Enhanced Therapeutic Impact of Shikonin-Encapsulated Exosomes in the Inhibition of Colorectal Cancer Progression.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy with high mortality rates and poor prognosis. Shikonin (SHK) has demonstrated extensive anti-tumor activity across various cancers, yet its clinical application is hindered by poor solubility, limited bioavailability, and high toxicity. This study aims to develop SHK-loaded exosomes (SHK-Exos) and assess their efficacy in CRC progression. Materials and Methods: Exosomes were isolated using ultracentrifugation and characterized via TEM, NTA, and western blotting. Their cellular internalization was confirmed through confocal microscopy post PKH67 labeling. Effects on cell behaviors were assessed using CCK-8 and Transwell assays. Cell cycle and apoptosis were analyzed via flow cytometry. A xenograft tumor model evaluated in vivo therapeutic potential, and tumor tissues were examined using H&E staining and in vivo imaging. Results: SHK-Exos demonstrated effective cell targeting and internalization in CRC cells. In vitro, SHK-Exos surpassed free SHK in inhibiting aggressive cellular behaviors and promoting apoptosis, while in vivo studies showed substantial efficacy in reducing tumor growth with excellent tumor targeting and minimal toxicity. Conclusions: Employing SHK-Exos effectively impedes CRC progression in vitro and in vivo, offering significant therapeutic potential. This research underscores the advantages of using autologous exosomes as a drug carrier, enhancing efficacy and reducing toxicity.

Chinese Herbal Medicine Combined With Liuzijue Exercise in Physiological Rehabilitation After Video-assisted Lung Lobectomy for Cancer: A Prospective Propensity Score Matching Study.

OBJECTIVE: To observe the clinical efficacy of Chinese herbal medicine combined with Liuzijue exercise on the physiological symptoms and quality of life (QoL) in postoperative patients with early-stage lung cancer. METHODS: One hundred and eighty-three lung cancer patients who underwent video-assisted thoracoscopic surgery (VATS) were categorize into either a traditional Chinese medicine treatment group (CM) or a control group (non-traditional Chinese medicine treatment, NC), among whom 73 underwent Chinese herbal medicine and Liuzijue therapy, while 110 underwent no comprehensive treatment with traditional Chinese medicine. The propensity score matching (PSM) method with a 1:2 ratio was used to balance the baseline characteristics and evaluate the efficacy of CM in improving postoperative symptoms and QoL. RESULTS: Cough, dyspnea, chest pain, and fatigue were the most common clinical symptoms after VATS. Except for chest pain, they were all correlated with the scope of operation (P < .05). After PSM, 165 patients were identified in the matched cohort, and the covariates of gender, age, operative site, and scope of operation were balanced between the 2 groups (P > .05). In the domain of global health status, the improvement in QoL in CM was greater than that in NC (6.06 ± 15.83 vs -1.06 ± 14.68, P = .005). In terms of symptoms, improvements in cough (1.69 ± 3.15 vs 0.38 ± 2.63, P = .006), dyspnea during climbing stairs (-10.30 ± 16.82 vs -1.82 ± 17.97, P = .004), and pain (-0.76 ± 1.32 vs -0.08 ± 1.31, P = .002) in CM were better than in NC. CONCLUSION: Comprehensive treatment with traditional Chinese medicine (TCM) can provide therapeutic benefits in physiological rehabilitation after VATS for cancer.

Combination of Brucea javanica oil emulsion and Aidi injection associated with the long­term survival of a patient with colon cancer and lung metastases post­chemotherapy: A case report.

Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide. Treatment options for patients with advanced CRC recurrence and metastases remain limited, particularly for those unable to withstand chemotherapy. Bruscea javanica oil emulsion (BJOE) and Aidi injection (ADI) are two plant-derived products that have antitumor effects. The current report presents the case of a patient with colon cancer and resectable lung metastases. Despite the surgical removal of the metastatic lesions, tumor recurrence was not prevented. The patient underwent three chemotherapy regimens following lung metastasis surgery, namely XELOX, single-agent irinotecan and single-agent tegafur-gimeracil-oteracil potassium capsule, but experienced intolerable adverse reactions with each, and disease progression was observed during subsequent follow-up. Nonetheless, the patient achieved a progression-free survival of >5 years under BJOE + ADI treatment and continues to receive BJOE + ADI treatment to date. Although further research is required to understand the effectiveness of this treatment combination, the present case may instill hope in the treatment of future patients.

Prognostic and therapeutic insights into colorectal carcinoma through immunogenic cell death gene profiling.

While the significance of immunogenic cell death (ICD) in oncology is acknowledged, its specific impact on colorectal carcinoma remains underexplored. In this study, we delved into the role of ICD in colorectal carcinoma, a topic not yet comprehensively explored. A novel ICD quantification system was developed to forecast patient outcomes and the effectiveness of immunotherapy. Utilizing single-cell sequencing, we constructed an ICD score within the tumor immune microenvironment (TIME) and examined immunogenic cell death related genes (ICDRGs). Using data from TCGA and GEO, we discovered two separate molecular subcategories within 1,184 patients diagnosed with colon adenocarcinoma/rectum adenocarcinoma (COADREAD). The ICD score was established by principal component analysis (PCA), which classified patients into groups with low and high ICD scores. Further validation in three independent cohorts confirmed the model's accuracy in predicting immunotherapy success. Patients with higher ICD scores exhibited a "hot" immune phenotype and showed increased responsiveness to immunotherapy. Key genes in the model, such as AKAP12, CALB2, CYR61, and MEIS2, were found to enhance COADREAD cell proliferation, invasion, and PD-L1 expression. These insights offered a new avenue for anti-tumor strategies by targeting ICD, marking advances in colorectal carcinoma treatment.

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.

Comprehensive Evaluation of Traditional Herbal Medicine Combined With Adjuvant Chemotherapy on Post-Surgical Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Gastric cancer is a common cause of global mortality, with significant challenges during treatment due to side effects and complications. Traditional herbal medicine (THM) has emerged as a potential adjuvant therapy to enhance cancer treatment by reducing side effects and bolstering the immune response. This study conducted a meta-analysis to assess the efficacy and safety of THM as an adjuvant therapy in post-surgical gastric cancer patients. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, CiNii, KMBASE, KISS, OASIS, RISS, and ScienceON databases were searched from inception through December, 2021. The outcomes considered in this analysis encompassed tumor response, quality of life (QoL), side effects, and tumor markers. Additionally, a frequency analysis of the most commonly used herbs in the included studies was conducted. A total of 36 randomized controlled trials (RCTs) were included, and data were extracted according to study design. The analysis compared groups receiving chemotherapy alone with those receiving both chemotherapy and THM treatment. RESULTS: The group receiving both chemotherapy and THM showed substantial improvement in tumor response compared to the chemotherapy-only control group (RR 1.25, 95% CI [1.09, 1.45]). QoL also significantly increased in the THM-treated group. Most drug adverse reactions displayed statistical significance, except for platelet reduction. Tumor markers CEA, CA19-9, and CA72-4 exhibited significant improvements, but CA125 did not. The 1, 2, and 3-year survival rates improved, with RR values of 1.08 (95% CI [1.02, 1.14]), 1.32 (95% CI [1.19, 1.47]), and 1.42 (95% CI [1.12, 1.79]) respectively. However, some publication bias was indicated. CONCLUSION: THM may offer potential benefits as a complementary approach to post-surgical anticancer therapy in gastric cancer patients. Improved tumor response, quality of life, and survival rates were reported. However, it is important to exercise caution due to the possibility of publication bias, and further research is needed to confirm these findings.Registration:PROSPERO CRD 42022354133.

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.

Study on the difference and regularity of tongue images in 309 patients with different pathological stages of non-small cell lung cancer.

BACKGROUND: Tongue diagnosis is a crucial traditional Chinese medicine (TCM) inspection method for TCM syndrome differentiation and treatment. OBJECTIVE: The primary research focus was on tongue image characteristic parameters of patients with non-small cell lung cancer (NSCLC). Analysis of the tongue image parameters of various pathological stages of NSCLC provides technical support for establishing an integrated Chinese and Western auxiliary diagnosis and efficacy evaluation medicine system for lung cancer that integrates tongue image features. METHODS: Tongue image characteristics of 309 patients with NSCLC and 206 controls were collected and analyzed clinically. The T-test or rank sum test and logistic regression analysis were applied to analyze the characteristics of tongue image indicators of different pathological stages of NSCLC. RESULTS: There were differences in tongue image characteristics in the NSCLC group compared to the control group. The tongue quality and brightness of the tongue coating in the NSCLC group increased, the red component was reduced, the tongue coating thickened, and the yellow component increased compared to the healthy control group. A comparison of tongue image indexes of NSCLC in different pathological stages showed that stage IV had lower TB-b and higher TB-a than stage I. In addition, stage IV had lower TB-b than stage II + III, showing an increase in the blue and red components of the tongue in stage IV and the appearance of cyanotic tongue features. CONCLUSION: The tongue image characteristics of NSCLC patients differed from those of the control group. Tongue imaging indicators can reflect the characteristics of tongue images of patients with NSCLC. The tongue image characteristics of patients with stage IV lung cancer are bluish and purple compared with those with stage I, II, and III. It is suggested that the tongue's image characteristics can be used as a reference for the pathological classification of NSCLC and judgment of the disease process.

Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung Cancer.

BACKGROUND: Bone metastasis is frequently common in advanced lung cancer with the major issue of a pathological fracture. Previous studies suggested that Astragalus membranaceus (Qi) and Ampelopsis japonica (Lian), which are used as folk medicine in China, have potential effects on inhibiting tumor growth and protecting bones, respectively. In this study, an experiment on the inhibitory effect of the Qilian formula (AAF) in vivo was designed to examine tumor growth in bone and osteoclast formation. MATERIALS AND METHODS: The bone metastasis xenograft models were established by implanting NCI-H460-luc2 lung cancer cells into the right tibiae bones of mice. After confirming the model's viability through optical imaging 7 days post-implantation, 2 groups, namely the AAF group and the control group, were administered 0.3 mL of AAF extract (9 g/kg/day) or normal saline via intragastric delivery for a duration of 4 weeks. Throughout the study, we longitudinally assessed tumor burden, bone destruction, and weight-bearing capacity in vivo using reporter gene bioluminescence imaging (BLI), micro-CT, and dynamic weight-bearing (DWB) tests. Mechanistic insights were gained through Hematoxylin-eosin (H&E) staining, immunohistochemical (IHC) analysis, western blotting, and flow cytometry. RESULTS: Qilian formula produced significant inhibition to the progress of bone destruction and tumor burden in the right tibiae bone in the treatment group. It was further evidenced by molecular imaging in vivo via small animal micro-CT and BLI with parametric quantification, characterizing significantly lower uptake of BLI signal in the treated tumor lesions and improving the pathological changes in the microstructure of bone. Furthermore, DWB tests revealed that Qilian formula treatment significantly maintained the weight-bearing capacity. According to immunohistochemical analysis, the effect of the Qilian formula appeared to involve the suppression of osteoclast formation by lower expression of the tartrate-resistant acid phosphatase. Cell apoptosis and death induction were evidenced by a higher percentage of Bal2、BAX and caspase 3 expressions of Qilian formula-treated tumor tissues. CONCLUSIONS: Our study demonstrated a significant inhibitory effect of the Qilian formula on the progression of osteolytic invasion in vivo by suppressing osteoclastogenesis and promoting apoptotic cell death.

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.

Exploring the Rules of Related Parameters in Transcutaneous Electrical Nerve Stimulation for Cancer Pain Based on Data Mining.

INTRODUCTION: This study aims to investigate the regularity of related parameters in the treatment of cancer pain using transcutaneous electrical nerve stimulation (TENS). METHODS: A comprehensive literature search was conducted in databases such as PubMed, Cochrane Library, Embase, Web of Science, OVID, CNKI, CBM, VIP, and WANNGFANG from inception up to December 2022. A database was established, and data mining techniques were applied to analyze the relevant TENS parameters. RESULTS: A total of 27 articles were included, encompassing nine current frequencies, four retention times, four treatment frequencies, and two wave types. On the basis of the analysis of parameter association rules, the most closely related parameter combination for clinical TENS in the treatment of cancer pain was a current frequency of 2/100 Hz, a treatment frequency of once a day, a retention time of 30 min, and the dilatational wave. Moreover, the study involved 22 acupuncture points distributed along 13 meridians. According to the analysis of acupuncture point association rules, Hegu (LI04), Zusanli (ST36), and Sanyinjiao (SP06) were the most closely related acupuncture points and could be used in combination for clinical TENS in cancer pain treatment. Furthermore, cluster analysis was conducted on acupuncture points with a frequency ≥ 5, resulting in three categories: the first category included Sanyinjiao (SP06), Zusanli (ST36), Hegu (LI04), Jiaji point, and Neiguan (PC06); the second category included Ashi point; and the third category included Back shu point. CONCLUSION: In the treatment of cancer pain using TENS, it is recommended to use a current frequency of 2/100 Hz, a treatment frequency of once a day, a retention time of 30 min, and the dilatational wave. The electrode positions were primarily selected from Ashi point, Back shu point, Sanyinjiao (SP06), Zusanli (ST36), Hegu (LI04), Jiaji point, and Neiguan (PC06) to achieve the best analgesic effect.

Effects of music therapy on anxiety in patients with cancer: study protocol of a randomised controlled trial.

INTRODUCTION: Although music therapy (MT) has been found to reduce anxiety in patients with cancer and delay tumour progression to some extent, its mechanism of action has not been determined. MT may reduce anxiety by reducing the concentrations of proinflammatory cytokines. The present study was designed to evaluate the effects of MT on anxiety and cytokine levels in patients with cancer. METHODS AND ANALYSIS: This randomised, open, single-centre parallel-controlled trial will randomise 60 patients with malignant tumours who meet the inclusion criteria in a 1:1 ratio to either an MT group or a non-MT (NMT) group. Patients in the MT group will receive emotional nursing care and individualised receptive MT for 1 week, whereas patients in the NMT group will receive emotional nursing care alone. Primary outcomes will include scores on the State-Trait Anxiety Inventory, Distress Thermometer and Hamilton Anxiety Scale. Secondary outcomes will include scores on the Quality of Life Questionnaire C30, serum concentrations of the cytokines interleukin (IL)-1ß, tumour necrosis factor-α, IL-2R, IL-4, IL-6, IL-8 and IL-10, serum concentrations of the neurotransmitters 5-hydroxytryptamine, dopamine, norepinephrine, adrenocorticotropic hormone and γ-aminobutyric acid, and determination of gut microbiota populations. ETHICS AND DISSEMINATION: On 5 August 2020, the study protocol was approved by the Research Ethics Committee of the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine of the Shanghai University of Traditional Chinese Medicine. The findings of this study will be published in peer-reviewed publications and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: CTR2000035244.

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.

Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/ß-catenin pathway.

Feiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival and overall survival of patients but drug resistance is inevitable. The current study evaluated the effects of FYN in osimertinib-resistant HCC827OR and PC9OR cells. FYN preferentially inhibited the proliferation and migration of HCC827OR and PC9OR cells. Moreover, FYN and osimertinib exhibited synergistic inhibitory effects on proliferation and migration. Real-time qPCR (RT-qPCR) and western blotting results indicated that FYN downregulated gene and protein levels of GSK3ß and SRFS1, which are enriched in the Wnt/ß-catenin pathway. Besides, FYN inhibited tumor growth and exhibited synergistic effects with osimertinib in vivo. Collectively, the results suggested that FYN exerted an anti-osimertinib resistance effect via the Wnt/ß-catenin pathway.

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].

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.

Newcastle disease virus degrades SIRT3 via PINK1-PRKN-dependent mitophagy to reprogram energy metabolism in infected cells.

Lacking a self-contained metabolism network, viruses have evolved multiple mechanisms for rewiring the metabolic system of their host to hijack the host's metabolic resources for replication. Newcastle disease virus (NDV) is a paramyxovirus, as an oncolytic virus currently being developed for cancer treatment. However, how NDV alters cellular metabolism is still far from fully understood. In this study, we show that NDV infection reprograms cell metabolism by increasing glucose utilization in the glycolytic pathway. Mechanistically, NDV induces mitochondrial damage, elevated mitochondrial reactive oxygen species (mROS) and ETC dysfunction. Infection of cells depletes nucleotide triphosphate levels, resulting in elevated AMP:ATP ratios, AMP-activated protein kinase (AMPK) phosphorylation, and MTOR crosstalk mediated autophagy. In a time-dependent manner, NDV shifts the balance of mitochondrial dynamics from fusion to fission. Subsequently, PINK1-PRKN-dependent mitophagy was activated, forming a ubiquitin chain with MFN2 (mitofusin 2), and molecular receptor SQSTM1/p62 recognized damaged mitochondria. We also found that NDV infection induces NAD+-dependent deacetylase SIRT3 loss via mitophagy to engender HIF1A stabilization, leading to the switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Overall, these studies support a model that NDV modulates host cell metabolism through PINK1-PRKN-dependent mitophagy for degrading SIRT3.Abbreviations: AMPK: AMP-activated protein kinase; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; ECAR: extracellular acidification rate; hpi: hours post infection LC-MS: liquid chromatography-mass spectrometry; mito-QC: mCherry-GFP-FIS1[mt101-152]; MFN2: mitofusin 2; MMP: mitochondrial membrane potential; mROS: mitochondrial reactive oxygen species; MOI: multiplicity of infection; 2-NBDG: 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose; NDV: newcastle disease virus; OCR: oxygen consumption rate; siRNA: small interfering RNA; SIRT3: sirtuin 3; TCA: tricarboxylic acid; TCID50: tissue culture infective doses.

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.

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.