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: To examine the impact of COVID-19 pandemic on the epidemic status of imported malaria and national malaria control program in China, so as to provide insights into post-elimination malaria surveillance. METHODS: All data pertaining to imported malaria cases were collected from Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 through December 31, 2021. The number of malaria cases, species of malaria parasites, country where malaria parasite were infected, diagnosis and treatment after returning to China, and response were compared before (from January 1, 2018 to January 22, 2020) and after the COVID-19 pandemic (from January 23, 2020 to December 31, 2021). RESULTS: A total of 2 054 imported malaria cases were reported in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 to December 31, 2021, and there were 1 722 cases and 332 cases reported before and after the COVID-19 pandemic, respectively. All cases were reported within one day after definitive diagnosis. The annual mean number of reported malaria cases reduced by 79.30% in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region after the COVID-19 pandemic (171 cases) than before the pandemic (826 cases), and the number of monthly reported malaria cases significantly reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region since February 2020. There was a significant difference in the constituent ratio of species of malaria parasites among the imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 146.70, P < 0.05), and P. falciparum malaria was predominant before the COVID-19 pandemic (72.30%), while P. ovale malaria (44.28%) was predominant after the COVID-19 pandemic, followed by P. falciparum malaria (37.65%). There was a significant difference in the constituent ratio of country where malaria parasites were infected among imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 13.83, P < 0.05), and the proportion of malaria cases that acquired Plasmodium infections in western Africa reduced after the COVID-19 pandemic that before the pandemic (44.13% vs. 37.95%; χ² = 4.34, P < 0.05), while the proportion of malaria cases that acquired Plasmodium infections in eastern Africa increased after the COVID-19 pandemic that before the pandemic (9.58% vs. 15.36%; χ² = 9.88, P = 0.02). The proportion of completing case investigation within 3 days was significantly lower after the COVID-19 pandemic than before the pandemic (96.69% vs. 98.32%; χ²= 3.87, P < 0.05), while the proportion of finishing foci investigation and response within 7 days was significantly higher after the COVID-19 pandemic than before the pandemic (100.00% vs. 98.43%; χ² = 3.95, P < 0.05). CONCLUSIONS The number of imported malaria cases remarkably reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region of China during the COVID-19 pandemic, with a decreased proportion of completing case investigations within 3 days. The sensitivity of the malaria surveillance-response system requires to be improved to prevent the risk of secondary transmission of malaria due to the sharp increase in the number of imported malaria cases following the change of the COVID-19 containment policy.
Humans ; Pandemics ; China/epidemiology* ; Incidence ; COVID-19/epidemiology* ; Malaria/prevention & control* ; Malaria, Falciparum/epidemiology*

OBJECTIVE: To investigate the infection and genotypes of Wolbachia in common mosquito species in Henan Province, so as to provide insights into management of mosquito-borne diseases. METHODS: Aedes, Culex and Anopheles samples were collected from cowsheds, sheepfolds and human houses in Puyang, Nanyang City and Xuchang cities of Henan Province from July to September, 2022, and the infection of Wolbachia was detected. The 16S rDNA and wsp genes of Wolbachia were amplified and sequenced. Sequence alignment was performed using the BLAST software, and the obtained 16S rDNA gene sequence was compared with the sequence of the 16S rDNA gene in GenBank database. In addition, the phylogenetic trees were created based on 16S rDNA and wsp gene sequences using the software MEGA 11.0. RESULTS: A total 506 female adult mosquitoes were collected from three sampling sites in Nanyang, Xuchang City and Puyang cities from July to September, 2022. The overall detection of Wolbachia was 45.1% (228/506) in mosquitoes, with a higher detection rate in A. albopictus than in Cx. pipiens pallens [97.9% (143/146) vs. 50.6% (85/168); χ² = 88.064, P < 0.01]. The detection of Wolbachia in Cx. pipiens pallens was higher in Xuchang City (96.8%, 62/64) than in Nanyang (15.6%, 7/45) and Puyang cities (27.1%, 16/59) (χ² = 89.950, P < 0.01). The homologies of obtained Wolbachia 16S rDNA and wsp gene sequences were 95.3% to 100.0% and 81.7% to 99.8%. Phylogenetic analysis based on wsp gene sequences showed Wolbachia supergroups A and B in mosquito samples, with wAlbA and wMors strains in supergroup A and wPip and wAlbB strains in supergroup B. Wolbachia strain wAlbB infection was detected in A. albopictus in Puyang and Nanyang Cities, while Wolbachia strain wPip infection was identified in A. albopictus in Xuchang City. Wolbachia strain wAlbA infection was detected in Cx. pipiens pallens sampled from three cities, and one Cx. pipiens pallens was found to be infected with Wolbachia strain wMors in Nanyang City. CONCLUSIONS Wolbachia infection is commonly prevalent in Ae. albopictus and Cx. pipiens pallens from Henan Province, and Wolbachia strains wAlbB and wAlbA are predominant in Ae. albopictus, while wPip strain is predominant in Cx. pipiens pallens. This is the first report to present Wolbachia wMors strain infection in Cx. pipiens pallens in Henan Province.
Animals ; Humans ; Phylogeny ; Wolbachia/genetics* ; Culex/genetics* ; Aedes/genetics* ; DNA, Ribosomal

OBJECTIVES: To investigate the influencing factors for asthma management and asthma control level in children. METHODS: A total of 202 children with a confirmed diagnosis of asthma were enrolled. The questionnaire of asthma control level and family management was used to investigate the influencing factors for asthma control level and the indicators of family management. The awareness of childhood asthma and its management was analyzed among the parents, as well as the influence on asthma control level in children, and the association between them was analyzed. RESULTS: Compared with the non-complete control group, the complete control group had significantly longer course of asthma and treatment time (P<0.05). The proportions of asthma attacks ≥3 times and aerosol treatment for asthma attacks >3 times in one year in the complete control group were significantly lower than those in the non-complete control group (P<0.05). The complete control group had a significantly lower proportion of children with frequent respiratory infection, wheezing during respiratory infection, or a family history of allergic diseases (P<0.05). The parents in the complete control group had significantly stronger awareness of short-term escalation to asthma medication after respiratory infection and significantly enhanced management of maintenance medication (P<0.05). Compared with the complete control group, the non-complete control group had a significantly higher proportion of children with abnormal pulmonary function at the initial stage (P<0.05). The level of asthma control in children was associated with short-term escalation to asthma medication during respiratory infection and initial lung function (P<0.05). CONCLUSIONS The level of asthma control in children is closely associated with the severity of asthma and the comprehensive management of childhood asthma. Early treatment and family management, especially escalation to asthma medication during the early stage of respiratory infection, are of great importance in asthma control. Citation:Chinese Journal of Contemporary Pediatrics, 2023, 25(1): 73-79.
Child ; Humans ; Asthma/diagnosis* ; Hypersensitivity/diagnosis* ; Lung ; Respiratory Tract Infections ; Parents ; Respiratory Sounds

BACKGROUND: The age, biomarkers, and clinical history (ABC)-atrial fibrillation (AF)-Stroke score have been proposed to refine stroke risk stratification, beyond what clinical risk scores such as the CHA2DS2-VASc score can offer. This study aimed to identify risk factors associated with thromboembolism and evaluate the performance of the ABC-AF-Stroke score in predicting thromboembolism in non-anticoagulated AF patients following successful ablations. METHODS: A total of 2692 patients who underwent successful ablations with discontinued anticoagulation after a 3-month blanking period in the Chinese Atrial Fibrillation Registry (CAFR) between 2013 and 2019 were included. Cox regression analysis was conducted to present the association of risk factors with thromboembolism risk. The ABC-AF-Stroke score was evaluated in terms of discrimination, including concordance index (C-index), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), clinical utilization by decision curve analysis (DCA), and calibration by comparing the predicted risk with the observed annualized event rate. RESULTS: After a median follow-up of 3.5 years, 64 patients experienced thromboembolism events. Age, prior history of stroke/transient ischemic attack (TIA), high-sensitivity cardiac troponin T (cTnT-hs), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independently associated with thromboembolism risk. The ABC-AF-Stroke score performed statistically significantly better than the CHA2DS2-VASc score in terms of C-index (0.67, 95% confidence interval [CI]: 0.59-0.74 vs. 0.60, 95% CI: 0.52-0.67, P = 0.030) and reclassification capacity. The DCA implied that the ABC-AF-Stroke score could identify more thromboembolism events without increasing the false positive rate compared to the CHA2DS2-VASc score. The calibration curve showed that the ABC-AF-Stroke score was well calibrated in this population. CONCLUSIONS In this real-world study enrolling non-anticoagulated AF patients following successful ablations, age, prior history of stroke/TIA, level of NT-proBNP, and cTnT-hs were independently associated with an increased risk of thromboembolism. The ABC-AF-Stroke score was well-calibrated and statistically significantly outperformed the CHA2DS2-VASc score in predicting thromboembolism risk.
Humans ; Anticoagulants/therapeutic use* ; Atrial Fibrillation/complications* ; East Asian People ; Ischemic Attack, Transient ; Registries ; Risk Assessment ; Risk Factors ; Stroke/etiology* ; Thromboembolism/etiology* ; Troponin T

Adult ; Humans ; Stomach ; Histiocytosis, Langerhans-Cell/diagnosis*

Humans ; Kidney/pathology*

Male ; Humans ; Spermatic Cord ; Mesothelioma ; Mesothelioma, Malignant

Humans ; Lung Neoplasms ; Soft Tissue Neoplasms

Humans ; Glomerulonephritis, Membranoproliferative/pathology* ; Fibronectins