effectively reversed the expression of key inflammatory markers in an IL-13-induced nasal mucosa inflammation model. Our findings suggest that RA’s multitargeted approach involves the modulation of critical inflammatory pathways, highlighting its therapeutic potential.

BACKGROUND:Mesenchymal stromal cell (MSC)-derived exosomes (MSC-Exo) have been recognized for their significant role in regulating macrophage polarization, a process crucial to the pathogenesis of abdominal aortic aneurysm (AAA). However, the therapeutic effects of MSC-Exo on AAA remain largely unexplored. Therefore, this study aimed to investigate the functional and mechanistic aspects of MSC-Exo in the progression of AAA. METHODS:The MSC-derived exosomes were characterized using Transmission Electron Microscopy, Nanoparticle Tracking Analysis, and Western blotting. An experimental mouse model of AAA was established through the administration of angiotensin II (Ang II) in male apoe-/- mice and calcium chloride (CaCl2) in male C57/B6 mice, with subsequent tail vein injection of exosomes to evaluate their efficacy against AAA. Macrophage polarization was assessed using immunofluorescence staining and WB analysis. Mechanistic analysis was performed using 4D Label-free Proteomics analysis. RESULTS:We found that intravenous administration of MSC-Exo induced M2 polarization of macrophages within an inflammatory environment, effectively impeding AAA development in Ang II or CaCl2-induced AAA model. The therapeutic efficacy of MSC-Exo treatment was dependent on the presence of macrophages. Mechanistically, MSC-Exo suppressed the levels of cluster of differentiation 74 (CD74), modulating macrophage polarization through the TSC2-mTOR-AKT pathway. These findings highlight the potential of MSC-Exo as a therapeutic strategy for AAA by modulating macrophage polarization.

Background: The prescription of Chinese herbal medicine (CHM) consists of multiple herbs that exhibit synergistic effects due to the presence of multiple components targeting various pathways. In clinical practice, the combination of Erchen decoction and Huiyanzhuyu decoction (EHD) has shown promising outcomes in treating patients with laryngeal squamous cell carcinoma (LSCC). However, the underlying mechanism by which EHD exerts its therapeutic effects in LSCC remains unknown. Methods: Online databases were utilized for the analysis and prediction of the active constituents, targets, and key pathways associated with EHD in the treatment of LSCC. The protein-protein interaction (PPI) network of common targets was constructed and visualized using Cytoscape 3.8.1 software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functional roles of core targets within the PPI network. Protein clustering was conducted utilizing the MCODE plug-in. The obtained results highlight the principal targets and pathways involved. Subsequently, clinical samples were collected to validate alterations in the levels of these main targets through Western blotting (WB) and immunohistochemistry (IHC). Furthermore, both in vivo and in vitro experiments were conducted to investigate the therapeutic effects of EHD on healing LSCC and elucidate its underlying mechanism. Additionally, to ensure experimental reliability and reproducibility, quality control measures utilizing HPLC were implemented for EHD herbal medicine. Results: The retrieval and analysis of databases in EHD medicine and LSCC disease yielded a total of 116 overlapping targets. The MCODE plug-in methods were utilized to acquire 8 distinct protein clusters through protein clustering. The findings indicated that both the first and second clusters exhibited a size greater than 6 scores, with key genes PI3K and ErbB occupying central positions, while the third and fourth clusters were associated with proteins in the PI3K, STAT3, and Foxo pathways. GO functional analysis reported that these targets had associations mainly with the pathway of p53 mediated DNA damage and negative regulation of cell cycle in terms of biological function; the death-induced signaling complex in terms of cell function; transcription factor binding and protein kinase activity in terms of molecular function. The KEGG enrichment analysis demonstrated that these targets were correlated with several signaling pathways, including PI3K-Akt, FoxO, and ErbB2 signaling pathway. On one hand, we observed higher levels of key genes such as P-STAT3 , P-PDK1 , P-Akt , PI3K , and ErbB2 in LSCC tumor tissues compared to adjacent tissues. Conversely, FOXO3a expression was lower in LSCC tumor tissues. On the other hand, the key genes mentioned above were also highly expressed in both LSCC xenograft nude mice tumors and LSCC cell lines, while FOXO3a was underexpressed. In LSCC xenograft nude mice models, EHD treatment resulted in downregulation of P-STAT3, P-PDK1, PI3K, P-AKT, and ErbB2 protein levels but upregulated FOXO3a protein level. EHD also affected the levels of P-STAT3, P-PDK1, PI3K, P-AKT, FOXO3a, and ErbB2 proteins in vitro: it inhibited P-STAT3, P-AKT, and ErbB2, while promoting FOXO3a; however, it had no effect on PDK1 protein. In addition, HPLC identified twelve compounds accounting for more than 30% within EHD. The findings from this study can serve as valuable guidance for future experimental investigations. Conclusion: The possible mechanism of EHD medicine action on LSCC disease is speculated to be closely associated with the ErbB2/PI3K/AKT/FOXO3a signaling pathway.

Allergic rhinitis (AR) is a common inflammatory disease of the nasal mucosa that is characterized by symptoms such as sneezing, nasal congestion, nasal itching, and rhinorrhoea. In recent years, acupoint herbal patching (AHP) therapy has gained a growing interest as a potential management option for AR. This systematic review and meta-analysis will evaluate the clinical research evidence on the effectiveness and safety of AHP as a treatment option for AR outside of the Sanfu or Sanjiu days (summer or winter solstice). The results of this review will provide up-to-date evidence-based guidance for healthcare providers and individuals seeking alternative treatments for AR. A comprehensive search of electronic databases (PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, China National Knowledge Infrastructure (CNKI), CQVIP, Sino-Med, and Wanfang Databases) will be conducted from their inception to June 2023. The inclusion criteria will be limited to randomized controlled trials that evaluate the effectiveness or efficacy of non-Sanfu or non-Sanjiu AHP for AR. The primary outcome measure will be the total nasal symptom score. The methodological quality of included studies will be assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2), and meta-analyses will be performed using RevMan (V.5.3) statistical software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to determine the certainty of evidence. This systematic review and meta-analysis will provide valuable insights into the effectiveness and safety of non-Sanfu or non-Sanjiu AHP as a treatment option for AR. The study aims to produce a high-quality review by adhering to PRISMA-P guidelines and using clinical guideline recommended outcome measures. The results of this review may offer additional treatment options for AR patients who seek complementary and alternative therapies, and hold significant implications for future research in this field. Overall, this study has the potential to inform clinical practice and improve patient outcomes. PROSPERO CRD42022181322.

Purpose:Myocardial ischemia-reperfusion injury after myocardial infarction has always been a difficult problem in clinical practice. Endothelial cells and their secreted extracellular vesicles are closely related to inflammation, thrombosis formation, and other processes after injury. Meanwhile, low-molecular-weight gelators have shown great potential for nasal administration. This study aims to explore the therapeutic effects and significance of endothelial cell-derived extracellular vesicles combined with a hydrogel for nasal administration on myocardial ischemia-reperfusion injury.Methods:We chose a gel system composed of a derivative of glutamine amide and benzaldehyde as the extracellular vesicle delivery vehicle. This hydrogel was combined with extracellular vesicles extracted from mouse aortic endothelial cells and administered multiple times intranasally in a mouse model of ischemia-reperfusion injury to the heart. The delivery efficiency of the extracellular vesicle-hydrogel combination was evaluated by flow cytometry and immunofluorescence. Echocardiography, TTC Evan's Blue and Masson's staining were used to assess mouse cardiac function, infarct area, and cardiac fibrosis level. Flow cytometry, ELISA, and immunofluorescence staining were used to investigate changes in mouse inflammatory cells, cytokines, and vascular neogenesis.Results:The vesicles combined with the hydrogel have good absorption in the nasal cavity. The hydrogel combined with vesicles reduces the levels of pro-inflammatory Ly6C (high) monocytes/macrophages and neutrophils. It can also reduce the formation of microcirculation thrombi in the infarcted area, improve endothelial barrier function, and increase microvascular density in the injured area. As a result, the heart function of mice is improved and the infarct area is reduced.Conclusion:We first demonstrated that the combination of extracellular vesicles and hydrogel has a better absorption efficiency in the nasal cavity, which can improve myocardial ischemia-reperfusion injury by inhibiting inflammatory reactions and protecting endothelial function. Nasal administration of vesicles combined with hydrogel is a potential therapeutic direction.

Dilated cardiomyopathy (DCM) is the major cause of heart failure and has a poor prognosis. The accumulating evidence points to an essential role of the inflammatory component in the process of DCM. Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are widely used to treat heart failure patients due to their cardiac benefits. However, their role in DCM remains unclear. We used the doxorubicin (Dox)-induced DCM model for our study. The SGLT2 inhibitor dapagliflozin (Dapa) improved cardiac function in mice treated with doxorubicin and attenuated the activation of the nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome pathway and the expression of inflammatory factors. In addition, dapagliflozin suppresses NLRP3 activation by decreasing p38-dependent toll-like receptor 4 (TLR4) expression. In our study, dagliflozin improves cardiac function in DCM by inhibiting the activity of the NLRP3 inflammasome.

OBJECTIVE:To assess whether a Methotrexate-based therapy could achieve more clinical benefit, we arranged a Simon 2-Stage Phase 1 Trial. Single-cell RNA sequencing and lipidomic profiling were performed to reveal the potential mechanisms. METHODS:Patients were enrolled in an open-label, Simon 2-stage, single-center, single-arm trial at Guangdong Provincial Hospital of Chinese Medicine. Main inclusion criteria were defined as follows: Aged 18 to 70, low to medium disease activity, fulfilled the RA classification criteria of EULAR/ACR 2010. Patients received the oral medication of MTX 10-15 mg weekly and natural product granules twice a day. Primary outcome was the American College of Rheumatology (ACR) 20% preliminary definition of improvement. Single-cell RNA sequencing(scRNA-seq) on peripheral blood mononuclear cells (PBMCs) was used to show the aberrant metabolism before and after the trial. Plasma lipidomic profiling quantified the lipid changes caused by this MTX-based therapy. Finally, post-hoc analysis on responders and non-responders were used for further analysis. RESULTS:Between October 2020 and June 2022, 46 patients received treatment, while 42 finished follow-ups. 27 of 46 (58.70%) patients achieved ACR20, and significant changes were observed in several secondary outcomes. Comparative scRNA-seq analysis before and after the treatment revealed that lipidomic metabolism was broadly downregulated. Plasma lipidomic profiling reveals that 40 lipids were observed significantly changed. Post-hoc analysis showed the lipid changes were separately linked to clinical parameters in responders and non-responders. CONCLUSION:The study reveals that the combination therapy of HQT+MTX is effective and has a certain correlation with lipid metabolism, but more rigorous study design is still needed to confirm this speculation.

Doxorubicin (Dox) is an anticancer drug widely used in tumor chemotherapy, but it has the side-effect of cardiotoxicity, which is closely related to mitochondrial damage. Mitochondrial dynamics is a quality control mechanism that usually helps to maintain a healthy mitochondrial pool. Trophoblast stem cell-derived exosomes (TSC-Exos) have been shown to protect cardiomyocytes from DOX-induced cardiotoxicity. To explore whether the cardioprotective role is mediated by the regulation of mitochondrial dynamic mechanism, TSC-Exos were isolated from human trophoblast stem cells by ultracentrifugation and characterized by Western blot and transmission electron microscopy. Cellular experiments of H9c2 cardiomyocytes co-cultured with Dox and TSC-Exos were performed in vitro to determine the levels of reactive oxygen species generation and apoptosis level. An animal model of heart failure was established by intraperitoneal injection of Dox in vivo, therapy mice were received additional intracardiac injection of TSC-Exos, then, the cardiac function, cardiomyocyte apoptosis and mitochondrial fragmentation were ameliorated. Histology assays suggest that Dox caused an increased tendency of mitochondrial fission, which was manifested by a decrease in the average size of mitochondria. By receiving TSC-Exos treatment, this effect was eliminated. In summary, these results suggest that TSC-Exos alleviate DOX-induced cardiotoxicity through antiapoptotic effect and improving mitochondrial fusion with an increase in Mfn2 expression. This study is the first to provide a potential new treatment scheme for the treatment of heart failure from the perspective of the relationship between TSC-Exos and mitochondrial dynamics.

目的:研究补肾强督治偻方(BSQD)的抗炎和免疫调节作用,为其临床治疗强直性脊柱炎(AS)提供科学依据.方法:利用脂多糖(LPS)刺激RAW264.7细胞构建体外炎症模型.在该模型上,分别运用噻唑蓝(MTT)实验检测细胞活性;格里斯试剂法(Griess)检测细胞上清液中一氧化氮(NO)含量;RT-PCR检测炎症相关基因mRNA的表达;免疫荧光检测蛋白的表达;高效液相色谱(HPLC)进行有效成分的鉴定.结果:MTT比色法显示浓度为400 μg/mL以内的BSQD对细胞活性无明显影响.与模型组比较,BSQD显著降低NO的释放(P＜0.01);在mRNA水平上,BSQD和塞来昔布均能显著降低LPS诱导的RAW264.7细胞上调的TNF-α、IL-6、IL-17、RORγt mRNA的表达(P＜0.01);蛋白水平上,免疫荧光结果显示高剂量的BSQD和塞来昔布均能明显抑制RAW264.7细胞IL-17的蛋白表达(P＜0.01);通过HPLC鉴定出BSQD水煎液中6种活性成分,分别为绿原酸、芒果苷、芍药内酯苷、补骨脂苷、芍药苷和蛇床子素.结论:BSQD具有较为显著的抗炎和免疫调节作用,是其治疗AS的现代生物学基础之一.

鼻咽癌是头颈部发病率和死亡率最高的恶性肿瘤之一,中医药干预给鼻咽癌患者带来较大的受益.本文介绍李云英分阶段治疗鼻咽癌经验.李云英认为鼻咽癌的中医论治可根据患者是否接受放化疗分为三阶段:放化疗前、放化疗中和放化疗后.放化疗前:实者泻之,消肿散结、解毒抗癌;放化疗中:攻补兼施、减毒增效,减轻毒副反应;放化疗后:补虚扶正、顾护气阴,治疗后遗症.鼻咽癌的中医分阶段疗法有提纲挈领、执简驭繁之效用,疗效确切,临床灵活运用对患者大有裨益,值得推广.

目的 探讨二陈汤合会厌逐瘀汤治疗喉癌的可能作用机制.方法 采用Hep2喉癌细胞株异位移植法建立喉癌荷瘤小鼠模型,将模型小鼠分为对照组,合方低、中、高剂量组,顺铂组,每组7只.合方低、中、高剂量组分别给予二陈汤合会厌逐瘀汤14.44、28.87、57.74g/(kg·d)灌胃,每日1次;顺铂组给予浓度为2 mg/kg的顺铂腹腔注射,隔日1次;对照组灌胃等体积蒸馏水,各组均给药3周.采用RT-PCR法检测小鼠肿瘤组织程序性死亡蛋白配体1(PD-L1)、白细胞介素6(IL-6)mRNA表达水平,Western blot法检测小鼠肿瘤组织PD-L1、磷酸化蛋白质酪氨酸激酶(p-JAK)、信号转导和转录活化因子3(STAT3)、磷酸化信号转导和转录活化因子3(p-STAT3)蛋白表达,免疫组化法检测小鼠肿瘤组织PD-L1蛋白表达.结果 与对照组比较,合方低、中、高剂量组和顺铂组小鼠肿瘤组织PD-L1 mRNA及蛋白表达均下降,合方低、中、高剂量组IL-6 mRNA表达亦下降,合方中、高剂量组和顺铂组STAT3、p-STAT3蛋白表达下降,合方高剂量组p-JAK1蛋白表达下降(P＜0.01).合方高剂量组PD-L1、IL-6 mRNA表达均低于合方低、中剂量组及顺铂组,合方高剂量组PD-L1蛋白表达低于合方中剂量组和顺铂组,合方高剂量组STAT3蛋白表达低于合方低、中剂量组和顺铂组,合方高剂量组p-STAT3蛋白表达低于合方中、低剂量组(P＜0.05或P＜0.01).结论 二陈汤合会厌逐瘀汤可能通过抑制IL-6/JAK1/STAT3信号通路,从而降低喉癌荷瘤裸鼠肿瘤组织PD-L1表达而发挥对喉癌的治疗作用,且以高剂量效果最好.

Erchen plus Huiyanzhuyu decoction (EHD), a Chinese herbal medicine (CHM) formula that consists of Erchen decoction and Huiyanzhuyu decoction, has achieved satisfactory results in the clinic. The main function of EHD is to remove phlegm and blood stasis, and EHD is suitable for phlegm-coagulation-blood-stasis (PCBS) syndrome in laryngeal cancer (LC). In this study, a xenograft mouse model of LC with PCBS syndrome was constructed by feeding a high-fat diet, swimming in ice water, and subcutaneously injecting epinephrine hydrochloride for 2 weeks. Based on the successful Chinese medicine syndrome model, Hep2-luciferase-GFP cells were injected subcutaneously under the armpit of the right upper limb in mice to form tumours. A mouse model of LC with PCBS syndrome was established via heterotopic transplantation. Then, the mice received intragastric administration of different concentrations of EHD daily, and cisplatin (DDP) was intraperitoneally injected every week for 21 days. Tumour fluorescence in mice was measured with a living animal imager on days 7, 14, 21, and 28 during treatment. The results of this experiment confirmed that a mouse model of Chinese medicine syndrome was successfully constructed. Moreover, EHD slowed the growth of xenograft tumours in nude mice; decreased the expression levels of STAT3, p-STAT3, and cyclin D1; and upregulated the expression level of P27. In brief, EHD inhibited laryngeal tumour growth in a xenograft mouse model of PCBS syndrome and regulated the STAT3/cyclin D1 signalling pathway. This study was the first to construct a Chinese medicine xenograft mouse model of LC with PCBS syndrome; in addition, this study clarified that EHD regulated the STAT3/cyclin D1 signalling pathway to inhibit the growth of LC and that EHD may be a promising novel therapeutic compound for the treatment of patients with LC.