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The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment (TIME). This study aimed to mechanistically assess whether Chang Wei Qing (CWQ) Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy. PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), rather than those with mismatch repair-proficient/microsatellite stable (pMMR/MSS) CRC. Hence, immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients. Flow cytometry was used to analyze T-lymphocytes in tumors from mice. Western blot was used to measure the expression of PD-L1 protein in mouse tumors. The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry. 16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice. Subsequently, Spearmanapos;s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes. The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins. In vivo, CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+ and PD-1+CD8+ T cells in tumors. Additionally, the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone. CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes, andActinobacteria. Additionally, the proportion of infiltrated CD8+PD-1+, CD8+, and CD3+ T cells were found to be positively correlated with the abundance of Akkermansia. Accordingly, CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.
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Neoplasias del Colon , Neoplasias Colorrectales , Microbioma Gastrointestinal , Animales , Ratones , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Linfocitos T CD8-positivos , Antígeno B7-H1 , ARN Ribosómico 16S , Neoplasias Colorrectales/metabolismo , Microambiente TumoralRESUMEN
Objective: Stent-assisted coiling has been increasingly used in the treatment of intracranial aneurysms. However, its application in ruptured bifurcation aneurysms remains controversial and challenging. This study aimed to present the safety and feasibility of low-profile visualized intraluminal support (LVIS™, LVIS, and LVIS Jr.) stent for acutely ruptured bifurcation aneurysms. Methods: A total of 41 patients with acutely ruptured intracranial aneurysms arising at the bifurcation were treated with LVIS™ stent-assisted coiling in our hospital between January 2017 and December 2021. The clinical data and angiographic results of the patients were analyzed. Results: Among these patients, all stents were successfully implanted. According to the immediate angiographic results, 29 aneurysms (70.7%) were completely occluded. Intraoperative thrombosis and hemorrhage occurred in two and one cases, respectively. No post-operative thrombosis or rebleeding events were observed. The clinical follow-up of all patients revealed that 38 (92.7%) cases had favorable outcomes (modified Rankin scale: 0-2). The angiographic results available for the 36 patients during the follow-up period revealed complete occlusion was achieved in 30 patients (83.3%) and residual neck in six patients. Conclusion: The LVIS™ stent-assistant coiling is a safe and feasible option for acutely ruptured bifurcation aneurysms. Further studies with a prospective design, a larger sample size, and long-term follow-up are needed to validate these findings.
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The endovascular intervention technique has gained prominence in the treatment of intracranial aneurysms due to its minimal invasiveness and shorter recovery time. A critical step of the intervention is the shaping of the microcatheter, which ensures its accurate placement and stability within the aneurysm sac. This is vital for enhancing coil placement and minimizing the risk of catheter kickback during the coiling process. Currently, microcatheter shaping is primarily reliant on the operator's experience, who shapes them based on the curvature of the target vessel and aneurysm location, utilizing 3D rotational angiography or CT angiography. Some researchers have documented their experiences with conventional shaping methods. Additionally, some scholars have explored auxiliary techniques such as 3D printing and computer simulations to facilitate microcatheter shaping. However, the shaping of microcatheters can still pose challenges, especially in cases with complex anatomical structures or very small aneurysms, and even experienced operators may encounter difficulties, and there has been a lack of a holistic summary of microcatheter shaping techniques in the literature. In this article, we present a review of the literature from 1994 to 2023 on microcatheter shaping techniques in endovascular aneurysm embolization. Our review aims to present a thorough overview of the various experiences and techniques shared by researchers over the last 3 decades, provides an analysis of shaping methods, and serves as an invaluable resource for both novice and experienced practitioners, highlighting the significance of understanding and mastering this technique for successful endovascular intervention in intracranial aneurysms.
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Objective: To evaluate the prognostic ability of systemic immune-inflammation index (SII) combine with quick Sequential Organ Failure Assessment (qSOFA) criteria in predicting the 28-day mortality of sepsis. Methods: A retrospective cohort study was conducted, with the population comprised in whom sepsis was confirmed. Clinical and laboratory data recorded were analyzed. The score of Sequential Organ Failure Assessment (SOFA), SII, qSOFA were calculated. Multivariable regression, receiver operating characteristic (ROC) analysis and Kaplan-Meier method were used to identify and compared the predictors of prognosis among SOFA, qSOFA, and the combination of SII with qSOFA. Results: A total of 349 patients admitted from December 2020 and December 2022 were included in the cohort. 95 (27.2%) of whom had died by day 28. The SII, SOFA, and qSOFA scores were significant higher in the non-survivors than that of survivors (P < 0.05), and identified as independent predictors of sepsis mortality. The addition of SII to qSOFA shown an area under receiver operator characteristic (AUROC) of 0.840 (95% CI: 0.787-0.884), manifested an effective ability in predicting poor outcome than other scoring systems. The optimum cutoff for SII (>1.7668) and qSOFA (>1) represented a high risk level in 28-day mortality of sepsis, were performed and identified in Kaplan-Meier survival curves (log-rank test, HR: 6.942, 95% CI: 3.976-12.121; P < 0.0001). Conclusion: The SII in addition to qSOFA provided an effective prognostic tool for predicting mortality in sepsis.
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Objective: Reyanning mixture has been demonstrated to be effective in treating infected patients during the outbreak pandemic of SARS-CoV-2 Omicron variant of Coronavirus disease 2019 (COVID-19) in Shanghai 2022. The aim of this study is to further investigate the role of Reyanning mixture specifically in the treatment of elderly patients. Methods: This study enrolled 1,102 elderly patients who were infected with SARS-CoV-2 Omicron variant. Of these, 291 patients received Reyanning mixture in conjunction with conventional Western medicine treatment were assigned to the treatment group, while 811 patients only received conventional Western medicine treatment were assigned to the control group. Clinical parameters including hospitalization duration, viral shedding time, and Cycle Threshold (Ct) values of novel coronavirus nucleic acid tests, as well as adverse events were recorded and analyzed in both groups. Results: There was no significant difference in baseline characteristics between two groups. In comparison to the control group, the treatment group demonstrated a substantial difference in hospitalization duration (median: 8 days vs. 10 days, HR: 0.638, 95% CI: 0.558-0.731, p < 0.001). The treatment group also showed a significantly shorter viral shedding time compared to the control group (median: 7 days vs. 8 days, HR: 0.754, 95% CI: 0.659-0.863, p < 0.001). Multivariate Cox proportional-hazards model analysis indicated that the use of Reyanning mixture was closely associated with a reduction in hospitalization duration (HR: 1.562, 95% CI: 1.364-1.789, p < 0.001) and viral shedding time (HR: 1.335, 95% CI: 1.166-1.528, p < 0.001). In addition, during the treatment process, no serious adverse event occurred in either group. Conclusion: The improvement of clinical parameters in the treatment group indicate a promising therapeutic benefit of Reyanning mixture for elderly patients infected with SARS-CoV-2 Omicron variant in the present study. Further investigations are required to validate this finding by examining the underlying mechanism and function of Reyanning mixture.
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Traditional Chinese medicine (TCM), including herbal medicine, acupuncture and meditation, has a wide range of applications in China. In recent years, herbal compounding and active ingredients have been used to control tumor growth, reduce suffering, improve quality of life, and prolong the life span of cancer patients. To reduce side effects, herbal medicine can be used in conjunction with radiotherapy and chemotherapy or can be used as an adjuvant to strengthen the immune effect of anticancer vaccines. In particular, in the immunosuppressed tumor microenvironment, herbal medicine can have antitumor effects by stimulating the immune response. This paper reviews the advances in research on antitumor immunomodulation in Chinese herbal medicine, including the regulation of the innate immune system, which includes macrophages, MDSCs, and natural killer cells, and the adaptive immune system, which includes CD4+ T cells, CD8+ T cells, and regulatory T cells (Tregs), to influence tumor-associated inflammation. In addition, a combination of active ingredients of herbal medicine and modern nanotechnology alter the tumor immune microenvironment. In recent years, immunological antitumor therapy in TCM has been applied on a reasonably large scale both nationally and internationally, and there is potential for further clinical expansion. Investigation of immune modulation mechanisms in Chinese herbal medicine will provide novel perspectives of how herbal medicine controls tumor growth and metastasis, which will contribute to the evolution of tumor research. Methodology: Experimental research between the years of 2012-2022, meta-analysis and reviews for the period 2002-2022 found on the Databases including PubMed, Embase, and the Cochrane database were used. The inclusion criteria were experimental research literature addressing the anti-tumor immunological effects of active ingredients and nanoparticles in Chinese herbal medicine. Exclusion criteria were articles that addressed Chinese herbal medicine and nano-formulations without discussing anti-tumor immunological effects in innate, adaptive immune cells, MDSCs, and nuclear factors.
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Quercetin can significantly inhibit the progression of colorectal cancer (CRC). However, its specific mechanism remains largely unclear. In this study, we aimed to explore the correlation among quercetin, tumour-associated macrophages (TAMs) and circular RNAs (circRNAs) in the progression of CRC and to present a novel strategy for the treatment of CRC. In this study, we revealed that quercetin could suppress the autophagy of M2-TAMs and induced their differentiation into M1-TAMs, by which quercetin significantly reversed the inhibition of M2-TAMS on CRC cell apoptosis and the promotion of M2-TAMS on CRC cell proliferation. Moreover, quercetin could promote the expression of downregulated hsa_circ_0006990 in CRC cells co-cultured with M2-TAMs, and the overexpression of hsa_circ_0006990 significantly reversed the anti-tumour effect of quercetin on CRC. Furthermore, we found quercetin can notably suppress the progression of CRC via mediation of the hsa_circ_0006990/miR-132-3p/MUC13 axis. In conclusion, our results suggested that quercetin inhibits the tumorigenesis of CRC via inhibiting the polarisation of M2 macrophages and downregulating hsa_circ_0006990. Our study provides useful insights for those exploring new methods of treating CRC.
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Objective: C49 is a chalcone derivative. The aim of the current study is to illuminate the efficacy of C49 in reversing multidrug resistance (MDR) in MCF-7/DOX cells and its underlying molecular mechanism. Methods: The cytotoxic effects of C49 on MCF-7/DOX cells were evaluated by MTT assay using different concentration (0-250 µmol/L) of C49. Cell proliferation was evaluated by colony formation assay. Cell death was examined by morphological analysis using Hoechst 33,258 staining. Flow cytometry and immunofluorescence were utilized to evaluate the intracellular accumulation of doxorubicin (DOX) and cell apoptosis. The differentially expressed genns between MCF-7 and MCF-7/DOX cells were analyzed by GEO database. The expression of PI3K/Akt pathway proteins were assessed by Western blot The activities of C49 combined with DOX was evaluated via xenograft tumor model in female BALB/c nude mice. Results: C49 inhibited the growth of MCF-7 cells (IC50 = 59.82 ± 2.10 µmol/L) and MCF-7/DOX cells (IC50 = 65.69 ± 8.11 µmol/L) with dosage-dependent and enhanced the cellular accumulation of DOX in MCF-7/DOX cells. The combination of C49 and DOX inhibited cell proliferation and promoted cell apoptosis. MCF-7/DOX cells regained drug sensibility with the combination treatment through inhibiting the expression of P-gp, p-PI3K and p-Akt proteins. Meanwhile, C49 significantly increased the anticancer efficacy of DOX in vivo. Conclusion: C49 combined with DOX restored DOX sensitivity in MCF-7/DOX cells through inhibiting P-gp protein.
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BACKGROUND: Immune checkpoint inhibitor therapy for non-small cell lung cancer is widely used in clinical practice. However, there has not been a systematic statistical proof of the efficacy of PD-1 inhibitors in patients with advanced cancer. This meta-analysis aims to evaluate its efficacy and related influencing factors, so as to provide a basis for clinical diagnosis and treatment. OBJECTIVE: To assess the effectiveness and safety of programmed death-1 (PD-1)/PD ligand 1 (PD-L1) inhibitors versus chemotherapy as second-line or late-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) via a systematic review of published randomized controlled trials (RCTs). METHODS: Studies were identified through PubMed, EMBASE, and Cochrane Library electronic databases. RevMan 5.3.5 was used to analyze the data extracted from all eligible studies. RESULTS: All 4122 eligible patients from 8 RCTs were included in this study. The meta-analysis showed that PD-1/PD-L1 inhibitors could significantly improve overall survival (hazards ratio [HR] 0.71, 95% confidence interval [CI] 0.66-0.77, Pâ<â.001), progression-free survival (HR 0.88, 95%CI 0.81-0.94, Pâ=â.01), and objective response rate (HR 2.03, 95%CI 1.66-2.49, Pâ<â.001) compared with chemotherapy drugs. The incidence of side effects of any grade (HR 0.34, 95%CI 0.29-0.39, Pâ<â.001) or grades 3 to 5 (HR 0.15, 95%CI 0.10-0.23, Pâ<â.001) consistently showed that PD-1/PD-L1 inhibitors were safer than chemotherapy. Furthermore, subgroup analysis based on tumor proportion score or pathology classification revealed that PD-1/PD-L1 inhibitors significantly improved overall survival compared with chemotherapy. CONCLUSION: As a second-line or late-line treatment, PD-1/PD-L1 inhibitors are safer and more effective than chemotherapy in patients with advanced NSCLC.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Adolescente , Adulto , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Adulto JovenRESUMEN
Due to the sequelae and recurrence in patients with COVID-19 after recovery. This article, based on the theory of "preventive treatment of diseases" in traditional Chinese medicine, which believes that the three pathogenic factors of epidemic toxin, dampness, and lung deficiency are the fundamental causes of the recurrence of COVID-19. The treatment strategies are to remove pathogenic factors, strengthen qi, nourish yin, clear heat, moisten dryness, and at the same time, reinforce the lung, spleen and kidney, and soothe the liver. Through a variety of treatments such as oral administration, external treatment, and skin absorption, it provides a new idea and method for the management of the recurrence of COVID-19.