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

Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

Objective To investigate the involvement of phosphofurin acidic cluster sorting protein-2(PACS-2)in mitochondrial function and apoptosis in N2a/APP695swe cells and further explore the role and significance of PACS-2 in the development of Alzheimer's disease(AD).Methods The CCK8 method was used to analyze the cell survival rate of N2a/APP695swe cells treated with different concentrations of tetrahydroxy stilbene glycoside(TSG)for 48h and to select the appropriate concentration of TSG for subsequent experiments.N2a/WT cells and N2a/APP695swe cells were routinely cultured in vitro,and the experimental cells were divided into 3 groups:blank control group(WT group):N2a/WT cells;model group(APP group):N2a/APP695swe cells;treatment group(TSG group):N2a/APP695swe cells with appropriate concentrations of TSG intervention.TUNEL method to observe apoptosis by fluorescence microscopy;JC-1 method for flow detection of cellular mitochondrial membrane potential;WB to detect protein expression of PACS-2;RT-qPCR to detect PACS-2 mRNA expression.Results CCK8 method was used to analyze the cell survival rate of different concentrations of TSG acting on cells after 48h:the protective effect of 100 μmol/L TSG was the most significant and the difference was statistically significant(P<0.01).The TUNEL method of fluorescence microscopy observed the apoptosis:compared with the WT group,the apoptosis rate of APP group was increased,compared with the APP group,the apoptosis rate of TSG group was decreased,and the differences were statistically significant(P<0.05).The JC-1 method was used to detect the mitochondrial membrane potential of cells:compared with the WT group,the membrane potential of APP group was decreased,compared with the APP group,the membrane potential of TSG group was increased,and the differences were statistically significant(P<0.05);Western blot(WB)detection of PACS-2 protein expression:compared with the WT group,PACS-2 expression was significantly higher in the APP group,and compared with the APP group,PACS-2 expression was significantly lower in the TSG group,with statistically significant differences(P<0.05);The RT-qPCR detected the mRNA expression of PACS-2:the expression of PACS-2 was elevated in the APP group compared with the WT group and decreased in the TSG group compared with the APP group,with statistically significant differences(P<0.05).Conclusion PACS-2 has an important role in the development of AD,and its upregulation may promote the development of AD.The cerebroprotective drug TSG may exert cytoprotective effects by downregulating PACS-2 to inhibit apoptosis and improve mitochondrial function in AD model cells.

Primary aldosteronism (PA) mainly includes aldosteronoma (APA) and idiopathic aldosteronism (IHA). APA often presents as unilateral adrenal nodules, but can also be accompanied by non-functional adrenal nodules, which leads to difficulty of the identification. In this paper, the clinical characteristics, diagnosis and treatment process of two cases of PA with non-functional adrenal nodules were analyzed and discussed to provide some references for the accurate diagnosis and treatment of PA.

In order to realize the diagnosis of slit lamp in cross-regional patients and improve the real-time and convenience of diagnosis,a remote slit lamp diagnosis platform based on Internet of Things(IoT)technology is designed.Firstly,the feasibility of remote slit lamp is analyzed.Secondly,the IoT platform architecture of doctor/server/facility(D/S/F)is proposed and a remote slit lamp is designed.Finally,the performance of the remote slit lamp diagnostic platform is tested.The platform solves the communication problem of distributed slit lamps and realizes respectively numerical control of multi-area slit lamp by multi-eye experts.The test results show that the remote control delay of the platform is less than 20 ms,which supports multiple experts to diagnose multiple patients separately.

Objective To evaluate the efficacy of Jianpi Yang'er Ointment for children with anorexia of spleen deficiency type in Lingnan area;To analyze its effects on children's intestinal flora and functional information by means of metagenome sequencing.Methods Totolly 144 children with anorexia in Guangzhou Women and Children Medical Center of Guangzhou Medical University from August 2022 to January 2023 were orally treated with Jianpi Yang'er Ointment,one bag per time,twice a day,after meal,for 28 d.Visits were conducted at 0 and 28 days,respectively,to measure height and body mass,record symptoms and signs,observe adverse reactions,collect feces,and fill out the"Clinical Index Scoring Table for Children with Spleen Deficiency Type Anorexia in Lingnan Area".Clinically cured children were included in the anorexia group,with healthy children as a healthy control group(HC group),perform metagenomic analysis on feces of HC group and anorexia group 0 and 28 days of treatment.Results Compared with 0 d of treatment,there was no significant difference in the height of children(P>0.05),while there was a significant difference in body mass(P<0.05),the total syndrome score,main symptom score,and secondary symptom score decreased at 28 d of treatment(P<0.05).The efficacy index was 57.03%,and the total effective rate was 99.31%(143/144).All patients did not experience symptoms such as allergies,vomiting,or diarrhea.7 clinically cured children and 6 healthy children were included in metagenome analysis on feces.PCoA showed that the structure of intestinal flora in anorexia group with 28 d treatment(JP2 group)was more similar to that in HC group at the phylum and genus levels;at the phylum level,there was no significant difference in the distribution of intestinal flora between anorexia group with 0 d treatment(JP1)group and JP2 group and HC group.At the genus level,compared with JP1 group,the abundance of Bacteroides in JP2 group decreased,but the difference was not statistically significant(P>0.05);at the species level,both JP1 and JP2 groups were mainly composed of Phocaeicola plebeius et al.and Bifidobacterium pseudocatenatum et al.The biomarker with significant differences between the two groups was s_Phascolarctobacterium_faecium,while the HC group was mainly composed of Prevotella copri and Bifidobacterium pseudocatenatum.The functional annotation results indicated that a significant change in microbial functional genes related to carbohydrate metabolism occurred after the treatment with Jianpi Yang'er Ointment.Conclusion Jianpi Yang'er Ointment can effectively improve the clinical symptoms of children with spleen deficiency anorexia in Lingnan area,adjust the structure of intestinal flora,increase the content of key probiotics,and regulate the production of intestinal microbiota short-chain fatty acids.

Purpose To use CT-arterial phase images of pre-treatment ovarian cancer patients,combined with deep learning algorithms and machine learning to build a model to predict the efficacy of neoadjuvant chemotherapy in ovarian cancer.Materials and Methods A total of 302 consecutive patients who underwent surgery and were pathologically diagnosed with ovarian cancer from March 2013 to August 2019 in Tianjin Medical University were retrospectively collected.All patients were partitioned into training and test sets according to the ratio of 7∶3.In the python environment,VGG13 model was integrated via combining deep learning network and machine learning,and features were filtered via least absolute shrinkage and selection operator algorithm to build a prediction model for classification and prediction of CT images.The area under the curve(AUC),accuracy,sensitivity,specificity,and Fl-Score were calculated,respectively.Results The AUC,accuracy,sensitivity,specificity,and Fl-Score of the model in the training set were 0.87,0.81,0.80,0.82 and 0.79,and 0.90,0.84,0.93,0.77 and 0.83 in the test set,respectively.The AUC of five-fold cross-validation were 0.86,0.88,0.88,0.90 and 0.87,respectively.Conclusion Predictive model based on CT images combined with deep learning and machine learning methods can provide a new clinical perspective for developing chemotherapy regimens for ovarian cancer.

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

Objective:To explore the prognostic evaluating value of serum tenascin-X in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods:The clinical data of 121 patients with STEMI in the Affiliated Sinopharm Dongfeng General Hospital, Hubei University of Medicine from August 2017 to August 2018 were retrospectively analyzed. The clinical data were collected, the serum tenascin-X level was measured by enzyme-linked immunosorbent assay. The patients were followed up for 3 years, the major adverse cardiovascular events (MACE) were identified as endpoint events. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum tenascin-X for MACE in patients with STEMI. The Kaplan-Meier survival curve was drawn, the rates of non-MACE survival in patients with different serum tenascin-X levels were analyzed by log-rank method. Multivariate Cox regression was used to analyze the independent risk factors of MACE in patients with STEMI.Results:Until the end of follow-up, among 121 patients with STEMI, 42 cases (34.7%) developed MACE (MACE group), and 79 cases had not MACE (non-MACE group). The left ventricular ejection fraction (LVEF) in the MACE group was significantly lower than that in the non-MACE group: (47.14 ± 6.70)% vs. (52.67 ± 4.41)%, the C-reactive protein (CRP), B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and tenascin-X were significantly higher than those in non-MACE group: (27.92 ± 8.06) mg/L vs. (8.77 ± 3.49) mg/L, (918.31 ± 315.47) μg/L vs. (220.47 ± 108.37) μg/L, (214.73 ± 80.46) μg/L vs. (81.35 ± 28.96) μg/L and (110.67 ± 42.55) μg/L vs. (65.21 ± 28.06) μg/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the area under the curve of serum tenascin-X to predict the MACE in patients with STEMI was 0.806 (95% CI 0.724 to 0.872), and the optimal cut-off was 93.25 μg/L, the sensitivity was 69.0%, the specificity was 86.1%. Kaplan-Meier survival curve analysis result showed that the rate of non-MACE in 80 patients with low serum tenascin-X level (<93.25 μg/L) was significantly higher than that in 41 patients with high serum tenascin-X level (≥93.25 μg/L): 83.8% vs. 29.3%, and there was statistical difference ( χ2 = 42.47, P<0.01). Multivariate Cox regression analysis result showed that the CRP, BNP and tenascin-X were the independent risk factors of MACE in patients with STEMI ( HR = 1.092, 1.001 and 1.018; 95% CI 1.051 to 1.135, 1.000 to 1.002 and 1.008 to 1.027; P<0.01 or <0.05). Conclusions:The significant increase in serum tendon protein X levels in patients with STEMI has predictive value for the MACE, and it is an independent predictor of MACE within 3 years.

Objective:To explore the clinical efficacy of DELTA endoscopic lumbar interbody fusion for the treatment of mild to moderate, single segment lumbar spondylolisthesis.Methods:A retrospective analysis was conducted on the clinical data of 48 surgical cases of grade Ⅰ to Ⅱ lumbar spondylolisthesis admitted to the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from February 2020 to March 2022. Among them, 24 cases treated with DELTA endoscopic lumbar interbody fusion surgery were classified as the DELTA group, and 24 cases treated with traditional minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) surgery were classified as the MIS-TLIF group. Two groups of patients were compared in terms of perioperative indicators (surgical time, postoperative drainage volume, incision length, hospital stay), clinical efficacy [Visual Analogue Scale (VAS) score for low back and leg pain, lumbar Japanese Orthopaedic Association Scores (JOA), improved MacNab standard excellence rate], and lumbar fusion rate (Bridwell intervertebral fusion grade).Results:The DELTA group had longer surgical time than the MIS-TLIF group, and the postoperative drainage volume, incision length, and hospital stay were all lower than the MIS-TLIF group, with statistically significant differences (all P<0.05). The VAS score of lower back and leg pain and lumbar JOA score of the two groups of patients at 1 week, 3 months, and the last follow-up were significantly improved compared to those before surgery (all P<0.01), and the DELTA group had better VAS score of lower back and leg pain and lumbar JOA score at all time points after surgery than the MIS-TLIF group, with statistically significant differences (all P<0.05). The improved MacNab standard was used to evaluate the efficacy of the two groups of patients at the last follow-up after surgery, and there was no statistically significant difference in the excellent and good rates ( P>0.05); There was no statistically significant difference ( P>0.05) in the fusion rate between the two groups. Conclusions:DELTA endoscopic lumbar interbody fusion has a significant therapeutic effect on lumbar spondylolisthesis, with the advantages of small surgical incision and fast recovery; After crossing the DELTA endoscopic learning curve and optimizing surgical procedures, this technology can become an alternative to MIS-TLIF technology.