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

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective To measure the abdominal muscle composition of maintenance dialysis patients using quantitative computed tomography(QCT)and to analyze its relationship with abdominal aortic calcification(AAC).Methods The abdominal CT data of 193 maintenance dialysis patients were analyzed retrospectively and their clinical data were collected.The abdominal muscle composi-tion,including muscle area and muscle fat area,was measured at the middle level of L3 vertebral by QCT.The abdominal aortic calcifica-tion scores(AACs)were calculated using the Agatston method.The groups were grouped according to the quartiles of AACs,and differences in muscle area,muscle fat area and their associated variables were compared between the four groups.The relationship between abdominal muscle composition and AAC was assessed using Spearman rank correlation analysis and partial correlation analysis.Results AACs were positively correlated with age,male,dialysis age,diabetes,hypertension,and abdominal muscle fat area(r=0.555,0.172,0.192,0.348,0.335,0.358,all P<0.05),while no significant correlation was found with abdominal muscle area.A partial correlation analysis controlling for age,sex,dialysis age,hypertension and diabetes showed that AACs were still positively correlated with abdominal muscle fat area(r=0.183,P=0.012).Conclusion Abdominal muscle fat area in maintenance dialysis patients is positively associ-ated with the degree of AAC,and high abdominal muscle fat area is a risk factor for AAC.Enhanced muscle exercise may prevent the risk of vascular calcification in dialysis patients.

Objective To analyze the changes in the amino acid composition and content of Eriobotryae folium in the twelve months,and to can provide a theoretical basis for the harvesting period and resource utilization of Eriobotryae folium.Methods The amino acid composition and content of Eriobotryae folium in different months were determined by high performance liquid chromatography with phenyl isothiocyanate pre-column derivation.SPSS22.0 software was used to analyze the statistical significance difference and data correlation.According to the ideal model proposed by the World Health Organization(WHO)and the Food and Agriculture Organization of the United Nations(FAO)and the amino acid ratio coefficient method proposed by Shengtao Zhu,the amino acids of Eriobotryae folium at different harvest periods were scored.Results There were seventeen kinds of amino acids,including seven essential amino acids(EAA),nine kinds of children's essential amino acids(CEAA),and nine kinds of medicinal amino acids in Eriobotryae folium at different harvesting periods.The seventeen amino acids were aspartic acid,glutamic acid,serine,glycine,histidine,arginine,threonine,alanine,proline,tyrosine,valine,methionine,cystine,isoleucine,leucine,phenylalanine,and lysine;and the average contents were 3.41-7.23,4.64-9.66,2.05-3.75,2.99-4.95,0.01-1.56,2.33-4.85,2.10-4.03,2.67-5.48,5.37-7.64,1.45-3.49,2.70-5.53,0.01-0.48,3.64-4.78,1.91-4.15,3.96-7.83,2.39-4.60,1.85-3.65 mg·g-1,respectively.There were significant differences in the contents of seventeen kinds of amino acids,total amino acids,total essential amino acids,total essential amino acids for children,medicinal amino acids,and bitter amino acids in Eriobotryae folium at different harvesting stages(P＜0.05).The content of bitter amino acids in total amino acids was stable,and there was no significant difference.The content of essential amino acids was from 44.26%to 50.33%in Eriobotryae folium at different harvesting periods,significantly higher than the WHO/FAO model value(35.00%).The mean values of EAA/NEAA(55.67%)and EAA/TFAA(35.74%)were close to 60%and 40%of the WHO/FAO model values,respectively.The highest content of seventeen kinds of amino acids in Eriobotryae folium was found in July and followed in November.SRC values ranged from 62.53 to 76.17;the highest value was November,the second was August,and the third was July.Lysine was the first limiting amino acid in Eriobotryae folium.Bitter amino acids were positively correlated with medicinal and total amino acids(P＜0.01).Conclusions The amino acids in Eriobotryae folium have a complete variety,reasonable composition,and good development and utilization value.The contents of amino acids in different months varied greatly.July and November were the optimal periods for the rational development and utilization of amino acids in Eriobotryae folium.

To clarify the content characteristics of mineral elements in different Artemisia argyi germplasm resources and their relationship with the quality properties of Artemisiae Argyi Folium, this study measured the content of 10 mineral elements including nitrogen(N), phosphorus(P), potassium(K), calcium(Ca), magnesium(Mg), aluminum(Al), manganese(Mn), iron(Fe), copper(Cu), and zinc(Zn) in 100 Artemisia argyi germplasm samples. Besides, their relationship with the quality properties of Artemisiae Argyi Folium was explored by correlation analysis, path analysis, and cluster analysis. The results demonstrated that the variation coefficient of the 10 mineral elements in Artemisiae Argyi Folium ranged from 12.23% to 64.38%, and the genetic diversity index from 0.97 to 3.09. The genetic diversities of N, P, and Zn were obvious. As revealed by the correlation analysis, N, P, and K showed strong positive correlations with each other. Except that Mg and Al were negatively correlated, Ca, Mg, Al, Mn, Fe, Cu, and Zn were positively correlated. The correlation analysis of mineral elements with the quality properties of Artemisiae Argyi Folium proved the significant correlations of 17 pairs of characters. According to the path analysis, P, K, Ca, and Mn greatly affected the yield of Artemisiae Argyi Folium, P, K, and Mg the output rate of moxa, N, P, and K the content of total volatile oil, P and K the content of eucalyptol, and P, K, and Ca the content of eupatilin. The 100 germplasm samples were clustered into three groups. Specifically, in cluster Ⅰ, the enrichment capacity of P, K, and Mg elements was strong, and the comprehensive properties of mineral elements were better, implying good development potential. Ca, Mn, Fe, and Zn elements in cluster Ⅱ and N and Al in cluster Ⅲ displayed strong enrichment capacities. This study has provided new ideas for resource evaluation and variety breeding of A. argyi and also reference for fertilizer application.
Artemisia/genetics* ; Iron ; Minerals/analysis* ; Plant Breeding ; Plant Leaves/chemistry*

Macrophages have a leading position in the tumor microenvironment (TME) which paves the way to carcinogenesis. Initially, monocytes and macrophages are recruited to the sites where the tumor develops. Under the guidance of different microenvironmental signals, macrophages would polarize into two functional phenotypes, named as classically activated macrophages (M1) and alternatively activated macrophages (M2). Contrary to the anti-tumor effect of M1, M2 exerts anti-inflammatory and tumorigenic characters. In progressive tumor, M2 tumor-associated macrophages (TAMs) are in the majority, being vital regulators reacting upon TME. This review elaborates on the role of TAMs in tumor progression. Furthermore, prospective macrophage-focused therapeutic strategies, including drugs not only in clinical trials but also at primary research stages, are summarized followed by a discussion about their clinical application values. Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.

The 13th World Congress of the International Hepato-Pancreato-Biliary Association was held from 4th to 7th September 2018 in Geneva,Switzerland.Thousands of wellknown specialists and scholars from 96 countries around the world were invited for the great event.The congress aimed to explore the latest achievements of diagnosis and treatment of hepatobiliary and pancreatic diseases from both the clinical and basic perspective.In this article,authors reviewed and analyzed the up-to-date research information and combined clinical researches of the author team,in order to share the experience and achievements in the field of hepato-pancreato-biliary surgery with colleagues and provide new information and inference for optimization of diagnosis and treatment in this field.

Objective To investigate the effects of exercise on knee cartilage tissue structure using quantitative MR T2 mapping. Methods Sagittal T2 maps of the knee joints of 26 healthy volunteers were obtained by using 3.0T MR before,immediately after, and 1 5 min after running.The original images were classified into three terms of knee cartilage T2 map after postreconstruction.The T2 values of regions of interest (ROC)(T2 pre ,T2 post ,T2 delay )in the superficial,middle and deep cartilage of femoral and tibial joint were measured.Statistical differences of cartilage T2 values of three terms after running were analyzed.Results For the tibial joint cartilage,the T2 pre ,T2 post ,T2 delay were (49.71 ± 1.95)ms,(44.30 ± 2.56)ms,(49.41 ± 1.62)ms in the superficial layer,respectively.The three terms T2 were (42.43 ± 2.23)ms,(39.01 ± 2.37)ms,(41.90±2.28)ms in the middle layer,respectively.The differences were statistically significant(F=55.673,16.759 respectively.P<0.001).While the three terms T2 were (19.39±2.13)ms,(19.20±2.22)ms, (19.49±2.05)ms in the deep layers cartilage,respectively.The differences were not statistically significant(F =0.122,P =0.886).And the differences between T2 pre and T2 post ,T2 post and T2 delay were statistically significant (all P <0.001)in superficial and middle alyers,but there were no significant difference between the T2 pre and T2 delay (P =0.610,0.403,respectively).For the femoral joint cartilage,the T2 pre ,T2 post ,T2 delay were (50.22 ± 1.47)ms,(45.60 ± 2.82)ms,(49.84 ± 1.84)ms in superficial layers,respectively.The three terms T2 were (42.67±2.23)ms,(39.36 ± 1.98)ms,(42.40 ± 2.57)ms in the middle layer,respectively.The differences were statistically significant (F=37.976,16.987 respectively,P<0.001).While the three terms T2 were (20.30±2.73)ms,(20.60±2.44)ms,(20.51± 2.24)ms in the deep layer,the differences were not statistically significant (F =0.098,P =0.907).And the differences between T2 pre and T2 post ,T2 post and T2 delay were statistically significant (all P <0.001)in superficial and middle layers,but there were no significant difference between the T2 pre and T2 delay (P=0.520,0.679,respectively). Spatial distribution of T2 values of articular cartilage from deep to superficial layers showed a ascending trend.T2 maps showed the spatial distribution trend of T2 value change.Conclusion T2 mapping can monitor quantitatively the changes of articular cartilage molecular structure after running.The change of articular cartilage T2 value after exercise is uneven and the change of articular cartilage structure after exercise is reversible.

Objective To investigate the clinical feasibility of contrast?enhanced three dimensional T2WI turbo?spin?echo sequence with short?term inversion recovery and sampling perfection using different flip angle evolutions (3D STIR T2WI SPACE) sequence in the brachial plexus neurography. Methods Thirty two patients were prospectively chosen and performed with brachial plexus plain scanning on a 3.0 T MR scanner by using plain and contrast?enhanced 3D STIR T2WI SPACE sequence. Thirteen of them underwent plain scan, 9 of them underwent contrast?enhanced scan, and 10 of them underwent both plain scan and enhanced scan. The visibility of the brachial plexus were scored and contrast to noise ratio (CNR) were measured by two experienced radiologists. The results between plain and contrast?enhanced imaging were compared by t test. The 10 subjects received both enhance and plain imaging, were performed with paired t test. Results In 32 patients, the visibility score of brachial plexus nerve and CNR were 7.8 ± 1.3 and 24.97±3.41 in the plain scan group, and 13.1±1.7 and 38.49±4.95 in enhanced scan group, respectively. There were statistically significant differences in the two groups(t=-11.72,P<0.01;t=-10.47, P<0.01). In 10 cases with plain and enhanced brachial plexus imaging, the average score of the brachial plexus were 7.4 ± 1.7 and 13.3 ± 1.6, the average CNR were 26.23 ± 4.43 and 38.19 ± 5.03 respectively. There were statistically significant differences (t=- 8.22, P<0.01; t=- 5.64,P<0.01). The score results were analyzed for consistency. Plain images Kappa value was 0.684, which shows moderate consistency and enhanced images Kappa value= 0.822, which shows excelent consistency. Conclusions The contrast?enhanced 3D STIR T2WI SPACE sequences may suppress background tissue signals, which is helpful to display brachial plexus, therefore it is of important value for the early diagnosis of brachial plexus neuropathy.