MMP14 is a diagnostic gene of intrahepatic cholangiocarcinoma associated with immune cell infiltration.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor of the hepatobiliary system with concealed onset, strong invasiveness and poor prognosis. AIM: To explore the disease characteristic genes that may be helpful in the diagnosis of ICC and affect immune cell infiltration. METHODS: We downloaded two ICC-related human gene expression profiles from GEO database as the training group (GSE26566 and GSE32958 datasets) for difference analysis, and performed enrichment analysis on differential genes. The least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF), three machine learning algorithms, were used to screen the characteristic genes. Double verification was carried out on GSE107943 and The Cancer Genome Atlas, two verification groups. Receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the diagnostic efficacy of genes for ICC. CIBERSORT and ssGSEA algorithms were used to evaluate the effect of characteristic genes on immune infiltration pattern. Human Protein Atlas (HPA) was used to analyze the protein expression level of the target gene. RESULTS: A total of 1091 differential genes were obtained in the training group. Enrichment analysis showed that the above genes were mainly enriched in small molecular catabolism, complement and coagulation cascade, bile secretion and other functions and pathways. Twenty-five characteristic genes were screened by LASSO regression, 19 by SVM-RFE algorithm, and 30 by RF algorithm. Three algorithms were used in combination to determine the characteristic gene of ICC: MMP14. The verification group confirmed that the genes had a high diagnostic accuracy (AUC values of the training group and the verification group were 0.960, 0.999, and 0.977, respectively). Comprehensive analysis of immune infiltration showed that MMP14 could affect the infiltration of monocytes, activated memory CD4 T cells, resting memory CD4 T cells, and other immune cells, and was closely related to the expression of CD200, cytotoxic T-lymphocyte-associated antigen 4, CD14, CD44, and other immune checkpoints. The results of immunohistochemistry in HPA database showed was indeed overexpressed in ICC. CONCLUSION: MMP14 can be used as a disease characteristic gene of ICC, and may regulate the distribution of immune-infiltrating cells in the ICC tumor microenvironment, which provides a new method for the determination of ICC diagnostic markers and screening of therapeutic targets.

Species richness disparity in tropical terrestrial herbaceous floras: Evolutionary insight from Collabieae (Orchidaceae).

Species richness is spatially heterogeneous even in the hyperdiverse tropical floras. The main cause of uneven species richness among the four tropical regions are hot debated. To date, higher net diversification rates and/or longer colonization time have been usually proposed to contribute to this pattern. However, there are few studies to clarify the species richness patterns in tropical terrestrial floras. The terrestrial tribe Collabieae (Orchidaceae) unevenly distributes in the tropical regions with a diverse and endemic center in Asia. Twenty-one genera 127 species of Collabieae and 26 DNA regions were used to reconstruct the phylogeny and infer the biogeographical processes. We compared the topologies, diversification rates and niche evolutionary rates of Collabieae and regional lineages on empirical samplings and different simulated samplings fractions respectively. Our results suggested that the Collabieae originated in Asia at the earliest Oligocene, and then independently spread to Africa, Central America, and Oceania since the Miocene via long-distance dispersal. These results based on empirical data and simulated data were similar. BAMM, GeoSSE and niche analyses inferred that the Asian lineages had higher net diversification and niche evolutionary rates than those of Oceanian and African lineages on the empirical and simulated analyses. Precipitation is the most important factor for Collabieae, and the Asian lineage has experienced more stable and humid climate, which may promote the higher net diversification rate. Besides, the longer colonization time may also be associated with the Asian lineages' diversity. These findings provided a better understanding of the regional diversity heterogeneity in tropical terrestrial herbaceous floras.

[Research progress in epigenetic pharmacological effects of rhein].

Rhein, which is one of the main active components of Rheum palmatum, has a range of pharmacological activities such as the regulation of the metabolism of glucose and lipids, anti-inflammatory, anti-tumor, anti-fibrosis, etc. Epigenetics refers to the heritable variation of gene expression without altering the DNA sequence. It is involved in the emergence and development of inflammation, renal fibrosis, diabetes, cancer, atherosclerosis, and other diseases, thus becoming a new strategy for the treatment of many di-seases. A series of studies have shown that epigenetic modification may be a common molecular mechanism of various pharmacological effects of rhein. This paper summarized the effects of rhein on the regulation of epigenetic modification and its underlying mechanisms, which involve the regulation of DNA methylation, protein acetylation, and RNA methylation, so as to provide a basis for the development and application of rhein.

Network Pharmacology-Based Approach Uncovers the Mechanism of GuanXinNing Tablet for Treating Thrombus by MAPKs Signal Pathway.

BACKGROUND: GuanXinNing tablet (GXNT), a traditional Chinese patent medicine, has been found to have remarkable antithrombotic effects and can effectively inhibit pro-thrombotic factors in previous studies. However, the mechanism of its antithrombotic effects remains little known. METHODS: In this study, we first determined and identified the sources of each main compound in GXNT using liquid chromatography-mass spectrometry (LC-MS). Through the approach of network pharmacology, we predicted the action targets of the active components, mapped the target genes related to thrombus, and obtained potential antithrombotic targets for active ingredients. We then performed gene ontology (GO) enrichment analyses and KEGG signaling pathway analyses for the action targets, and constructed networks of active component-target and active component-target-pathway for GXNT. Additionally, we evaluated the pharmacodynamic effects of GXNT on thrombus using the rat thrombus model induced by FeCl3, observed the effects of antiplatelet aggregation via platelet assay, and further verified the results predicted by network pharmacology via Western blot. RESULTS: In total, 14 active ingredients were identified in GXNT, and 83 action targets were predicted, 17 of which are antithrombotic targets that potentially participate in processes including response to oxidative stress and positive regulation of blood vessel endothelial cell migration. KEGG pathway analyses revealed that the predicted action targets were involved in multiple signal pathways, such as MAPK, IL-17, and platelet activation. Pharmacodynamics study found that GXNT could significantly reduce the thrombus length and weight, lower platelet aggregation function, and decrease the levels of Fbg and PAI-1. In addition, GXNT could significantly increase 6-keto-PGF1α content and regulate the ratio of TXB2/6-keto-PGF1α, while not having dramatic effects on TXB2. GXNT was also observed to visibly inhibit maximum platelet aggregation. Herein, we further studied the thrombus-related MAPKs signaling pathway and found that GXNT could significantly reduce the phosphorylation levels of p38MAPK, ERK, and JNK proteins in platelet. CONCLUSIONS: This study revealed the pharmacodynamic material basis of GXNT and its potential multicomponent-multitarget-multipath pharmacological effects, confirmed the antithrombotic effects of GXNT, and showed that its mechanism may be related to inhibiting phosphorylation of p38, ERK, and JNK proteins in MAPKs signaling pathway, partially verifying the results from network pharmacology. The results from this study could provide a theoretical basis for the development and clinical application of GXNT.

Low molecular weight heparin monotherapy for recurrent abortion with antiphospholipid system: A protocol of a systematic review.

BACKGROUND: Previous clinical studies reported low molecular weight heparin (LMWH) monotherpay has been utilized for the treatment of recurrent abortion (RCA) with antiphospholipid system (APS). However, its efficacy is still inconclusive. This systematic review aims to assess its efficacy and safety for patients with RCA and APS. METHODS: A systematic literature search for article up to February 2019 will be conducted in 9 databases: Cochrane Library, EMBASE, MEDILINE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. Inclusion criteria are randomized control trials of LMWH monotherpay for patients with RCA and APS. The Cochrane risk of bias tool will be used to evaluate the methodological quality for each qualified study. The summary results will be showed by using fixed-effects and random-effects models for pooling the data based on the heterogeneity of included studies. RESULTS: This systematic review will assess the clinical efficacy and safety of LMWH monotherpay in treating RCA with APS. The primary outcome is pregnancy loss. The secondary outcomes include frequency of preterm delivery, live birth rates, maternal and fetal complications, as well as adverse events. CONCLUSION: The findings of this study will summarize the present evidence to judge whether LMWH monotherpay is an effective therapy for patients with RCA and APS. DISSEMINATION AND ETHICS: The findings of this study will be published by through peer-reviewed journals. This study does not needs ethic documents, because it will not analyze individual patient data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121064.

Simultaneous determination of stilbenes, phenolic acids, flavonoids and anthraquinones in Radix polygoni multiflori by LC-MS/MS.

A simple and sensitive method was developed for the simultaneous determination of stilbenes, phenolic acid, flavonoids and anthraquinones in Radix polygoni multiflori by liquid chromatography tandem mass spectrometry (LC-MS/MS). The separation was completed on an Eclipse Plus C(18) (50 mm × 3.0 mm, 1.8 µm) column using 0.05% (v/v) formic acid and acetonitrile as mobile phases. The correlation coefficients of all the calibration curves were higher than 0.9990. The recoveries ranged from 95.9% to 106%. Relative standard deviations of intra and inter-day precisions were lower than 6.51%. The validated method was successfully applied to quantify stilbenes, phenolic acid, flavonoids and anthraquinones, which provided a new basis for overall assessment on quality of Radix polygoni multiflori.

[Tracheal stent implantation for the treatment of tumor-induced acute airway stenosis].

BACKGROUND & OBJECTIVE: Tumor-induced acute airway stenosis is a medical emergency. Metal airway stent implantation can relieve dyspnea of patients suffering from this symptom and provide time for their further treatment. This study was to investigate the clinical application, efficacy, and complication management of tracheal stent implantation for the treatment of tumor-induced acute airway stenosis. METHODS: Nickel-titanium (Ni-Ti) alloy stent implantation was performed under the guidance of fiber-optic bronchoscopy in 52 patients with tumor-induced acute airway stenosis. RESULTS: Stent implantation was successful in all 52 patients. Dyspnea in all patients was significantly relieved. Values of arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and Karnofsky performance status (KPS) changed from (7.74+/-0.99) kPa, (5.37+/-0.39) kPa, and (68.85+/-8.08) preoperatively to (11.12+/-0.61) kPa, (4.58+/-0.30) kPa, and (84.62+/-5.03) postoperatively (P<0.01). The three-year survival rate was higher in lymphoma group than in lung cancer or esophageal cancer group. Postoperative complications were properly managed in all cases after symptomatic treatments. CONCLUSIONS: Tracheal stent implantation is an effective palliative treatment for acute dyspnea caused by local tumor compression or tumor invasion of large airways. It can rescue patients at risk for airway obstruction, improve the quality of life in terminal cancer patients, and provide further treatment opportunities for them.