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

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

Objective : To examine the causal relationship between ulcerative colitis (UC) and pancreatitis, to provide basis for early screening of pancreatitis among UC patients. Methods: Genomic data of UC were obtained from 47 745 European individuals pooled by the International Inflammatory Bowel Disease Genetics Consortium, including 156 116 single nucleotide polymorphism (SNP), and genomic data of pancreatitis were obtained from 198 166 European individuals pooled from FinnGen, including 16 380 428 SNPs. Mendelian randomization (MR) analysis was performed using the inverse variance weighted (IVW) method with 72 UC-associated SNPs as instrumental variables and pancreatitis as the study outcome. The heterogeneity was assessed using Cochran Q test, the horizontal pleiotropy was assessed using MR-Egger regression, MR-PRESSO was performed with the exclusion of outliers, and effect of individual SNP on the results was tested with the leave-one-out method. Results: MR analysis results showed that patients with genetically predicted UC had an increased risk of pancreatitis relative to those without UC (OR=1.076, 95%CI: 1.019-1.136, P<0.05). Cochran Q test showed no heterogeneity (P>0.05), and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables (P>0.05). The MR analysis results were robust after removing SNP one by one. Conclusions Genetically predicted UC is associated with an increased risk of pancreatitis. The screening for pancreatitis risk should be enhanced in patients with UC.

Objective:To explore the value of contrast enhancement T1 fluid-attenuated inversion recovery sequence (CE-T1FLAIR) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in detecting metastases.Methods:One hundred and seventy-six patients with pathologically diagnosed malignant tumors and brain metastases accepted enhanced 3.0T MRI scan in Department of Medical Imaging, He'nan Provincial Cancer Hospital from October 2023 to February 2024 were enrolled. Lianying's intelligent brain metastasis AI-assisted detection system and sequences of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR were used to detect the brain metastasis lesions, respectively. Length of the lesions was measured according to Lianying's intelligent brain metastasis AI-assisted detection system, and all lesions were divided into 3 categories: <3 mm, 3-10 mm, and >10 mm. Differences in detection rate in brain metastases of different lengths and locations among the 3 sequences were compared.Results:Detection rates of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR, and FSE CE-T1FLAIR in brain metastases were 99.67%, 90.52%, and 71.02%, which were decreased successively, with significant differences ( P<0.05). Detection rates of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR in brain metastases with length<3 mm (99.24%, 79.95% and 46.45%) or length of 3-10 mm (100%, 98.19% and 87.53%) were decreased successively, with significant differences ( P<0.05). Detection rates of MATRIX CE-T1FLAIR (100%, 80.56% and 64.24%), 3D GRE_fsp CE-T1FLAIR (100%, 97.25% and 76.11%), and FSE CE-T1FLAIR (100%, 91.18% and 70.59%) in metastases at the superficial area of the brain convexity, gray-white matter junction area, and cerebellum were decreased successively, with significant differences ( P<0.05). Detection rates of FSE CE-T1FLAIR in brain metastases in the basal ganglia and brainstem (69.33% and 50%) were significantly lower than those of MATRIX CE-T1FLAIR and 3D GRE_fsp CE-T1FLAIR (97.33% and 92.86%; 88% and 78.57%, P<0.05). Conclusion:MATRIX CE-T1FLAIR sequence is better than 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR sequences in detecting brain metastases, especially for metastases with length<10 mm and metastases located at the superficial area of the brain convexity, gray-white matter junction area and cerebellum.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

Objective:To compare the diagnostic values of C-TIRADS, ACR-TIRADS and EU-TIRADS.Methods:According to the classification methods of the 3 guidelines, the ultrasonographic features of 283 thyroid nodules from 266 patients in Sir Run Run Shaw Hospital from January 2019 to June 2020 were analyzed retrospectively. The pathological results were taken as the gold standard, the malignant percentage of different classification was calculated, the ROC curve was plotted, the area under the ROC curve (AUC) and the best diagnostic cut-off value were calculated, and the diagnostic values of the three guidelines were compared. According to the FNA recommendations of the guidelines, the recommended number of thyroid nodules and the detection rate of malignant nodules in different guidelines were analyzed.Results:The AUCs of C-TIRADS, ACR-TIRADS and EU-TIRADS were 0.80, 0.66, 0.61, respectively. The AUC of C-TIRADS was higher than those of ACR-TIRADS and EU-TIRADS ( P<0.001, P<0.001). The best diagnostic cutoff values of C-TIRADS, ACR-TIRADS and EU-TIRADS were 4C, 5 and 5, respectively. Under the critical points, the sensitivities of the 3 guidelines were 95.27%, 98.10%, 99.53%, the specificities were 54.17%, 33.33%, 20.83%, respectively. There was no significant difference in the number of FNA recommendations among the 3 guidelines(all P>0.05), their FNA recommendations were highly consistent (Kappa>0.9). Conclusions:The diagnostic value of C-TIRADS in the classification of benign and malignant thyroid nodules is higher than those of ACR-TIRADS and EU-TIRADS. The best critical value for diagnosis of thyroid nodules is C-TIRADS 4C. The three guidelines are similar in the number of FNA recommendations and the detection rate of malignancy.

Objective To investigate the correlation between Young′s elastic modulus (EI) using shear wave elastography (SWE) and liver pathology .Methods Liver biopsy was performed on 231 patients with chronic hepatitis B (CHB) under supersonic guidance ,and SWE with EI of liver was obtained concurrently .The correlation between measured liver stiffness and pathology was analyzed by using the liver pathology as golden standards .One‐way analysis of variance and Spearman rank correlation analysis were performed for the comparison between groups and correlation between two variables , respectively .Receiver operating characteristic (ROC) curve was used to explore the predictive value of shear modulus for the liver inflammation grades and fibrosis stages .Results The EI medians of different liver inflammation grades were 6 .78 kPa (G1) ,7 .30 kPa (G2) ,9 .93 kPa (G3) and 14 .93 kPa (G4) , respectively ,which were statistically different (H=55 .19 ,P<0 .01) .And EI medians of various fibrosis stages were 6 .62 kPa (S0 -S1) ,7 .15 kPa (S2) ,9 .78 kPa (S3) and 14 .62 kPa (S4) ,respectively , which were also significantly different (H=62 .14 ,P<0 .01) .EI was positively correlated with both liver inflammation grades (r=0 .454 6 ,P<0 .01) and liver fibrosis stages (r=0 .505 6 ,P<0 .01) .The areas under the ROC for G≥2 ,G≥3 and G=4 were 0 .68 (95% CI:0 .61 -0 .75) ,0 .77 (95% CI:0 .70 -0 .84) and 0 .85 (95% CI:0 .77-0 .92) ,respectively .The areas under the ROC for S≥2 ,S≥3 and S=4 w ere 0 .73 (95% C I:0 .66 -0 .79 ) ,0 .78 (95% C I:0 .72 -0 .85 ) and 0 .83 (95% C I:0 .75 -0 .91 ) , respectively .Conclusion The EI measured by SWE is correlated with liver pathology of CHB patients , which may be used to dynamically monitor the progress of liver fibrosis .

Objective To explore the value of shear wave elastrography (SWE) in diagnosis of prostate cancer.Methods SWE quantitative elastography was preformed in 55 patients with suspected prostate cancer,to obtain the elastic modulus (mean,maximum).Each patient underwent sonography-guided prostatic biopsy on the same day.With the pathologic results as reference,ROC curves were used to assess diagnostic performance.Results ①Pathological tests showed that 39 lesions were benign(hyperplasia) and 16 lesions were malignant.The mean elasticity value of benign lesions was (39.04 ± 8.22) kPa,and the maximum value was (54.10 ± 9.18)kPa,whereas of malignant ones were (53.31 ± 3.92)kPa and (68.71 ±2.57)kPa,respectively (P ＜0.05).② The area under the ROC curve (AZ) of the maximum and mean elasticity value was 0.951 and 0.944.Taking 48.07 kPa as the threshold of the mean elasticity value,the sensitivity was 91.8％ and the specificity was 89.7％.Then taking 65.50 kPa as the threshold of the maximum elasticity value,the sensitivity was 92.1％ and the specificity was 87.5％.Conclusions SWE is helpful to diagnose and differentiate prostate diseases by measuring elastic modulus.