Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

With the extensive application of surgical robots represented by Da Vinci in minimally invasive surgical procedures, robotic technology has gradually extended to the field of flexible endoscopic surgery like digestive endoscopy. Many studies have shown that surgical robots can also improve the operational efficiency and safety of flexible endoscopic surgery and optimize the learning curve. However, due to the narrow and tortuous lumen of digestive tract, the development and design of flexible digestive endoscopic surgical robot is relatively more difficult. In this paper, the research and development characteristics of the flexible digestive endoscopic surgical robot are introduced from the aspects of carrier length, flexibility and ergonomics, and its future clinical application is prospected, with a view to facilitating the application of the flexible surgical robot in the minimally invasive surgical procedures of natural passages such as digestive, respiratory and urinary tract.

Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor control.However,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade.Using single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in TIL-Bs.HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering.This classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to immunotherapy.We found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients.Overall,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.

With the extensive application of surgical robots represented by Da Vinci in minimally invasive surgical procedures, robotic technology has gradually extended to the field of flexible endoscopic surgery like digestive endoscopy. Many studies have shown that surgical robots can also improve the operational efficiency and safety of flexible endoscopic surgery and optimize the learning curve. However, due to the narrow and tortuous lumen of digestive tract, the development and design of flexible digestive endoscopic surgical robot is relatively more difficult. In this paper, the research and development characteristics of the flexible digestive endoscopic surgical robot are introduced from the aspects of carrier length, flexibility and ergonomics, and its future clinical application is prospected, with a view to facilitating the application of the flexible surgical robot in the minimally invasive surgical procedures of natural passages such as digestive, respiratory and urinary tract.

Objective To compare the efficacy of endoscopic submucosal dissection(ESD)using the flexible auxiliary single-arm transluminal endoscopic robot(FASTER)with that of the traditional technique,and explore a safer and more efficient ESD operation method.Methods FASTER-assisted ESD and traditional ESD were used to operate in the isolated pig esophagus model.The differences of total procedure time,ESD time,the rate of direct-vision dissection,complete en bloc resection and complication rate between the two groups were compared and analyzed.Results The total procedure time[(19.2±2.9)and(28.9±8.2)min]and ESD time[(13.0±2.9)and(21.6±8.3)min]were significantly shorter in FASTER-assisted ESD group than those in traditional ESD group,the differences were statistically significant(P<0.01);The rate of direct-vision dissection was significantly higher than that of the traditional ESD(96.2%and 65.4%),the difference was statistically significant(P=0.014).Muscle layer injury rate was significantly lower than of the traditional group(19.2%and 69.2%),the difference was statistically significant(P<0.01).There was no significant difference in complete en bloc resection rate and perforation rate between the two groups(P>0.05).These advantages were more apparent in esophageal non-gravity lesions.Conclusion Esophageal ESD assisted by FASTER is safer and more efficient than traditional ESD.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

The incidence and mortality of digestive system tumors are increasing year by year,which seriously threatens human life and health.In recent years,it has been found that long noncoding RNA(lncRNA)is involved in regulating the proliferation,migration,and invasion of digestive system tumors.This article reviewed the progress of research on lncRNA in digestive system tumors.

Objective To investigate the predictive value of preoperative bi-parametric MRI radiomics for the International Society of Urological Pathology(ISUP)grading of prostate cancer(PCa).Methods One hundred and sixty-five patients with PCa confirmed by pathology were analyzed retrospectively.According to the ISUP grading system,PCa patients were divided into five subgroups:G1 group(Gleason score=6),G2 group(Gleason score=3+4),G3 group(Gleason score=4+3),G4 group(Gleason score=8)and G5 group(Gleason score=9 or 10).A total of 3 948 radiomics features were extracted from T2WI,diffusion weighted imaging(DWI),and apparent diffusion coefficient(ADC)images of each patient.Patients were classified into two categories based on Gleason score≥4+3 or ≤3+4.A radiomics signature(Rad-score)was constructed after reduction of dimension by the minimum redundancy maximum relevance(mRMR)and the least absolute shrinkage and selection operator(LASSO).The Spearman rank correlation test was used to evaluate the correlation between Rad-score and ISUP grading groups.The Kruskal-Wallis test was used to compare the difference of Rad-score among the five groups.Results Eleven most valuable features were selected as the Rad-score after reducing the dimension by mRMR and LASSO algorithm.Moderate correlation existed between Rad-score and ISUP grading(r=0.53,P＜0.05).There were significant differences in Rad-score between G1 and G2 groups and G3,G4 and G5 groups(P＜0.05),no significant difference existed between the remained two groups(P＞0.05).The area under the curve(AUC)of receiver operating characteristic(ROC)curve for Rad-score were 0.827,0.762,0.563,0.657,0.698 for G1,G2,G3,G4 and G5 groups,respectively.Conclusion The radiomics based on bi-parametric MRI can be used to predict grade 1,2 PCa patients in the ISUP grading system.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

The incidence and mortality of digestive system tumors are high,and the trend is increasing year by year,and the early onset is hidden,difficult to detect,and seriously threaten human health.In recent years,it has been found that long noncoding RNA(lncRNA),as a new class of non-coding RNA,plays an important role in the occurrence and development of tumors,influencing the occurrence and development of tumors by regulating the malignant biological characteristics of tumor cells such as proliferation,invasion and metastasis.Further study on the role of lncRNA in digestive system tumors can further discover its diagnosis and treatment methods,and provide new ideas for reducing the incidence and mortality of digestive system tumors.This article reviewed the progress of research in lncRNA in digestive system tumors.