Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

Objective To investigate the effect of interleukin-9(IL-9)on the growth of lung adenocarcinoma in mice and its possible mechanism of action.Methods Mouse lung adenocarcinoma CMT167 cells were inoculated subcutaneously in BALB/C mice to construct a subcutaneous transplantation tumor model of mouse lung adenocarcinoma and to observe the effect of IL-9 on the growth of mouse tumors.Flow cytometry(FCM)and Western blot(WB)were used to detect the expression of IL-9 recep-tor(IL-9R)in mouse lung adenocarcinoma CMT167 cells.CMT167 cells were treated with different concentrations of IL-9 in vitro,and changes in cell viability and apoptosis were observed at different time points.Changes in the percentages of myeloid-derived immunosuppressive cells(MDSCs),CD4+T cells,and CD8+T cells in the tumor tissues of mice were analyzed by using FCM.Results Compared with mice in control group,the growth of mouse lung subcutaneous graft tumors was significantly in-hibited,and the weight of graft tumor was reduced after IL-9 treatment(both P＜0.01).Compared with the control group,the expression of IL-9R in mouse lung adenocarcinoma CMT167 cells was significantly increased(P＜0.01).After treatment with different concentrations of IL-9 in vitro,there were no significant changes in the viability and apoptosis of mouse lung adenocar-cinoma CMT167 cells compared to the control group.The number of MDSCs in mouse tumor tissues was decreased after IL-9 treatment(P＜0.05),while proportions of CD4+T cells and CD8+T cells in tumor tissues were increased(P＜0.01).Conclu-sion IL-9Reduces the number of MDSCs and increases the proportions of CD4+T cells and CD8+T cells in mouse tumor tis-sues,therefore inhibits the growth of lung adenocarcinoma tumors in mice.

Objective:To predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer based on preoperative inflammatory and immune nutritional indicators,and to construct a nomo-gram prediction model,providing a basis and tool for preoperative diagnosis of lymph node metastasis in cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 307 patients preoperatively diag-nosed with early-stage cervical cancer who underwent surgical treatment at the Obstetrics and Gynecology De-partment of the Second Affiliated Hospital of Zhengzhou University from January 2018 to July 2023.R software was used to randomize the groups into a training set(n=231)and a validation set(n=76)in a 3∶1 ratio.Uni-variate and multivariate logistic regression analyses were employed to identify factors influencing lymph node me-tastasis in patients preoperatively diagnosed with early-stage cervical cancer.R software was used to establish a nomogram prediction model and draw receiver operating characteristic(ROC)curves and calibration curves for validation.Results:① The results of univariate logistic regression analysis showed that positive lymphovascular invasion,platelet-to-lymphocyte ratio(PLR)≥151.70,neutrophil-to-white blood cell ratio(NWR)≥0.65,plate-let-to-albumin ratio(PAR)≥ 4.94,preoperative systemic immune-inflammation index(SII)≥604.03,and sys-temic inflammatory response index(SIRI)≥ 1.05 were associated with lymph node metastasis(P＜0.05).②Multivariate logistic regression analysis found that positive lymphovascular invasion,NWR≥0.65,and PAR≥4.94 were independent risk factors for lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer(OR＞1,P＜0.05).③ A nomogram was constructed to predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer.The ROC curve shows an area under the train-ing set curve(AUC)of 0.821 and a validation set AUC of 0.858.The calibration curve shows an average abso-lute error of 0.024 for the training set and 0.059 for the validation set.Conclusions:The prediction model for lymph node metastasis in cervical cancer constructed using preoperative inflammatory and immune nutritional indi-cators such as NWR,PAR is helpful for gynecological oncologists to predict lymph node metastasis in cervical cancer patients before surgery.

Objective:To predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer based on preoperative inflammatory and immune nutritional indicators,and to construct a nomo-gram prediction model,providing a basis and tool for preoperative diagnosis of lymph node metastasis in cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 307 patients preoperatively diag-nosed with early-stage cervical cancer who underwent surgical treatment at the Obstetrics and Gynecology De-partment of the Second Affiliated Hospital of Zhengzhou University from January 2018 to July 2023.R software was used to randomize the groups into a training set(n=231)and a validation set(n=76)in a 3∶1 ratio.Uni-variate and multivariate logistic regression analyses were employed to identify factors influencing lymph node me-tastasis in patients preoperatively diagnosed with early-stage cervical cancer.R software was used to establish a nomogram prediction model and draw receiver operating characteristic(ROC)curves and calibration curves for validation.Results:① The results of univariate logistic regression analysis showed that positive lymphovascular invasion,platelet-to-lymphocyte ratio(PLR)≥151.70,neutrophil-to-white blood cell ratio(NWR)≥0.65,plate-let-to-albumin ratio(PAR)≥ 4.94,preoperative systemic immune-inflammation index(SII)≥604.03,and sys-temic inflammatory response index(SIRI)≥ 1.05 were associated with lymph node metastasis(P＜0.05).②Multivariate logistic regression analysis found that positive lymphovascular invasion,NWR≥0.65,and PAR≥4.94 were independent risk factors for lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer(OR＞1,P＜0.05).③ A nomogram was constructed to predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer.The ROC curve shows an area under the train-ing set curve(AUC)of 0.821 and a validation set AUC of 0.858.The calibration curve shows an average abso-lute error of 0.024 for the training set and 0.059 for the validation set.Conclusions:The prediction model for lymph node metastasis in cervical cancer constructed using preoperative inflammatory and immune nutritional indi-cators such as NWR,PAR is helpful for gynecological oncologists to predict lymph node metastasis in cervical cancer patients before surgery.

Patients with gastric cancer are at high risk for venous thromboembolism(VTE)and bleeding,and patients who develop VTE are often associated with poor outcomes,making it clinically challenging to identify and manage the risk of thrombosis in patients with gastric cancer.Risk factors for VTE in gastric cancer patients include age,obesity,surgery,chemotherapy,etc.It is essential to identify high-risk patients and adopt aggressive prevention strategies.The main strategy to prevent and treat VTE is the use of anticoagulant drugs.This article discusses guidelines and recent studies for the prevention and treatment of VTE in patients with gastric cancer to help clinicians make individualized decisions for their patients and maximize clinical outcomes for their patients.

Patients with primary membranous nephropathy(PMN)tend to develop thrombosis,especially in the early phase of the disease.The pathogenesis of thrombosis is multifactorial,with hypoalbuminemia being widely regarded as an inde-pendent risk factor.Other factors include proteinuria,M-type phospholipase A2 receptor antibody,and D-dimer.Although prophy-lactic anticoagulation therapy is frequently used in clinical practice to prevent thrombosis in PMN patients,there are still many un-resolved issues regarding the optimal prevention of thrombosis in this condition.The timing of prophylactic anticoagulation,the threshold of serum albumin level,and the choice of treatment regimen are still lacking consensus.This article reviewed the relevant literature on these topics,aiming to establish a standard for thrombosis prevention and treatment for this population in the future and provide guidance for clinical practice.

Objective To investigate the effect and possible mechanism of microRNA-26a(miR-26a)on the syn-thesis of extracellular matrix(ECM)induced by high glucose(HG)in renal tubular epithelial cells(RTECs).Methods A model of diabetic kidney disease(DKD)was constructed by inducing RTECs with HG.MiR-26a was overexpressed in HG-induced RTECs,and RT-qPCR and Western blot were used to assess the effects of miR-26a on ECM synthesis and ferroptosis-related markers in HG-treated RTECs.Ferrostatin(Fer-1)was used to inhibit ferroptosis in the DKD model,and its impact on ECM synthesis was evaluated.RT-qPCR and Western blot were performed to measure ferroptosis-related markers,and fluorescence microscopy was used to observe the intensity of reactive oxygen species(ROS).Results Compared with the control group,the expression of miR-26a decreased in HG-treated cells,while the expression levels of ECM synthesis-related indexes fibronectin and collagen Ⅰ in-creased.After overexpressing miR-26a,the HG+miR-26a group showed a significant increase in miR-26a expres-sion and a decrease in fibronectin and collagen Ⅰ expression compared to the HG group.In terms of ferroptosis,the protein and mRNA expression of SLC7A11 and GPX4 significantly decreased,the expression of TFR-1 and AC-SL4 significantly increased,and the fluorescence intensity of ROS was significantly enhanced in the HG group com-pared with the control group.Inhibition of ferroptosis in the HG+Fer-1 group resulted in significant changes in fer-roptosis and ECM synthesis-related indicators expression levels compared to the HG group.Furthermore,re-expres-sion of miR-26a in the HG+miR-26a led to significant changes in ferroptosis-related indicators expression levels and decreased ROS fluorescence intensity compared to the HG group.Conclusions In HG-induced RTECs,miR-26a inhibits the occurrence of ferroptosis,thus reducing ECM synthesis.

Objective To investigate the association between intraoperative hypotension and post-operative acute kidney injury(AKI)in patients undergoing brain tumor resections.Methods A total of 428 patients undergoing elective craniotomy for tumor resection were selected,276 males and 152 females,aged≥18 years,BMI 15-36 kg/m2,ASA physical statusⅡ orⅢ.Based on postoperative occurrence of AKI,the patients were divided into two groups:the AKI group and the control group.This study defined three thresholds for hypotension,including MAP during surgery below 65 mmHg,60 mmHg,and 55 mmHg.Multivariate logistic regression was used to analyze the correlation between intraoperative hypotension and postoperative AKI under three thresholds.Results A total of 107 patients had postoperative AKI.The re-sults of multivariable regression analysis indicated that intraoperative MAP＜65 mmHg(OR = 1.11,95%CI 1.03-1.20,P = 0.010)and intraoperative MAP＜60 mmHg(OR = 1.12,95%CI 1.02-1.23,P = 0.017)were associated with postoperative AKI.Conclusion Intraoperative MAP＜65 mmHg or 60 mmHg is associated with postoperative AKI in patients undergoing brain tumor resection.

Objective: To assess the efficacy and safety of combining traditional Chinese medicine (TCM), specifically Chinese herbal medicine (CHM), with Western medicine (WM), compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis (BCET-OP) by meta-analysis. Methods: Thirty-eight randomized controlled trials involving 2170 participants were analyzed. Eight databases were searched for articles published between inception and December 2023. Quality assessment was performed using the Risk of Bias 2 tool. Results: Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density (BMD) (P < .001, mean difference (MD) = 0.07, 95% confidence interval (CI): 0.06 to 0.08), lumbar vertebrae T-score (P = .0005, MD = 0.21, 95%CI: 0.09 to 0.33) and collum femoris BMD (P = .01, MD = 0.10, 95%CI: 0.02 to 0.19). No significant difference was observed between the groups in the collum femoris T-score and estradiol levels. Bone gla-protein levels were significantly increased in the TCM-WM group (P = .0002, MD = 0.52, 95%CI: 0.25 to 0.79). Beta-CrossLaps decreased significantly in the TCM-WM group (P = .0008, MD = −0.10, 95%CI: −0.16 to −0.04). No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase, in procollagen type I N-terminal propeptide, and in the Kupperman index. The visual analog score (VAS) was decreased in the TCM-WM group compared to the WM group (P < .001, MD = −1.40, 95%CI: −1.94 to −0.87). No significant difference in adverse events was observed between the two groups. Conclusion Combining CHM with WM in patients with BCET-OP significantly improved BMD, T-score, and certain bone turnover markers and reduced the VAS score, indicating potential benefits for bone health and related pain. Adverse event analysis revealed no differences between the groups, supporting the feasibility of the combination therapy. However, further research, particularly in diverse populations, is required.

Objective:To predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer based on preoperative inflammatory and immune nutritional indicators,and to construct a nomo-gram prediction model,providing a basis and tool for preoperative diagnosis of lymph node metastasis in cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 307 patients preoperatively diag-nosed with early-stage cervical cancer who underwent surgical treatment at the Obstetrics and Gynecology De-partment of the Second Affiliated Hospital of Zhengzhou University from January 2018 to July 2023.R software was used to randomize the groups into a training set(n=231)and a validation set(n=76)in a 3∶1 ratio.Uni-variate and multivariate logistic regression analyses were employed to identify factors influencing lymph node me-tastasis in patients preoperatively diagnosed with early-stage cervical cancer.R software was used to establish a nomogram prediction model and draw receiver operating characteristic(ROC)curves and calibration curves for validation.Results:① The results of univariate logistic regression analysis showed that positive lymphovascular invasion,platelet-to-lymphocyte ratio(PLR)≥151.70,neutrophil-to-white blood cell ratio(NWR)≥0.65,plate-let-to-albumin ratio(PAR)≥ 4.94,preoperative systemic immune-inflammation index(SII)≥604.03,and sys-temic inflammatory response index(SIRI)≥ 1.05 were associated with lymph node metastasis(P＜0.05).②Multivariate logistic regression analysis found that positive lymphovascular invasion,NWR≥0.65,and PAR≥4.94 were independent risk factors for lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer(OR＞1,P＜0.05).③ A nomogram was constructed to predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer.The ROC curve shows an area under the train-ing set curve(AUC)of 0.821 and a validation set AUC of 0.858.The calibration curve shows an average abso-lute error of 0.024 for the training set and 0.059 for the validation set.Conclusions:The prediction model for lymph node metastasis in cervical cancer constructed using preoperative inflammatory and immune nutritional indi-cators such as NWR,PAR is helpful for gynecological oncologists to predict lymph node metastasis in cervical cancer patients before surgery.