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 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.