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.

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.

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 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.