Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.
Humans ; Neoplasms/metabolism* ; Cyclin-Dependent Kinases/antagonists & inhibitors* ; Cyclins/metabolism* ; Proteolysis ; Antineoplastic Agents/pharmacology* ; Molecular Targeted Therapy ; Proteasome Endopeptidase Complex/metabolism* ; Animals

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:The clinical characteristics of pregnant women with HELLP syndrome before and after delivery and the risk factors of pregnancy outcomes were analyzed.Methods:A retrospective analysis was con-ducted on 126 cases of HELLP syndrome admitted to The Affiliated Suzhou Hospital of Nanjing Medical University from January 2010 to May 2021,divided into prenatal HELLP group[n=108,98 cases with severe preeclampsia(SPE)]and postpartum HELLP group(n=18,15 cases with SPE),to compare the differences in clinical charac-teristics and pregnancy outcomes between the two groups with the different onset time and whether they were complicated with SPE.Results:①Compared with the postpartum HELLP group,the prenatal HELLP group had higher systolic blood pressure in the third trimester of pregnancy,shorter time from preeclampsia to HELLP syn-drome,higher liver function abnormalities,lower platelet counts,and lower 24-hour urinary protein,with statistically significant differences(P＜0.05).There was no statistically significant differences in adverse pregnancy outcomes and neonatal prognosis between the two groups(P＞0.05).②When combined with SPE,the antenatal HELLP group had a shorter interval from preeclampsia to HELLP syndrome,lower platelet counts,and higher liver en-zymes than the postpartum HELLP group,with statistically significant differences(P＜0.05).③There was no sig-nificant difference in clinical features between the antenatal HELLP group and the postpartum HELLP group when not complicated with SPE(P＞0.05).Conclusions:There is only one difference between prenatal and postnatal HELLP syndrome in terms of the speed of disease progression,the time taken from preeclampsia to HELLP syn-drome,and both can lead to serious maternal and neonatal complications,which should be identified early in clini-cal practice.

Objective:To analyze the whole genome sequence and key site mutations of hepatitis B virus (HBV) in patients with different stages of disease progression, and to understand the relationship between HBV genetic characteristics and disease progression.Methods:Serum samples and basic information of hepatitis B patients with asymptomatic HBV carrier, chronic hepatitis B patients, cirrhosis patients and primary hepatocellular carcinoma patients were collected. Nested PCR was used to amplify the samples to obtain HBV whole gene sequences. Phylogenetic trees were constructed to determine the genotype of the samples, and gene mutations of the samples were analyzed combined with reference sequences of each type.Results:A total of 256 samples were successfully amplified, including 68 asymptomatic HBV carrier patients, 118 CHB patients, 15 LC patients and 55 HCC patients, and five genotypes (B, C, D, I and C/D) were detected. The result of comparative analysis showed that the mutation rate of 56 nucleotide sites was significantly different among the four groups ( P<0.05). In addition to the discovery of C105T, A1762T/G1764A and G1899A and other previously reported key site mutations, the mutation rates of T53A, C1485T and C1628T in newly diagnosed HCC group were significantly higher than those in other groups, and the mutation rates of T2150G and T2151C in asymptomatic HBV infection group were significantly higher than those in other groups. A total of 26 sequences were deleted, mainly distributed in the pre-C and pre-S regions. The deletion mutation rate in the HCC group was significantly higher than that in the other groups. Conclusions:The data of this study indicate that some nucleotide substitution mutations and deletion mutations may be closely related to the occurrence and development of HBV-related diseases, and HCC patients are more likely to have gene mutations than non-HCC patients. These result provide a reference for understanding the relationship between viral mutation and the progression of HBV infection-related diseases.