Clinical efficacy and potential mechanism of ginseng polysaccharides in the treatment of non-small cell lung cancer based on meta-analysis associated with network pharmacology.

Background: The ginseng polysaccharide injection is a well-known traditional Chinese medicine often employed as a supplementary treatment for cancer. This treatment can not only alleviate the adverse effects caused by tumor radiotherapy and chemotherapy but also enhance the immune system of individuals diagnosed with lung cancer. It is important to acknowledge the efficacy of ginseng polysaccharide injection in the treatment of non-small cell lung cancer (NSCLC). However, these small-sample studies may have certain biases, and the underlying mechanisms of ginseng polysaccharides therapy for NSCLC are still unclear. Methods: The present study involved a systematic review of the literature on randomized controlled trials (RCTs) focusing on using ginseng polysaccharide injection as a therapeutic approach for NSCLC. Seven databases were searched for eligible studies published before April 2023. Two researchers independently managed data extraction, risk of bias assessment, and data analyses using RevMan 5.3 software. In network pharmacology, we thoroughly searched the relevant literature on ginseng polysaccharides (GPs) and the PubChem database. This search aimed to identify the main active ingredients and targets associated with ginseng polysaccharides. Subsequently, we compared these targets with those of NSCLC and utilized bioinformatics techniques to analyze and explore their potential interactions. Results: A total of 11 RCTs involving 845 patients with NSCLC were included in the meta-analysis. The meta-analysis revealed that ginseng polysaccharide injection combined significantly improved the objective response rate [RR = 1.45, 95% CI (1.26, 1.67), P < 0.00001]. Furthermore, it was observed that ginseng polysaccharide injection increased the serum levels of CD4+ T-lymphocytes (CD4+ T) [MD = 8.98, 95% CI (5.18, 12.78), P < 0.00001], and decreased the serum levels of CD8+ T-lymphocytes (CD8+ T) [MD = -2.68, 95% CI (-4.66, -0.70), P = 0.008]. Through network pharmacology analysis, a total of 211 target genes of GPs and 81 common targets were identified. GAPDH, EGFR, VEGFA, JUN, SRC, CASP3, STAT3, CCND1, HSP90AA1, and MMP9 were identified as the core target proteins. Additionally, KEGG enrichment analysis revealed 122 relevant signaling pathways, including Pathways in cancer, PD-L1 expression and PD-1 checkpoint pathway in cancer, and Proteoglycans in cancer. Conclusion: Ginseng polysaccharide injection can improve the ORR of patients with NSCLC, increase the serum levels of CD4+ T, and decrease the serum levels of CD8+ T. The potential mechanism may be associated with the PD-1/PD-L1 signaling pathway.

Exploration of Molecular Targets and Mechanisms of Curcumin in the Treatment of COVID-19 with Depression by an Integrative Pharmacology Strategy.

BACKGROUND: Coronavirus disease 2019 (COVID-19) not only causes a range of respiratory symptoms but also has a great impact on individual mental health. With the global pandemic of SARS-CoV-2, the incidence of COVID-19 comorbid with depression has increased significantly. Curcumin, a natural polyphenol compound, has been shown to have antidepressant and anti-coronavirus activities. METHODS: This study aimed to explore the molecular targets and underlying biological mechanisms of curcumin in the treatment of COVID-19 with depression through an integrative pharmacology strategy, including target prediction, network analysis, PPI analysis, GO and KEGG enrichment analyses, and molecular docking. RESULTS: After a comprehensive search and thorough analysis, 8 core targets (ALB, AKT1, CASP3, STAT3, EGFR, PTGS2, FOS, and SERPINE1) were identified. GO and KEGG enrichment analysis results revealed that the pathways related to viral infection, immune regulation, neuronal reorganization, apoptosis, and secretion of inflammatory cytokines were involved in the pathological process. Furthermore, molecular docking showed that curcumin could spontaneously bind to the SARS-CoV-2-related receptor proteins and the core targets with a strong binding force. CONCLUSION: The potential pharmacological mechanisms of curcumin in COVID-19 comorbid depression were evaluated. Curcumin can be used as a therapeutic agent for COVID-19 comorbid depression. One of the potential mechanisms may be to reduce the inflammatory response and suppress the cytokine storm by regulating the JAK-STAT signaling pathway and MAPK signaling pathway. These findings may help to overcome the impact of the COVID-19 pandemic on psychological health.

Effect of Cinobufacini plus platinum-based chemotherapy regimen on the immune function of patients with non-small-cell lung cancer: A meta-analysis.

Background: Cinobufacini is a Chinese medicinal preparation extracted from the traditional Chinese medicine toad skin and is commonly used clinically as an adjuvant treatment for malignant tumours. Purpose: To systematically evaluate the effects of Cinobufacini combined with a first-line platinum-based chemotherapy regimen in patients with non-small-cell lung cancer (NSCLC), especially in terms of immune function. Materials and methods: Eight electronic databases were searched for randomised controlled trials (RCTs) investigating Cinobufacini in conjunction with platinum-based chemotherapy for NSCLC (stage III-IV) published from 2012 to the present. GRADE Pro GDT was used to assess RCT quality and meta-analysis was performed mainly using Review Manager version 5.4, with the assistance of Stata version 16.0 (StataCorp LLC, College Station, TX, USA), and trial sequential analysis software. Results: A total of 35 studies were included. Meta-analysis revealed that the combination therapy group exhibited a better disease control rate (DCR) [OR = 2.63, 95%CI (2.15, 3.21), P < 0.00001], with a higher one-year [OR = 2.41,95% CI (1.75,3.33), P < 0.00001], and two-year [OR = 2.28, 95% CI (1.56,3.33), P < 0.00001] survival rate, plus lower leukocyte toxicity [OR = 0.40, 95%CI (0.33,0.49), P < 0.00001]. For immune function, the combination of chemotherapy with Cinobufacini effectively increased the proportion of CD3+ [SMD = 1.15, 95% CI (0.89,1.42), P < 0.00001], CD4+ [SMD = 1.60, 95%CI (1.26,1.94), P < 0.00001] and the CD4+/CD8+ ratio [SMD = 2.15, 95% CI (1.45,2.86), P < 0.00001] in peripheral blood. Conclusion: The addition of Cinobufacini to platinum-based chemotherapies for advanced NSCLC significantly improved clinical efficacy, enhanced immune function, and reduced chemotherapeutic toxicity, irrespective of administration and treatment duration.

Clinical efficacy and safety of NSCLC ancillary treatment with compound Kushen injection through immunocompetence regulation: A systematic review and meta-analysis.

BACKGROUND: Compound Kushen injection (CKI) is a Chinese patented medicine that improves the immunity level of cancer patients and inhibits tumor cell proliferation and metastasis. Clinically, CKI is widely used in combination with platinum-based chemotherapy (PBC) for non-small cell lung cancer (NSCLC) treatment. This study attempted to systemically evaluate the efficacy and safety of a combination of CKI and PBC for NSCLC treatment by modulating the immune function. PURPOSE: To evaluate the clinical efficacy and safety of CKI in combination with PBC for NSCLC. MATERIALS AND METHODS: English and Chinese databases were retrieved for randomized controlled trials (RCTs) of NSCLC treatment using a combination of CKI and PBC, and the changes of peripheral blood T lymphocytes (such as CD3+ T cells, CD4+ T cells, CD8+ T cells), and CD4+/CD8+ T cell ratio among NSCLC patients were detected before and after treatment using CKI with PBC. The search deadline was set as November 2021. The systemic evaluation was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodology and quality of each study included in the systemic evaluation were assessed. Review Manager 5.4, Stata12.0, and trial sequential analysis (TSA) were used for data analysis. The outcome indicators were qualified using GRADEprofiler software. RESULTS: A total of 25 RCTs involving 2460 cases of patients were included. The results showed that the combination of CKI with PBC effectively increased the objective response rate (ORR) [relative risk (RR) = 1.31, 95% confidence interval (CI) (1.19, 1.44)] and disease control rate (DCR) [RR = 1.16, 95%CI (1.09,1.23)], regulated the expression of peripheral blood T lymphocytes (such as CD3+T cells, CD4+T cells, CD8+T cells, and CD4+/CD8+T cell ratio), upregulated the level of serum immunoglobulins (such as IgA, IgG, and IgM), and reduced the frequency of gastrointestinal reaction, marrow inhibition, hepatorenal toxicity, reduction of white blood cells and blood platelets, baldness, infection, neutrophilic granulocyte counts, diarrhea, or constipation. According to subgroup analysis results, chemotherapy cycles (1-2) had a more significant effect on DCR. A combination of CKI and GP regimens had better effects on improving CD3+T cell levels, and there were no significant changes among other chemotherapies regiments. CONCLUSION: A combination of CKI and PBC had a marked effect in improving tumor response, priming immune function, and decreasing the frequency of adverse reactions, which was safe for NSCLC treatment.

Effect of kangai injection combined with platinum-based chemotherapy on the immune function of patients with advanced non-small-cell lung cancer: A meta-analysis.

BACKGROUND: Kangai injection (KAI) is a well-known Chinese patent medicine applied for several different types of cancers in the clinic as an auxiliary therapeutic approach, which is refined from three herbal extracts (Astragalus, Ginseng and Matrine). PURPOSE: To systematically evaluate the effect of combination treatment of platinum-based chemotherapy and KAI on patients with advanced non-small-cell lung cancer (NSCLC). STUDY DESIGN: A meta-analysis of randomized clinical trials. MATERIALS AND METHODS: The randomized controlled trials (RCTs) about stage Ⅲ-Ⅳ NSCLC using KAI combined platinum-based chemotherapy were electronically retrieved from eight electronic databases up to July 2021. We applied RevMan 5.4, Stata 16.0, TSA 0.9.5.10 Beta and GRADE Pro-GDT to evaluate the quality of the included RCTs and perform the meta-analysis. RESULTS: 19 RCTs were included, consisting a total sample size of 1,389 cases. Meta-analysis revealed that compared with chemotherapy alone, KAI combined with platinum-based chemotherapy was associated with significantly higher objective response rate (ORR) [RR = 1.36, 95%CI (1.21,1.54), p< 0.00001], higher disease control rate (DCR) [RR = 1.15, 95%CI (1.09,1.21), p< 0.00001], greater Karnofsky performance status (KPS) [RR = 1.75, 95%CI (1.41,2.18), p< 0.00001], lower white blood cell toxicity [RR = 0.67, 95%CI (0.55,0.82), p = 0.0001], lower platelet toxicity [RR = 0.60, 95%CI (0.47,0.75), P  < 0.0001], and lower incidence of vomiting [RR = 0.66, 95%CI (0.57,0.76), p< 0.00001]. In terms of the immune function, KAI united with chemotherapy significantly raised the ratio of CD3+ cells [MD = 10.65, 95%CI (8.21,13.09), p< 0.00001], CD4+ cells [MD = 7.67, 95%CI (6.31,9.03), p< 0.00001], NK cells [MD = 4.97, 95%CI (3.03,6.92), p< 0.00001], and CD4+/ CD8+ [MD = 0.32, 95%CI (0.19,0.45), p< 0.00001], and decreased the percentage of CD8+ cells [MD = -5.56, 95%CI (-7.51,-3.61), p< 0.00001]. CONCLUSIONS: This meta-analysis identified that the combination treatment of KAI and platinum-based chemotherapy was more beneficial to patients with advanced NSCLC when compared to chemotherapy alone, which could significantly improve the clinical efficacy, enhance the immune function, and reduce chemotherapy toxicity. Our study provides a theoretical basis and treatment guidance for patients with NSCLC.

Cognitive Computing-Based CDSS in Medical Practice.

Importance. The last decade has witnessed the advances of cognitive computing technologies that learn at scale and reason with purpose in medicine studies. From the diagnosis of diseases till the generation of treatment plans, cognitive computing encompasses both data-driven and knowledge-driven machine intelligence to assist health care roles in clinical decision-making. This review provides a comprehensive perspective from both research and industrial efforts on cognitive computing-based CDSS over the last decade.Highlights. (1) A holistic review of both research papers and industrial practice about cognitive computing-based CDSS is conducted to identify the necessity and the characteristics as well as the general framework of constructing the system. (2) Several of the typical applications of cognitive computing-based CDSS as well as the existing systems in real medical practice are introduced in detail under the general framework. (3) The limitations of the current cognitive computing-based CDSS is discussed that sheds light on the future work in this direction.Conclusion. Different from medical content providers, cognitive computing-based CDSS provides probabilistic clinical decision support by automatically learning and inferencing from medical big data. The characteristics of managing multimodal data and computerizing medical knowledge distinguish cognitive computing-based CDSS from other categories. Given the current status of primary health care like high diagnostic error rate and shortage of medical resources, it is time to introduce cognitive computing-based CDSS to the medical community which is supposed to be more open-minded and embrace the convenience and low cost but high efficiency brought by cognitive computing-based CDSS.

Vitamin A equivalency and apparent absorption of beta-carotene in ileostomy subjects using a dual-isotope dilution technique.

The objective was to quantify the vitamin A equivalency of beta-carotene in two diets using a dual-isotope dilution technique and the apparent beta-carotene absorption as measured by the oral-faecal balance technique. Seventeen healthy adults with an ileostomy completed the 4-week diet-controlled, cross-over intervention study. Each subject followed both diets for 2 weeks: a diet containing vegetables low in beta-carotene content with supplemental beta-carotene in salad dressing oil ('oil diet'; mean beta-carotene intake 3.1 mg/d) and a diet containing vegetables and fruits high in beta-carotene content ('mixed diet'; mean beta-carotene intake 7.6 mg/d). Daily each subject consumed a mean of 190 microg [13C10]beta-carotene and 195 microg [13C10]retinyl palmitate in oil capsules. The vitamin A equivalency of beta-carotene was calculated as the dose-corrected ratio of [13C5]retinol to [13C10]retinol in serum. Apparent absorption of beta-carotene was determined with oral-faecal balance. Isotopic data quantified a vitamin A equivalency of [13C10]beta-carotene in oil of 3.6:1 (95 % CI 2.8, 4.6) regardless of dietary matrices differences. The apparent absorption of (labelled and dietary) beta-carotene from the 'oil diet' (30 %) was 1.9-fold higher than from the 'mixed diet' (16 %). This extrinsic labelling technique can measure precisely the vitamin A equivalency of beta-carotene in oil capsules, but it does not represent the effect of different dietary matrices.

Vitamin A equivalency of beta-carotene in healthy adults: limitation of the extrinsic dual-isotope dilution technique to measure matrix effect.

Data on the vitamin A equivalency of beta-carotene in food are inconsistent. We quantified the vitamin A equivalency (microg) of beta-carotene in two diets using the dual-isotope dilution technique and the oral-faecal balance technique. A diet-controlled, cross-over intervention study was conducted in twenty-four healthy adults. Each subject followed two diets for 3 weeks each: a diet containing vegetables low in beta-carotene with supplemental beta-carotene in salad dressing oil ('oil diet') and a diet containing vegetables and fruits high in beta-carotene ('mixed diet'). During all 6 weeks, each subject daily consumed a mean of 55 (sd 0.5) microg [13C10]beta-carotene and 55 (sd 0.5) microg [13C10]retinyl palmitate in oil capsules. The vitamin A equivalency of beta-carotene was calculated as the dose-corrected ratio of [13C5]retinol to [13C10]retinol in serum and from apparent absorption by oral-faecal balance. Isotopic data quantified a vitamin A equivalency of [13C10]beta-carotene in oil of 3.4 microg (95 % CI 2.8, 3.9), thus the bio-efficacy of the beta-carotene in oil was 28 % in the presence of both diets. However, data from oral-faecal balance estimated vitamin A equivalency as 6:1 microg (95 % CI 4, 7) for beta-carotene in the 'oil diet'. beta-Carotene in the 'oil diet' had 2.9-fold higher vitamin A equivalency than beta-carotene in the 'mixed diet'. In conclusion, this extrinsic labelling technique cannot measure effects of mixed vegetables and fruits matrices, but can measure precisely the vitamin A equivalency of the beta-carotene in oil capsules.