Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective To determine the diagnostic criteria of quantitative syndrome differentiation of toxin syndrome of diabetic kidney disease.Methods The questionnaire scale was developed through literature research and expert consultation.Points were assigned for the 5 major symptoms in 294 patients with DKD,and according to the TCM syndrome differentiation standard of toxic syndrome syndrome formulated by experts,it is divided into toxic syndrome group and non-toxic syndrome group.The symptom items were screened from the aspects of sensitivity,differentiation and representativeness by statistical method,and the weight value of the items was given by factor analysis.The threshold and the best diagnosis model were determined under the ROC curve.Finally,through the verification group data to verify the scale model,evaluate the diagnostic ability of the scale,and finally construct the diagnostic standard scale model of DKD toxin syndrome.Results 14 symptom items were selected as TCM related symptoms of DKD toxin syndrome,and the diagnostic threshold was determined to be 140.The diagnostic criteria of quantitative syndrome differentiation of DKD toxin syndrome were as follows:total score=fatigue * 10+edema * 10+turbid urine * 10+sore waist and knees * 10+dizziness * 10+tongue purple * 10+dark complexion * 9+limb numbness * 8+loose stools * 7+dry mouth * 4+dry eyes * 4+frequent urination at night * 3+abdominal distension * 3+greasy moss * 3.The degree of each item without this symptom should be multiplied by weight value by 0,mild by weight by 1,moderate by weight by 2,severe by weight by 3,and the total score≥140 could be diagnosed as toxin syndrome.The verification results showed that the sensitivity of the study group was 92.24%,the specificity was 96.19%,the Kappa value was 0.882,and the sensitivity,specificity and Kappa value of the verification group were 87.50%,96.97%and 0.836,respectively.Conclusion The standard scale of DKD toxin syndrome differentiation and diagnosis is constructed,and it has good diagnostic ability,which provides certain application value for clinical and scientific research.

Objective:To explore the latent profiles of work withdrawal behaviors of junior nurses and their relationship with workplace social capital.Methods:Using the convenience sampling method, from July to August 2023, 348 junior nurses from five Class Ⅲ and seven ClassⅡ public hospitals in Ningxia Hui Autonomous Region were selected as the research objects. They were investigated with a General Information Questionnaire, the Work Withdrawal Behavior Scale, and the Workplace Social Capital Scale. Latent profile analysis was used to explore the categories of work withdrawal behaviors of junior nurses, and the differences in workplace social capital levels among junior nurses of different categories were compared.Results:A total of 348 questionnaires were recovered online in this survey, and 342 questionnaires were valid, with a valid rate of 98.3%. The work withdrawal behaviors of 342 junior nurses could be divided into three latent profiles, including 246 junior nurses (71.9%) in the low psychological-low behavioral withdrawal group, 81 junior nurses (23.7%) in the high psychological-low behavioral withdrawal group, and 15 junior nurses (4.4%) in the high psychological-high behavioral withdrawal group. The results of the unordered multinomial Logistic regression analysis showed that gender, whether they love nursing work or not, the average number of night shifts per month, the workplace social capital, and working years were the influencing factors of the work withdrawal behaviors of junior nurses ( P<0.05) . There were statistically significant differences in the workplace social capital among the three categories of junior nurses ( H=83.82, P<0.01) . Conclusions:There are three categories of work withdrawal behaviors among junior nurses, and there are differences in workplace social capital among junior nurses of different categories. Nursing managers should intervene and support junior nurses according to the characteristics of different categories to improve their workplace social capital levels.

Objective To determine the diagnostic criteria of quantitative syndrome differentiation of toxin syndrome of diabetic kidney disease.Methods The questionnaire scale was developed through literature research and expert consultation.Points were assigned for the 5 major symptoms in 294 patients with DKD,and according to the TCM syndrome differentiation standard of toxic syndrome syndrome formulated by experts,it is divided into toxic syndrome group and non-toxic syndrome group.The symptom items were screened from the aspects of sensitivity,differentiation and representativeness by statistical method,and the weight value of the items was given by factor analysis.The threshold and the best diagnosis model were determined under the ROC curve.Finally,through the verification group data to verify the scale model,evaluate the diagnostic ability of the scale,and finally construct the diagnostic standard scale model of DKD toxin syndrome.Results 14 symptom items were selected as TCM related symptoms of DKD toxin syndrome,and the diagnostic threshold was determined to be 140.The diagnostic criteria of quantitative syndrome differentiation of DKD toxin syndrome were as follows:total score=fatigue * 10+edema * 10+turbid urine * 10+sore waist and knees * 10+dizziness * 10+tongue purple * 10+dark complexion * 9+limb numbness * 8+loose stools * 7+dry mouth * 4+dry eyes * 4+frequent urination at night * 3+abdominal distension * 3+greasy moss * 3.The degree of each item without this symptom should be multiplied by weight value by 0,mild by weight by 1,moderate by weight by 2,severe by weight by 3,and the total score≥140 could be diagnosed as toxin syndrome.The verification results showed that the sensitivity of the study group was 92.24%,the specificity was 96.19%,the Kappa value was 0.882,and the sensitivity,specificity and Kappa value of the verification group were 87.50%,96.97%and 0.836,respectively.Conclusion The standard scale of DKD toxin syndrome differentiation and diagnosis is constructed,and it has good diagnostic ability,which provides certain application value for clinical and scientific research.

Objective:To explore the latent profiles of work withdrawal behaviors of junior nurses and their relationship with workplace social capital.Methods:Using the convenience sampling method, from July to August 2023, 348 junior nurses from five Class Ⅲ and seven ClassⅡ public hospitals in Ningxia Hui Autonomous Region were selected as the research objects. They were investigated with a General Information Questionnaire, the Work Withdrawal Behavior Scale, and the Workplace Social Capital Scale. Latent profile analysis was used to explore the categories of work withdrawal behaviors of junior nurses, and the differences in workplace social capital levels among junior nurses of different categories were compared.Results:A total of 348 questionnaires were recovered online in this survey, and 342 questionnaires were valid, with a valid rate of 98.3%. The work withdrawal behaviors of 342 junior nurses could be divided into three latent profiles, including 246 junior nurses (71.9%) in the low psychological-low behavioral withdrawal group, 81 junior nurses (23.7%) in the high psychological-low behavioral withdrawal group, and 15 junior nurses (4.4%) in the high psychological-high behavioral withdrawal group. The results of the unordered multinomial Logistic regression analysis showed that gender, whether they love nursing work or not, the average number of night shifts per month, the workplace social capital, and working years were the influencing factors of the work withdrawal behaviors of junior nurses ( P<0.05) . There were statistically significant differences in the workplace social capital among the three categories of junior nurses ( H=83.82, P<0.01) . Conclusions:There are three categories of work withdrawal behaviors among junior nurses, and there are differences in workplace social capital among junior nurses of different categories. Nursing managers should intervene and support junior nurses according to the characteristics of different categories to improve their workplace social capital levels.

OBJECTIVE: Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro. METHODS: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining. RESULTS: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism. CONCLUSION Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

Objective To explore the risk factors for the prognosis of interventional treatment of multiple pelvic fractures with bleeding.Methods A total of 82 patients with multiple pelvic fractures with bleeding were selected.All patients underwent interventional treatment and were divided into a death group(n=9)and a survival group(n=73)based on their treatment prognosis.The data of the two groups were reviewed and the complications,abbreviated injury scale(AIS),Glasgow prognostic score(GPS),and injury severity score(ISS)between the two groups were compared,and multivariate logistic regression was used to explore the influencing factors of patients prognosis.Results Eighty-two patients with multiple pelvic fractures with bleeding had 9 deaths after interventional treatment,with a mortality rate of 10.98％.The univariate results showed that there were statistical differences in the mortality rate of patients with multiple pelvic fractures with bleeding after interventional treatment,as well as the time to hospital after injury,combined trauma,blood transfusion,and surgical time(P＜0.05).The total incidence of respiratory failure,shock and infection in the death group(44.44％)were higher than those in the survival group(15.07％)(P＜0.05).The AIS,ISS,and acute physiology and chronic health evaluationⅡ(APACHE Ⅱ)in the death group were higher than those in the survival group(P＜0.05);The GPS was lower than that of the survival group(P＜0.05);The multivariate logistic results showed that the time to hospital after injury,combined trauma,blood transfusion,surgical time,complications,AIS,ISS,APACHE Ⅱ and GPS were the influencing factors for the mortality rate of patients with multiple pelvic fractures with bleeding treated with intervention(P＜0.05).Conclusion The proportion of deaths in patients with multiple pelvic fractures with bleeding is often influenced by factors such as complications,time to hospital after injury,combined trauma,AIS,GPS,and ISS.However,early interventional treatment is recommended to improve the patient's treatment prognosis with minimal trauma and good results.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Objective To investigate the predictive value of heart rate(HR),C-reactive protein(CRP),amino-probrain natriuretic hormone(NT-proBNP),myoglobin(MYO)and other clinical indicators for left ventricular systolic dysfunction(LVSD)in the patients with acute myocardial infarction(AMI)after percuta-neous coronary intervention(PCI)under different body mass index(BMI)stratification.Methods A total of 353 patients with AMI admitted and treated in the First Hospital of Lanzhou University from January 2020 to December 2020 were selected as the study subjects.The Simpson method was adopted to detect the left ven-tricular ejection fraction(LVEF).The study subjects with LVEF＜0.05 were included in the LVSD group,while those with LVEF ≥0.5 were included in the control group.The AMI patients were divided into the lean/normal type(BMI＜24 kg/m2)and overweight/obese type(BMI≥24 kg/m2)according to BMI.The general data of the patients,laboratory indexes and myocardial enzyme indicators were collected.The different groups with different BMI stratifications conducted the comparison.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were adopted to analyze the predictive efficiency of differ-ent indicators.Results There were 153 cases of lean/normal type AMI,in which there were 54 cases in the LVSD group and 99 cases in the control group.Among 200 cases of overweight/obese type AMI,60 cases were in the LVSD group and 140 cases were in the control group.In the patients with lean/normal AMI,HR,CRP,NT-proBNP,MYO and cTnl levels in the LVSD group were higher than those in the control group,and the differences were statistically significant(P＜0.05).In the patients with overweight/obese type AMI,HR,CRP,NEUT,PLT and NT-proBNP levels in the LVSD group were higher than those in the control group,the age was lower than that in the control group,and the differences were statistically significant(P＜0.05).In the patients with the lean/normal type AMI,HR was the best factor for single index prediction effect,AUC was 0.701(95％CI:0.612-0.790).HR+MYO+CRP was the best factors combination of com-bination prediction for LVSD in the patients with lean/normal type AMI.AUC was 0.769(95％CI:0.690-0.849).In the patients with overweight/obese AMI,NT-proBNP was the best factor for the best effect of sin-gle indicator prediction,AUC was 0.706(95％CI:0.613-0.786);NT-proBNP+CRP was the best factor combination in the combination for predicting LVSD in the patients with overweight/obese type AMI,AUC was 0.761(95％CI:0.687-0.833).Conclusion In the patients with different BMI stratifications of AMI,the combination prediction has a better predictive effect than the single indicator.HR+MYO+CRP has the better pre-dictive effect for LVSD in the patients with lean/normal type AMI,while NT-proBNP-+CRP has better predictive effect for LVSD in the patients with overweight/obese type AMI.