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.

Lysine acetyltransferase KAT2A modulates ferroptosis during colorectal cancer development.

BACKGROUND: Histone modifications, especially the lysine acetylation, have drawn increasing attention in cancer research area. The aim of this research is to explore the molecular mechanisms underlying the regulation of lysine acetyltransferase 2 A (KAT2A) on colorectal cancer (CRC). METHODS: Clinical samples were collected from patients with CRC. The expression and correlation between KAT2A and ferroptosis suppressor SLC7A11 and glutathione peroxidase 4 (GPX4) were measured by qPCR and Pearson correlation analysis. NCP cells were transfected with KAT2A overexpression vectors or siRNAs. The proliferation of cells was measured by CCK-8 and colony formation assay. Cell migration and invasion was analyzed by Transwell. The accumulation of lipid peroxidation, ferrous iron, and malondialdehyde (MDA) were analyzed to determine cell ferroptosis. The expression of cell metastasis biomarkers was measured by western blotting assay. Interaction between KAT2A with GPX4 gene was measured by chromatin immunoprecipitation (ChIP). RESULTS: The KAT2A, GPX4, and SLC7A11 expression was notably elevated in tumor tissues compared with the paired non-tumor tissues from CRC patients. The expression of KAT2A showed positive correlation with GPX4 and SLC7A11. Overexpression of KAT2A recovered the cell proliferation, migration, and invasion of CRC cells that suppressed by ferroptosis inducer erastin, along with deceased levels of ROS, iron, Fe2+, and MDA. Overexpression of KAT2A suppressed E-cadherin level and increased N-cadherin, Snail, and Vimentin expression in CRC cells. KAT2A interacted with GPX4 promoter region. CONCLUSIONS: In conclusion, our findings demonstrated that KAT2A modulates the histone acetylation of GPX4 to regulate proliferation, metastasis, and ferroptosis of CRC cells.

Active post-transcriptional regulation and ACLY-mediated acetyl-CoA synthesis as a pivotal target of Shuang-Huang-Sheng-Bai formula for lung adenocarcinoma treatment.

BACKGROUND: New therapeutic approaches are required to improve the outcomes of lung cancer (LC), a leading cause of cancer-related deaths worldwide. Chinese herbal medicine formulae widely used in China provide a unique opportunity for improving LC treatment, and the Shuang-Huang-Sheng-Bai (SHSB) formula is a typical example. However, the underlying mechanisms of action remains unclear. PURPOSE: This study aimed to confirm the efficacy of SHSB against lung adenocarcinoma (LUAD), which is a major histological type of LC, unveil the downstream targets of this formula, and assess the clinical relevance and biological roles of the newly identified target. METHODS: An experimental metastasis mouse model and a subcutaneous xenograft mouse model were used to evaluate the anti-cancer activity of SHSB. Multi-omics profiling of subcutaneous tumors and metabolomic profiling of sera were performed to identify downstream targets, especially the metabolic targets of SHSB. A clinical trial was conducted to verify the newly identified metabolic targets in patients. Next, the metabolites and enzymes engaged in the metabolic pathway targeted by SHSB were measured in clinical samples. Finally, routine molecular experiments were performed to decipher the biological functions of the metabolic pathways targeted by SHSB. RESULTS: Oral SHSB administration showed overt anti-LUAD efficacy as revealed by the extended overall survival of the metastasis model and impaired growth of implanted tumors in the subcutaneous xenograft model. Mechanistically, SHSB administration altered protein expression in the post-transcriptional layer and modified the metabolome of LUAD xenografts. Integrative analysis demonstrated that SHSB markedly inhibited acetyl-CoA synthesis in tumors by post-transcriptionally downregulating ATP-citrate lyase (ACLY). Consistently, our clinical trial showed that oral SHSB administration declined serum acetyl-CoA levels of patients with LC. Moreover, acetyl-CoA synthesis and ACLY expression were both augmented in clinical LUAD tissues of patients, and high intratumoral ACLY expression predicted a detrimental prognosis. Finally, we showed that ACLY-mediated acetyl-CoA synthesis is essential for LUAD cell growth by promoting G1/S transition and DNA replication. CONCLUSION: Limited downstream targets of SHSB for LC treatment have been reported in previous hypothesis-driven studies. In this study, we conducted a comprehensive multi-omics investigation and demonstrated that SHSB exerted its anti-LUAD efficacy by actively and post-transcriptionally modulating protein expression and particularly restraining ACLY-mediated acetyl-CoA synthesis.

Combinatorial screening SlipChip for rapid phenotypic antimicrobial susceptibility testing.

Antimicrobial resistance (AMR) by bacteria is a serious global threat, and a rapid, high-throughput, and easy-to-use phenotypic antimicrobial susceptibility testing (AST) method is essential for making timely treatment decisions and controlling the spread of antibiotic resistant micro-organisms. Traditional culture-based methods are time-consuming, and their capability to screen against a large number of different conditions is limited; meanwhile genotypic based methods, including sequencing and PCR based methods, are constrained by rarely identified resistance genes and complicated resistance mechanisms. Here, a combinatorial-screening SlipChip (cs-SlipChip) containing 192 nanoliter-sized compartments is developed which can perform high-throughput phenotypic AST within three hours by monitoring the bacterial growth within nanoliter-sized droplets with bright-field imaging and analyzing the changes in bacterial number and morphology. The minimum inhibitory concentration (MIC) of Escherichia coli ATCC 25922 against four antibiotics (ampicillin, ciprofloxacin, ceftazidime, and nitrofurantoin) can be measured in one chip within 3 hours. Furthermore, five antibiotic-resistant E. coli strains were isolated from patients diagnosed with urinary tract infections (UTIs), and an individual isolate was tested using four antibiotics and eleven antibiotic combinations simultaneously with three different concentrations of each. The results from the cs-SlipChip agree with those of a VITEK 2 automated system. This cs-SlipChip provides a practical high-throughput and rapid phenotypic method for AST and can also be used to screen different chemicals and antibiotic combinations for the treatment of multiple antibiotic-resistant bacteria.

To study the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer based on network pharmacology.

The aim of the study wasto explore the target and potential mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer infection by network pharmacology. The target information of baicalein and flavonin was mined from CTD database and Swiss database. Genecards database, DRUGBANK database, and OMIM database were used to search for lung cancer related genes. The target protein network map (PPI) was drawn by using the STRING database analysis and Cytoscape3.7.1 software. With the help of Perl language, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene function analysis (GO) enrichment analysis were carried out by using the biological program package of R language. In total, 347 biological targets of Astragaloside and Scutellariae Radix were identified through the collection and analysis of multiple databases. In total, 1526 lung cancer targets were obtained from a multi-disease database. The "component-target" network of Astragaloside and Scutellariae Radix was constructed, and the protein interaction network (PPI) of the overlapping targets was analyzed to identify the key targets of drug-influenced diseases. In addition, KEGG pathway analysis and GO enrichment analysis were performed on the overlapping targets to explore the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer. Scutellariae Radix and Astragaloside have the characteristics of multi-component, multi-target and multi-pathway in the treatment of lung cancer, which provides a new idea and scientific basis for further research on the molecular mechanism of the antilung cancer effect of Scutellariae Radix and Astragaloside.

Feiyanning downregulating CXCLs/CXCR2 axis to suppress TANs infiltration in the prevention of lung cancer metastasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Tumor-associated neutrophils (TANs) play an important role in tumor metastasis. The Traditional Chinese medicine (TCM) Feiyanning (FYN) has been clinically proven to effectively prevent the recurrence and metastasis of lung cancer, improve immunity, and prolong the survival period of lung cancer patients. However, its anti-metastatic immune mechanism has not been fully elucidated. To this end, we studied the mechanism of FYN's regulation of neutrophils infiltration in the tumor microenvironment (TME). AIM OF THE STUDY: To explore the anti-metastatic mechanism of FYN from the perspective of anti-immunosuppressive phenotype neutrophils infiltration in the TME. MATERIALS AND METHODS: TCM network pharmacological analysis was used to predict Feiyanning effective target. Flow cytometry was used to detect the proportion of immune cell subsets in the TME. Lung metastases were investigated in C57 mice by tail vein injection. Protein expression was evaluated by immunohistochemistry and Western blot. Gene expression was evaluated by qRT-PCR. RESULTS: FYN could reshape the tumor immune microenvironment. It prevents Tregs, M2 macrophages, and neutrophils infiltration, as well as recruits T cells, NK cells, and DCs, and improves DCs activation. In addition, FYN could regulate the polarization of TANs, inhibit the infiltration of neutrophils with an immunosuppressive phenotype, downregulate CXCLs/CXCR2 axis and inhibitory factors like Arg-1 and TGF-ß, and up-regulate the immune effector molecule ICAM-1. Furthermore, FYN increases anti-tumor immune effects in the TME to prevent tumor cells from spreading to the lungs. CONCLUSION: This study clarifies the potential mechanism of FYN in regulating neutrophils infiltration and anti-metastasis. FYN may regulate neutrophils infiltration in the TME by regulating CXCLs/CXCR2 axis.

Mechanism underlying the effect of Liujunzi decoction on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy.

OBJECTIVE: To further clarify the anticancer mechanisms of Liujunzi decoction and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer (NSCLC) by re-analyzing differential gene expression profile of peripheral blood mononuclear cells (PBMCs) from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy. METHODS: The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database. Differentially expressed genes (DEGs) were screened by paired sample t-test and the multiple ratio method. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed using the DAVID database. The protein-protein interaction (PPI) network was constructed using interaction gene library retrieval tools and Cytoscape software. RESULTS: A total of 162 DEGs were identified, with 67 upregulated genes and 95 downregulated genes. The functional distribution of Gene Oncology (GO) genes showed that DEGs were mostly concentrated in extracellular regions, calcium ion binding, and transcriptase activity. KEGG pathway analysis showed that cytokine-cytokine receptor interactions were significantly enriched. PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree: IL2, PIWIL4, DICER1, PIWIL2, SAA1, XCL1, IL22RA1, ARHGAP11A, DCP1A, and GDNF. Among them, the central protein-coding gene with the highest node degree was IL2. In addition, the central protein-coding genes with high node degrees and high molecular complex detection (MCODE) scores were PIWIL4, DICER1, PIWIL2, and DCP1A, all of which are related to tumor development. CONCLUSIONS: One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data. IL2, PIWIL4, DICER1, PIWIL2, and DCP1A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC. Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.

Oleanolic acid blocks the purine salvage pathway for cancer therapy by inactivating SOD1 and stimulating lysosomal proteolysis.

Metabolic reprogramming is a core hallmark of cancer and is key for tumorigenesis and tumor progression. Investigation of metabolic perturbation by anti-cancer compounds would allow a thorough understanding of the underlying mechanisms of these agents and identification of new anti-cancer targets. Here, we demonstrated that the administration of oleanolic acid (OA) rapidly altered cancer metabolism, particularly suppressing the purine salvage pathway (PSP). PSP restoration significantly opposed OA-induced DNA replication and cell proliferation arrest, underscoring the importance of this pathway for the anti-cancer activity of OA. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and 5'-nucleotidase (5'-NT), two metabolic enzymes essential for PSP activity, were promptly degraded by OA via the lysosome pathway. Mechanistically, OA selectively targeted superoxide dismutase 1 (SOD1) and yielded reactive oxygen species (ROS) to activate the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/macroautophagy pathway, thus eliciting lysosomal degradation of HGPRT and 5'-NT. Furthermore, we found that the PSP was overactivated in human lung and breast cancers, with a negative correlation with patient survival. The results of this study elucidated a new anti-cancer mechanism of OA by restraining the PSP via the SOD1/ROS/AMPK/mTORC1/macroautophagy/lysosomal pathway. We also identified the PSP as a new target for cancer treatment and highlighted OA as a potential therapeutic agent for cancers with high PSP activity.

Study on the structure-activity relationship of dihydroartemisinin derivatives: Discovery, synthesis, and biological evaluation of dihydroartemisinin-bile acid conjugates as potential anticancer agents.

A series of dihydroartemisinin derivatives was synthesized, and their anti-proliferation activity against cancer cells was evaluated. Structure-activity relationship studies led to the discovery of dihydroartemisinin-bile acid conjugates that exhibit broad-spectrum anti-proliferation activities. Among them, the dihydroartemisinin-ursodeoxycholic acid conjugate (49) was the most potent, with IC50 values between 0.04 and 0.96 µM when tested to determine its inhibitory properties against 15 various cancer cell lines. In vivo experiments showed that compound 49 effectively suppressed tumor growth in an A549 cell xenograft model at the dosage of 10 mg/kg body weight and in Lewis lung cancer cell transplant model at the dosage of 12 mg/kg body weight.

Feiyanning Formula Induces Apoptosis of Lung Adenocarcinoma Cells by Activating the Mitochondrial Pathway.

Feiyanning formula (FYN) is a traditional Chinese medicine (TCM) prescription used for more than 20 years in the treatment of lung cancer. FYN is composed of Astragalus membranaceus, Polygonatum sibiricum, Atractylodes macrocephala, Cornus officinalis, Paris polyphylla, and Polistes olivaceous, etc. All of them have been proved to have anti-tumor effect. In this study, we used the TCM network pharmacological analysis to perform the collection of compound and disease target, the prediction of compound target and biological signal and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. It was found that the activation of mitochondrial pathway might be the molecular mechanism of the anti-lung cancer effect of FYN. The experimental results showed that FYN had an inhibitory effect on the growth of lung cancer cells in a dose-dependent and time-dependent manner. Moreover, FYN induced G2/M cell cycle arrest and apoptotic cell death as early as 6 h after treatment. In addition, FYN significantly induced mitochondrial membrane depolarization and increased calreticulin expression. Metabolomics analysis showed the increase of ATP utilization (assessed by a significant increase of the AMP/ATP and ADP/ATP ratio, necessary for apoptosis induction) and decrease of polyamines (that reflects growth potential). Taken together, our study suggested that FYN induced apoptosis of lung adenocarcinoma cells by promoting metabolism and changing the mitochondrial membrane potential, further supporting the validity of network pharmacological prediction.

Chinese herbal medicine Feiyanning cooperates with cisplatin to enhance cytotoxicity to non-small-cell lung cancer by inhibiting protective autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Feiyanning (FYN), the Chinese herbal medicine (CHM), has been used to manage non-small cell lung cancer (NSCLC) for the past 23 years. Chemotherapeutic drugs can induce autophagy in cancer cells to protect themselves from death. However, FYN can inhibit the protective autophagy in cancer cells. We investigated the biological mechanisms on the synergistic effects of FYN combined with chemotherapy in lung cancer cells. MATERIALS AND METHODS: We analyzed the effective chemical components for the quality control of FYN using the UPLC-Q-TOF-MS.The cell proliferation ability was detected by the cell counting kit-8 (CCK-8) and colony formation. The cell apoptosis was determined with Flow cytometry. Expression of important differential proteins were detected by western blot. Autophagy structure was observed by TEM (Tansmission electron microscopy). Tandem mCherry-EGFP-LC3B immunofluorescence was used to measure autophagic flux. RESULTS: Both FYN and cisplatin significantly induced apoptosis and inhibited cell proliferation in A549 cells. FYN reduced cell viability and increased apoptotic cell populations less effectively than cisplatin. FYN cooperated with cisplatin suppressed the cell viability, colony formation, as well as increased the cell apoptosis rate, and the expression of cleaved caspase-3 and PARP. FYN inhibited autophagy in A549 cells, which characterized by the decrease of autophagosome formation, lysosomal fusion, LC3B-II accumulation and SQSTM1 degradation, down-regulation of ATG5 and ATG7. Protective autophagy in A549 cells was induced by cisplatin. Suppression of the autophagic response using chloroquine (CQ) which is autophagy inhibitor improved the ability of cisplatin to kill cancer cells, as did FYN combined with cisplatin. CONCLUSION: In summary, we revealed that the synergistic mechanism of FYN and cisplatin is that FYN inhibited the protective autophagy induced by cisplatin in A549 cells.

Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p.

Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and the underlying mechanisms of Astragaloside IV (AS) and saponins of rhizoma polygonati (SRP), the two main bioactive ingredients of Shuanghuang Shengbai granule, on CTX-induced myelosuppression. CTX inhibited the proliferation and promoted apoptosis in bone marrow hematopoietic stem cells (BMHSCs), accompanied by the increased expression of miR-142-3p. AS and/or SRP treatment could alleviate CTX-induced cell injury and suppress the expression of miR-142-3p. Over-expression of miR-142-3p partially reversed the therapeutic effect of AS and/or SRP on CTX-induced cell injury in BMHSCs. Further mechanism exploration discovered that HMGB1 was the target gene of miR-142-3p, and miR-142-3p negatively regulated the expression of HMGB1. To further explore the function of AS and/or SRP in vivo, we constructed a lung cancer xenograft combined with CTX-induced myelosuppression mouse model, and we found that AS and SRP remarkably reversed the CTX-induced reduction of white blood cells, bone marrow nucleated cells, and thymus index in vivo and did not affect the chemotherapy effect of lung cancer. Collectively, our results strongly suggested that AS and SRP could improve the hematopoietic function of myelosuppressed lung cancer mice, and their effects may be related to the inhibition of miR-142-3p expression in BMHSCs.

Targeting macrophage priming by polyphyllin VII triggers anti-tumor immunity via STING-governed cytotoxic T-cell infiltration in lung cancer.

Stimulator of interferon genes (STING) controlled innate immune pathway is essential for host defense against pathogenic infection and effective anti-tumor adaptive immunity initiation. Although macrophages transformed across diverse phenotypes play crucial roles in anti-tumor immune response, events determining this transformation and the host-intrinsic role of STING in this process remain controversial. Here we report how STING signaling acts as a key switch to dominate the gene expression patterns of macrophage transformation for promoting priming and releasing immunosuppression. Furthermore, polyphyllin VII, a potential STING agonist, exerts anti-tumor efficacy upon macrophages priming and subsequent cytotoxic T lymphocytes intratumoral infiltration. Meanwhile, the simultaneous PD-L1 amplification on macrophages in response to PP VII is also ruled by STING, thus PP VII may benefit immune-checkpoint blockade therapy for combining. Moreover, PP VII suppresses carcinogenesis upon restraining the immunosuppressed macrophage transformation. This is due to the boosted STING that negatively regulates a STAT3 propagated crosstalk between immune cells and tumor cells. Overall, PP VII-stimulated STING in macrophages provides a paradigm for anti-tumor, and if possible, anti-infection immunotherapy.

Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer.

Although osimertinib, an EGFR tyrosine kinase inhibitor, has become the standard therapy for treating non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, upregulation of MCL-1 induces acquired resistance to osimertinib. Bufalin, a natural digoxin-like ingredient isolated from a traditional Chinese medicine Chan Su, has been shown to downregulate MCL-1 in NSCLC cells. However, whether bufalin reverses this acquired resistance to osimertinib in NSCLC cells remains unclear. In this study, bufalin reduced cell viability and promoted apoptosis in osimertinib-resistant cells. Moreover, co-treatment with bufalin and osimertinib restored the sensitivity of osimertinib-resistant cells to osimertinib-induced growth regression and apoptosis in vitro and in vivo. Mechanistically, MEK/ERK-dependent MCL-1 phosphorylation and Ku70-mediated MCL-1 overexpression confer osimertinib resistance in EGFR-mutant NSCLC cells. In osimertinib-resistant cells, bufalin modulates Ku70-mediated MCL-1 degradation, but not MEK/ERK/MCL-1 signaling. In conclusion, our study suggests that bufalin eliminates resistance to osimertinib by inhibiting Ku70-mediated MCL-1 overexpression, indicating that a combination of osimertinib and bufalin could be an effective additional treatment to overcome acquired resistance to osimertinib in NSCLC cells.

Change of Inflammatory Factors in Patients with Acute Coronary Syndrome.

BACKGROUND: Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance. METHODS: A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed. RESULTS: The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively). CONCLUSIONS: The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.

Clinical practice guidelines for the treatment of primary liver cancer with integrative traditional Chinese and Western medicine.

Traditional Chinese medicine (TCM) is an important part of the treatment of primary liver cancer (PLC) in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical practice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the methodological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.

Treatment of Advanced Non-small-Cell Lung Cancer with Qi-Nourishing Essence-Replenishing Chinese Herbal Medicine Combined with Chemotherapy.

BACKGROUND: To evaluate the effect of qi-nourishing essence-replenishing Chinese herbal medicine combined with chemotherapy in survival of advanced non-small-cell lung cancer(NSCLC) patients with essence and qi deficiency. METHODS: A prospective multi-centered randomized controlled study was conducted, and 266 advanced NSCLC patients were enrolled. 126 patients in control group received Vinorelbine plus cisplatin(NP) chemotherapy combined with symptom-oriented Chinese herbs medication(without qi-nourishing essence-replenishing herbs);140 patients in experimental group received NP chemotherapy combined with qi-nourishing essence-replenishing Chinese herbal medication(Kangliu Zengxiao Decoction and modified Feiyanning Decoction, during and after chemotherapy respectively). RESULTS: One patient in control and 2 in experimental group were excluded for failure to complete two cycles of chemotherapy. During follow-up, 17 and 7 patients in control and experimental group were excluded respectively(4 and 4 for taking Gefetinib after disease progression, 4 and 2 for receiving other chemotherapeutic regimens, 9 and 1 for lost to follow-up). 239 patients were included in the final analysis (131 in experimental group and 108 in control). Median overall survival in experimental group was significantly longer than control group (14.87vs.12.97 months,P = 0.027). In experimental and control group, 1-year, 3-year, 5-year, 7-year, and 9-year survival rates were 57% vs. 53%, 17% vs. 8%, 10% vs. 2%, 6% vs. 0%, and 6% vs. 0%, respectively. CONCLUSION: Qi-nourishing essence-replenishing Chinese herbal medicine combined with chemotherapy improves survival of advanced NSCLC patients with essence and qi deficiency.

B-Site Cation-Ordered Double-Perovskite Oxide as an Outstanding Electrode Material for Supercapacitive Energy Storage Based on the Anion Intercalation Mechanism.

Perovskite oxides are highly promising electrodes for oxygen-ion-intercalation-type supercapacitors owing to their high oxygen vacancy concentration, oxygen diffusion rate, and tap density. Based on the anion intercalation mechanism, the capacitance is contributed by surface redox reactions and oxygen ion intercalation in the bulk materials. A high concentration of oxygen vacancies is needed because it is the main charge carrier. In this study, we propose a B-site cation-ordered Ba2Bi0.1Sc0.2Co1.7O6-δ as an electrode material with an extremely high oxygen vacancy concentration and oxygen diffusion rate. A maximum capacitance of 1050 F g-1 was achieved, and a high capacitance of 780 F g-1 was maintained even after 3000 charge-discharge cycles at a current density of 1 A g-1 with an aqueous alkaline solution (6 M KOH) electrolyte, indicating an excellent cycling stability. In addition, the specific volumetric capacitance of Ba2Bi0.1Sc0.2Co1.7O6-δ reaches up to 2549.4 F cm-3 based on the dense construction and high tap density (3.2 g cm-3). In addition, an asymmetric supercapacitor was constructed using activated carbon as a negative electrode, and it displayed the highest specific energy density of 70 Wh kg-1 at the power density of 787 W kg-1 in this study.

Shuanghuang Shengbai granule cures myelosuppression and suppresses lung cancer progression: mechanism and therapeutic targets from the aspect of microRNAs.

BACKGROUND: Shuanghuang Shengbai granule is effective in curing cyclophosphamide-induced myelosuppression without promoting lung cancer development. This study aims to investigate its mechanism and therapeutic targets. METHODS: Nude mice with lung cancer were treated with physiological saline (control), cyclophosphamide, or cyclophosphamide + Shuanghuang Shengbai. MicroRNA microarray was used to investigate the differentially expressed microRNAs in lung cancer stem cells or bone marrow hematopoietic stem cells between the three groups. MicroRNA expressions were confirmed using quantitative real time-polymerase chain reaction. RESULTS: Cyclophosphamide suppressed tumor growth and decreased the ratio of SP+ lung cancer stem cells (P<0.05). Shuanghuang Shengbai further decreased the ratios of SP+ and CD24+IGF1R+ lung cancer stem cells (P<0.05). Shuanghuang Shengbai completely reversed the cyclophosphamide-induced decreases in white blood cells, proliferation index of bone marrow cells, and the ratio of CD34+SCA1+ bone marrow hematopoietic stem cells (P<0.05). We found 45 and 343 altered microRNAs for SP+ lung cancer stem cells and CD34+SCA1+ bone marrow hematopoietic stem cells, respectively. Moreover, miR-32*, miR-466i-5p, and mmu-miR-669c in SP+ lung cancer stem cells were confirmed, as well as mmu-miR-106b*, mmu-miR-144, mmu-miR-669k*, mmu-miR-142-3p, mmu-miR-210, and mmu-miR-223 in CD34+SCA1+ bone marrow hematopoietic stem cells. CONCLUSION: Shuanghuang Shengbai might promote the proliferation of CD34+SCA1+ bone marrow hematopoietic stem cells via up-regulating mmu-miR-106b*, mmu-miR-144, and mmu-miR-669k*, as well as down-regulating mmu-miR-142-3p, mmu-miR-210, and mmu-miR-223. Shuanghuang Shengbai might further inhibit the proliferation of SP+ lung cancer stem cells via enhancing the expressions of miR-32*, miR-466i-5p, and mmu-miR-669c. These might be the mechanism and therapeutic targets of Shuanghuang Shengbai granule.