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.

Objective To investigate the prevalence and risk factors of work-related musculoskeletal disorders (WMSDs) among construction workers. Methods A total of 5 783 workers were selected as participants from 12 construction companies in Guangdong Province, Guangxi Zhuang Autonomous Region and Zhejiang Province using a convenient sampling method. The revised Musculoskeletal Disorders Questionnaire was used to investigate the prevalence and influencing factors of WMSDs. Results The prevalence of WMSDs was 27.4% among the construction workers. The prevalence of WMSDs in shoulder, neck, waist/lower back and hand/wrist was 10.6%, 9.5%, 9.5% and 9.4% respectively, which was higher than that in other body parts. Bianry logistic regression analysis showed that the risk of WMSDs in construction workers with junior high school education and below was higher than that of high school/ college and above (P<0.05). The risk of WMSDs was higher in drinkers than that in non-drinkers (P<0.01). The worse the health status of construction workers, the higher the risk of WMSDs (P<0.01). The risk of WMSDs in those who exercised once or twice a month was lower than that in those who did not exercise (P<0.05). The risk of WMSDs was higher in construction workers with longer working hours in uncomfortable postures and greater back bending amplitude at work (all P<0.01). The risk of WMSDs in construction workers with hands holding above the shoulder was higher than that with hands below the shoulder (P<0.05). Construction workers who repeated the same work daily, involved in high-temperature work, often worked overtime, had insufficient rest time, and had a shortage of department personnel had a relatively high risk of WMSDs (all P<0.01). Conclusion The prevalence of WMSDs among the construction workers was relatively high, and the most common WMSDs occurred in shoulder, neck, waist/lower back and hand/wrist. Individual characteristic, work type, work posture and work organization are the influencing factors of WMSDs. Comprehensive measures, especially ergonomic measures based on personal and occupational characteristics should be taken to reduce the risk of WMSDs among construction workers.

Objective To analyze the effect of hand transmitted vibration on fingertip thermotactile perception threshold (TPT) among grinding workers in a sports equipment manufacturing enterprise. Methods A total of 151 male grinding workers from a sports equipment manufacturing enterprise in Guangdong Province were enrolled in the vibration exposure group, and 51 male workers without hand-transmitted vibration exposure were enrolled in the control group, using the judgment sampling method. Basic health conditions of the workers were surveyed in both groups. The TPTs of the distal phalanges of the index and little fingers on both hands were tested using an HVLab thermal perception tester. Results The detection rates of finger numbness and tingling among workers in the vibration exposure group were higher than those in the control group (92.1% vs 7.8% and 59.6% vs 0.0%, respectively, both P<0.01). The detection rates of numbness or tingling of different fingers in the vibration exposure group descended in the following order: index finger, middle finger, ring finger, thumb and little finger. The hot threshold of the index finger and little finger increased (all P<0.01), while the cold threshold decreased (all P<0.01) in the vibration exposure group, compared with the control group. The results of generalized linear regression analysis showed that with the increase of the duration of hand-transmitted vibration, the hot threshold of the index finger and the little finger of both hands increased (all P<0.01), and the cold threshold decreased (all P<0.01). The hot thresholds of workers with numbness of both the index fingers and left little finger were higher than those of workers without numbness of the same finger (all P<0.05). The hot threshold of workers with tingling of the left index finger was higher than those without tingling (P<0.05). The cold thresholds of workers with tingling of the both index fingers and left little finger were lower than those without tingling of the same finger (all P<0.05). The hot threshold of the right little finger increased with age (P<0.01), while the cold thresholds of both little fingers decreased with age (all P<0.01). Conclusion Hand-transmitted vibration exposure increases fingertip hot threshold and decreases fingertip cold threshold of workers exposed to hand-transmitted vibration. Years of service in hand-transmitted vibration work, finger numbness or tingling, and age were influencing factors of TPT. Fingertip TPT examination can be used to assist in the early detection of vibration-induced nerve injury in workers exposed to hand-transmitted vibration.

Objective To investigate the effects of Tongyangxiao(TYX)lotion on the healing of infected wounds and the expression of interleukin(IL)-1β and inhibitor of nuclear factor κBα(IκBα)/p65 in rats.Methods Fifty rats were randomly assigned to the model group,potassium permanganate(PP)group,and low-,medium-,and high-dose(TYX-L,TYX-M,TYX-H)groups,with 10 rats in each group.An open infection model of full-thickness skin defects was established,and the rats in each group were treated with the corresponding medicinal solution for dressing changes once a day for a total of 14 days.The wound healing of rats was observed,and immunofluorescence,immunohistochemistry,and Western blotting were used to detect the nuclear translocation rate of p65 and the expression levels of IL-1β,p-IκBα/IκBα,and p-p65/p65 proteins in the granulation tissue.Results Compared with the model group,the wound healing rates of both the TYX-M group and the TYX-H group increased on the 7th day of treatment(P<0.05).Compared with the model group and the PP group,the wound healing rates of the TYX-L group,the TYX-M group and the TYX-H group increased on the 14th day of treatment(P<0.05).On the 7th day of treatment,the expression of IL-1β in the TYX-M group was lower than that in the PP group and the Model group(P<0.05),and the p-IκBα/IκBα ratio in the TYX-H group was lower than that in the PP group and the model group(P<0.05).The nuclear translocation rates of p65 in the TYX-L group,TYX-M group and TYX-H group were lower than those in the PP group and model group(P<0.05).On the 14th day of treatment,the p-p65/p65 ratio in the TYX-H group and the TYX-M group was lower than that in the model group(P<0.05),and the IL-1β in the TYX-L group,the TYX-M group,and the TYX-H group and p-IκBα/IκBα ratio in the TYX-H group were lower than those in the PP group and the model group(P<0.05).Conclusion The mechanism of TYX lotion in promoting the healing of infected wounds was associated with the suppression of the activation of NF-κB signaling pathway and alleviation of inflammatory responses.

Objective To investigate the effects of Tongyangxiao(TYX)lotion on the healing of infected wounds and the expression of interleukin(IL)-1β and inhibitor of nuclear factor κBα(IκBα)/p65 in rats.Methods Fifty rats were randomly assigned to the model group,potassium permanganate(PP)group,and low-,medium-,and high-dose(TYX-L,TYX-M,TYX-H)groups,with 10 rats in each group.An open infection model of full-thickness skin defects was established,and the rats in each group were treated with the corresponding medicinal solution for dressing changes once a day for a total of 14 days.The wound healing of rats was observed,and immunofluorescence,immunohistochemistry,and Western blotting were used to detect the nuclear translocation rate of p65 and the expression levels of IL-1β,p-IκBα/IκBα,and p-p65/p65 proteins in the granulation tissue.Results Compared with the model group,the wound healing rates of both the TYX-M group and the TYX-H group increased on the 7th day of treatment(P<0.05).Compared with the model group and the PP group,the wound healing rates of the TYX-L group,the TYX-M group and the TYX-H group increased on the 14th day of treatment(P<0.05).On the 7th day of treatment,the expression of IL-1β in the TYX-M group was lower than that in the PP group and the Model group(P<0.05),and the p-IκBα/IκBα ratio in the TYX-H group was lower than that in the PP group and the model group(P<0.05).The nuclear translocation rates of p65 in the TYX-L group,TYX-M group and TYX-H group were lower than those in the PP group and model group(P<0.05).On the 14th day of treatment,the p-p65/p65 ratio in the TYX-H group and the TYX-M group was lower than that in the model group(P<0.05),and the IL-1β in the TYX-L group,the TYX-M group,and the TYX-H group and p-IκBα/IκBα ratio in the TYX-H group were lower than those in the PP group and the model group(P<0.05).Conclusion The mechanism of TYX lotion in promoting the healing of infected wounds was associated with the suppression of the activation of NF-κB signaling pathway and alleviation of inflammatory responses.

By extracting quantitative radiomic features from regions of interest in medical images and correlating them with the biological features and heterogeneity of tumors, radiomics can provide critical information and a basis for personalized precision diagnosis and treatment. Peritumoral regions contain a wealth of microbiological information. Therefore, chest CT peritumoral radiomics, which can provide quantitative non-invasive assessment for patients with non-small cell lung cancer (NSCLC) by mining the deep heterogeneity of peritumoral regions, has broad prospects for future clinical applications. Given the rapid progress in computer and medical big data techniques, as well as the in-depth efforts in multi-center, high-quality, and large-sample data in the future, it is reasonably believed that radiomics research will be gradually normalized and reproducible. This is conducive to the translation and application of radiomics research to clinical practice, thus laying a foundation for personalized and accurate diagnosis, treatment, and follow-up for lung cancer patients.

Objective To explore the value of shear wave elastography(SWE)in the early assessment of hepatic and renal fibrosis in patients with metabolic associated fatty liver disease(MAFLD).Methods A total of 52 MAFLD patients admitted to the Second Affiliated Hospital of Wenzhou Medical University from July 2023 to May 2024 were selected as MAFLD group,and 40 non-MAFLD patients treated during the same period were served as control group.General information,laboratory data and ultrasound data were collected and compared between two groups.The differences as well as the correlation of the indicators between two groups were compared.The value of SWE in hepatic fibrosis and renal fibrosis in MAFLD patients was assessed.Results Liver function indicators,uric acid and aspartate aminotransferase-to-platelet ratio index(APRI)in MAFLD group were higher than those in control group(P＜0.01);There were no statistically significant differences between two groups in fibrosis 4 index,estimated glomerular filtration rate,serum creatinine and blood urea nitrogen(P＞0.05).The brightness of the liver,liver-kidney ratio,and liver elasticity value were higher in MAFLD group than those in control group(P＜0.05);There was no significant difference in the elasticity value of the right renal cortex between two groups(P＞0.05).Liver elasticity values was positively correlated with alanine aminotransferase(ALT);The liver-kidney ratio was positively correlated with body mass index(BMI),ALT,aspartate aminotransferase,alkaline phosphatase,y-glutamyl transferase and APRI.No significant correlation was found between the right renal cortex elasticity and BMI,estimated glomerular filtration rate,serum creatinine,blood urea nitrogen,or serum uric acid.Conclusion SWE helps in early identification of liver hardness in the MAFLD patients.But the application of SWE in early renal fibrosis in the MAFLD patients needs further evaluation.

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.

Objective To investigate the impact of type 2 inflammation markers blood eosinophils(EOS)and fractional exhaled nitric oxide(FeNO)on bronchodilator responsiveness(BDR)in patients with chronic obstructive pulmonary disease(COPD).Methods This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October,2019 to October,2023,who all underwent bronchial dilation test(BDT)of the large and small airways.Based on smoking history,blood EOS,and FeNO,these patients were divided group A(blood EOS<300/μL+FeNO<35 ppb+smoking history<20 pack-years),group B(blood EOS<300/μL+FeNO<35 ppb+smoking history≥20 pack-years),group C(blood EOS≥300/μL or FeNO≥35 ppb+smoking history≥20 pack-years),and group D(blood EOS≥300/μL or FeNO≥35 ppb+smoking history<20 pack-years)for analyzing the relationship between clinical indexes and BDR.Results BDR evaluation based on forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),and maximum mid-expiratory flow(MMEF)yielded consistent results,all showing a younger mean age,higher FeNO levels,and higher blood EOS counts and percentages in patients positive for BDT(P<0.05).The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D.The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D.In the overall patients,age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF(P<0.05).Conclusion Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients,and their clinical significance needs further investigation.

Objective To explore the mechanism of Tongyangxiao Lotion(TYX)for promoting wound healing following surgery for anal fistula.Methods The active ingredients and drug targets of TYX were explored using TCMSP and BATMAN databases,and the targets associated with wound healing were screened using GeneCards and OMIM databases;the intersecting drug and wound-related targets were analyzed with protein-protein interaction(PPI)analysis and GO and KEGG enrichment analyses.In 25 SD rat models with simulated anal fistula surgery,the effect of wound dressing with TYX at low,medium and high doses(once daily for 14 days)on wound healing were assessed in comparison with potassium permanganate(PP)solution.The granulation tissues collected from the wounds were examined for pathological changes with HE staining and for TNF-α expression using immunohistochemistry.The expressions of 1β,TNF-α,IL-6 mRNA and proteins in the granulation tissue were detected using RT-qPCR,Western blotting or ELISA.Results Network pharmacology analysis yielded 156 common targets between TYX and wound healing,and among them IL-1β,TNF-α,and IL-6 were identified as potential targets of TYX for promoting wound healing.Six core components of TYX were capable of binding to IL-1β,TNF-α,and IL-6 with binding energies all below-6.0 Kcal/mol.In the rat models,the wounds with TYX and PP solution dressing showed significantly reduced inflammatory cell infiltration and increased fibroblasts and collagen deposition.TYX at the 3 doses and PP solution all significantly reduced the expressions of IL-6,IL-1β,TNF-α mRNA and IL-6 protein in the granulation tissues,but TYX at the medium and high doses produced significantly stronger effects than PP solution for lowering TNF-α protein expression and mRNA expressions of TNF-α and IL-6.Conclusion TYX accelerates wound healing by down-regulating the inflammatory factors and reducing inflammation in the wounds.