Transcriptomic sequencing analysis of key long noncoding RNAs and mRNAs expression profiles in postoperative recurrence of hepatocellular carcinoma.

BACKGROUND: Recurrence is the main cause of death in hepatocellular carcinoma (HCC) patients after liver resection. OBJECTIVE: The long non-coding RNAs (lncRNAs) have been reported participated in progression and prognosis of HCC, however, the vital role of lncRNA in postoperative recurrence of HCC has rarely been systematically identified. METHODS: RNA-sequencing (RNA-seq) was performed between orthotopic model of HCC and hepatoma postoperative recurrent model to comprehensively analyze the integrated transcriptome expression profiles of lncRNA and mRNA. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was then conducted to quantify the expression levels of DElncRNAs and their target mRNAs. RESULTS: In our study, 211 lncRNAs (P-value < 0.05) and 1125 mRNAs (P-adjust < 0.05) were significantly differentially expressed (DE) between two groups. Moreover, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DElncRNAs and DEmRNAs were mainly enriched in lipid metabolism, including Arachidonic acid metabolism, PPAR signaling pathway, Steroid hormone biosynthesis, Linoleic acid metabolism, Inflammatory mediator regulation of TRP channels, and Fatty acid degradation. Furthermore, we constructed lncRNA-mRNA interaction networks and protein-protein interaction (PPI) network, and verified by qRT-PCR, suggesting that increased DEIncRNAs (XLOC_063499 and XLOC_042016) may prevent HCC recurrence after surgery by upregulating on targeted cytochrome P450 (CYP) family genes in the lipid metabolism pathway, such as cyp3a16, cyp3a44, cyp2c39, cyp2c40 and cyp2c68. CONCLUSION: Overall, Our findings provided new insights for further investigation of biological function in lncRNA related HCC recurrence.

ECFuse: Edge-Consistent and Correlation-Driven Fusion Framework for Infrared and Visible Image Fusion.

Infrared and visible image fusion (IVIF) aims to render fused images that maintain the merits of both modalities. To tackle the challenge in fusing cross-modality information and avoiding texture loss in IVIF, we propose a novel edge-consistent and correlation-driven fusion framework (ECFuse). This framework leverages our proposed edge-consistency fusion module to maintain rich and coherent edges and textures, simultaneously introducing a correlation-driven deep learning network to fuse the cross-modality global features and modality-specific local features. Firstly, the framework employs a multi-scale transformation (MST) to decompose the source images into base and detail layers. Then, the edge-consistent fusion module fuses detail layers while maintaining the coherence of edges through consistency verification. A correlation-driven fusion network is proposed to fuse the base layers containing both modalities' main features in the transformation domain. Finally, the final fused spatial image is reconstructed by inverse MST. We conducted experiments to compare our ECFuse with both conventional and deep leaning approaches on TNO, LLVIP and M3FD datasets. The qualitative and quantitative evaluation results demonstrate the effectiveness of our framework. We also show that ECFuse can boost the performance in downstream infrared-visible object detection in a unified benchmark.

Chinese and Western Integrative Medicine for Stage IIIb-IVb Non-Small Cell Lung Cancer: Design and Rationale of a Multi-center, Prospective Registry (NSCLC-Chinese and Western Integrative Medicine cohort).

INTRODUCTION: This planned multicenter observational study will evaluate the overall survival of those undergoing integrated Chinese and Western medicine for stage IIIb-IVb non-small cell lung cancer and analyze the factors related to the prognosis. METHOD AND ANALYSIS: The prospective cohort will enroll patients with stage IIIb-IVb NSCLC from March 1, 2019, to December 31, 2025, and follow them for 5 years. We plan to collect data on the patients' demographics, treatment, overall survival, and factors related to the prognosis. ETHICS AND DISSEMINATION: The institutional review board and ethics committee reviewed the study protocol. All patients will provide informed consent before enrollment.Trial registration number: ChiCTR1900021430.

Case Report: Clinical benefit from multi-target tyrosine kinase inhibitor and PARP inhibitor in a patient with cancer of unknown primary with BRCA1 large genomic rearrangement.

Background: Cancer of unknown primary (CUP), which accounts for 3%-5% of new cancer cases every year, involves the presence of a type of histologically confirmed metastatic tumors whose primary site cannot be confirmed by conventional diagnostic methods. This difficulty in identifying the primary site means that CUP patients fail to receive precisely targeted therapy. Most patients are treated with empiric chemotherapy, with a median survival of 6 months and even poorer prognosis within an unfavorable subset of CUP. Case report: An 80-year-old woman presented with masses in the abdomen. Following comprehensive imagological and immunohistochemical examinations, she was diagnosed with CUP. She emphatically declined chemotherapy; thus, anlotinib has been administered with patient consent since 02/07/2019, and stable disease (SD) was observed for 2 years. During subsequent treatment, a large genomic rearrangement in BRCA1 was identified in the patient via NGS, and SD was observed for a further 6 months following olaparib treatment. The type of LGR identified in this patient was discovered to be BRCA1 exon 17-18 inversion (inv), which has never been previously reported. Conclusion: For CUP patients, a chemo-free regimen seems to be acceptable as a first-line treatment, and NGS-guided targeted treatment could improve patient outcomes.

Yifei Sanjie Formula or Placebo With Anlotinib as Second-Line or Above Treatment for Metastatic Non-Small-Cell Lung Cancer: Study Protocol for a Double-Blind, Placebo-Controlled Randomized Pilot Study.

BACKGROUND: Anlotinib is used as a third-line treatment for advanced non-small-cell lung cancer (NSCLC), but has limited clinical benefits and several side effects, such as diarrhea and acneiform skin rash. Traditional Chinese Medicine (TCM) is commonly used to treat cancers in China. Chinese herbal medicines may have the potential as adjuvant therapies to reduce toxicity and improve the efficacy of treatments for NSCLC. Given the positive outcomes of basic research, we plan to evaluate whether the addition of the Chinese herbal medicine Yifei Sanjie formula (YFSJF) to anlotinib can improve the progression-free survival (PFS) of advanced NSCLC patients. METHODS: A multicenter, randomized, double-blind, placebo-controlled parallel-group controlled pilot trial will be performed. Forty eligible patients will be randomized in a ratio of 1:1 to the intervention (YFSJF + anlotinib) and control (placebo + anlotinib) groups. Participants will be advised to take 12 mg/day of anlotinib on days 1 to 14 of each 21-day cycle. YFSJF or placebo will be administered (15 g twice daily) during each cycle until progression of disease (PD). The primary outcome will be progression-free survival (PFS), and the secondary outcomes will be overall survival (OS), the objective response rate (ORR), and patient-reported outcomes (PRO). Tumors will be assessed based on RECIST v. 1.1 after every 2 cycles of treatment. The M. D. Anderson Symptom Inventory-Lung Cancer (MDASI-LC) will be used to evaluate PRO at baseline and weekly thereafter until PD. DISCUSSION: This will be the first trial to evaluate the effectiveness and safety of TCM combined with anlotinib for the treatment of NSCLC. The results of this randomized controlled trial will fill a gap in the research by showing whether YFSJF combined with anlotinib can improve PFS in NSCLC patients. TRIAL REGISTRATION: The study was registered on June 8th, 2021 on Chinese Clinical Registry; registration number ChiCTR2100047143. (https://www.chictr.org.cn/index.aspx). ETHICS AND DISSEMINATION: The Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine approved the study protocol (approval no.: K2020151, 2021/08/19). The study will also be supervised and managed by the Ethics Committee.

Posterior reversible encephalopathy syndrome associated with use of anlotinib to treat squamous cell carcinoma of the cervix: case report and literature review.

Background: Posterior reversible encephalopathy syndrome (PRES), a neurological disorder with an unknown aetiology, is characterised by visual impairment, headache, vomiting, seizures, and transient alterations in consciousness. Case report: We present the case of a 49-year-old woman with advanced cervical carcinoma who received second-line therapy with oral anlotinib (12 mg, days 1-14, every 21 days) and injectable tislelizumab (200 mg, day 1, every 21 days). After 7 days of anlotinib administration, she began experiencing symptoms suggestive of PRES and was diagnosed on day 11. Interruption of anlotinib and supportive treatment led to recovery of her binocular vision. The Naranjo score (+5) graded the causality of this reaction as probable, suggesting the possibility that the event may have been an adverse reaction to anlotinib. Ethics: This case report was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Reference no. K-2023-068, 2023/06/09). Informed consent was obtained from the patient and her family.

Zhengyuan capsules for the treatment of chemotherapy-induced cancer-related fatigue in stage IIIB-IV unresectable NSCLC: study protocol for a randomized, multi-center, double-blind, placebo-controlled clinical trial.

Background: Patients with advanced non-small cell lung cancer (NSCLC) frequently experience cancer-related fatigue (CRF) during or after chemotherapy. Traditional Chinese medicine (TCM) can effectively relieve CRF, although the clinical evidence is insufficient due to the absence of extensive and rigorous clinical studies. Zhengyuan capsules have both tonifying and dispersing effects, and its ability to alleviate CRF has been verified in mice. This study aimed to provide evidence for the role of proprietary Chinese medicines in alleviating CRF in advanced NSCLC patients. Methods: A multi-center, randomized, double-blind, placebo-controlled clinical trial has been designed to evaluate the efficacy and safety of Zhengyuan capsules for CRF in stage IIIB-IV unresectable NSCLC patients undergoing chemotherapy. Thirty eligible participants will be randomized into two groups at a 1:1 ratio during chemotherapy using the centralized interactive web response system. All patients will receive conventional platinum-based dual-drug chemotherapy and Zhengyuan capsules or simulant for 42 consecutive days starting on the first day of the first week of chemotherapy. The primary outcome is the difference between baseline and post-treatment CRF in the two groups, which will be assessed using the Brief Fatigue Inventory (BFI) score. Secondary outcome measurements include the Revised Piper's Fatigue Scale (RPFS)-Chinese Version, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Module C30 (EORTC QLQ-C30) v3.0 combined with EORTC QLQ-LC13 (Lung Cancer 13), clinical symptom score, hematology exploratory index, and progression-free survival. And safety indicators such as blood, urine, fecal routine, liver and kidney function, coagulation, and electrocardiogram will be performed before chemotherapy. Data will be analyzed according to intention-to-treat (ITT) and per-protocol (PP) principles; Empowerstats and R will be applied for statistical analysis. Discussion: This trial will provide data on the efficacy and safety of Zhengyuan capsules for treating CRF in stage IIIB-IV unresectable NSCLC patients undergoing chemotherapy. It will also provide a basis for the feasibility of a large-scale clinical trial. Trial Registration: The clinical trial was registered on 19 November 2020 through https://www.chictr.org.cn (registration number: ChiCTR2000040061).

Efficacy of Disitamab Vedotin in a heavily pre-treated HER2 positive lung adenocarcinoma patient: case report and literature review.

Cancer therapies targeting human epidermal growth factor receptor 2 (HER2) have been attracting increasing attention worldwide, especially in lung adenocarcinoma. Disitamab vedotin is an antibody-drug conjugate designed for targeting HER2 that has been approved for urothelial carcinoma and gastric cancer. However, there is still a lack of clinical evidence for applying Disitamab vedotin in lung adenocarcinoma. Herein, we reported a case of a 52-year-old man with advanced lung adenocarcinoma carrying HER2 amplification as well as HER2 immunohistochemistry (IHC) 2 + who underwent treatment with Disitamab vedotin after disease progression. The patient was treated with chemotherapy, anti-angiogenesis therapy, and immunotherapy as first-line therapy, achieving a remarkable progression-free survival of 16 months. After the disease continued to continuous progress, the patient was administrated with Disitamab vedotin, which resulted in improvement of both the lung lesions and the brain lesions. Our findings provide a valuable reference for the utilization of Disitamab Vedotin in HER2 IHC2+ lung adenocarcinoma.

Mechanism of a Herbal Formula Associated with Prognosis and Immune Infiltration in LIHC: Transcriptomics Analysis and Molecular Dynamics Simulations.

Background: The aim of this study is to explore the interactions between effective monomers of herbal formulas and their therapeutic targets using systems biology approaches which may be a promising approach to unraveling their underlying mechanisms. Shentao Ruangan decoction (STRGD), which has been experimentally, clinically demonstrated to be effective in treating liver hepatocellular carcinoma (LIHC), was selected. Methods: Bioactive ingredients and drug targets of STRGD were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform and BATMAN-TCM databases. LIHC-related differentially expressed genes (DEGs) and key modules were identified by a weighted gene coexpression network analysis using The Cancer Genome Atlas data. The Kaplan-Meier analysis was used to investigate the relationship between STRGD tumor targets and patients survival. The CIBERSORT deconvolution algorithm was used to analyze the correlation between STRGD tumor targets and infiltrating immune cells. Enrichment analysis was used to analyze biological functions. Interactions between STRGD compounds and LIHC-immune-related genes were investigated using molecular docking and MDS. Results: We identified 24 STRGD tumor targets, which were found to be correlated with survival and the level of immune cell infiltration in LIHC patients. Immune infiltration, gene set enrichment, and Kyoto Encyclopedia of Genes and Genomes analyses highlighted the roles of T and B cell subsets, which were both related to activator protein 1 (AP1), in STRGD action. Docking studies and HPLC indicated that tanshinone IIA is the main compound of STRGD in LIHC treatment, and MDS showed that the potential LIHC-immune-related targets 1FOS and 1JUN firmly bind to tanshinone IIA. Conclusions: The mechanisms of STRGD in improving the immune and survival status of LIHC patients include interactions between STRGD compounds and LIHC-immune-related targets. The findings of this study can guide research studies on the potential usefulness of tanshinone IIA in the development of drugs targeting 1JUN and 1FOS for the treatment of LIHC.

Metabolomics and integrated network pharmacology analysis reveal SNKAF decoction suppresses cell proliferation and induced cell apoptisis in hepatocellular carcinoma via PI3K/Akt/P53/FoxO signaling axis.

BACKGROUND: There is no comprehensive treatment method for hepatocellular carcinoma (HCC); hence, research and development are still focused on systemic therapies, including drugs. Sinikangai fang (SNKAF) decoction, a classic Chinese herbal prescription, has been widely used to treat liver cancer. However, there is no research on its core active component and target. METHODS: Mouse models were established to measure the anticancer effect of SNKAF decoction on HCC. Further, we investigated the effect of SNKAF decoction on inhibition of hepatoma cells proliferation using cell viability, cloning and invasion assays in vitro. The components of SNKAF were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and TCM@Taiwan database. Metabolomic analysis was used to identify the potential genes and pathways in HCC treated with SNKAF decoction. Then, the expression of phosphoinositide 3-kinase (PI3K), Akt, P53, FoxO proteins of the potential signal pathways were detected using Western blot. RESULTS: The animal experiments showed that SNKAF decoction inhibited tumor growth (P < 0.05) and induced no weight loss in the mice. In vitro data showed that HCCLM3 and MHCC97H cell proliferation was inhibited by SNKAF serum in a time- and concentration dependent manner. Further combined analysis network pharmacology with metabonomics showed that 217 target genes overlapped. The core target genes included BCL2, MCL1, Myc, PTEN, gsk3b, CASP9, CREB1, MDM2, pt53 and CCND1. Cancer-associated pathways were largely involved in SNKAF mechanisms, including P53, FoxO, and PI3K/Akt signaling pathways, which are closely related to induced-tumor cell apoptosis. In addition, Western bolt verified that 10% SNKAF serum significantly affected the main proteins of PI3K/Akt/P53/FoxO signaling pathway in both cell lines. CONCLUSION: SNKAF decoction-containing serum inhibited HCCLM3 and MHCC97H cell proliferation, migration, invasion, and induced-tumor cell apoptosis in-vivo. We confirmed that SNKAF decoction is a promising alternative treatments for HCC patients.

Potential driving forces and probabilistic health risks of heavy metal accumulation in the soils from an e-waste area, southeast China.

The integrated analysis of the distribution characteristics, health risks, and source identification of heavy metals is crucial for formulating prevention and control strategies for soil contamination. In this study, the area around an abandoned electronic waste dismantling center in China was selected as the research area. The probabilistic health risks caused by heavy metals were evaluated by the Monte Carlo simulation. Random forest, partial least squares regression, and generalized linear models were utilized to predict heavy metal distributions and identify the potential driving factors affecting heavy metal accumulation in soil. The relationships of spatial variation between the heavy metal contents and environmental variables were further visualized. The results revealed that cadmium (Cd) and copper (Cu) were the primary soil pollutants in the study area and caused high ecological risks. The probabilistic health risk assessment indicated that the non-carcinogenic and carcinogenic risks for all populations were acceptable. However, children are more susceptible to heavy metal soil contamination than adults. The sensitivity analyses indicated that the total contents of soil heavy metals and soil ingestion rate were the dominant factors affecting human health. The random forest model, with R2 values of 0.41, 0.65, 0.57, 0.71, and 0.58 for Cd, Cu, Ni, Zn, and Pb, respectively, predicted the heavy metal concentrations better than the other two models. The distance to the nearest industrial enterprise, industrial output, and agricultural chemical input were the main factors affecting Cd, Cu, Zn, and Pb accumulations in the soil, and soil pH and soil parent material were the primary factors influencing Ni accumulation in the soil. The visualization results of the geographically weighted regression model showed a significant relationship between soil heavy metal contents and industrial activity level. This study could be utilized as a reference for policymakers to formulate prevention and control strategies for heavy metal pollution in agricultural areas.

Database mining and animal experiment-based validation of the efficacy and mechanism of Radix Astragali (Huangqi) and Rhizoma Atractylodis Macrocephalae (Baizhu) as core drugs of Traditional Chinese medicine in cancer-related fatigue.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, Traditional Chinese medicine (TCM) is often used as the main therapy for cancer-related fatigue (CRF). However, there is limited evidence to prove its therapeutic effect and mechanism. AIM OF THE STUDY: We aimed to provide a basis for the therapeutic effect of TCM for CRF. MATERIALS AND METHODS: We performed a meta-analysis to investigate the efficacy of TCM treatment for CRF. Through frequency statistics and association rule mining, we screened the core Chinese medicine components, Astragalus mongholicus Bunge., root (Radix astragali, Huangqi) and Atractylodes macrocephala Koidz., rhizome (Rhizoma atractylodis macrocephalae, Baizhu). We then used animal experiments to verify the effectiveness of these two TCMs and changes in related indicators in mice. Relevant molecular mechanisms were explored through network pharmacological analysis. RESULTS: Twenty-four randomised control trials (RCTs) involving 1865 patients were included in the meta-analysis. TCM produced more positive effects on CRF than standard therapy alone. Radix astragali and Rhizoma atractylodis macrocephalae, as the core drug pair for the treatment of CRF, enhanced the physical fitness of mice; reduced abdominal circumference, level of inflammatory factors, and tumour weight; and increased body weight and blood sugar. Network pharmacology analysis showed that the mechanism of action of Radix astragali and Rhizoma atractylodis macrocephalae on CRF mainly involved compounds, such as quercetin, kaempferol and luteolin, acting through multiple targets, such as Protein kinase B α (AKT1), Tumour necrosis factor (TNF), and Interleukin-6 (IL-6). These molecules regulate cytokines, cancer signalling, and metabolic pathways and confer an anti-CRF effect. CONCLUSIONS: TCM may be a promising therapy to relieve CRF in cancer patients. Our research may provide a reference for the clinical application of TCM for treating CRF.

DNA damage repair gene mutations predict the efficacy of platinum-based chemotherapy and immunotherapy plus platinum-based chemotherapy in advanced non-small cell lung cancer: a retrospective Chinese cohort study.

Background: Platinum-based chemotherapy (PC) and immunotherapy plus platinum-based chemotherapy (IPC) remain the first-line treatment for advanced NSCLC. But only a minority patients benefit from PC, and existing biomarkers, such as PD-L1, have been shown to be defective in predicting the efficacy of IPC. Highlighting the need to identify novel biomarkers for the efficacy of PC and IPC. DNA damage repair (DDR) mutations are known to predict response to PC in solid tumors. However, the predictive value of DDR in PC and IPC of NSCLC remains unclear. Methods: Patients diagnosed with advanced or metastatic NSCLC were retrospectively included if they underwent next generation sequencing prior to starting treatment. Primary endpoints were to explore whether DDR mutations (DDRmut) are associated with clinical outcomes of PC and IPC. Secondary end point were to explore the association between DDRmut and the choice to add immunotherapy to chemotherapy, and the impact of different DDR pathways on efficacy in PC and IPC. Results: DDRmut showed a strong association with tumor mutation burden-high (TMB-H) versus DDR wild-type (DDRwt) and higher rates of PD-L1 TPS ≥50% positivity. In 63 patients treated with PC, ORRs were 15.38% and 2.86% for DDRmut and DDRwt subgroup (P=0.1536), and DCRs were 88.46% and 45.72% (P=0.00097) at 6 months after PC. The DDRmut patients had significantly improved median PFS (mPFS) and median overall survival (mOS) than DDRwt group (mPFS: 7.6 vs. 3.9 months, HR =1.93, 95% CI: 1.09 to 3.14, P=0.0220. mOS: 29.9 vs. 20.7 months, HR =2.31, 95% CI: 1.09 to 4.9, P=0.0250). Moreover, among 37 patients treated with IPC, ORRs were 45% and 11.76% for DDRmut and DDRwt patients (P=0.0365), and the DCRs were 95% and 70.58% (P=0.0752), respectively at 6 months after IPC. The DDRmut patients had significantly improved mPFS compared to the DDRwt group (19.5 vs. 4.5 months, HR =3.28, 95% CI: 1.53 to 9.56, P=0.0022). In DDRmut group, mPFS of IPC recipients was significantly better than that of PC recipients (19.5 vs. 7.6 months, HR =2.09, 95% CI: 0.98 to 4.42, P=0.050). Conclusions: There is potential for DDR to serve as a positive predictor of PC and IPC in advanced NSCLC patients.

Efficacy of Osimertinib in NSCLC Harboring Uncommon EGFR L861Q and Concurrent Mutations: Case Report and Literature Review.

The efficacy of first-and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients with the EGFR L861Q mutation has been studied previously. However, there is little evidence on the efficacy of osimertinib in NSCLC patients with uncommon mutations. Here, we report the case of a 68-year-old man with advanced NSCLC with concurrent EGFR L861Q mutation as well as TP53 and RB1 mutations. The patient was treated with osimertinib as first-line therapy and achieved a remarkable progression-free survival of 15 months. His symptoms were significantly alleviated and the dose was well tolerated. The findings of the present study indicate that osimertinib might be a good treatment option for NSCLC patients with the L861Q mutation.

[Analysis of prescription regularity of traditional Chinese medicine for colorectal cancer based on data mining].

The tumor prescriptions contained in Dictionary of Tumor Formulas, Compendium of Good Tumor Formulas, Chinese Pharmacopoeia, Ministry of Health Drug Standards for Chinese Medicine Formulas and National Compilation of Standards for Proprietary Chinese Medicines were selected and organized to construct a database for tumor prescriptions, and the data mining techniques were applied to investigate the prescription regularity of colorectal cancer prescriptions. The formula data were extracted after screening in strict accordance with the inclusion and exclusion criteria, and were then analyzed with Microsoft Excel 2010 for frequency statistics, Apriori block provided by SPSS Clementine 12.0 software for correlation rule analysis, and arules and arulesViz packages in R 4.0.2 software for correlation rule visualization. In addition, SPSS 18.0 software was used for cluster analysis and factor analysis, in which cluster analysis was performed by Ochiai algorithm with bicategorical variables in systematic clustering method and factor analysis was performed mainly with principal component analysis. A total of 285 prescriptions were included in the statistical analysis, and the frequency statistics showed that 43 herbs had been used more than 16 times. The association rules analysis showed that 26 high-frequency me-dicine pair rules were obtained, and the association rules for those dispelling evil spirits, strengthening the body, resolving stasis, dispelling dampness, etc. were visualized. In the cluster analysis, we generated a dendrogram from which 7 groups of traditional Chinese medicines with homogeneity were extracted. 10 common factors were obtained in the factor analysis. The types of herbal medicines involved in the colorectal cancer prescription included anti-cancer antidotes, strengthening and tonifying medicines, blood-regulating medicines, and expectorant medicines, corresponding to the treatment for eliminating evil spirits, strengthening, resolving stasis, and expectorating dampness. The prescriptions for anti-cancer detoxification were normally based on the pairs composed of Scutellaria barbata-Hedyotis diffusa and Sophora flavescens, Sargentodoxa cuneata, S. barbata, often combined with stasis relieving drug and dampness eliminating drug, reflecting the characteristics of treatment for both toxicity and stasis, dampness and toxicity simultaneously. The prescriptions for strengthening the righteousness and tonifying the deficiency were composed of Astragalus membranaceus and Atractylodes macrocephala mainly, exerting the effect of benefiting Qi, strengthening the spleen and drying dampness, tonifying kidney and essence, tonifying blood and invigorating blood. Meanwhile, anti-cancer detoxification medicines shall be reduced as much as possible. The compatibility of the medicines for the intestinal tract reflected the principle of using the right medicine for the right condition and eliminating evil spirits or strengthening the body, as appropriate.

DNA repair genes are associated with tumor tissue differentiation and immune environment in lung adenocarcinoma: a bioinformatics analysis based on big data.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. DNA repair genes (DRGs) is important in lung cancer. The relationship between the immune environment and the expression levels of DRGs in LUAD remains unclear. The purpose of this study is to assess the relationship between DRGs and the immune environment and clinical characteristics of LUAD. METHODS: Data of 169 LUAD cases were obtained from cbioportal. The RNA-seq data came from the The Cancer Genome Atlas (TCGA) database. We collected DRGs from the Reactom database (KW0037, Reactom.org). The 302 genes expressed in each sample were analyzed by hierarchical clustering and grouped using the Gene Cluster 3.0 program. The Java Treeview program was used to generate heat maps of cluster indications and tumor staging patterns. GraphPad Prism 8 was used to draw survival curves and compare overall survival (OS). For single genes, an OS difference analysis between low and high expression populations was performed in GraphPad Prism 8. RESULTS: Matrix clustering showed no difference in the prognosis of the two clusters. The comparison of subgroups showed that Subcluster 1 (SC1) had the best prognosis, and Subcluster 2 (SC2) had the worst. There was a significant difference in tumor grades between Cluster 1 and Cluster 2 (P=0.01). There were significant differences in smoking status, histological grade and adenocarcinoma subtype among subgroups. In Subcluster 3 (SC3), the proportion of poorly differentiated cases was highest. Immunological index analysis showed that there were significant differences between Cluster 1 and Cluster 2 in interferon, macrophages, monocytes, neutrophils, natural killer (NK) cells, and T cells. Tumor purity, interferon, macrophages, monocytes, neutrophils, NK cells, T cells, translation, and proliferation all showed significant differences between subgroups. In SC2, the proliferation index increased (0.082 vs. 0.070); the protein translation index decreased (0.134 vs. 0.137); and the interferon level increased (0.099 vs. 0.097). In SC3, the proliferation index decreased (0.076 vs. 0.071); the protein translation index decreased (0.140 vs. 0.136); and the level of neutrophils increased (0.083 vs. 0.086). CONCLUSIONS: The differences of DRGs in LUAD are related to tissue differentiation and immune indicators but not to prognosis.

Network Pharmacology/Metabolomics-Based Validation of AMPK and PI3K/AKT Signaling Pathway as a Central Role of Shengqi Fuzheng Injection Regulation of Mitochondrial Dysfunction in Cancer-Related Fatigue.

Chinese herbal medicines have multiple targets and properties, and their use in multidisciplinary cancer therapies has consequently received increasing attention. Here, we have investigated the possible active ingredients associated with cancer-related fatigue (CRF) in the Shengqi Fuzheng Injection (SFI). In vitro cell models were used to measure the regulation effects of SFI on CRF. Metabolomic analysis was used to identify the potential genes and pathways in C2C12 mouse myoblasts treated with SFI, and the interaction of compounds and CRF targets was predicted using network pharmacology and molecular docking analyses. The putative pathways were further verified using immuno-blotting assays. The results showed that SFI significantly inhibited muscle cell apoptosis and increased the mitochondrial membrane potential of muscle cells. The network pharmacology analysis results identified 36 candidate compounds, and 244 potential targets were yielded by SFI, and they shared 10 key targets associated with cancer-related fatigue. According to the enrichment analysis and experimental validation, SFI might ameliorate muscle cell mitochondrial function by activating AMPK and inhibiting the PI3K/Akt signaling pathways, and the expression changes of mitochondrial metabolic enzymes MnSOD and apoptosis-associated proteins Bax and Bcl-2 were also triggered. The functions and mechanisms of SFI in anticancer-related fatigue were found here to be at least partly due to the targeting of the AMPK and PI3K/Akt signaling pathways, and this has highlighted new potential applications for network pharmacology when researching Chinese Medicines.

Adjuvant EGFR-TKIs for Patients With Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Meta-Analysis of 1,283 Patients.

BACKGROUND: Cisplatin-based chemotherapy was previously considered as the standard adjuvant therapy for improved overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. However, the benefit was limited due to high risks of recurrence and adverse events. In the present study, the efficacy of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutant patients after surgery was investigated using the latest updated data. METHODS: This meta-analysis included a comprehensive range of relevant studies identified from database searches. Disease-free survival (DFS) and OS with hazard ratios (HRs) were calculated using random-effect or fixed-effect models. Subgroup analysis was also performed. RESULTS: A total of seven randomized clinical trials were included in the meta-analysis and involved 1,283 NSCLC patients harboring EGFR mutations. In resected EGFR-mutant NSCLC patients, adjuvant EGFR-TKIs were significantly better than chemotherapy in terms of DFS (HR: 0.41; 95%CI: 0.24-0.70, P = 0.001), without showing any benefit in OS (HR: 0.72; 95%CI: 0.37-1.41, P = 0.336). No significant difference in DFS was observed between patients with EGFR exon 19 deletion and those with L858R mutation. Resected EGFR-mutant NSCLC patients treated with osimertinib experienced improved DFS and a lower risk of brain recurrence than those treated with gefitinib or erlotinib. Adjuvant EGFR-TKIs reduced the risk of bone and lung relapse, without decreasing the risk of local recurrence and liver relapse. CONCLUSION: This meta-analysis shows that adjuvant EGFR-TKI therapy could significantly prolong DFS in patients with resected EGFR-mutant NSCLC. Treatment with osimertinib showed improved DFS with a lower risk of brain recurrence than treatment with gefitinib or erlotinib for resected disease.

Effects of magnetic biochar-microbe composite on Cd remediation and microbial responses in paddy soil.

There is growing global interest in the bioremediation of cadmium (Cd) using combinations of biochar and microorganisms. However, the interactions among biochar, introduced and indigenous microorganisms remain unclear. Accordingly, a 90 day microcosm experiment was conducted to investigate this by adding Bacillus sp. K1 strain inoculated rice straw biochar (SBB) and magnetic straw biochar (MBB) into a Cd contaminated paddy soil from Hunan, China. All treatments were incubated aerobically (60% water holding capacity) or anaerobically for 90 d. During both soil incubations, Bacillus sp. K1 successfully colonized in soil with composites applications. Soil pH was significantly increased from acid to neutral, and available Cd decreased with the addition of both composites. The better remediation efficiency of MBB than SBB under anerobic conditions was attributed to the transformation of acetic acid-extractable Cd into the residual fraction, caused by Cd2+ bonding with crystal Fe3O4. The application of the two kinds of composites caused similar changes to both microbial communities. There was a slight decrease in indigenous microbial alpha diversity with the MBB aerobic application, while the total population number of bacteria was increased by 700%. Both the redundancy analysis and Mantel analyses indicated that pH and microbial biomass C contributed to the colonization of Bacillus sp. K1 with SBB under aerobic conditions, and with MBB under anerobic conditions, respectively. The research provides a new insight into interactive effects and investigates immobilization mechanisms involved of bacterial/biochar composites in anaerobic and aerobic soils.

Combination of Cordycepin and Apatinib Synergistically Inhibits NSCLC Cells by Down-Regulating VEGF/PI3K/Akt Signaling Pathway.

BACKGROUND: The application of apatinib is immensely limited by its acquired drug resistance. This research investigates whether cordycepin, a component from Cordyceps could synergize with apatinib to improve its anticancer effect on non-small cell lung cancer (NSCLC) cells. METHODS: The NSCLC cell lines A549, PC9, and H1993, and human bronchial epithelial (HBE) cell line Bears-2B were used in this study. Cell counting kit 8, colony formation assays, wound healing assay, transwell assay, and flow cytometry analysis were performed to assess the cell viability, the migration ability, and invasion ability of the cells. Kyoto encyclopedia of genes and genomes (KEGG), western blotting and molecular docking was applied to analyze the possible pathways affected by cordycepin. RESULTS: The combination of cordycepin and apatinib in a ratio of 5:1 synergistically reduced proliferation of NSCLC cells, inhibited cell migration and invasion, increased cell apoptosis by altering cell cycle in NSCLC A549 and PC9 cells. The VEGF/PI3K/Akt pathway was inhibited after treatment with cordycepin and apatinib. CONCLUSION: Our findings demonstrated that the combination of cordycepin and apatinib has synergistically anticancer effect on NSCLC cells by down-regulating VEGF/PI3K/Akt signaling pathway. This result indicated that cordycepin and apatinib could be a promising drug combination against NSCLC.