Targeted protein degradation via nanoparticle-based universal strategy modifies nanoparticles with antibodies and ingeniously utilizes its cellular transport characteristics. This strategy achieved targeted degradation of extracellular proteins without complex design.Image 1.

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Purpose: To intelligently diagnose whether there is bladder outlet obstruction (BOO) in female with decent detrusor contraction ability by focusing on urodynamic study (UDS) data. Materials and Methods: We retrospectively reviewed the UDS data of female patients during urination. Eleven easily accessible urinary flow indicators were calculated according to the UDS data of each patient during voiding period. Eight diagnosis models based on back propagation neural network with different input feature combination were constructed by analyzing the correlations between indicators and lower urinary tract dysfunction labels. Subsequently, the stability of diagnostic models was evaluated by five-fold cross-validation based on training data, while the performance was compared on test dataset. Results: UDS data from 134 female patients with a median age of 51 years (range, 27–78 years) were selected for our study.Among them, 66 patients suffered BOO and the remaining were normal. Applying the 5-fold cross-validation method, the model with the best performance achieved an area under the receiver operating characteristic curve (AUC) value of 0.949±0.060 using 9 UDS input features. The accuracy, sensitivity, and specificity for BOO diagnosis model in the testing process are 94.4%, 100%, and 89.3%, respectively. Conclusions The 9 significant indicators in UDS were employed to construct a diagnostic model of female BOO based on machine learning algorithm, which performs preferable classification accuracy and stability.

Objective To explore the relationship between non-high density lipoprotein cholesterol(non-HDL-C)level and leptomeningeal collateral circulation in patients with acute middle cerebral artery occlusion.Methods A total of 85 patients with first-onset acute cerebral infarction with middle cerebral artery M1 segment occlusion were enrolled.According to the results of DSA,LMC circulation was assessed by American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology Collateral Circulation Assess-ment System.All patients were assigned to better LMC circulation group(score 2～4,n = 30)and worse LMC circulation group(score 0～1,n = 55),and the levels of non-HDL-C were compared between the two groups.Results The levels of LDL-C and non-HDL-C in worse LMC circulation group were significantly higher than those of the better LMC circulation group(P = 0.026,P = 0.010).non-HDL-C was an independent risk factor for the worse LMC circulation(OR = 3.019,95%CI:1.053～8.658,P = 0.04).LMC circulatory score of patients was negatively correlated with the levels of non-HDL-C level(r =-0.228,P = 0.036).The AUC of non-HDL-C predicted for the worse LMC circulation was 0.638(95%CI:0.521～0.755,P = 0.036).Conclusions non-HDL-C in patients with acute cerebral infarction was significantly related to worse LMC circulation,and was a risk factor for worse LMC circulation.It is suggested that the higher expression of non-HDL-C could be used to predict worse LMC circulation as a serological indicator.

Objective:To explore the risk stratification value of HEART score combined with cardiac troponin (cTn) in emergency patients with chest pain.Methods:A total of 11 583 patients with chest pain who visited the Emergency Department of Zhongshan Hospital Affiliated to Fudan University from January to December 2019 were retrospectively collected. Patients who unfinished 0 h high-sensitivity cardiac troponin T (hs-cTnT) or electrocardiogram diagnosed ST-segment elevation myocardial infarction (STEMI) or lost to follow-up were excluded, and 7 057 patients were finally included. The final diagnosis of chest pain and the occurrence of major adverse cardiovascular events within 6 mon (6 m MACEs) were followed up by telephone and medical history. The HEART score of each patient was calculated by two attending physicians, and the patients were divided into the low-risk group (0-3 points), intermediate-risk group (4-6 points) and high-risk group (7-10 points) according to the final score. The risk stratification performance and safety of HEART score were observed and analyzed. A total of 1 884 patients who completed serial hs-cTnT tests were divided into groups according to HEART score (≤3 as low-risk group) and HEART score combined with serial hs-cTnT pathway (HEART score ≤3 and two hs-cTnT measurements <0.03 ng/mL as the low-risk group). The sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of each diagnostic method were calculated to compare the diagnostic performance of the two predictive values.Results:The patients were divided into 3 groups by HEART score : 2 765 (39.2%) patients in the low-risk group, 3 438 (48.7%) in the intermediate-risk group, and 854 (12.1%) in the high-risk group. The incidence of 6 m MACEs in each group was 1.2%, 18% and 55.3%, respectively. When the low-risk threshold was 2, 23.1% of patients entered the low-risk group and the incidence of 6 m MACEs was 0.9%. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive performance of the HEART score for 6 m MACEs, and the final AUC was 0.831 ( P=0.006, 95% CI: 0.819-0.843). Regarding the occurrence of NSTEMI at the time of this visit, 4 (0.8%) patients were misdiagnosed by using the HEART score alone. Combined with serial troponin detection, the diagnostic SE and NPV were both 100%; at the same time, the diagnostic SE and NPV of 6 m MACEs in patients increased from 98.1% (95% CI: 96.9%-99.1%), 97.9% (95% CI: 96.2%-99%) to 99.1% (95% CI: 97.9%-99.7%) and 98.9% (95% CI: 97.4%-99.6%), the diagnosis SE and NPV of 6 m myocardial infarction and cardiac death in patients increased from 98% (95% CI: 96%-99.2%), 98.6% (95% CI: 97%-99.4%) to 99.2% (95% CI: 97.6%-99.8%) and 99.3% (95% CI: 98.1%-99.9%). Conclusions:The HEART score can be used for risk assessment in emergency patients with chest pain, and a threshold of 2 is recommended for the low-risk group. The diagnostic performance of HEART score combined with serial cTn is better than that of HEART score alone.

Objective:To investigate the clinical characteristics of patients with acute aortic dissection (AAD) through a retrospective and observational study, and to construct an early warning model of AAD that could be used in the emergency room.Methods:The data of 11 583 patients in the Emergency Chest Pain Center from January to December 2019 were retrospectively collected from the Chest Pain Database of Zhongshan Hospital Affiliated to Fudan University. Inclusion criteria: patients with chest pain who attended the Emergency Chest Pain Center between January and December 2019. Exclusion criteria were 1) younger than 18 years, 2) no chest/back pain, 3) patients with incomplete clinical information, and 4) patients with a previous definite diagnosis of aortic dissection who had or had not undergone surgery. The clinical data of 9668 patients with acute chest/back pain were finally collected, excluding 53 patients with previous definite diagnosis of AAD and/or without surgical aortic dissection. A total of 9 615 patients were enrolled as the modeling cohort for early diagnosis of AAD. The patients were divided into the AAD group and non-AAD group according to whether AAD was diagnosed. Risk factors were screened by univariate and multivariate logistic regression, the best fitting model was selected for inclusion in the study, and the early warning model was constructed and visualized based on the nomogram function in R software. The model performance was evaluated by accuracy, specificity, sensitivity, positive likelihood ratio and negative likelihood ratio. The model was validated by a validation cohort of 4808 patients who met the inclusion/exclusion criteria from January 2020 to June 2020 in the Emergency Chest Pain Center of the hospital. The effect of early diagnosis and early warning model was evaluated by calibration curve.Results:After multivariate analysis, the risk factors for AAD were male sex ( OR=0.241, P<0.001), cutting/tear-like pain ( OR=38.309, P<0.001), hypertension ( OR=1.943, P=0.007), high-risk medical history ( OR=12.773, P<0.001), high-risk signs ( OR=7.383, P=0.007), and the first D-dimer value ( OR=1.165, P<0.001), Protective factors include diabetes( OR=0.329, P=0.027) and coronary heart disease ( OR=0.121, P<0.001). The area under the ROC curve (AUC) of the early diagnosis and warning model constructed by combining the risk factors was 0.939(95 CI:0.909-0.969). Preliminary validation results showed that the AUC of the early diagnosis and warning model was 0.910(95 CI:0.870-0.949). Conclusions:Sex, cutting/tear-like pain, hypertension, high-risk medical history, high-risk signs, and first D-dimer value are independent risk factors for early diagnosis of AAD. The model constructed by these risk factors has a good effect on the early diagnosis and warning of AAD, which is helpful for the early clinical identification of AAD patients.

Objective:To investigate the effects of preoperative mammalian target of rapamycin(mTOR )inhibitor on partial nephrectomy for renal angiomyolipoma associated with tuberous sclerosis complex (TSC-RAML).Methods:A retrospective analysis was conducted on clinical data from 13 patients who were diagnosed with TSC-RAML and treated at Peking Union Medical College Hospital between August 2019 and July 2022. This cohort included 4 males and 9 females, with ages ranging from 22 to 66 years. All patients underwent partial nephrectomy, with 2 patients requiring two-stage surgeries due to bilateral RAMLs, resulting in a total of 15 surgeries being performed. Preoperative mTOR inhibitors, specifically everolimus (10 mg/d) or sirolimus (2 mg/d), were administered orally for at least 3 months prior to 7 of the surgeries. The effects of mTOR inhibitors on tumor size, tumor computed tomography attenuation value (CT value), and tumor CT enhancement were evaluated. The comparison of surgery-related clinical parameters was conducted between patients who received preoperative mTOR inhibitors and those who did not to assess the influences of mTOR inhibitors on surgery.Results:Compared to the baseline tumor, there was a significant reduction in tumor diameter after mTOR treatment [(6.4±3.1) cm vs. (8.7±3.9)cm], as well as in the CT value in both the unenhanced phase[(-18.63±48.73)HU vs. (-2.13±51.58)HU] and corticomedullary phase[(13.25±64.01)HU vs. (47.25±66.99)HU]. Additionally, tumor CT enhancement also decreased as compared with that before treatment [(31.88±18.20)HU vs. (49.38±20.63)HU]. Patients who received preoperative mTOR inhibitor showed a trend towards shorter operative time for removing per milliliter of tumor compared to those without preoperative mTOR inhibitor [1.06(0.18, 2.40) min/ml vs. 1.98(0.39, 5.03) min/ml] and so was the renal artery clamping time [0.17(0.03, 0.79) min/ml vs. 0.34(0.10, 1.71) min/ml]. Additionally, the amount of intraoperative bleeding for removing per milliliter of tumor was lower in patients with preoperative mTOR inhibitors compared to those without [0.72(0.19, 0.88) ml/ml vs. 1.69(0.59, 4.54) ml/ml].Conclusions:The administration of mTOR inhibitors before partial nephrectomy in patients with TSC-RAM have the potential to reduce tumor size and blood supply, as well as operative time, renal artery clamping time and intraoperative bleeding, which might contribute to surgery safety and preservation of renal function.

Objective:To explore the self-conscious health status and related influencing factors of greenhouse agricultural workers in Beijing suburb, so as to provide scientific basis for developing strategies to improve and promote the occupational health conditions of those workers.Methods:According to the production characteristics and scale of the main agricultural districts or counties in the suburb of Beijing, 182 agricultural production personnel were randomly selected to investigate the general situation, occupational situation and self-conscious health status during June 2018 to December 2019. The relevant factors which may affect the self-conscious health conditions were also analyzed by statistical methods.Results:The detection or reported rate of self-conscious health problems was 51.6% (94/182) , among which 29.1% (53/182) workers reported musculoskeletal disorder diseases and 21.4% (39/182) workers reported nervous system diseases. And the self-conscious health status of greenhouse agricultural workers were statistically different in household registration, gender, marital status, working years, mixing or spraying pesticides, smoking or eating in the greenhouse ( P<0.05) . Moreover, gender, mixing or spraying pesticide, eating and smoking behavior in the workplace all had an impact on the risk of self-conscious health status of greenhouse agricultural workers ( P< 0.05) . Specifically, male is the protective factor to reduce the occurrence of self-conscious symptoms of greenhouse agricultural workers ( OR=0.447, 95% CI: 0.234~0.852) , while mixing or spraying pesticides and smoking or eating behaviors in the workplace are the risk factors ( OR=1.055, 2.524; 95% CI: 0.503~2.210, 1.107~5.755) . Conclusion:Reducing pesticide use from the source thus minimize related exposure opportunities, strengthening occupational health education thus foster good hygienic habits and improve individual protection consciousness are of great significance for the health protection of greenhouse agricultural workers in Beijing suburb.

Objective:To explore the self-conscious health status and related influencing factors of greenhouse agricultural workers in Beijing suburb, so as to provide scientific basis for developing strategies to improve and promote the occupational health conditions of those workers.Methods:According to the production characteristics and scale of the main agricultural districts or counties in the suburb of Beijing, 182 agricultural production personnel were randomly selected to investigate the general situation, occupational situation and self-conscious health status during June 2018 to December 2019. The relevant factors which may affect the self-conscious health conditions were also analyzed by statistical methods.Results:The detection or reported rate of self-conscious health problems was 51.6% (94/182) , among which 29.1% (53/182) workers reported musculoskeletal disorder diseases and 21.4% (39/182) workers reported nervous system diseases. And the self-conscious health status of greenhouse agricultural workers were statistically different in household registration, gender, marital status, working years, mixing or spraying pesticides, smoking or eating in the greenhouse ( P<0.05) . Moreover, gender, mixing or spraying pesticide, eating and smoking behavior in the workplace all had an impact on the risk of self-conscious health status of greenhouse agricultural workers ( P< 0.05) . Specifically, male is the protective factor to reduce the occurrence of self-conscious symptoms of greenhouse agricultural workers ( OR=0.447, 95% CI: 0.234~0.852) , while mixing or spraying pesticides and smoking or eating behaviors in the workplace are the risk factors ( OR=1.055, 2.524; 95% CI: 0.503~2.210, 1.107~5.755) . Conclusion:Reducing pesticide use from the source thus minimize related exposure opportunities, strengthening occupational health education thus foster good hygienic habits and improve individual protection consciousness are of great significance for the health protection of greenhouse agricultural workers in Beijing suburb.