Identification of a distal enhancer that determines the expression pattern of acute phase marker C-reactive protein.

C-reactive protein (CRP) is a major acute phase protein and inflammatory marker, the expression of which is largely liver specific and highly inducible. Enhancers are regulatory elements critical for the precise activation of gene expression, yet the contributions of enhancers to the expression pattern of CRP have not been well defined. Here, we identify a constitutively active enhancer (E1) located 37.7 kb upstream of the promoter of human CRP in hepatocytes. By using chromatin immunoprecipitation, luciferase reporter assay, in situ genetic manipulation, CRISPRi, and CRISPRa, we show that E1 is enriched in binding sites for transcription factors STAT3 and C/EBP-ß and is essential for the full induction of human CRP during the acute phase. Moreover, we demonstrate that E1 orchestrates with the promoter of CRP to determine its varied expression across tissues and species through surveying activities of E1-promoter hybrids and the associated epigenetic modifications. These results thus suggest an intriguing mode of molecular evolution wherein expression-changing mutations in distal regulatory elements initiate subsequent functional selection involving coupling among distal/proximal regulatory mutations and activity-changing coding mutations.

Phytochemical library screening reveals betulinic acid as a novel Skp2-SCF E3 ligase inhibitor in non-small cell lung cancer.

Skp2 is overexpressed in multiple cancers and plays a critical role in tumor development through ubiquitin/proteasome-dependent degradation of its substrate proteins. Drugs targeting Skp2 have exhibited promising anticancer activity. Here, we identified a plant-derived Skp2 inhibitor, betulinic acid (BA), via high-throughput structure-based virtual screening of a phytochemical library. BA significantly inhibited the proliferation and migration of non-small cell lung cancer (NSCLC) through targeting Skp2-SCF E3 ligase both in vitro and in vivo. Mechanistically, BA binding to Skp2, especially forming H-bonds with residue Lys145, decreases its stability by disrupting Skp1-Skp2 interactions, thereby inhibiting the Skp2-SCF E3 ligase and promoting the accumulation of its substrates; that is, E-cadherin and p27. In both subcutaneous and orthotopic xenografts, BA significantly inhibited the proliferation and metastasis of NSCLC through targeting Skp2-SCF E3 ligase and upregulating p27 and E-cadherin protein levels. Taken together, BA can be considered a valuable therapeutic candidate to inhibit metastasis of NSCLC.

Frequency of ST-segment elevation myocardial infarction, non-ST-segment myocardial infarction, and unstable angina: results from a Southwest Chinese Registry.

The burden of cardiovascular disease is predicted to escalate in developing countries. The aim of this study is to assess the characteristics, management strategies and outcomes of the patients with acute coronary syndrome (ACS) who were admitted to hospitals under the chest pain center mode in southwest P. R. China. Adults hospitalized with a diagnosis of ACS were enrolled in the retrospective, observational registry between January 2017 and June 2019 at 11 hospitals in Chengdu, P. R. China. The collected data included the patients' baseline characteristics, clinical management and in-hospital outcomes. After Statistical analysis, (1) A total of 2857 patients with ACS, among which 1482 have ST-segment elevation myocardial infarction (STEMI), 681 have non-STEMI (NSTEMI) and 694 have unstable angina (UA) were enrolled in the study. (2) 61.3% of the ACS patients received reperfusion therapy. More patients with STEMI underwent percutaneous coronary intervention (PCI) compared with NSTEMI/UA patients (80.6% vs. 38.8%, P < 0.001), while thrombolytics were administered in only 1.8% of STEMI patients. (3) The median time from symptoms to hospital was 190 min (IQR 94-468) in STEMI, 283 min (IQR 112-1084) in NSTEMI and 337 min (IQR 97-2220) in UA (P < 0.001), and the door-to-balloon time for primary PCI (pPCI) was 85 min (IQR 55-121) in STEMI. (4) The in-hospital outcomes for STEMI patients included death (8.1%) and acute heart failure (22.6%), while the outcomes for those with NSTEMI and UA were better: death (4.0% and 0.9%, P < 0.001) and acute heart failure (15.3% and 9.9%, P < 0.001). (5) Antiplatelet drugs, lipid-lowering drugs, ß-blockers and angiotensin-converting enzyme inhibitors (ACEI) /angiotensin receptor blockers (ARB) were used in about 98.3%, 95.0%, 67.7% and 54.3% of the ACS patients, respectively. Therefore, the management capacity in Chengdu has relatively increased compared with previous studies, but important gaps still exist compared with developed countries, especially regarding the management of the NSTEMI/UA patients.

6-O-angeloylplenolin exerts neuroprotection against lipopolysaccharide-induced neuroinflammation in vitro and in vivo.

Neuroinflammation is one of the critical events in neurodegenerative diseases, whereas microglia play an important role in the pathogenesis of neuroinflammation. In this study, we investigated the effects of a natural sesquiterpene lactone, 6-O-angeloylplenolin (6-OAP), isolated from the traditional Chinese medicine Centipeda minima (L.) A.Br., on neuroinflammation and the underlying mechanisms. We showed that treatment with lipopolysaccharide (LPS) caused activation of BV2 and primary microglial cells and development of neuroinflammation in vitro, evidenced by increased production of inflammatory cytokines TNF-α and IL-1ß, the phosphorylation and nuclear translocation of NF-κB, and the transcriptional upregulation of COX-2 and iNOS, leading to increased production of proinflammatory factors NO and PGE2. Moreover, LPS treatment induced oxidative stress through increasing the expression levels of NOX2 and NOX4. Pretreatment with 6-OAP (0.5-4 µM) dose-dependently attenuated LPS-induced NF-κB activation and oxidative stress, thus suppressed neuroinflammation in the cells. In a mouse model of LPS-induced neuroinflammation, 6-OAP (5-20 mg·kg-1·d-1, ip, for 7 days before LPS injection) dose-dependently inhibited the production of inflammatory cytokines, the activation of the NF-κB signaling pathway, and the expression of inflammatory enzymes in brain tissues. 6-OAP pretreatment significantly ameliorated the activation of microglia and astrocytes in the brains. 6-OAP at a high dose caused a much stronger antineuroinflammatory effect than dexamethansone (DEX). Furthermore, we demonstrated that 6-OAP pretreatment could inhibit LPS-induced neurite and synaptic loss in vitro and in vivo. In conclusion, our results demonstrate that 6-OAP exerts antineuroinflammatory effects and can be considered a novel drug candidate for the treatment of neuroinflammatory diseases.

[Currency Survey and Influencing Factors Analysis on the Knowledge and Behavior Related to Brucellosis among Occupational Workers in Jianyang City].

OBJECTIVE: To investigate the status and influencing factors of the knowledge and behavior related to brucellosis among occupational workers in Jianyang city, and to provide basic information for developing regional specific strategies for brucellosis prevention and control. METHODS: With multistage cluster random sampling, occupational workers aged ≥18 yr. who had been in contact with sheep and their products were interviewed through a questionnaire about demographic characteristic, knowledge, and behavior related to brucellosis. The knowledge and practice scores were described as frequency and percentage, and the awareness rate of knowledge about brucellosis was calculated. Unconditional logistic regression model was used to analyze the influencing factors of knowledge and behavior related to brucellosis. RESULTS: In total, 378 workers were recruited. The minority (25.1%) of the workers had heard of brucellosis, and the awareness rate of brucellosis was 22.0%. Occupational protective behaviors were poor, and the scoring rates of wearing protective clothes, mask and gloves were 58.7%, 76.5%, 71.7% respectively. The results of multivariate logistic regression analysis revealed that the awareness rate of knowledge about brucellosis decreased with age, while the low educational level was found to be associated with low awareness of knowledge about brucellosis, and occupation type had association with the awareness rate of knowledge. Besides, the awareness of knowledge about brucellosis was a protective factor and occupation type were associated with the behavior related to brucellosis. CONCLUSIONS: The knowledge and behavior related to brucellosis are poor among occupational workers in Jianyang. It is necessary to continuously implement targeted health education and health promotion programs in this region, and the people with low education level and livestock farmers should be paid special attention to.

The effect of hydration on the electronic structure and stability of the superalkali cation Li3.

The interaction of the superalkali cation Li3+ with water molecules, as well as the structures and stability of the resulting water complexes are theoretically studied at the MP2/6-311++G(d,p) level. A great number of geometrical configurations were obtained for the Li3+(H2O)n (n = 1-5) complexes and Li3+ is found to have a maximum coordination number of four. Natural population analysis shows that the charge distribution of Li3+ becomes seriously uneven upon interaction with five water molecules, so it loses ring conjugation and splits in the lowest-energy isomer of Li3+(H2O)5. Localized molecular orbital energy decomposition analysis indicates a dominant contribution of electrostatic interactions to the binding of water molecules to Li3+, which is similar to the case of lithium ion hydrates. However, as the number of water ligands reaches five, the contribution of the exchange-repulsion energy exhibits a sharp increase and even exceeds that of the electrostatic term.

Does Alkaline-Earth-Metal-Based Superalkali Exist?

A series of MkF2k-1+ (M = Mg, Ca; k = 2, 3) cations have been theoretically investigated to make a new attempt to design superalkali species. As expected, most of these cations were identified as pseudoalkali or even superalkali cations in view of their low electron affinities (EAs). The stability of these cationic clusters is indicated by considerable HOMO-LUMO gaps and positive dissociation energies. More intriguingly, these alkaline-earth-metal-based cations have advantages over alkali-metal-based superalkalis in two aspects: (1) they possess much larger binding energy values; (2) they can keep the chemical stability along with the increasing cluster size. Therefore, it is proposed here that the alkaline-earth-metal atoms could partner with halogens to construct stable cations of low EA value, which may add new candidates to the superalkali family.

[Shenfu injection induces the apoptosis of prostate cancer PC-3 cells].

OBJECTIVE: To study the effect of Shenfu Injection (SF) on the apoptosis of prostate cancer PC-3 cells and its possible mechanism. METHODS: We divided prostate cancer PC-3 cells into a blank control group and three experimental groups, the latter treated with SF at 50, 100, and 200 microl/ml, respectively, for 24, 48, and 72 hours. Then we determined the proliferation of the cells by MTT assay, measured their apoptosis by Annexin V/PI flow cytometry, and detected the expression of P53 mRNA by RT-qPCR. RESULTS: Compared with the blank control group, the survival rates of the prostate cancer PC-3 cells in the 50, 100, and 200 microl/ml SF groups were (93.76 +/- 2.63)%, (81.21 +/- 1.80)% and (18.01 +/- 3.84)% at 24 hours, (94.67 +/-1.11)%, (78.33 +/- 2.89)% and (10.34 +/- 1.44)% at48 hours, and (91.30 +/- 0.47)%, (36.67 +/- 1.56)% and (1.33 +/- 0.32)% at 72 hours, all significantly increased in a dose- and time-dependent manner (P < 0.05). The expression of p53 mRNA was also markedly increased in all the three experimental groups at 48 hours (P < 0. 05). CONCLUSION: SF can inhibit the proliferation and induce the apoptosis of PC-3 cells, which may due to its upregulation of the p53 mRNA expression.

Understanding key determinants of health climate in building construction projects.

Health climate is critical for achieving a better health performance in building construction projects. However, the topic is rarely investigated by extant literature. The aim of this study is to identify key determinants of health climate in building construction projects. To achieve this goal, a hypothesis was established between practitioners' perceptions of health climate and their health status, based on a comprehensive literature review and structured interviews conducted with experienced experts. Then, a questionnaire was developed and administered for data collection. Partial least-squares structural equation modeling was used for data processing and hypothesis test. Results showed that health climate in building construction projects is positively correlated with the health status of the practitioners, and that employment involvement was the most important determinant of health climate in building construction projects, followed by management commitment, and supportive environment. Moreover, significant factors under each determinant of health climate were also disclosed. As limited research has been conducted to examine health climate in building construction projects, this study bridges the knowledge gap and is a contributory work to the current body of knowledge of construction health. Additionally, the findings of this study can provide authorities and practitioners with a deeper understanding of construction health and thereby helping them bring forward more feasible measures to improve health in building construction projects. Thus, this study is useful to the practice as well.

Aggressive variant prostate cancer: A case report and literature review.

BACKGROUND: Aggressive variant prostate cancer (AVPC) is a rare disease that progresses rapidly. The first-line treatment for AVPC is currently unknown. We examined a rare case of AVPC with rare brain and bladder metastases. A summary review of the mechanism of development, clinicopathological manifestations, associated treatments and prognosis of this disease is presented. CASE SUMMARY: The patient was diagnosed with prostate cancer (PCA), and was actively treated with endocrine therapy, radiotherapy, chemotherapy, and traditional Chinese medicine. Unfortunately, he was insensitive to treatment, and the disease progressed rapidly. He died five years after being diagnosed with PCA. CONCLUSION: We should reach consensus definitions of the AVPC and other androgen receptor-independent subtypes of PCA and develop new biomarkers to identify groups of high-risk variants. It is crucial to complete a puncture biopsy of the tumor or metastatic lesion as soon as possible in patients with advanced PCA who exhibit clinical features such as low Prostate-specific antigen levels, high carcinoembryonic antigen levels, and insensitivity to hormones to determine the pathological histological type and to create a more aggressive monitoring and treatment regimens.

Effect of complete revascularization in acute coronary syndrome after 75 years old: insights from the BleeMACS registry.

BACKGROUND: The prognostic benefit of complete revascularization in elderly patients (aged over 75 years) with multi-vessel disease and acute coronary syndrome (ACS) is currently unclear. This study aimed to determine the long-term prognostic impact of complete revascularization in this population. METHODS: We conducted this study using data obtained from the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) registry, which was carried out from 2003 to 2014. The objective was to categorize older patients diagnosed with ACS into two groups: those who underwent complete revascularization and those who did not. Propensity score matching and the Kaplan-Meier analysis were employed to examine differences in one-year clinical outcomes. The primary endpoint was major adverse cardiovascular event (MACE), which encompassed a combination of all-cause mortality and myocardial infarction. RESULTS: Out of 1263 patients evaluated, 445 patients (35.2%) received complete revascularization. Patients who underwent complete revascularization had a higher prevalence of hypertension and prior percutaneous coronary intervention compared to those who did not. During the one-year follow-up period, complete revascularization was associated with a significantly decreased risk of MACE [13.7% vs. 20.5%, hazard ratio (HR) = 0.63, 95% CI: 0.45-0.88, P = 0.007] and a lower risk of myocardial infarction (5.9% vs. 9.9%, HR = 0.55, 95% CI: 0.33-0.92, P = 0.02). However, it was not linked to a lower risk of all-cause death (9.5% vs. 13.5%, HR = 0.68, 95% CI: 0.45-1.02, P = 0.06). Similar results were observed in the subgroup analysis. CONCLUSIONS: Long-term clinical improvements were observed in ACS patients aged over 75 years with multi-vessel disease who achieved complete revascularization. Therefore, adhering to guidelines for complete revascularization should be recommended for elderly patients.

Effect of botanical drugs in improving symptoms of hypertensive nephropathy: Analysis of real-world data, retrospective cohort, network, and experimental assessment.

Background/aim: Hypertensive nephropathy (HN) is a common complication of hypertension. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy. However, botanical drug prescriptions have not been summarized. The purpose of this study is to develop a prescription for improving hypertensive nephropathy, explore the evidence related to clinical application of the prescription, and verify its molecular mechanism of action. Methods: In this study, based on the electronic medical record data on Hypertensive nephropathy, the core botanical drugs and patients' symptoms were mined using the hierarchical network extraction and fast unfolding algorithm, and the protein interaction network between botanical drugs and Hypertensive nephropathy was established. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. Hierarchical clustering was used to screen for effective botanical drugs. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Animal experiments were performed at the target and pathway levels to analyze the mechanism. Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. In total, 76 effective compounds were obtained using the K-nearest neighbors model, and seven botanical drugs were identified as Gao Shen Formula by hierarchical clustering. Compared with the classical model, the Area under the curve (AUC) value of the K-nearest neighbors model was the best; retrospective cohort verification showed that Gao Shen Formula reduced serum creatinine levels and Chronic kidney disease (CKD) stage [OR = 2.561, 95% CI (1.025-6.406), p < 0.05]. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1ß, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways. Conclusion: In the retrospective cohort, we observed that the clinical application of Gao Shen Formula alleviates the decrease in renal function in patients with hypertensive nephropathy. It is speculated that Gao Shen Formula acts by reducing inflammatory reactions, inhibiting renal damage caused by excessive activation of the renin-angiotensin-aldosterone system, and regulating energy metabolism.

Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p-PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn.

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.

High expression of nuclear Snail, but not cytoplasmic staining, predicts poor survival in nasopharyngeal carcinoma.

BACKGROUND: Transcription factor Snail has been shown to promote tumor progression and metastasis in various cancers. However, its clinical significance in nasopharyngeal carcinoma (NPC) is still scanty. We have explored the clinical significance of Snail expression and its association with patient outcome in NPC. METHODS: Immunohistochemistry was used to examine the expression levels of Snail in 122 patients with NPC. RESULTS: Cytoplasmic Snail was detected in 37.7 %, and nuclear staining was detected in 49.2 % of primary tumors, respectively. No significant associations were found between cytoplasmic Snail and the clinicopathologic variables except lymph node metastasis (P = 0.042). However, nuclear Snail was significantly associated with tumor stage (P = 0.003), T classification (P = 0.045), lymph node metastasis (P = 0.019), distant metastasis (P = 0.003), and reduced E-cadherin expression (P = 0.021). Patients with high nuclear Snail expression, but not cytoplasmic staining, had significantly shorter survival than those with low expression (P < 0.001). Significantly, nuclear Snail was an independent prognostic predictor for NPC (P < 0.001). Furthermore, the prognostic impact was largely limited to stage III-IV patients. CONCLUSIONS: We demonstrated first that nuclear Snail, but not cytoplasmic staining, predicts worse outcome. In addition, the prognostic value in stage III-IV suggests that nuclear Snail could be a potential therapeutic target for late stage of NPC patients.

Tumour budding and the expression of cancer stem cell marker aldehyde dehydrogenase 1 in nasopharyngeal carcinoma.

AIMS: To detect the prognostic significance of tumour budding and its expression of aldehyde dehydrogenase 1 (ALDH1) in nasopharyngeal carcinoma (NPC). METHODS AND RESULTS: Tumour budding was investigated in 105 patients with NPC by immunohistochemistry for pan-cytokeratin (AE1/AE3). The intensity of budding correlated strongly with T classification (P=0.008), lymphatic invasion (P<0.001), vascular invasion (P=0.029), lymph node metastasis (P < 0.001), and clinical stage (P=0.010). Univariate analysis revealed that patients with high budding grade had poorer survival than those with low grade (P=0.002). Multivariate analysis showed that tumour budding was an independent predictor of survival (P=0.001). Furthermore, budding cells showed high-level expression of the cancer stem cell (CSC) marker ALDH1. Budding cells with high-level ALDH1 expression contributed to several aggressive behaviours and poor survival (P=0.000). CONCLUSIONS: We describe, for the first time, the presence of tumour budding and its correlation with aggressive tumour behaviour and poor patient survival in NPC. The degree of tumour budding could be a valuable predictive factor in NPC. In addition, we show, also for the first time, that budding cells in NPC might possess the invasive and metastatic properties of CSCs.

Nuclear expression of N-cadherin correlates with poor prognosis of nasopharyngeal carcinoma.

AIMS: To investigate the aberrant expression of N-cadherin in nasopharyngeal carcinoma (NPC) and its prognostic significance. METHODS AND RESULTS: Immunohistochemical staining for N-cadherin protein was performed on tissue microarray (TMA) from 122 NPC patients. Cytoplasmic N-cadherin was observed in 42.6% and nuclear N-cadherin in 45.1% of NPC tissues. High expression of cytoplasmic and nuclear N-cadherin was associated with a majority of the clinicopathological variables, including lymph node metastasis, distant metastasis and clinical stage. Cytoplasmic N-cadherin was associated positively with nuclear N-cadherin expression (P = 0.000). In univariate analysis, cytoplasmic N-cadherin showed no significant impact on patient prognosis. In contrast, the overall survival was significantly shorter in patients with high nuclear N-cadherin than those with low levels of staining (P = 0.002). A high expression of nuclear N-cadherin predicted poorer survival in patients with late stage disease (P = 0.033), but not those with early tumour stage. In addition, multivariate analysis showed nuclear N-cadherin to bean independent prognostic marker for NPC patients (P = 0.024). CONCLUSIONS: Nuclear N-cadherin expression may represent a valuable prognostic marker in NPC patients, especially those with late stage disease.

Neoplastic spindle cells in nasopharyngeal carcinoma show features of epithelial-mesenchymal transition.

AIM: To investigate whether the neoplastic spindle cells in nasopharyngeal carcinoma (NPC) are associated with the process of epithelial-mesenchymal transition (EMT). METHODS AND RESULTS: We used immunohistochemistry to analyse the expression of cytokeratin, E-cadherin, ß-catenin, vimentin, fibronectin, Snail1, Slug and aldehyde dehydrogenase 1 (ALDH1) in 115 cases of NPC in which there were neoplastic spindle cells; in 47 cases a neoplastic squamous cell component was also present. There was no significant difference in the expression of cytokeratin observed in the neoplastic spindle cells (P = 0.644), compared to the squamous component whereas E-cadherin expression was reduced. By contrast, the expression of ß-catenin, vimentin, fibronectin, Snail1, Slug and ALDH1 was up-regulated in the spindle cells (all P = 0.000). Furthermore, E-cadherin expression was associated negatively with ß-catenin (P < 0.001), vimentin (P < 0.001), fibronectin (P < 0.001), Slug (P < 0.001) and ALDH1 (P < 0.001) in neoplastic spindle cells, but did not correlate with Snail1 expression (P = 0.093). CONCLUSIONS: Our findings demonstrate for the first time that EMT might play an important role in the development of neoplastic spindle cells in NPC.

Identifying the Antitumor Effects of Curcumin on Lung Adenocarcinoma Using Comprehensive Bioinformatics Analysis.

Background: As the main component of turmeric (Curcuma longa L.), curcumin is widely used in the treatment of various diseases. Previous studies have demonstrated that curcumin has great potential as a therapeutic agent, but the lack of understanding of the functional mechanism of the drug has hindered the widespread use of the natural product. In the present study, we used comprehensive bioinformatics analysis and in vitro experiments to explore the anti-tumor mechanism of curcumin. Materials and Methods: LUAD mRNA expression data were obtained from TCGA database and differentially expressed genes (DEGs) were identified using R software. Functional enrichment analysis was conducted to further clarify its biological properties and hub genes were identified by a protein-protein interaction (PPI) network analysis. Survival analysis and molecular docking were used to analyze the effectiveness of the hub genes. By an in vitro study, we evaluated whether curcumin could influence the proliferation, migration, and invasion activities of LUAD cells. Results: In this study, 1783 DEGs from LUAD tissue samples compared to normal samples were evaluated. Functional enrichment analysis and the PPI network revealed the characteristics of the DEGs. We performed a topological analysis and identified 10 hub genes. Of these, six genes (INS, GCG, SST, F2, AHSG, and NPY) were identified as potentially effective biomarkers of LUAD. The molecular docking results indicated that curcumin targets in regulating lung cancer may be INS and GCG. We found that curcumin significantly inhibited the proliferation, migration, and invasion of LUAD cells and significantly decreased the expression of the INS and GCG genes. Conclusion: The results of this study suggest that the therapeutic effects of curcumin on LUAD may be achieved through the intervention of INS and GCG, which may act as potential biomarkers for LUAD prevention and treatment.

Mild haemoglobin drop and clinical outcomes in acute coronary syndrome patients: finding from the BleeMACS registry.

BACKGROUND: Haemoglobin drop is common in acute coronary syndrome (ACS) patients and correlates with poor prognosis. However, the association between mild haemoglobin drop and adverse clinical outcome remains insufficiently investigated. This study aimed to examine the association between in-hospital haemoglobin drop and risk for adverse clinical outcomes in ACS patients, especially those with mild drop. METHODS: Included patients from the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) registry were categorized into three groups by the presence and amount of in-hospital haemoglobin drop (non-drop, mild drop and severe drop). The cut-off point between mild drop and severe drop is ≥ 3 g/dL. Multivariate Cox regression was used to assess the association between haemoglobin drop and major adverse cardiac endpoints (MACE). Patients taking potent P2Y12 inhibitors were selected for the additional analysis. Propensity score matching was used to avoid selective bias in the additional analysis. RESULTS: Of 6911 patients, 4949 patients (71.6%) experienced in-hospital haemoglobin drop. Compare with non-drop group, patients with haemoglobin drop had higher risk of MACE [adjusted hazard ratio (HR) = 1.36, 95% CI: 1.03-1.80 for mild drop group; adjusted HR = 1.70, 95% CI: 1.07-2.68 for severe drop group]. Patients in mild drop group were less likely to receive potent P2Y12 inhibitors at discharge (mild drop group vs. severe drop group vs. non-drop group: 10.9% vs. 10.7% vs. 23.8%). After propensity score matching adjustment among patients with potent P2Y12 inhibitors, patients in mild drop group were not associated with an increased risk of MACE than those in non-drop group (adjusted HR = 1.52, 95% CI: 0.49-4.72). CONCLUSIONS: In-hospital haemoglobin drop was common in ACS patients and associated with a higher risk for adverse events. Reduced prescription for potent P2Y12 inhibitors may be responsible for poor prognoses among patients with mild haemoglobin drop.

Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers.

Chinese herbal medicines offer a rich source of anti-cancer drugs. Differences between the pharmacology of Chinese herbal medicines and modern synthetic chemicals hinder the development of drugs derived from herbal products. To address this challenge, novel omics approaches including transcriptomics, proteomics, genomics, metabolomics, and microbiomics have been applied to dissect the pharmacological benefits of Chinese herbal medicines in cancer treatments. Numerous Chinese herbal medicines have shown potential anti-tumor effects on different gastrointestinal (GI) cancers while eliminating the side effects associated with conventional cancer therapies. The present study aimed to provide an overview of recent research focusing on Chinese herbal medicines in GI cancer treatment, based on omics approaches. This review also illustrates the potential utility of omics approaches in herbal-derived drug discovery. Omics approaches can precisely and efficiently reveal the key molecular targets and intracellular interaction networks of Chinese herbal medicines in GI cancer treatment. This study summarizes the application of different omics-based approaches in investigating the effects and mechanisms of Chinese herbal medicines in GI cancers. Future research directions are also proposed for this area of study.