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 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.

BACKGROUND:Some patients with cervical spondylosis have not been fully corrected sagittal position balance after cervical surgery,and this continuous sagittal position imbalance may be an important reason for the poor long-term clinical outcome of patients. OBJECTIVE:To analyze the correlation between the cervical sagittal position balance parameters and their changes and the clinical efficacy of patients in the unbalanced state after anterior cervical decompression and fusion and to explore the necessity of surgical correction of sagittal balance in order to improve the clinical effect in the later stage. METHODS:A retrospective analysis was performed on 125 patients with cervical spondylosis who underwent anterior cervical decompression and fusion in the Department of Spinal Surgery of Affiliated Hospital of Southwest Medical University from July 2019 to July 2022.Follow-up patients had good postoperative recovery(neck disability index score less than 10%one week after surgery)and had complete follow-up data.According to the axial vertical distance(C2-7 SVA)in sagittal position one week after surgery,patients were divided into type I imbalance group(C2-7 SVA loss≤5 mm,n=27),type Ⅱ imbalance group(C2-7 SVA loss>5 mm,and≤10 mm,n=19),and type Ⅲ imbalance group(C2-7 SVA loss>10 mm,n=12),and non-unbalanced group(C2-7 SVA in the normal range,n=67).The changes of visual analog scale score and neck disability index were compared among groups postoperatively and the last follow-up,as well as the changes of imaging sagittal balance parameters C2-7 cobb angle,C2-7 SVA value,neck inclination angle,T1 inclination angle,and thoracic entrance angle.The correlation between the late clinical effect and postoperative cervical sagittal disequilibrium was explored. RESULTS AND CONCLUSION:(1)There was no statistical difference in general data among the four groups(P>0.05).All patients underwent successful surgery without serious complications and postoperative wound infection.The follow-up time was more than 1 year.(2)There was no significant difference in preoperative symptom score and clinical efficacy one week after surgery(P>0.05).At the last follow-up,pain visual analog scale score,neck disability index and C2-7 SVA were lower than those before surgery but higher than those one week after surgery(P<0.05).C2-7 cobb angle was increased compared with those before operation(P<0.05).T1 inclination angle was decreased compared with those before operation(P<0.05).(3)Pearson correlation test showed that the change of neck disability index was positively correlated with the change of C2-7 SVA(P<0.05).(4)It is indicated that anterior cervical decompression and fusion is effective in the treatment of cervical spondylosis,and can effectively relieve the symptoms of patients.Patients with more severe cervical sagittal disequilibrium after surgery had worse curative effect in the later period.Continuous sagittal disequilibrium in patients with cervical spondylosis after surgery is an important cause of poor curative effect in the later stage.Clinicians should pay more attention to the correction of cervical sagittal balance before and during surgery,formulate surgical strategies and plans according to sagittal balance parameters before surgery,and correct C2-7 SVA intraoperatively to the normal range.

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 factors influencing the pregnancy rate after fallopian tube recanalization(FTR),and to construct and validate a nomogram prediction model.Methods The clinical data of a total of 322 female patients with tubal obstructive infertility,who received FTR at the Wuhan Municipal Third Hospital of China between January 2018 and December 2022,were retrospectively analyzed.According to whether the female patient had natural pregnancy or not within 12 months after FTR treatment,the female patients were divided into the pregnant group and the non-pregnant group.Logistic regression analysis was used to determine the independent factors influencing pregnancy.The female patients were randomly divided into training group and validation group at 1∶1 ratio.A nomogram model was constructed in the training group,and the predictive efficacy of the model was verified in the validation group by using receiver operating characteristic(ROC)curves,calibration curves and decision curve analysis(DCA).Results The natural pregnancy rate at one year after FTR was 45.34％(146/322).Age＞35 years,primary infertility,duration of infertility＞3 years,distal fallopian tube obstruction,and moderate to severe tubal lesion were the independent risk factors affecting the pregnancy rate after FTR(all P＜0.05).The constructed nomogram model had a good differentiation and calibration ability and it carried a high degree of clinical utility.Conclusion The nomogram model constructed in this study can effectively predict the risk of infertility within one year after FTR treatment,which is helpful for formulating the individualized therapeutic scheme for infertility female patients.

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.