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.

Bioinformatics and System Biology Approach to Reveal the Interaction Network and the Therapeutic Implications for Non-Small Cell Lung Cancer Patients With COVID-19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the leading cause of coronavirus disease-2019 (COVID-19), is an emerging global health crisis. Lung cancer patients are at a higher risk of COVID-19 infection. With the increasing number of non-small-cell lung cancer (NSCLC) patients with COVID-19, there is an urgent need of efficacious drugs for the treatment of COVID-19/NSCLC. Methods: Based on a comprehensive bioinformatic and systemic biological analysis, this study investigated COVID-19/NSCLC interactional hub genes, detected common pathways and molecular biomarkers, and predicted potential agents for COVID-19 and NSCLC. Results: A total of 122 COVID-19/NSCLC interactional genes and 21 interactional hub genes were identified. The enrichment analysis indicated that COVID-19 and NSCLC shared common signaling pathways, including cell cycle, viral carcinogenesis, and p53 signaling pathway. In total, 10 important transcription factors (TFs) and 44 microRNAs (miRNAs) participated in regulations of 21 interactional hub genes. In addition, 23 potential candidates were predicted for the treatment of COVID-19 and NSCLC. Conclusion: This study increased our understanding of pathophysiology and screened potential drugs for COVID-19 and NSCLC.

Exploring the mechanism of aidi injection for lung cancer by network pharmacology approach and molecular docking validation.

BACKGROUND: Aidi injection (ADI) is an effective Traditional Chinese medicine preparation widely used for lung cancer. However, the pharmacological mechanisms of ADI on lung cancer remain to be elucidated. METHODS: A network pharmacology (NP)-based approach and the molecular docking validation were conducted to explore underlying mechanisms of ADI on lung cancer. The compounds and target genes were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (Batman-TCM) database. The STRING database was utilized for protein interaction network construction. The R package clusterProfiler was used for bioinformatics annotation of hub target genes. The gene expression analysis and survival analysis were performed based on The Cancer Genome Atlas (TCGA) database. The Autodock Vina was used for molecular docking validation. RESULTS: A total of five key compounds with 324 putative target genes were screened out, and 14 hub target genes were identified for treating lung cancer. Six hub genes could influence the survival of non-small cell lung cancer (NSCLC) patients. Of these hub genes, the expression pattern of EGFR, MYC, PIK3CA, and SMAD3 were significantly higher in the LUSC, while PIK3CA and RELA expressed lower in the LUAD group and LUSC group, respectively. These six hub genes had good docking affinity with the key compounds of ADI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that ADI may exert therapeutic effects on lung cancer by regulating critical pathways including the thyroid hormone signaling pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway. CONCLUSIONS: The present study explored the potential pharmacological mechanisms of ADI on lung cancer, promoting the clinical application of ADI in treating lung cancer, and providing references for advanced researches.

Durable Clinical Response of Advanced Lung Adenocarcinoma Harboring EGFR-19del/T790M/BRAFV600E Mutations After Treating with Osimertinib and Dabrafenib Plus Trametinib: A Case Report.

EGFR-T790M and BRAFV600E are the common resistance mechanisms to EGFR-tyrosine kinase inhibitors (TKIs). Standard treatment for the triple mutations of EGFR-19del, T790M, and BRAFV600E is still under debate. Herein, we present a case of therapeutic efficacy of osimertinib and dabrafenib plus trametinib on a 63-year-old man with advanced lung adenocarcinoma. This patient reached a remarkable progression-free survival of 9 months without any serious adverse reaction. At the progression of the disease, C797S mutation in cis was detected by liquid biopsy. Subsequently, brigatinib with cetuximab was administered but no curative effect was observed. Then, therapy was changed to apatinib combined with osimertinib. The subsequent CT scan showed that the lesions reached stable disease (SD), and the survival benefit has been evaluated. This case showed that the combination treatment of osimertinib and dabrafenib plus trametinib might be a great treatment option for NSCLC patients with triple mutations (EGFR-19del/T790M/BRAFV600E).

A Comprehensive Network Pharmacology-Based Strategy to Investigate Multiple Mechanisms of HeChan Tablet on Lung Cancer.

BACKGROUND: HeChan tablet (HCT) is a traditional Chinese medicine preparation extensively prescribed to treat lung cancer in China. However, the pharmacological mechanisms of HCT on lung cancer remain to be elucidated. METHODS: A comprehensive network pharmacology-based strategy was conducted to explore underlying mechanisms of HCT on lung cancer. Putative targets and compounds of HCT were retrieved from TCMSP and BATMAN-TCM databases; related genes of lung cancer were retrieved from OMIM and DisGeNET databases; known therapeutic target genes of lung cancer were retrieved from TTD and DrugBank databases; PPI networks among target genes were constructed to filter hub genes by STRING. Furthermore, the pathway and GO enrichment analysis of hub genes was performed by clusterProfiler, and the clinical significance of hub genes was identified by The Cancer Genome Atlas. RESULT: A total of 206 compounds and 2,433 target genes of HCT were obtained. 5,317 related genes of lung cancer and 77 known therapeutic target genes of lung cancer were identified. 507 unique target genes were identified among HCT-related genes of lung cancer and 34 unique target genes were identified among HCT-known therapeutic target genes of lung cancer. By PPI networks, 11 target genes AKT1, TP53, MAPK8, JUN, EGFR, TNF, INS, IL-6, MYC, VEGFA, and MAPK1 were identified as major hub genes. IL-6, JUN, EGFR, and MYC were shown to associate with the survival of lung cancer patients. Five compounds of HCT， quercetin, luteolin, kaempferol, beta-sitosterol, and baicalein were recognized as key compounds of HCT on lung cancer. The gene enrichment analysis implied that HCT probably benefitted patients with lung cancer by modulating the MAPK and PI3K-Akt pathways. CONCLUSION: This study predicted pharmacological and molecular mechanisms of HCT against lung cancer and could pave the way for further experimental research and clinical application of HCT.

Bacteria and poisonous plants were the primary causative hazards of foodborne disease outbreak: a seven-year survey from Guangxi, South China.

BACKGROUND: Foodborne diseases are a worldwide public health problem. However, data regarding epidemiological characteristics are still lacking in China. We aimed to analyze the characteristics of foodborne diseases outbreak from 2010 to 2016 in Guangxi, South China. METHODS: A foodborne disease outbreak is the occurrence of two or more cases of a similar foodborne disease resulting from the ingestion of a common food. All data are obtained from reports in the Public Health Emergency Report and Management Information System of the China Information System for Disease Control and Prevention, and also from special investigation reports from Guangxi province. RESULTS: A total of 138 foodborne diseases outbreak occurred in Guangxi in the past 7 years, leading to 3348 cases and 46 deaths. Foodborne disease outbreaks mainly occurred in the second and fourth quarters, and schools and private homes were the most common sites. Ingesting toxic food by mistake, improper cooking and cross contamination were the main routes of poisoning which caused 2169 (64.78%) cases and 37 (80.43%) deaths. Bacteria (62 outbreaks, 44.93%) and poisonous plants (46 outbreaks, 33.33%) were the main etiologies of foodborne diseases in our study. In particular, poisonous plants were the main cause of deaths involved in the foodborne disease outbreaks (26 outbreaks, 56.52%). CONCLUSIONS: Bacteria and poisonous plants were the primary causative hazard of foodborne diseases. Some specific measures are needed for ongoing prevention and control against the occurrence of foodborne diseases.

Chaperone-mediated autophagy substrate proteins in cancer.

All intracellular proteins undergo continuous synthesis and degradation. Chaperone-mediated autophagy (CMA) is necessary to maintain cellular homeostasis through turnover of cytosolic proteins (substrate proteins). This degradation involves a series of substrate proteins including both cancer promoters and suppressors. Since activating or inhibiting CMA pathway to treat cancer is still debated, targeting to the CMA substrate proteins provides a novel direction. We summarize the cancer-associated substrate proteins which are degraded by CMA. Consequently, CMA substrate proteins catalyze the glycolysis which contributes to the Warburg effect in cancer cells. The fact that the degradation of substrate proteins based on the CMA can be altered by posttranslational modifications such as phosphorylation or acetylation. In conclusion, targeting to CMA substrate proteins develops into a new anticancer therapeutic approach.

Non-Obese Diabetes and Its Associated Factors in an Underdeveloped Area of South China, Guangxi.

BACKGROUND: Little research has been conducted on the prevalence of diabetes mellitus in underdeveloped areas in China, especially stratified into obesity and non-obese diabetes. The aim of the present study was to investigate the prevalence and associated factors of non-obese diabetes in an underdeveloped area in South China, Guangxi. METHODS: Data derived from the Chinese Health and Nutrition Survey 2010-2012 involved a sample of 3874 adults from Guangxi. Questionnaires and oral glucose-tolerance tests were conducted, and fasting and 2-h glucose levels and serum lipids were measured. Logistic regression analysis was performed to assess associated factors for non-obese diabetes. RESULTS: 68.2% and 62.2% of instances of newly detected diabetes were those of non-obese diabetes based on BMI (NODB) and based on WC (NODW), respectively. The male sex, an age older than 50 years, lower education, hypertension, and hypertriglyceridemia were significantly associated with a higher risk of both NODB and NODW, while some associated factors for NODB were found different from those associated with NODW, and an interaction effect was found to increase the risk of NODW. CONCLUSIONS: Our study indicated that non-obese diabetes was highly prevalent in an underdeveloped area of South China. Non-obese diabetes should be considered for increased public attention in these areas.

[Efficacy on depression in breast cancer treated with acupuncture and auricular acupressure].

OBJECTIVE: To compare the efficacy difference in treatment of depression in breast cancer between the combined therapy of acupuncture and auricular acupressure and western medication. METHODS: Sixty patients were randomized into an observation group and a control group, 30 cases in each one. In the observation group, the combined therapy of acupuncture and auricular acupressure was adopted. The main acupoints of acupuncture were Hegu (LI 4), Tai-chong (LR 3), Baihui (GV 20), Zusanli (ST 36), Qihai (CV 6), etc. The supplementary acupoints were combined according to the syndrome differentiation. The treatment was given once every day, 5 treatments a week, at the interval of 2 days among weeks. The auricular acupressure was applied to gan (CO12, liver), pi (CO13, spleen), neifenmi (CO18, endocrine), etc., once every 4 days, on each side in one treatment. In the control group, fluoxetine hydrochloride capsules were prescribed for oral administration, 20 mg, once a day. The Hamilton depression rating scale (HAMD) was used to assess the disease severity and efficacy before treatment, in 4 and 8 weeks of treatment separately. HAMD factor changes were observed before treatment and at the end of the 8th week. The Asberg antidepressants scale (SERS) was applied to safety assessment. RESULTS: The total effective rate was 86.7% (26/30) in the observation group, better than 63.3% (19/30) in the control group (P<0.05). At the end of the 4th and 8th weeks, HAMD scores were all reduced apparently in the two groups (all P<0.01). At the end of the 8th week, the scores of the HAMD factor 1 (anxiety/somatic system), factor 5 (retardation) and factor 6 (sleep disturbance) were all reduced as compared with those before treatment in the two groups (all P<0.01); the results in the observation group were better than those in the control group (P<0.05, P<0.01). SERS score in the observation group was lower obviously than that in the control group (P<0.01). CONCLUSION: The combined therapy of acupuncture and auricular acupressure achieves the antidepression effect in treatment of depression in breast cancer and has less side effects and high safety. The efficacy is superior to fluoxetine hydrochloride capsules.

Burden of self-reported acute gastrointestinal illness in China: a population-based survey.

BACKGROUND: Acute gastrointestinal illness (AGI) is an important public-health problem worldwide. Previous national studies of the incidence of AGI in China were performed decades ago, and detailed information was not available. This study therefore sought to determine the magnitude, distribution, and burden of self-reported AGI in China. METHODS: Twelve-month, retrospective face-to-face surveys were conducted in 20 sentinel sites from six provinces between July 2010 and July 2011. RESULTS: In total, 39686 interviews were completed. The overall adjusted monthly prevalence of AGI was 4.2% (95% confidence interval, 4.0-4.4), corresponding to 0.56 episodes of AGI per person-year. Rates of AGI were highest in children aged < 5 years. Healthcare was sought by 56.1% of those reporting illness. Of the cases who visited a doctor, 32.7% submitted a stool sample. The use of antibiotics was reported by 49.7% of the cases who sought medical care and 54.0% took antidiarrhoeals. In the multivariable model, gender, age, education, household type, residence, season, province and travel were significant risk factors of being a case of AGI. CONCLUSIONS: This first population-based study in China indicated that AGI represents a substantial burden of health. Further research into the specific pathogens is needed to better estimate the burden of AGI and foodborne disease in China.