Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Objective:To study the complete genome characterization of Human Astrovirus (HAstV) in Shandong Province.Methods:Stool samples from acute flaccid paralysis (AFP) surveillance in Shandong Province from 2020 to 2022 were collected, and HAstV nucleic acid was examined by real-time quantitative PCR (qPCR). Next-generation sequencing (NGS) was conducted for the positive samples to obtain complete genome sequences and identify the genotype. Homology comparison and phylogenetic analysis were performed by using BioEdit and Mega software.Results:A total of 667 samples were examined by qPCR, of which 14 were HAstV-positive (2.1%), including HAstV-1 ( n=6), MLB1 ( n=6), MLB2 ( n=1), and VA2 ( n=1). The complete genome sequences were obtained from 11 samples. The six HAstV-1 sequences of this study had 98.2% to 99.9% nt similarities with each other and 87.6% to 98.6% with those from other regions. The four MLB1 sequences of this study had 99.1% to 99.9% nt similarities with each other and 92.2% to 99.4% with those from other regions. The VA2 sequence of this study had 96.0% to 96.3% nt similarities with those from other regions. Phylogenetic analysis based on ORF2 region showed that the local HAstV-1 sequences were most closely related to Japanese strains, and had distinct topology with phylogenies based on ORF1a and ORF1b regions. Conclusion:The complete genome sequences of 11 HAstV strains are obtained, and the VA2 complete genome is found.

Objective To study the mechanism of Chaihu Guizhi Decoction(CGD)in the treatment of influenza and staphylococcus aureus co-infection.Methods The co-infection model of influenza and staphylococcus aureus was established and CGD was used to intervene.The chemical components of CGD were qualitatively analyzed by UPLC-Q-Exactive/MS technology.The potential action targets of chemical components in CGD and the related targets of influenza Staphylococcus aureus co-infection were mined by network pharmacology method.The"component target disease"network was constructed.Core targets were selected according to degree ranking.Core action pathways were enriched by KEGG analysis and GO annotation analysis.The core target was verified by RT-qPCR,and the interaction between the core component and the key target was verified by molecular docking.Results CGD could significantly improve the decrease of body weight and thymus index(P<0.05)caused by co-infection.The lung index(P<0.05),relative amount of MmRNA expression(P<0.05)and bacterial load(P<0.05)were decreased,and the survival rate was improved.51 chemical constituents were identified from CGD.Through network pharmacological analysis,107 related targets corresponding to CGD treatment of bacterial pneumonia secondary to influenza were excavated.TNF,AKT1,ALB,VEGFA,MAPK3,PTGS2,STAT3,EGFR and other targets with strong correlation,mainly involved Fc epsilon RI signal pathway,GnRH signal pathway,NF-κB signal path,etc.Molecular docking study showed that the main active component of CGD,including oroxyloside,baicalein and wogonin have strong affinity with TNF,PTGS2 and EGFR targets.Compared with co-infection model group,in CGD group TNF-α、EGFR and PTGS2 increased significantly(P<0.05).Conclusion The main active ingredient of CGD is oroxyloside,baicalein and wogonin.TNF-α,PTGS2,EGFR and other targets to played a role in the treatment of influenza staphylococcus aureus co-infection.

OBJECTIVE To distinguish Anoectochilus roxburghii and relative species by near infrared(NIR) spectroscopy combined with chemometrics, and to establish a prediction model for rapid determine polysaccharides contents in Anoectochilus roxburghii. METHODS The NIR spectroscopy of Anoectochilus roxburghii, Anoectochilus formosanus Hayata and Ludisia discolor were collected. The prepossessing of original spectrum was optimization through accuracy of classification in the NIR model, and six supervised pattern recognition algorithms such as decision tree, K-nearest neighbor algorithm, random forest, partial least squares regression discriminant analysis, linear discriminant analysis and support vector machine(SVM) were applied to identify effect of the classification effect, optimum algorithm and then establish qualitative model. The content of polysaccharides in 76 batches of Anoectochilus roxburghii samples were examined by ultraviolet visible spectrophotometry combined with phenol sulfuric acid method. In order to select optimization algorithm, six quantitative stoichiometry algorithms consisted of SVM, extreme learning machines, decision trees, random forests, principal component regression and partial least squares regression(PLS) were used to connect polysaccharide content and the NIR spectroscopy in Anoectochilus roxburghii respectively. The best method for determining the content of Anoectochilus roxburghii polysaccharides was further optimized by spectra pretreatment, band selection and number of band variables based on successive projection algorithm(SPA). RESULTS The NIR discriminant analysis model was established by SVM with SNV+SG+2ndD, and the classification accuracy was best. The prediction performance was evaluated based on the radial basis kernel function algorithm combined with confusion matrix and ROC curve, and the model performance was good. In addition, the quantitative analysis model was constructed by continuous projection-partial least squares by the prepossessing of SNV+SG+2ndD and the optimal band of 7 000-4 000 cm-1 with 97 of variables number. The accuracy was 0.992, which was the highest. The root mean square error calibration set, correlation coefficient of calibration set, and the root mean square error in validation set, correlation coefficient of validation set were 0.625, 0.993, 0.767, 0.992, separately. The prediction deviation was 8.467, and relative deviation of prediction set was less than 10%. CONCLUSION The established NIR-SVM qualitative model and SPA-PLS quantitative model are accurate and reliable, which are enable to identify Anoectochilus roxburghii and determine polysaccharide content nondestructively. It is a new and promising method for rapid evaluation of Anoectochilus roxburghii quality.

Chronic subdural hematoma (cSDH) occurs in acute subdural hemorrhage after head trauma or converts from effusion. Traditional treatment is based on conservative treatment and surgical drainage. The effective rate of conservative treatment is only 3%-18%; even with drilling drainage treatment, the recurrence rate is as high as 33%. Recently, the middle meningeal artery embolization technique based on pathological analysis can greatly reduce the recurrence rate, and the operation is simple and curative effect is exact. This article reviews the pathogenesis of cSDH and progress of interventional therapy.

Objective This study was to evaluate the clinical outcomes of orbital blowout fracture repair using the individual titanium mesh bent by computer-aided rapid prototyping . Methods The CT imaging data of 11 cases of orbital blowout fracture were analyzed.The subciliary approach was used for the exposure of the fractures .An appropriate 3D-printed titanium mesh pre-bent by computer-aided rapid prototyping was selected and implanted according to the characteristics of a given defect .The surgical results were analyzed by evaluating diplopia , eyeball movement , enophthalmos , and the position of the titanium mesh and comparing the orbital vol-ume before and after surgery . Results All the operations were successfully accomplished .No remolding or trimming was needed for the pre-bent titanium mesh and implanted titanium mesh was tightly fixed to the orbital wall .The patients were followed up for 3 -12 months, which revealed no symptoms of diplopia in any of the patients . Volumetric analysis showed a significantly reduced orbital volume difference from (2.60 ±0.43) mL preoperatively to (-0.07 ±0.62) mL postoperatively (P<0.01).Enophthalmos was desirably correc-ted, with the enophthalmos difference decreased from (2.35 ±0.81)mm preoperatively to (-0.10 ±0.52) mm postoperatively (P<0.01).No extra-ocular muscle limitation was observed . Conclusion The individual titanium mesh bent with computer-aided rapid prototyping technology can be applied to orbital blowout fracture repair , which may achieve a high success rate of anatomic restoration of the orbital volume and effective prevention of enophthalmos .

Objective Carotid body tumor is closely related to carotid artery .How to deal with carotid artery is the guaranty of successful surgery .The aim of this study was to summary the experience of keeping carotid artery continuity in the treatment of 15 carotid body tumor cases . Methods Clinical data of 15 cases with 17 carotid body tumors , in which 2 patients had bilateral tumors , were collected.The 17 carotid body tumors were classified as Shamblin I (6 cases),Ⅱ(6 cases) andⅢ(5 cases).Fifteen tumors were dissected simplely.Among these 15 tumors, three of Shamblin Ⅱand two of Shamblin Ⅲunderwent repair of the break of carotid artery.The rest two of Shamblin Ⅲunderwent tumor and external carotid artery excision and internal carotid artery repairment .Matas pressing test of carotid artery or carotid artery balloon occlusion test was not performed in any patient . Results All 17 tumors were successfully excised .None of the 17 tumors underwent anastomosis or reconstruction of internal carotid artery or arteria carotis com -mun.The continuity of carotid artery or internal carotid artery was kept in all the patients after tumor excision .Hoarseness and bucking induced by the injury of vagus nerve occurred in 13 cases, and bucking recovery in all the cases after 2 years follow up, and only one case remained mild hoarseness .Hypoglossal nerve injury occurred in 4 cases with tongue deviation , and the symptom recovery after 6 months follow up.No one had recurrent by the follow-up period ranging from 1 to 9 years. Conclusion Most carotid body tumors could be completely resected by tumor dissection method with the accurate treatment , thereby the continuity of carotid artery could be kept.The Matas pressing test of carotid artery or carotid artery balloon occlusion test is not necessarily to every patient .

Objective Parotidectomy and superficial parotidectomy are traditional surgical treatment to the malignant parotid gland tumour although they have many defects.The aim of this study was to analyze the feasibility of individualized treatment to patient according to tumor`s size and TNM stage. Methods Thirty three patients with low grade malignant parotid gland tumours from Dec 2005 to Dec 2010 were recruited in the present study.All the patients received the territorial surgical resection firstly.Then, 9 cases re-ceived the expanded territorial surgical resection (1 case had recurrent probability, accepted adjuvant radiotherapy).Sixteen cases un-derwent parotidectomy with complete tumor resection ( 2 case had envelope invasion, accepted adjuvant radiotherapy) .Eight cases ac-cepted adjuvant radiotherapy(4 cases on T1 and T2 stage preserved facial nerve although the nerves adhering to tumors, and other 4 ca-ses on T4a stage accepted facial nerve excision ) . Results Follow up ranged from 3.5 to 8.5 years and no recurrences were docu-mented.9 patients who accepted territorial surgical resection showed fine facial symmetry.8 cases of them without adjuvant radiotherapy had good salivary secretion.Nine cases of other 24 patients showed temporary facial nerve injury and recovered within 1 to 4 months. Four cases with facial nerve excision showed permanental facial paralysis. Conclusion To protect the function of parotid gland to the greatest extent, the small low grade malignant parotid gland tumors without facial nerve invasion could have territorial surgical resection. Combined territorial surgical resection with postoperative adjuvant radiation therapy is useful to avoid the tumors recurrence and en-croachment of facial nerve to protect the facial nerve function.