Objective: To study the efficacy network and potential mechanisms of effects of Chaihu Longgu Muli Decoction in the treatment of essential hypertension by using network pharmacology methods. Methods: TCMSP, TCMID, and Stitch were used to obtain the components and their corresponding targets. PubMed, CTD, TTD, OMIM, and DrugBank were used to search disease targets of essential hypertension. The common targets between components and disease targets were screened and builded the “compound - target” efficacy network and the protein-protein interaction network by STRING and Cytoscape. The key components and core targets of Chaihu Longgu Muli Decoction in the treatment of hypertension were screened in these networks. Finally, relevant software was applied to GO analysis and pathway analysis of core targets to predict potential mechanisms. Results: A total of 137 components of Chaihu Longgu Muli Decoction and 168 targets of essential hypertension were screened. According to the analysis, quercetin, β-sitosterol, kaempferol, and stigmasterol were found as the four key components and 12 core targets such as IL-6, AKT1, and MAPK8 were found involving the Chaihu Longgu Muli Decoction-induced treatment of essential hypertension. The result of GO analysis and KEGG pathway analysis showed that the mechanisms of Chaihu Longgu Muli Decoction for treating essential hypertension were related to pathways such as activation of AP-1 family transcription factors, interleukin-10 signaling, interleukin-4 signaling, interleukin-13 signaling, the intrinsic pathway of apoptosis, and MAPK targeting/by MAP kinase-mediated nuclear events. Conclusion: The mechanisms of the effect of Chaihu Longgu Muli Decoction in the treatment of essential hypertension were through the above-mentioned “multi-components-multi-targets-multi-pathways”. This study provides a foundation for further investigation of the effective compound and specific mechanisms of Chaihu Longgu Muli Decoction in the treatment of essential hypertension.

Objective Combined with the patients arthritis symptoms and signs,TCM syndrome differentiation of rheumatoid arthritis was undertaken to investigate TCM syndrome distribution.Methods A total of 656 patients of rheumatoid arthritis from October 1st 2010 to January 1st 2012 hospitalized in Shandong Qingdao Combine Traditional Chinese and Western Medicine hospital were untaken TCM syndrome differentiation according to their symptoms and signs.Results The main syndromes of rheumatoid arthritis patients were cold-dampness blockage syndrome and liver and kidney deficiency syndrome,followed by cold-wind blockage syndrome,deficiency of Qi and blood syndrome,and dampness-heat blockage syndrome.The highest scores of ESR and C reactive protein appeared in dampness-heat blockage syndrome group,with ESR being (56.23 ± 13.87) ram/h,CRP being (69.49± 21.56) mg/L.These values showed significant difference than other syndrome group (P ＜ 0.05).There was no significant difference of rheumatoid factor,immunoglobulin IgG,IgA,IgM values among these syndrome groups (P＞0.05).Comparison of age,course of disease showed the liver and kidney deficiency syndrome group (age was 59.3± 12.15,duration was 7.98 ± 3.76)and Qi and blood deficiency syndrome group (age was 52.5± 11.5,duration was 6.56±3.12) were significant higher than cold-dampness blockage syndrome,damp-heat blockage syndrome group and cold-wind blockage syndrome group with the age of (46.2± 11.12) and (45.8± 11.60),(43.5± 12.50) respectively and course of (5.56±2.76),(5.78±2.98),(5.12±2.32) respectively (P＜0.05).Conclusion The main TCM syndromes of rheumatoid arthritis patients in Qingdao area were cold-dampness syndrome,liver and kidney deficiency syndrome,followed by cold-wind blockage sydrome,Qi and blood deficiency syndrome,damp-heat blockage syndrome.Among all syndromes,relatively high age and disease course of patients appeared in liver and kidney deficiency syndrome and Qi and blood deficiency syndrome.

OBJECTIVETo summarize the recent findings of dysregulation of signaling pathways and miRNAs in chronic lymphocytic leukemia (CLL).

DATA SOURCESWe searched PubMed database with the keywords "chronic lymphocytic leukemia", "signal pathway", or "miRNA" for relevant articles in recent years.

STUDY SELECTIONResearch articles and reviews about signaling pathways and miRNAs in CLL were chosen for review.

RESULTSDysregulation of signaling pathways, such as B cell receptor , toll-like receptor, PI3K, nuclear factor κB, notch signaling pathway, Wnt/Fzd signaling pathway, and Hedgehog and Janus kinases/signal transducers and activators of transcription signaling pathway, as the terminal events of the aberrant gene expression and the pro-survival effects of microenvironment, plays a crucial role in the process of CLL. miRNAs, a novel found noncoding RNA, which regulate gene expression at transcription or post-transcription level and correlate with pathogenesis of CLL provide us new avenues to better evaluating prognosis and therapy of it.

CONCLUSIONFurther investigation of the dysregulation of signaling pathways and miRNAs and their relationship may provide us a new prospective to understand the pathogenesis of CLL and may provide us new strategies to resolve the clinical nodi in treatment of CLL.

Animals ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; genetics ; Signal Transduction ; genetics ; physiology

Humans ; Bone Cements/adverse effects* ; Paralysis/etiology*

BACKGROUNDCornea epithelial cells play early and crucial roles in the initiation of ocular surface responses to pathogens. Participation of toll-like receptor (TLR) 2 and TLR4, which are major forms of fungi receptors, may be involved in Aspergillus fumigatus induced immune responses. The objective of the present study was to examine whether inactive Aspergillus fumigatus conidia induce NF-kappaB activation and production of proinflammatory cytokines, and whether the expression of TLR2 and TLR4 were amplified by conidia in cultured immortalized human corneal epithelial cells (THCEs). This may contribute to our knowledge of the mechanism by which the host cornea can successfully defend against invasive fungi.

METHODSAspergillus fumigatus conidia were used to challenge THCE cells. THCE cells were harvested after 0.5, 1, 2 or 4 hours incubation. Real-time quantitative PCR was performed to determine the expression of TLR2, TLR4, TNF-alpha and IL-8. Western blotting was performed to determine the expression of NF-kappaB. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression of TNF-alpha and IL-8. And the release of TNF-alpha and IL-8 in the cell supernatant were also assessed by ELISA with or without pretreatment with TLR2 and TLR4 neutralizing antibodies.

RESULTSAspergillus fumigatus conidia elicited the expression of TLR2, TLR4, TNF-alpha and IL-8 mRNA in THCEs. Exposure of THCE cells to Aspergillus fumigatus conidia resulted in NF-kappaB activation, which increased at 30 minutes (increased from 11.35+/-2.74 in the controls to 19.12+/-3.48, P<0.05) and thereafter increased steadily up to 4 hours after challenge (P<0.01). Concomitant with NF-kappaB activation, secretion of TNF-alpha and IL-8 in conidia-challenged cells was increased in a time-dependent manner. Incubation of THCE cells with TLR2 antibody or TLR4 antibody before conidia challenge resulted in inhibition of conidia-induced TNF-alpha and IL-8 secretion (P<0.05), TLR2 antibody and TLR4 antibody together significantly increased inhibition of the conidia-induced secretion of TNF-alpha and IL-8 from THCE cells (P<0.01).

CONCLUSIONAspergillus fumigatus conidia stimulates THCEs inflammatory response through a pathway dependent on TLR2 and TLR4 signaling.

Aspergillus fumigatus ; immunology ; Cells, Cultured ; Epithelium, Corneal ; cytology ; immunology ; Humans ; Interleukin-8 ; biosynthesis ; NF-kappa B ; metabolism ; Toll-Like Receptor 2 ; physiology ; Toll-Like Receptor 4 ; physiology ; Tumor Necrosis Factor-alpha ; biosynthesis

OBJECTIVETo review the current research into Foxp3(+) regulatory T cells (Treg) cell surface molecules, plasticity of Treg cells and mechanisms of Treg cell suppression and to explore the possibilities to interfere in Treg cell suppression of anti-tumor immunity.

DATA SOURCESA literature search of all English articles was performed on the online electronic PubMed database dated 1995 to 2010. The keywords searched included: CD4(+)CD25(+)Foxp3(+) regulatory T lymphocytes, cancer, and immunotherapy. After finding relevant articles within these search limits, a manual search was conducted through the references from these articles.

STUDY SELECTIONArticles regarding the role of Treg cells in tumor immunity and the utility of Treg cells in tumor immunotherapy.

RESULTSThe results show that significant numbers of Treg cells are found in many tumors and it has been shown that the number of tumor infiltrating Treg cells correlates with adverse clinic outcomes. Treg cells are emerging as a key component of acquired tolerance to tumors.

CONCLUSIONSSeveral mechanisms of immunosuppression can be mediated by Treg cell function. Distinct immunosuppressive molecules expressed by Treg cells or diverse molecules related to Treg induction or migration represent potential drug targets for cancer immunotherapy.

Forkhead Transcription Factors ; metabolism ; Humans ; Immunosuppression ; methods ; Immunotherapy ; methods ; Neoplasms ; immunology ; therapy ; T-Lymphocytes, Regulatory ; metabolism

OBJECTIVETo review the role of cyclic adenosine monophosphate (cAMP) signal pathway in the pathogenesis of lymphoma and explore a potential lymphoma therapy targeted on this signaling pathway.

DATA SOURCESThe data cited in this review were mainly obtained from the articles listed in Medline and PubMed, published from January 1995 to June 2009. The search terms were "cAMP" and "lymphoma".

STUDY SELECTIONArticles regarding the role of the cAMP pathway in apoptosis of lymphoma and associated cells and its potential role in targeted therapy of lymphoma.

RESULTSIn the transformation of lymphocytic malignancies, several signal pathways are involved. Among of them, the cAMP pathway has attracted increasing attention because of its apoptosis-inducing role in several lymphoma cells. cAMP pathway impairment is found to influence the prognosis of lymphoma. Targeted therapy to the cAMP pathway seems to be a new direction for lymphoma treatment, aiming at restoring the cAMP function.

CONCLUSIONScAMP signal pathway has different effects on various lymphoma cells. cAMP analogues and phosphodiesterase 4B (PDE4B) inhibitors have potential clinical significance. However, many challenges remain in understanding the various roles of such agents.

Animals ; Cyclic AMP ; metabolism ; Humans ; Lymphoma ; metabolism ; Models, Biological ; Signal Transduction ; physiology

OBJECTIVETo review the recent studies about the role of indoleamine 2,3-dioxygenase (IDO) in tumor induced tolerance.

DATA SOURCESPublished articles (1978 - 2009) on IDO and tumor induced tolerance were selected from Medline.

STUDY SELECTIONArticles selected were relevant to development of IDO in tumor induced tolerance. Of all originally identified articles, 50 specially addressed the stated purpose.

RESULTSRecent work has revealed IDO at high levels in tumors and in tumor-draining lymph nodes and a close relationship between IDO activity and the regulatory T cells.

CONCLUSIONUp-regulation of IDO is proven to be a mechanism of acquired tolerance in tumors, in which the closely coupled positive feedback system between IDO and regulatory T cells may be considered to play an important role.

Animals ; Gene Expression Regulation, Neoplastic ; physiology ; Humans ; Immune Tolerance ; physiology ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism ; Neoplasms ; enzymology ; immunology

Lumbago disease is a common disease, which mainly manifested as acute or chronic pain in the lumbar spine or paraspinal region, mainly represented by lumbar disc herniation in clinical practice. The new drug, Yaotongning Capsule with better efficacy for lumbago in clinic, is made of Strychni Semen Pulveratum, Eupolyphaga Steleophaga, Cyathulae Radix, Glycyrrhizae Radix et Rhizoma, Ephedrae Herba, Olibanum and Myrrh (prepared with vinegar), scorpion, Bombyx Batryticatus (bran fried), and Atractylodis Rhizoma (bran fried). This paper analyzes the etiology and pathogenesis of lumbar intervertebral disc herniation through traditional Chinese medicine, and explores the mechanism of treating lumbar intervertebral disc herniation with Yaotongning Capsule from the perspective of prescription theory, so as to provide theoretical basis for clinical application of Yaotongning Capsule.

Since the coronavirus disease 2019 (COVID-19) outbreak, National Health Commission of the People's Republic of China and local departments have released a number of diagnosis and treatment plans for COVID-19. One of the recommended prescriptions for severe stage treatment is Huanglian Jiedu Decoction, whose TCM syndrome is corresponding to the severe syndrome of dual blaze of qi and nutrient in the COVID-19 protocol of Diagnosis and Treatment of Novel Coronavirus Pneumonia (trial version 7). Huanglian Jiedu Decoction can be used in the treatment of syndrome of dual blaze of qi and nutrient. Syndrome of dual blaze of qi and nutrient is with consumption of nutrient yin of body fluid, pathogenic qi always triumphing over healthy qi, excessive noxious heat from qi and nutrient, Huanglian Jiedu Decoction has the efficacy of clearing heat and detoxicating. It can achieve the therapeutic purpose of nourishing yin and protecting yin by removing evil spirits. Modern pharmacological studies have shown that Huanglian Jiedu Decoction has potential effects of anti-inflammatory and antipyretic, antiviral, antioxidant, regulating immunity and protecting viscera and tissues in the treatment of COVID-19 with severe syndrome of dual blaze of qi and nutrient. In this paper, the pathogenesis evolution of COVID-19 with severe syndrome of dual blaze of qi and nutrient, the relationship between prescriptions and syndromes of Huanglian Jiedu Decoction and its modern pharmacological effects was analyzed, so as to provide a basis for the effective treatment of Huanglian Jiedu Decoction in COVID-19 with severe syndrome of dual blaze of qi and nutrient.