Therapeutic Mechanism of Xiaoqinglong Decoction against COVID-19 Based on Network Pharmacology and Molecular Docking Technology.

BACKGROUND: A xiaoqinglong decoction (XQLD) has been proven effective in treating severe coronavirus disease 2019 (COVID-19) cases; however, the mechanism remains unclear. OBJECTIVE: In the current study, we used network pharmacology and molecular docking technology to identify the effective components, potential targets, and biological pathways of XQLD against COVID-19. METHODS: Public databases were searched to determine the putative targets of the active compounds of XQLD and COVID-19-related targets. STRING and Cytoscape were used to establish the protein-protein interaction network and drug component, along with the target-pathway network. The DAVID database was used to enrich the biological functions and signaling pathways. AutoDock Vina was used for virtual docking. RESULTS: We identified 138 active compounds and 259 putative targets of XQLD. Biological network analysis showed that quercetin, beta-sitosterol, kaempferol, stigmasterol, and luteolin may be critical ingredients of XQLD, whereas VEGFA, IL-6, MAPK3, CASP3, STAT3, MAPK1, MAPK8, CASP8, CCL2, and FOS may be candidate drug targets. Enrichment analysis illustrated that XQLD could function by regulating viral defense, inflammatory response, immune response, and apoptosis. Molecular docking results showed a high affinity between the critical ingredients and host cell target proteins. CONCLUSION: This study uncovered the underlying pharmacological mechanism of XQLD against COVID-19. These findings lay a solid foundation for promoting the development of new drugs against severe acute respiratory syndrome coronavirus-2 infection and may contribute to the global fight against the COVID-19 pandemic.

IL-27 mediates anti-inflammatory effect in cigarette smoke induced emphysema by negatively regulating IFN-γ producing cytotoxic CD8+ T cells in mice.

Chronic airway inflammation mediated by CD8+ T lymphocytes contributes to the pathogenesis of Chronic obstructive pulmonary disease (COPD). Deciphering the fingerprint of the chronic inflammation orchestrated by CD8+ T cells may allow the development of novel approaches to COPD management. Here, the expression of IL-27 and IFN-γ+ CD8+ Tc1 cells were evaluated in patients with COPD and in cigarette smoke-exposed mice. The production of IL-27 by marrow-derived dendritic cells (mDCs) in response to cigarette smoke extract (CSE) was assessed. The role of IL-27 in IFN-γ+ CD8+ Tc1 cells was explored. We demonstrated that elevated IL-27 was accompanied by an exaggerated IFN-γ+ CD8+ Tc1 response in a smoking mouse model of emphysema. We noted that lung dendritic cells were one of the main sources of IL-27 during chronic cigarette smoke exposure. Moreover, CSE directly induced the production of IL-27 by mDCs in vitro. IL-27 negatively regulated the differentiation of IFN-γ+ CD8+ Tc1 cells isolated from cigarette smoke-exposed mice in a STAT1- and STAT3-independent manner. Systemic administration of recombinant IL-27 attenuated IFN-γ+ CD8+ Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL-27 negatively regulates IFN-γ+ CD8+ Tc1 response in the late stage of chronic cigarette smoke exposure, which may provide a new strategy for the anti-inflammatory treatment of smoking-related COPD/emphysema.

The effect of platelet-rich plasma on the fusion rate and clinical outcome of spinal fusion surgery: A systematic review and meta-analysis.

BACKGROUND: Platelet-rich plasma (PRP) is widely used in many orthopedic surgeries and spinal disease treatments; however, the effect of PRP on spinal fusion remains controversial. QUESTIONS/PURPOSES: To assess the fusion rate and clinical results of PRP compared with non-PRP administration in the treatment of spinal fusion with regard to decreasing pain and improving healing and function. PATIENTS AND METHODS: Studies comparing PRP to non-PRP treatment with respect to the fusion rate and clinical outcome in patients who underwent spinal fusion surgery were included. RESULT: Three randomized controlled trials (RCTs) and 7 prospective cohort studies were identified. The spinal fusion rate was not significantly different between the groups in all RCTs or cohort studies at the final follow-up. In comparison, PRP significantly reduced pain after surgery as evaluated in the RCT analysis and the complication rate did not differ significantly between the two groups. CONCLUSION: According to the available studies, PRP does not contribute to the union rate, relieve pain or increase the complication rate in spinal fusion surgery. As clinical heterogeneity exists in these studies, further large, well-designed RCTs that focus on the standard assessment of PRP are needed.

Hepatic epithelioid hemangioendothelioma: Update on diagnosis and therapy.

With an estimated incidence of only 1-2 cases in every 1 million people, hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular endothelial cell tumor occurring in the liver and consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix. HEHE is characterized as a low-to-moderate grade malignant tumor and is classified into three types: solitary, multiple, and diffuse. Both the etiology and characteristic clinical manifestations of HEHE are unclear. However, HEHE has a characteristic appearance on imaging including ultrasound, magnetic resonance imaging, and positron emission tomography/computerized tomography. Still, its diagnosis depends mainly on pathological findings, with immunohistochemical detection of endothelial markers cluster of differentiation 31 (CD31), CD34, CD10, vimentin, and factor VIII antigen as the basis of diagnosis. Hepatectomy and/or liver transplantation are the first choice for treatment, but various chemotherapeutic drugs are reportedly effective, providing a promising treatment option. In this review, we summarize the literature related to the diagnosis and treatment of HEHE, which provides future perspectives for the clinical management of HEHE.

Fast-growing epithelioid hemangioendothelioma of the liver: A case report.

RATIONALE: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver with malignant potential. It can be of solitary type, multifocal type, or diffuse type. Although there are some characteristic features on radiologic imaging, the definitive diagnosis of HEH is based on histopathology. The surgical treatment of HEH includes liver resection and transplant. PATIENT CONCERNS: A middle-aged woman presented with easy fatiguability and anorexia for 1 month was found to have multifocal lesions on radiological imaging. DIAGNOSIS: HEH was diagnosed by needle biopsy. It can be seen from imaging that this case is a multifocal form. The largest lesion increased from 3 to 3.3 cm within 2 months, with an increase of 9.45%; no other relevant literatures have been reported. INTERVENTIONS: The possibility of liver transplantation was suggested to the patient. However, the patient refused transplantation and was successfully treated by radical right hepatectomy and resection of the left lobe lesion. OUTCOMES: She remained disease-free throughout a year follow-up period. CONCLUSION: HEH is a rare disease with characteristic radiological and pathological features. Although liver transplantation is the preferred treatment for multifocal HEH, surgical excision represents one alternative when the lesions can be guaranteed to be completely excised.

iATC-FRAKEL: a simple multi-label web server for recognizing anatomical therapeutic chemical classes of drugs with their fingerprints only.

MOTIVATION: Anatomical therapeutic chemical (ATC) classification system is very important for drug utilization and studies. Correct prediction of the 14 classes in the first level for given drugs is an essential problem for the study on such system. Several multi-label classifiers have been proposed in this regard. However, only two of them provided the web servers and their performance was not very high. On the other hand, although some rest classifiers can provide better performance, they were built based on some prior knowledge on drugs, such as information of chemical-chemical interaction and chemical ontology, leading to limited applications. Furthermore, provided codes of these classifiers are almost inaccessible for pharmacologists. RESULTS: In this study, we built a simple web server, namely iATC-FRAKEL. This web server only required the SMILES format of drugs as input and extracted their fingerprints for making prediction. The performance of the iATC-FRAKEL was much higher than all existing web servers and was comparable to the best multi-label classifier but had much wider applications. Such web server can be visited at http://cie.shmtu.edu.cn/iatc/index. AVAILABILITY AND IMPLEMENTATION: The web server is available at http://cie.shmtu.edu.cn/iatc/index. CONTACT: chen_lei1@163.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

iATC-NRAKEL: an efficient multi-label classifier for recognizing anatomical therapeutic chemical classes of drugs.

MOTIVATION: The anatomical therapeutic chemical (ATC) classification system plays an increasingly important role in drug repositioning and discovery. The correct identification of classes in each level of such system that a given drug may belong to is an essential problem. Several multi-label classifiers have been proposed in this regard. Although they provided satisfactory performance, the feature extraction procedures were still rough. More refined features may further improve the predicted quality. RESULTS: In this article, we provide a novel multi-label classifier, called iATC-NRAKEL, to predict drug ATC classes in the first level. To obtain more informative drug features, we employed the drug association information in STITCH and KEGG, which was organized by seven drug networks. The powerful network embedding algorithm, Mashup, was adopted to extract informative drug features. The obtained features were fed into the RAndom k-labELsets (RAKEL) algorithm with support vector machine as the basic classification algorithm to construct the classifier. The 10-fold cross-validation of the benchmark dataset with 3883 drugs showed that the accuracy and absolute true were 76.56 and 74.51%, respectively. The comparison results indicated that iATC-NRAKEL was much superior to all previous reported classifiers. Finally, the contribution of each network was analyzed. AVAILABILITY AND IMPLEMENTATION: The codes of iATC-NRAKEL are available at https://github.com/zhou256/iATC-NRAKEL.

Comparison of therapeutic effect between percutaneous kyphoplasty and pedicle screw system on vertebral compression fracture.

OBJECTIVE: To compare the clinical efficacy of percutaneous kyphoplasty (PKP) with pedicle screw system (PS) in the treatment of vertebral compression fracture(VCF). METHODS: Eighty-six patients with VCF were treated either by PKP (Group A, n equal to 30) or PS (Group B, n equal to 56). The anterior, intermediate, and posterior heights of the vertebrae body, visual analogue pain scale (VAS) before and after operation, the duration of operation, and amount of blood loss between two groups were compared. RESULTS: No statistical difference was noted regarding the vertebral height between two groups. Significant difference was seen in VAS, duration of operation and amount of blood loss between the two groups (P less than 0.01). CONCLUSIONS: Percutaneous kyphoplasty has the similar therapeutic efficacy with pedicle screw system in treatment of VCF with a minimal invasion, less operation time and blood loss. For those with posterior wall destruction, PS is deemed favorable.

Biomechanical analysis of fracture fixation with external fixator in vivo.

OBJECTIVE: To investigate the different ways of measuring the main axial strain during treatment with an external fixator and to find the suitable compression loaded by the external fixator at an early stage. METHODS: Eighteen healthy big-ear rabbits were randomly divided into two groups according to different measuring methods: Group A and Group B. In Group A, a strain gauge was affixed to the external tibial cortex with 502 glue, and in Group B, a bone cement-coated strain gauge was installed on the internal tibial cortex. Groups A and B were divided into two subgroups A1, A2 and B1, B2, respectively, according to the pressure of half of and the same as the body weight. A Z-shaped left mid-shaft tibial osteotomy was performed and fixed by an external fixator. RESULTS: The scaler curves of Group A changed dramatically during the early stage. The trendlines of the internal and external cortex went consistently after reaching the stable stage while the latter strain value was higher than the former. The time for Group B reaching the stable stage was short, but its absolute strain value was less than that of Group A. Before they were pressed to the stable stage, the declined speed of Subgroup A1 was more slowly than that of Subgroup A2 while the results of Subgroups B1 and B2 were same. Group A had an ascending trend after it declined while Group B didn't have. After they reached the stable stage, both Subgroups A1 and A2 had a declining trend while Subgroup A2 was more quickly than Subgroup A1, Subgroup B1 was kept at a definite level while Subgroup B2 fluctuated. CONCLUSIONS: The axial strain under external fixator can be measured by bone cement coated-strain gauge in vivo. The data may suggest that half of the body weight load was suitable for external fixator.