Clinical Efficacy and Gut Microbiota Regulating-Related Effect of Si-Jun-Zi Decoction in Postoperative Non-Small Cell Lung Cancer Patients: A Prospective Observational Study.

BACKGROUND: Postoperative non-small cell lung cancer (NSCLC) patients frequently encounter a deteriorated quality of life (QOL), disturbed immune response, and disordered homeostasis. Si-Jun-Zi Decoction (SJZD), a well-known traditional Chinese herbal formula, is frequently employed in clinical application for many years. Exploration is underway to investigate the potential therapeutic effect of SJZD for treating postoperative NSCLC. OBJECTIVE: To assess the efficacy of SJZD on QOLs, hematological parameters, and regulations of gut microbiota in postoperative NSCLC patients. METHODS: A prospective observational cohort study was conducted, enrolling 65 postoperative NSCLC patients between May 10, 2020 and March 15, 2021 in Yueyang Hospital, with 33 patients in SJZD group and 32 patients in control (CON) group. The SJZD group comprised of patients who received standard treatments and the SJZD decoction, while the CON group consisted of those only underwent standard treatments. The treatment period was 4 weeks. The primary outcome was QOL. The secondary outcomes involved serum immune cell and inflammation factor levels, safety, and alterations in gut microbiota. RESULTS: SJZD group showed significant enhancements in cognitive functioning (P = .048) at week 1 and physical functioning (P = .019) at week 4. Lung cancer-specific symptoms included dyspnea (P = .001), coughing (P = .008), hemoptysis (P = .034), peripheral neuropathy (P = .019), and pain (arm or shoulder, P = .020, other parts, P = .019) eased significantly in the fourth week. Anemia indicators such as red blood cell count (P = .003 at week 1, P = .029 at week 4) and hemoglobin (P = .016 at week 1, P = .048 at week 4) were significantly elevated by SJZD. SJZD upregulated blood cell cluster differentiation (CD)3+ (P = .001 at week 1, P < .001 at week 4), CD3+CD4+ (P = .012 at week 1), CD3+CD8+ (P = .027 at week 1), CD19+ (P = .003 at week 4), increased anti-inflammatory interleukin (IL)-10 (P = .004 at week 1, P = .003 at week 4), and decreased pro-inflammatory IL-8 (P = .004 at week 1, p = .005 at week 4). Analysis of gut microbiota indicated that SJZD had a significant impact on increasing microbial abundance and diversity, enriching probiotic microbes, and regulating microbial biological functions. CONCLUSIONS: SJZD appears to be an effective and safe treatment for postoperative NSCLC patients. As a preliminary observational study, this study provides a foundation for further research.

Predicting the mechanism of action of YQYYJD prescription in the treatment of non-small cell lung cancer using transcriptomics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Yiqi Yangyin Jiedu (YQYYJD) in the treatment of advanced lung cancer has been reported in clinical trials. However, the key anti-lung cancer herbs and molecular mechanisms underlying its inhibition of lung cancer are not well-understood. AIM OF THE STUDY: To identify the key anti-lung cancer herbs in the YQYYJD formula and investigate their therapeutic effect and potential mechanism of action in non-small cell lung cancer (NSCLC) using transcriptomics and bioinformatics techniques. MATERIALS AND METHODS: A mouse Lewis lung carcinoma (LLC) subcutaneous inhibitory tumor model was established with 6 mice in each group. Mice were treated with the YQYYJD split formula: Yiqi Formula (YQ), Yangyin Formula (YY), and Ruanjian Jiedu Formula (RJJD) for 14 days. The tumor volume and mouse weight were recorded, and the status of tumor occurrence was further observed by taking photos. The tumor was stained with hematoxylin-eosin to observe its histopathological changes. Immunohistochemistry was used to detect the expression of the proliferation marker Ki67 and the apoptotic marker Caspase-3 in tumor tissues. Flow cytometry was used to detect the number of CD4+ and CD8+ T cells and cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in the spleen and tumor tissues. The differential genes of key drugs against tumors were obtained by transcriptome sequencing of tumors. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed on differential genes to obtain pathways and biological processes where targets were aggregated. TIMER2.0 and TISIDB databases were used to evaluate the impact of drugs on immune cell infiltration and immune-related genes. The binding activity of the key targets and compounds was verified by molecular docking. RESULTS: YQ, YY, and RJJD inhibited the growth of subcutaneous transplanted tumors in LLC mice to varying degrees and achieved antitumor effects by inhibiting the expression of tumor cell proliferation, apoptosis, and metastasis-related proteins. Among the three disassembled prescriptions, YQ better inhibited the growth of subcutaneous transplanted tumors in LLC mice, significantly promoted tumor necrosis, significantly increased the expression of Caspase-3 protein in tumor tissue, and significantly decreased the expression of Ki-67 (P < 0.05), thereby increasing the infiltration of CD8+ T cells. YQ significantly increased the expression of CD4+ and CD8+ T cells in tumor and splenic tissues of tumor-bearing mice and up-regulated the expression of IL-2 and IFN-γ. Transcriptome sequencing and bioinformatics results showed that after YQ intervention, differentially expressed genes were enriched in more than one tumor-related pathway and multiple immune regulation-related biological functions. There were 12 key immune-related target genes. CONCLUSION: YQ was the key disassembled prescription of YQYYJD, exerting significant antitumor effects and immune regulation effects on NSCLC. It may have relieved T cell exhaustion and regulated the immune microenvironment to exert antitumor effects by changing lung cancer-related targets, pathways, and biological processes.

Intrapleural injection of brucea javanica oil emulsion provided a long-term benefits in patient with malignant pleural effusion from pleural mesothelioma: A case report.

Malignant pleural mesothelioma (MPM) is a severe form of cancer that originates from mesothelium cells. Around 54-90% of mesotheliomas are associated with pleural effusions. Brucea Javanica Oil Emulsion (BJOE) is the processed oil derived from the seeds of Brucea javanica, which has shown potential as a treatment option for several types of cancer. Here, we present a case study of a MPM patient with malignant pleural effusion who received intrapleural injection of BJOE. The treatment resulted in the complete response of pleural effusion and chest tightness. While the precise mechanisms underlying the therapeutic effects of BJOE for pleural effusion are not yet fully understood, it has demonstrated a satisfactory clinical response without significant adverse effects.

Research on Electroacupuncture Parameters for Cancer Pain Based on Data Mining.

BACKGROUND: Cancer pain, a common complication of this disease, has been widely treated by electroacupuncture in recent years. However, there are numerous treatment parameters that are not conducive to clinical translation applications. This study aims to summarize the stimulation parameters commonly used in electroacupuncture treating cancer pain by data mining and visualization techniques to provide a basis for the future acupuncture technology transformation and selection of optimal stimulation parameters. METHODS: Nine databases, including Pubmed, Cochrane Library, Embase, Web of Science, OVID, China National Knowledge Infrastructure Database, China Biology Medicine disk, China Science and Technology Journal Database, and Wanfang Database, were searched for clinical studies on electroacupuncture treatment cancer pain published between January 2012 and September 2022. A database was established using Microsoft Excel 2020 and analyzed with SPSS Modeler 18.1 software and SPSS statistics 26.0 software. RESULTS: Twenty-four articles were included according to the established criteria. The most used electroacupuncture stimulation parameters were a dilatational wave, the current frequency of 2/100 Hz, stimulation duration of 30 minutes per treatment, and frequency of treatment once a day. Fifty-eight acupoints were mentioned, and the total frequency of acupoints involved was 156 times. The most used ones include Zusanli (ST36), Sanyinjiao (SP06), Hegu (LI04), Neiguan (PC06), Quchi (LI11), Taichong (LR03), Ashi point, Jiaji point, and those most generally used acupoints that are closely arranged on the Stomach Channel of Foot Yangming and the Spleen Channel of Foot Taiyin. The association analysis of acupoints revealed that the most supported acupoint pair was Sanyinjiao (SP06) and Zusanli (ST36). Cluster analysis demonstrated 3 groups, 1 for obligatory acupoints, 1 for Ashi point, and the third for Jiaji point. CONCLUSIONS: A dilatational wave, the current frequency of 2/100 Hz, 30-minute stimulation, and acupoints of the Stomach Channel of Foot Yangming and the Spleen Channel of Foot Taiyin selection are frequently used in electroacupuncture for treating cancer pain. Due to the limitations of this study, further research and more standardized, multi-center, large-sample clinical trials can be carried out to guide optimizing acupuncture treatment schemes and promote the formation of TCM-characteristic technologies for cancer pain.

Irritability and risk of lung cancer: a Mendelian randomization and mediation analysis.

BACKGROUND: There is no research to prove the association between irritability and lung cancer, our study performed a Mendelian randomization (MR) approach to elucidate the causal relationship of irritability with lung cancer risk. METHODS: Genome-wide association studies (GWAS) data of irritability, lung cancer and gastroesophageal reflux disease (GERD) were downloaded from a public database for two-sample MR analysis. Independent single-nucleotide polymorphisms (SNPs) associated with irritability and GERD were selected as instrumental variables (IVs). Inverse variance weighting (IVW) and weighted median method were used to analyze causality. RESULTS: There is an association between irritability and lung cancer risk (ORIVW = 1.01, 95% CI = [1.00, 1.02], P = 0.018; ORweighted median = 1.01, 95% CI = [1.00, 1.02], P = 0.046), and GERD might account for about 37.5% of the association between irritability and lung cancer. CONCLUSIONS: This study confirmed the causal effect between irritability and lung cancer through MR analysis, and found that GERD played an essential mediating role in this relationship, which can partly indicate the role of the "inflammation-cancer transformation" process in lung cancer.

Existence and distribution of novel phylotypes of Nitrospira in water columnsof the South China Sea.

In the biological nitrogen cycle, nitrite oxidation is performed by nitrite oxidation bacteria, of which Nitrospira is widespread and diverse. Communities of Nitrospira were collected at 25-1500 m depths in the South China Sea. Phylogenetic diversity, community composition, and environmental factors were investigated using high-throughput sequencing targeting the nxrB gene and statistical analyses. The community composition of Nitrospira varied spatially and by depth. Among the 24 OTUs with relatively high abundance, 70% were unclassified and not affiliated with the known Nitrospira genus, suggesting a previously unrecognized high diversity of marine Nitrospira. Five known Nitrospira genera were detected, of which the common marine Nitrospira marina was not the dominant species, whereas Candidatus Nitrospira lenta and Candidatus Nitrospira defluvii dominated in shallow habitats. Comammox Candidatus Nitrospira nitrosa was discovered in the marine ecosystem. The niche differentiation of versatile Nitrospira species was mainly shaped by nitrate, temperature, and DO.

Dysbiosis of the Gut Microbiome Is Associated With Histopathology of Lung Cancer.

Lung cancer is a malignancy with high incidence and mortality worldwide. Previous studies have shown that the gut microbiome plays an important role in the development and progression of metabolic cancers. However, data on the characteristics of the gut microbiome with different histopathology types of lung cancer remain scant. We collected stool samples from 28 healthy people (HP) and 61 lung cancer patients. The lung cancer patients were classified into three types according to their histopathology: Atypical Adenomatous Hyperplasia/Adenocarcinoma in situ (AAH/AIS), Minimally Invasive Adenocarcinoma (MIA), and Invasive Adenocarcinoma (IA). In addition, we employed 16S rRNA gene amplicon sequencing to analyze the characteristics of the gut microbiome in these patients. Our analysis revealed that the categorized cancer patients had unique intestinal flora characteristics, and had lower density and flora diversity compared to healthy people. Besides, the structure of the flora families and genera was more complex, and each group presented specific pathogenic microbiota. The patients in the AAH/AIS group and HP group had relatively similar flora structure compared with the IA and MIA groups. In addition, we identified several flora markers that showed significant changes with the development of lung cancer. Lung cancer gut microbiota showed a decrease in short-chain fatty acids (SCFAs) producing and anti-inflammatory bacteria compared to healthy people, while some pathogenic bacteria such as proinflammatory or tumor-promoting bacteria were more abundant in lung cancer patients. On the other hand, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Group (COG) annotation demonstrated suppression of some dominant metabolism-related pathways in lung cancer. These findings provide new biomarkers for the diagnosis and prognostic assessment of lung cancer and lay the basis for novel targeted therapeutic strategies for the prevention and treatment of lung cancer. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03244605].

Niche differentiation of ammonia-oxidizing archaea and related autotrophic carbon fixation potential in the water column of the South China Sea.

The significant primary production by ammonia-oxidizing archaea (AOA) in the ocean was reported, but the carbon fixation process of AOA and its community composition along the water depth remain unclear. Here, we investigated the abundance, community composition, and potential carbon fixation of AOA in water columns of the South China Sea. Higher abundances of the amoA and accA genes of AOA were found below the euphotic zone. Similarly, higher carbon fixation potential of AOA, evaluated by the ratios of amoA to accA gene, was also observed below euphotic zone and the ratios increased with increasing water depth. The vertical niche differentiation of AOA was further evidenced, with the dominant genus shifting from Nitrosopelagicus in the epipelagic zone to uncultured genus in the meso- and bathypelagic zones. Our findings highlight the higher carbon fixation potential of AOA in deep water and the significance of AOA to the ocean carbon budget.

Chinese Herbal Medicine (Yiqi-Yangyin-Jiedu Decoction) Combined With Osimertinib as First-Line Treatment in EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer (CATLA-2): A Study Protocol for a Double-Blind Randomized Controlled Trial.

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the prognosis of non-small cell lung cancer (NSCLC) with EGFR mutation-positive. Although third-generation EGFR-TKI osimertinib is demonstrated with superior efficacy compared with first-generation EGFR-TKIs, acquired resistance to EGFR-TKIs remains the bottleneck. The Chinese herbal medicine (CHM) Yiqi-Yangyin-Jiedu decoction (YYJD) has been shown to delay acquired resistance to first-generation EGFR-TKIs in the CATLA study, but there is no high-level evidence for its effect when combined with osimertinib. This trial aims to evaluate the efficacy and safety of YYJD combined with osimertinib as first-line treatment in EGFR mutation-positive advanced NSCLC. Methods: This is a double-blind, multi-center, randomized controlled trial conducted in eight hospitals in China. A total of 314 participants will be randomly assigned to the osimertinib plus YYJD group (O+YYJD) or the osimertinib plus placebo group (O+placebo). Treatment will last until disease progression or death. Patients diagnosed with advanced NSCLC harboring EGFR Ex19del or L858R will be enrolled if they are ready to take osimertinib as first-line treatment, aged 18-74 years old, and provide signed informed consent. The primary outcome is progression-free survival (PFS). The secondary outcomes include a comparison of overall survival (OS), objective response rate (ORR), disease control rate (DCR), and quality of life (QoL). The analysis will be based on intention-to-treat and per-protocol subject analysis principles. Discussion: The goal of this trial is to evaluate the efficacy and safety of YYJD when added to osimertinib as first-line treatment in EGFR mutation-positive advanced NSCLC.

[Blade acupuncture combined with functional exercise for chronic pain after non-small cell lung cancer surgery: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of blade acupuncture combined with functional exercise for chronic pain after non-small cell lung cancer surgery. METHODS: A total of 62 patients with chronic pain after surgery for non-small cell lung cancer were randomly divided into an observation group and a control group, 31 cases in each group. The patients in the control group were treated with functional exercise. On the base of the treatment in the control group, the patients in the observation group were treated with blade acupuncture at the tendon nodes or painful points, once a week for 4 weeks. The visual analogue scale (VAS) scores of pain before treatment and day 1, day 7, day 14, day 28 of treatment and day 90, day 180 when follow up were compared between the two groups; the brief pain inventory (BPI) scores before and after treatment were compared between the two groups. RESULTS: The VAS score in the observation group at each time point after treatment was lower than that before treatment (P<0.01), and lower than that in the control group (P<0.01). Compared before treatment, the daily life score, emotion score, walking ability score, sleep score and life enjoyment score and total score of BPI in the observation group were reduced after treatment (P<0.05), and the daily life score, emotion score, sleep score and total score of BPI in the observation group were lower than those in the control group (P<0.05). CONCLUSION: The blade acupuncture combined with functional exercise could effectively alleviate the chronic pain after non-small cell lung cancer surgery, improve the quality of life of patients, and the effect is lasting and stable.

miRNA-576 Alleviates the Malignant Progression of Atherosclerosis through Downregulating KLF5.

OBJECTIVE: To elucidate the role of microRNA-576 (miRNA-576) in alleviating the deterioration of atherosclerosis (AS) through downregulating krüpple-like factor 5 (KLF5). MATERIALS AND METHODS: The AS model in mice was first constructed. Body weight, inflammation degrees, blood lipid, and relative levels of KLF5, miRNA-576, caspase-3, and bcl-2 in AS mice and control mice were compared. Dual-luciferase reporter gene assay was performed to evaluate the binding between miRNA-576 and KLF5. RAW264.7 cells were treated with 200 mg/L ox-LDL for establishing in vitro high-fat model. Regulatory effects of miRNA-576/KLF5 on relative levels of ß-catenin and inflammatory factors in RAW264.7 cells were explored. RESULTS: Body weight was heavier in AS mice than in controls. Protein levels of KLF5 and caspase-3 were upregulated, while bcl-2 was downregulated in AS mice. In particular, protein level of KLF5 was highly expressed in aortic tissues of AS mice. TC and LDL increased, and HDL decreased in AS mice compared with controls. Inflammatory factor levels were markedly elevated in AS mice. KLF5 was verified to be the target gene binding miRNA-576. Overexpression of miRNA-576 downregulated KLF5, inflammatory factors, and ß-catenin in ox-LDL-treated RAW264.7 cells. Regulatory effect of miRNA-576 on the release of inflammatory factors in RAW264.7 cells could be partially abolished by KLF5. CONCLUSIONS: miRNA-576 alleviates malignant progression of AS via downregulating KLF5.

Anticancer Action of Xiaoxianxiong Tang in Non-Small Cell Lung Cancer by Pharmacological Analysis and Experimental Validation.

Xiaoxianxiong Tang (XXXT) is a well-known traditional Chinese medicine formula. Evidence is emerging supporting the benefits of XXXT in ameliorating therapy for non-small cell lung cancer (NSCLC). The purpose of this study aimed to explore the effects and mechanisms of XXXT through network pharmacological analysis and biological validation. TCMSP database was used to identify potentially active compounds in XXXT with absorption, distribution, metabolism, excretion screening, and their potential targets. The disease targets related to NSCLC were predicted by searching for Therapeutic Target database, GeneCards database, DrugBank database, and DisGeNET database. Of the 4385 NSCLC-related targets, 156 targets were also the targets of compounds present in XXXT. Subsequently, GO function and KEGG pathway enrichment and PPI network analyses revealed that, of the 95 targets and 20 pathways influenced by 20 ingredients in XXXT, 20 targets were associated with patient survival, and XXXT could exert an inhibitory action on the PI3K-AKT signaling pathway. Moreover, XXXT restrained the proliferation of A549 and H460 cells in a concentration-dependent manner and suppressed the mRNA and protein levels of key targets CCNA2, FOSL2, and BIRC5 closely linked to the PI3K-AKT pathway. Hence, XXXT has the potential to improve therapy for NSCLC by targeting the PI3K-AKT signaling pathway.

MiR-182-5p promotes the Metastasis and Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer by Targeting EPAS1.

Background: Dysregulation of microRNAs (miRNAs) is associated with the pathogenesis of non-small cell lung cancer (NSCLC). However, the mechanisms through which miR-182-5p regulate NSCLC progression have not been established. This study aimed at evaluating the expression levels of miR-182-5p in human NSCLC and its function in lung cancer cells. Endothelial PAS Domain-containing protein 1 (EPAS1; also referred to as hypoxia-inducing factor 2A, HIF-2α) is a transcription factor that is responsible for induction of genes related to cell survival under hypoxia conditions. Hypoxia, an inherent feature of solid tumors, is associated with aggressive phenotypes, as well as resistance to radiotherapy and chemotherapy, which predict metastasis and poor prognosis. Methods: The Cancer Genome Atlas (TCGA) dataset was used to investigate the association between miR-182-5p expression and clinicopathological characteristics as well as prognosis of NSCLC patients. Target genes of miR-182-5p were identified using the PITA, miRmap, microT, miRanda, PicTar, and TargetScan prediction tools. Transwell assays were performed to determine the potential functions of miR-182-5p in lung cancer cells. Luciferase reporter assays were performed to analyze regulation of the putative target of miR-182-5p while western blot assays were used to validate the luciferase results. Results: miR-182-5p was found to be upregulated in NSCLC tissues and acted as an independent prognostic factor for tumor recurrence in NSCLC patients. Functionally, overexpression of miR-182-5p promoted lung cancer cell migration and invasion. Genome-wide gene expression analysis and luciferase report assays revealed that EPAS1 is a direct target of miR-182-5p. EPAS1 was negatively correlated with miR-182-5p expression in NSCLC tissues. Univariate and multivariate survival analyses identified EPAS1 as an independent prognostic factor for overall survival (OS) in NSCLC. Conclusions: These findings imply that miR-182-5p promotes NSCLC progression by targeting EPAS1 and is, therefore, a potential indicator of tumor recurrence in NSCLC patients.

Chinese Herbal Medicine Combined With First-Generation EGFR-TKIs in Treatment of Advanced Non-Small Cell Lung Cancer With EGFR Sensitizing Mutation: A Systematic Review and Meta-Analysis.

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly improve prognosis of advanced NSCLC patients harboring EGFR sensitizing mutation. However, acquired resistance to EGFR-TKIs limits the good outcomes. Chinese herbal medicine (CHM) has been used for NSCLC patients receiving EGFR-TKIs for more than 10°years as an adjuvant treatment. Methods: Studies were searched from China BioMedical Literature, Chinese National Knowledge Infrastructure, Cqvip Database, Wanfang Database, MEDLINE (PubMed), EMBASE (Ovid), Google Scholar, and Cochrane Library from inception to March, 2021. Randomized controlled clinical trials (RCT) comparing EGFR-TKIs + CHM (TKIs + CHM) versus EGFR-TKIs with/without placebo (TKIs ± placebo) in participants with advanced NSCLC harboring EGFR sensitizing mutation were included in this study. Two authors screened all references, assessed the risk of bias and extracted data independently. Data were summarized using hazard ratio (HR) and risk ratios (RR), with 95% confidence intervals (CI) for binary outcomes. Meta-analysis was performed using random effects model. Overall quality of evidence was assessed using GRADE. Results: A total of 9 RCTs (1137 participants, 581 in the TKIs + CHM group and 556 in the TKIs ± placebo group) were included in this review. Only first-generation EGFR-TKIs were included. Most trials included used oral CHM preparations to tonify Qi and/or Yin. Treatment lasted from enrollment until disease progression (PD) or intolerable adverse events (AE). Combination of CHM with EGFR-TKIs improved median progression-free survival (mPFS) (HR,0.59; 95% CI, 0.52-0.68; P < 0.00001) and objective response rate (ORR) (RR, 1.23; 95% CI, 1.13-1.34; P < 0.00001) compared with used of EGFR-TKIs ± placebo. CHM reduced AE associated with EGFR-TKIs such as cutaneous toxicity (RR, 0.58; 95% CI, 0.46-0.73; P < 0.00001) and diarrhea (RR, 0.43; 95% CI, 0.30-0.60; P < 0.00001). Conclusion: Combination therapy of CHM and EGFR-TKIs significantly delays acquired resistance while improving ORR to EGFR-TKIs. Furthermore, CHM reduces AE induced by EGFR-TKIs. More international multi-centered, double-blinded, placebo-controlled, well-designed clinical trials are needed in future research.

A TCM Formula YYWY Inhibits Tumor Growth in Non-Small Cell Lung Cancer and Enhances Immune-Response Through Facilitating the Maturation of Dendritic Cells.

In worldwide, lung cancer has a major socio-economic impact and is one of the most common causes of cancer-related deaths. Current therapies for lung cancer are still quite unsatisfactory, urging for alternative new treatments. Traditional Chinese Medicine (TCM) is currently increasingly popular and exhibits a complicated intervention in cancers therapy. In this study, we evaluated the anti-tumor effect and explored the mechanisms of a TCM formula Yangyinwenyang (YYWY) in non-small cell lung cancer (NSCLC) models. YYWY induced the apoptosis of lung cancer cells in vitro. In Lewis NSCLC-bearing mice model, YYWY significantly inhibited the tumor growth. Further, RNA-seq analysis and immunostaining of the tumor tissue implied the critical role of YYWY in the regulation of immune response, especially the dendritic cells (DCs) in the effect of YYWY. Therefore, we focused on DCs, which were the initiator and modulator of the immune response. YYWY facilitated the maturation of DCs through MAPK and NF-κB signaling pathways and promoted the release of the cytokines IFN-γ, interleukin (IL)-1ß, IL-2, IL-12, and tumor necrosis factor (TNF)-α by DCs. Moreover, the YYWY-matured DCs enhanced the proliferation of T cells and promoted the differentiation of T cells into T helper Th1 and cytotoxic T cell (CTL). In addition, YYWY increased the ratio of Th1/Th2 (IFN-γ/IL-4 radio). Collectively, our findings clearly suggested that YYWY exerted an anti-tumor effect on NSCLC, at least partially through facilitating the mature DCs to activate the proliferation and differentiation of T cells.

New primers, taxonomic database and cut-off value for processing nxrB gene high-throughput sequencing data by MOTHUR.

To analyse the diversity of Nitrospira with functional nxrB genes, we designed and optimized a new primer set, Nxr-f27/Nxr-r617, and constructed a database for taxonomic classification. We also propose a cut-off value for processing the high-throughput sequencing data with MOTHUR.

Spatio-temporal shifts in community structure and activity of nirS-type denitrifiers in the sediment cores of Pearl River Estuary.

Denitrification, an important process in microbial mediated nitrogen cycle, plays important roles in nitrogen loss in estuarine sediments. However, the function of denitrifiers in the estuarine subsurface sediments remained poorly understood. In this study, we analyzed the potential activity, abundance and community structure of nirS-type denitrifiers using 15N-labeled incubation quantitative-PCR and high throughput sequencing techniques in sediment cores from Pearl River Estuary (PRE). Results showed that subsurface sediments had nearly same level denitrification potential activity compare to surface sediments, although the abundance of nirS gene decreased sharply from surface to bottom in sediment cores. Meanwhile, nirS gene abundance exhibit significant temporal variations, which is consistent with denitrification potential activity. Moreover, the community structure and diversity of nirS-type denitrifiers in sediment cores exhibited remarkable temporal shift pattern. For spatial variation, no significant difference was observed of denitrifiers community structure in each sediment core from the surface to the subsurface, while there were significant different diversity characteristic among different cores. Redundancy analysis (RDA) showed that multiple environmental factors including salinity, pH, oxidation-reduction potential, nutrient content and organic substances synergistically shaped the diversity and distribution of nirS-type denitrifers in PRE sediments. Our results showed that nirS-type denitrifers played important roles in the nitrogen removal in subsurface sediments of PRE.

The effect of comprehensive rehabilitation program plus chemotherapy on quality of life in patients with postoperative non-small-cell lung cancer: study protocol of a multicenter randomized clinical trial.

BACKGROUND: Comprehensive rehabilitation therapy based on traditional Chinese medicine (TCM) has been widely applied in various cancer treatments in China. Thus far, Chinese herbal medicine (CHM) has been shown effective in reducing the adverse effects of chemotherapy and improving the quality of life (QoL) during chemotherapy. The purpose of the present study is to compare the effects of CHM plus Liu Zi Jue (LZJ) exercises with CHM plus rehabilitation education and with placebo plus rehabilitation education in patients who have undergone complete resection for nonsmall-cell lung cancer (NSCLC) followed by postoperative adjuvant chemotherapy. METHODS AND DESIGN: A multicenter, randomized clinical trial will be performed with 354 stage Ib-IIIa NSCLC patients in five centers in China. Patients satisfying the inclusion criteria will be randomly divided into three groups according to a 1:1:1 ratio: intervention group A (IGA), intervention group B (IGB), and control group (CG). Each group will receive adjuvant platinum-based doublet chemotherapy for a total of four cycles. IGA participants will receive chemotherapy combined with CHM and LZJ exercises, IGB participants will receive chemotherapy combined with CHM and rehabilitation education, and CG participants will receive chemotherapy combined with placebo and rehabilitation education. The herbal treatment patients will be given granules daily and LZJ exercises will be performed four times per week during chemotherapy. The primary outcome is QoL, which will be assessed with the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C43 scale in each cycle. The secondary outcomes include the 2-year disease-free survival rate, disease-free survival, TCM symptoms, tumor markers, safety, and adverse events. After treatment, the patients will be followed up every 3 months within 2 years and every 6 months after 2 years until disease recurrence and/or metastasis. DISCUSSION: Our previous study reported that CHM in combination with chemotherapy could lower the overall incidence of adverse events but increased digestive and gastrointestinal side effects compared with chemotherapy alone in postoperative NSCLC patients. This study will lay a foundation for the effectiveness of chemotherapy with or without a comprehensive rehabilitation program for QoL in patients with postoperative NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03372694. Retrospectively registered on 17 December 2018.

Adjuvant Chemotherapy with Chinese Herbal Medicine Formulas Versus Placebo in Patients with Lung Adenocarcinoma after Radical Surgery: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: The toxicity and side effects caused by adjuvant chemotherapy (ACT) after radical surgery for lung adenocarcinoma (LAC) lead to early termination frequently. This study was conducted to provide an objective basis for the effect of Chinese herbal medicine formulas (CHMFs) combined with chemotherapy in reducing toxicity and enhancing efficacy of ACT. METHOD: From February 17th, 2012 to March 20th, 2015, 233 patients from 7 hospitals diagnosed with LAC in IB~IIIA stage were randomly assigned into ACT + CHMF group (116 patients) and ACT + placebo group (117 patients). CHMF was taken orally until the end of chemotherapy. Chemotherapy-related toxic, side effects were investigated as the primary outcome. Disease-free survival (DFS) and overall survival (OS) were used as the secondary outcome. RESULTS: At one week following chemotherapy, the incidence of dry mouth, diarrhea and thrombocytopenia significantly decreased in CHMF group (P = 0.017, P = 0.033, P = 0.019, respectively). At two weeks following chemotherapy, fatigue and diarrhea were more obvious in the placebo group (P = 0.028, P = 0.025, respectively). In addition, patients in the CHMF group showed an increase in median DFS from 37.1 to 51.5 months compared with placebo group although there was no statistical significance (P = 0.16). In the stage IB subgroup, the CHMF group had a significantly better DFS (HR (95% CI) = 0.53 (0.28-0.99), P = 0.046). There was no significant difference in OS between the groups (P = 0.72). CONCLUSION: For patients with LAC, ACT combined with CHMF after radical surgery can prolong the DFS time especially in the early stage, and reduces the chemotherapy-related toxic and side effects. TRIAL REGISTRATION: NCT01441752. Registered 14 July, 2011.

CPF impedes cell cycle re-entry of quiescent lung cancer cells through transcriptional suppression of FACT and c-MYC.

Blockade of cell cycle re-entry in quiescent cancer cells is a strategy to prevent cancer progression and recurrence. We investigated the action and mode of action of CPF mixture (Coptis chinensis, Pinellia ternata and Fructus trichosanthis) in impeding a proliferative switch in quiescent lung cancer cells. The results indicated that CPF impeded cell cycle re-entry in quiescent lung cancer cells by reduction of FACT and c-MYC mRNA and protein levels, with concomitant decrease in H3K4 tri-methylation and RNA polymerase II occupancy at FACT and c-MYC promoter regions. Animals implanted with quiescent cancer cells that had been exposed to CPF had reduced tumour volume/weight. Thus, CPF suppresses proliferative switching through transcriptional suppression of FACT and the c-MYC, providing a new insight into therapeutic target and intervention method in impeding cancer recurrence.