The inhibition of cyclin-dependent kinases (CDKs) is considered a promising strategy for cancer treatment due to their role in cell cycle regulation. However, CDK inhibitors with no selectivity among CDK families have not been approved. A CDK inhibitor with high selectivity for CDK4/6 exhibited significant treatment effects on breast cancer and has become a heavy bomb on the market. Subsequently, resistance gradually decreased the efficacy of selective CDK4/6 inhibitors in breast cancer treatment. In this review, we first introduce the development of selective CDK4/6 inhibitors and then explain the role of CDK2 activation in inducing resistance to CDK4/6 inhibitors. Moreover, we focused on the development of CDK2/4/6 inhibitors and selective CDK2 inhibitors, which will aid in the discovery of novel CDK inhibitors targeting the cell cycle in the future.
Humans ; Cell Cycle/drug effects* ; Protein Kinase Inhibitors/chemistry* ; Cyclin-Dependent Kinases/metabolism* ; Neoplasms/genetics* ; Antineoplastic Agents/pharmacology* ; Animals ; Breast Neoplasms/enzymology* ; Cyclin-Dependent Kinase 4/metabolism*

Dental implantology has developed rapidly for over half a century,since pure titanium(99.7％)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95％.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.

Dental implantology has developed rapidly for over half a century,since pure titanium(99.7％)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95％.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.

BACKGROUND: Mis Seven implant has become more and more popular in oral implant restoration, and the clinical application in dentate-deficient patients remains to be studied. OBJECTIVE: To explore the short-term effects of the Mis Seven implant system on fixed restorations in dentition loss. METHODS: Nineteen patients undergoing fixed dental prostheses with the Mis Seven system due to dentition loss at the Department of Implants of the Stomatological Hospital of Guangzhou Medical University between April 2015 and December 2017 were included. Three patients had missing maxillary and maxillary dentition and unilateral maxillary teeth. Six patients were loss of maxillary dentition, and there were 10 cases of unilateral mandibular dentition missing. The total dental implants were 134. All cases were implanted and fixed for one stage. Clinical examination, alveolar bone and inter-implant image performance and post-load repair effect at 6, 12 and 24 months of follow-up were used as evaluation indicators. RESULTS AND CONCLUSION: (1) In 134 implants, failure was in 2 cases due to surrounding tissue infection. The success rate of before implant restoration was 98.51％, and the success rate after repair was 100％. (2) The stability of dentition of 19 patients was good, showing good occlusion. No mechanical complications or biological complications occurred. The stability of the restoration was 100％. (3) The vertical absorption of bone tissue around all implants was less than 0.2 mm at 6, 12, 24 months after repair, suggesting that the implant has no obvious edge bone resorption. The gingival tissues around all implants were healthy, and no unhealed inflammation or hyperkeratosis appeared. (4) These results imply that the Mis Seven system in the dentition defect fixation exhibits good short-term clinical results.

Objective To understand the current state of research and clinical application of α-asarone injection.Method Literature search was conducted and the pharmacology, toxicology, preparation, clinical application and adverse reactions of α-asarone were reviewed.Results α-asarone injection has strong relieving effects on cough and asthma, but the quality of production is varying, adverse reactions are often reported, and the toxicological effects need to be further investigated.Conclusions α-asarone injection has a certain clinical effect, but the reports of related adverse reactions are gradually increased.Its toxicity remains to be further studied, and the product quality standard system and instructions need also to be further improved.

BACKGROUND: Trabecular metal has been reported to provide enough physiologic support for new bone formation, to induce bone ingrowth and osseointegration so as to achieve the biological synosteosis; therefore, it is available for improving the initial and second stability of the dental implant.OBJECTIVE: To explore the stress distributional differences between porous tantalum trabecular metal (PTTM) dental implant and conventional titanium (TI) dental implant in the zone of mandibular premolar using three-dimensional finite element analysis.METHODS: Three-dimensional finite element models emulating PTTM and TI dental implants were established using Mimics16.0 and CATIA in the zone of mandibular premolar with three types of bone (II, III, IV). Then 100 N force was applied on the abutment at a 45° angle to the vertical axis of the implants in software of MSC Patran2010 and Nastran2010, then the representative von Mises stress nodes were calculated and sampled randomly, and finally the von Mises stress distributional differences between two types of implants were analyzed using SPSS 20.0 statistical software.RESULTS AND CONCLUSION: (1) The Von Mises stresses around the two types of implants both focused on the interface of the cortical bone-abutment-implant region, and the stress was relatively less for the corresponding trabecular bone. (2) If the bone quality was similar, the average von Mises stress of PTTM was higher than that of TI dental implants, but there was no significant difference (P > 0.05). As the bone density lowered (II-IV), the average Von Mises stresses were both increased, and the increasing rate of PTTM was higher than that of TI in bone of II-III, and was lower than that of TI in bone of III-IV. In this experiment, there were no significant stress distributional differences between PTTM and TI dental implant. However, with the bone density reduction, the increasing rate of average Von Mises stress for PTTM was lowered than that for TI dental implants in bone of III-IV, which suggests that PTTM dental implant may be more beneficial for the primary and secondary stability in osteoporosis patients undergoing dental implantation.

To explore novel scopoletin derivatives with more potent antiproliferative activity, a series of compounds were designed and synthesized(10a-10i)by linking benzamide to scopoletin′s framework. Their structures were determined by ESI-MS, IR and 1H NMR. The antiproliferative activity of the synthetic derivatives against human cancer cells MCF-7, A549 and HCT-116 was evaluated by MTT assay. Preliminary experimental results showed that compound 10g was the most potent one, whose antiproliferative activity was stronger than that of the positive control scopoletin and sunitinib.

Objective To investigate the diagnosis and therapy of the sclerosing hemangioma of the lung.Mothods The case history of 15 patients were analyzed retrospectively and summarized the diagnosis and therapy of the Sclerosing hemangioma of the lung.Results There were 2 males and 13 females(1:6.5).No patients were diagnosed this disease before operation for there were no specific imageology features.The tumor cell indicated pantomorphia and there were 3 cases were misdiagnosed during the operation frozen section pathology.The optimization therapy methods was to resect the tumor with the VATS.The prognosis of this disease was well and there were no cases recurrence in these 15 patients.Conclusion The sclerosing hemangioma of the lung was the benign tumor and there were no specific imageology features.The misdiagnosis was frequently before operation.To resect the tumor with the VATS was the optimal therapy method.

Objective To report the experience of lung transplantation with size reduced graft lung.Methods Four cases receiving lung transplantation with size reduced graft lung were analyzed retrospectively.In case 1,left lung transplantation combined with contra-hteral lung volume mduction.In case 2,right lung transplantation Wag individually performed with partially msecfion of upper lobe of graft lung.In case 3.bilateral sequential lung transplantation wag performed using graft lung with partially resection of bilateral upper lobes.In the remained ease,bilateral sequential lung tansplantation was performed using graft lung with resection of right lower lobe.Results All the size reduced graft lungs had good functions during the peri-operation period.Case 1 and case 2 still survived without obvious complication.Case 3 experienced temporary air leak on the 5th day postoperation and cured by water seal drainage but died of abrupt bronchorrhea due to aspergillus infection on the 32th day postoperation.The last cage experienced smoothly recovery excepted fatal virus pneumonia 2 months postopemtion.Conclusion Size reduced graft lungs can be successfully used for transplantation.