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.

Objective To explore the targets and mechanisms of Tongguanteng Injection in inhibiting the proliferation and migration of cervical cancer.Methods The biological activity of Tongguanteng Injection in inhibiting human cervical cancer SiHa cells was determined by MTT method.Detecting the effect of Tongguanteng Injection on SiHa cell migration through wound healing assay.Using network pharmacology to collect the key targets for treating cervical cancer,and perform molecular docking and enrichment analysis on the targets.Immunohistochemistry and Western blot were used to detect the key proteins to validate the network pharmacology predictions.Result Tongguanteng Injection significantly inhibited the proliferation and migration in a dose-dependent manner in human cervical cancer SiHa cells.Based on the main active ingredients of Marsdenia tenacissima,81 therapeutic targets for cervical cancer were obtained,which may treat cervical cancer by affecting key proteins such as FGF2,MAPK1,and MAPK3.Immunohistochemical results indicated that FGF2,MAPK1 and MAPK3 were expressed in cervical cancer tissues.The western bolt assays showed that Tongguanteng Injection could significantly reduce the FGF2 protein expression.Meanwhile,the MAPK1 and MAPK3 protein expressions were significantly increased.Conclusion Tongguanteng Injection may regulate the FGF2,MAPK1 and MAPK3,effectively impede the proliferation and migration of cervical cancer.

Osteoarthritis is a chronic degenerative joint disorder that adversely affects the quality of life of patients.Its pathological characteristics mainly involve the degeneration,destruction,and functional loss of articular cartilage.As one of the most crucial structures in the joint,articular cartilage is an avascular tissue composed of extracellular matrix synthesized by sparsely distributed chondrocytes.Chondrocyte apoptosis is one of the programmed cell death modalities of chondrocytes.During the normal physiological process,the proliferation and apoptosis of chondrocytes maintain a dynamic equilibrium,jointly safeguarding the homeostasis of articular cartilage.However,in the osteoarthritis process,the stimulation of related cytokines after tissue damage induces an imbalance between chondrocyte proliferation and apoptosis,resulting in excessive chondrocyte apoptosis,and subsequently leading to the degradation and degeneration of cartilage.Clinically,traditional Chinese medicine and its related therapeutic approaches remain one of the principal means for treating osteoarthritis in China.The traditional Chinese medicine,which are bioactive compounds extracted from traditional herbal medicines,has gradually gained recognition thanks to their convenient to take and remarkable therapeutic effect.Therefore,this review takes the signaling pathways involved in the inhibition of chondrocyte apoptosis by traditional Chinese medicine as the entry point,systematically retrieves and screens and summarizes relevant studies at home and abroad in the past five years,and analyzes the mechanism of action of related signaling pathways in the treatment of chondrocyte apoptosis in osteoarthritis by traditional Chinese Medicine,providing new options for the pharmacological treatment of osteoarthritis.

Objective To explore the targets and mechanisms of Tongguanteng Injection in inhibiting the proliferation and migration of cervical cancer.Methods The biological activity of Tongguanteng Injection in inhibiting human cervical cancer SiHa cells was determined by MTT method.Detecting the effect of Tongguanteng Injection on SiHa cell migration through wound healing assay.Using network pharmacology to collect the key targets for treating cervical cancer,and perform molecular docking and enrichment analysis on the targets.Immunohistochemistry and Western blot were used to detect the key proteins to validate the network pharmacology predictions.Result Tongguanteng Injection significantly inhibited the proliferation and migration in a dose-dependent manner in human cervical cancer SiHa cells.Based on the main active ingredients of Marsdenia tenacissima,81 therapeutic targets for cervical cancer were obtained,which may treat cervical cancer by affecting key proteins such as FGF2,MAPK1,and MAPK3.Immunohistochemical results indicated that FGF2,MAPK1 and MAPK3 were expressed in cervical cancer tissues.The western bolt assays showed that Tongguanteng Injection could significantly reduce the FGF2 protein expression.Meanwhile,the MAPK1 and MAPK3 protein expressions were significantly increased.Conclusion Tongguanteng Injection may regulate the FGF2,MAPK1 and MAPK3,effectively impede the proliferation and migration of cervical cancer.

Osteoarthritis is a chronic degenerative joint disorder that adversely affects the quality of life of patients.Its pathological characteristics mainly involve the degeneration,destruction,and functional loss of articular cartilage.As one of the most crucial structures in the joint,articular cartilage is an avascular tissue composed of extracellular matrix synthesized by sparsely distributed chondrocytes.Chondrocyte apoptosis is one of the programmed cell death modalities of chondrocytes.During the normal physiological process,the proliferation and apoptosis of chondrocytes maintain a dynamic equilibrium,jointly safeguarding the homeostasis of articular cartilage.However,in the osteoarthritis process,the stimulation of related cytokines after tissue damage induces an imbalance between chondrocyte proliferation and apoptosis,resulting in excessive chondrocyte apoptosis,and subsequently leading to the degradation and degeneration of cartilage.Clinically,traditional Chinese medicine and its related therapeutic approaches remain one of the principal means for treating osteoarthritis in China.The traditional Chinese medicine,which are bioactive compounds extracted from traditional herbal medicines,has gradually gained recognition thanks to their convenient to take and remarkable therapeutic effect.Therefore,this review takes the signaling pathways involved in the inhibition of chondrocyte apoptosis by traditional Chinese medicine as the entry point,systematically retrieves and screens and summarizes relevant studies at home and abroad in the past five years,and analyzes the mechanism of action of related signaling pathways in the treatment of chondrocyte apoptosis in osteoarthritis by traditional Chinese Medicine,providing new options for the pharmacological treatment of osteoarthritis.

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.