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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.

Proteins are fundamental carriers as the structural elements and biochemically active entities responsible for catalysis, transport, and regulation. These functions are depending on the protein folding into precise three-dimensional structures, interacting with ligands, and conformational changes. This article reviews the recent progress of nanopores in single-molecule protein sensing, involving the identification of polypeptides and proteins, the conformation changes of protein folding, the molecular structure responsible to the pH of solutions, the molecular interactions, and protein sequencing. These studies provide clues to understand life activities and facilitate the early diagnosis of diseases and design of drugs for precise treatment.
Nanopores ; Proteins/chemistry* ; Biosensing Techniques/methods* ; Protein Folding ; Humans

Objective To evaluate the efficiency of colored Doppler ultrasound for the differential diagnosis of benign and malignant thyroid nodules. Methods A total of 150 patients with thyroid nodules admitted to Wuwei Municipal People’s Hospital, Anhui Province, China during the period from July 2018 to December 2023 were enrolled. All patients underwent colored Doppler ultrasound of the thyroid gland and pathological examination of the thyroid nodules. The pathological examination of the thyroid nodules served as a gold standard to evaluate the value of colored Doppler ultrasound for the differential diagnosis of benign and malignant thyroid nodules. In addition, the value of different ultrasound image features for differential diagnosis of benign and malignant thyroid nodules was evaluated. Results With the pathological examination of the thyroid nodules as a gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the colored Doppler ultrasound were 100.00%, 95.87%, 85.29%, 95.87%, and 96.67% for the differential diagnosis of benign and malignant thyroid nodules. For differential diagnosis of benign and malignant thyroid nodules, a > 1 ratio of longitudinal to transverse diameters of thyroid nodules, irregular margin, and microcalcification showed a 100.00% sensitivity, irregular acoustic halos showed a 100.00% specificity, and microcalcification had the highest accuracy (98.00%). Conclusion Colored Doppler ultrasound has a high value for the differential diagnosis of benign and malignant thyroid nodules. A > 1 ratio of longitudinal to transverse diameters of thyroid nodules, irregular margin, and microcalcification provide valuable insights into the differentiation between benign and malignant thyroid nodules.

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.

AIM: To analyze and screen influencing factors of diabetic patients complicated with retinopathy, and establish and validate prediction model of nomogram.METHODS: A total of 1 252 patients from the Diabetes Complications Early Warning Dataset of the National Population Health Data Archive(PHDA)between January 2013 to January 2021 were selected and randomly divided into a modeling group(n=941)and a validation group(n=311). Univariate analysis, LASSO regression and Logistic regression analysis were used to screen out the influencing factors of diabetic retinopathy, and a nomogram prediction model was established. The receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve were used to evaluate the model. The clinical benefit was evaluated by the decision curve analysis(DCA).RESULTS: Age, hypertension, nephropathy, systolic blood pressure(SBP), glycated hemoglobin(HbA1c), high-density lipoprotein cholesterol(HDL-C), and blood urea(BU)were the influencing factors of diabetic retinopathy. The area under the curve(AUC)of the modeling group was 0.792(95%CI: 0.763-0.821), and the AUC of the validation group was 0.769(95%CI: 0.716-0.822). The Hosmer-Lemeshow goodness of fit test and calibration curve suggested that the theoretical value of the model was in good agreement(modeling group: χ2=14.520, P=0.069; validation group: χ2=14.400, P=0.072). The DCA results showed that the threshold probabilities range was 0.09-0.89 for modeling group and 0.07-0.84 for the validation group, which suggested the clinical net benefit was higher.CONCLUSION: This study constructed a risk prediction model including age, hypertension, nephropathy, SBP, HbA1c, HDL-C, and BU. The model has a high discrimination and consistency, and can be used to predict the risk of diabetic retinopathy in patients with diabetes.

Objective To evaluate the efficiency of colored Doppler ultrasound for the differential diagnosis of benign and malignant thyroid nodules. Methods A total of 150 patients with thyroid nodules admitted to Wuwei Municipal People’s Hospital, Anhui Province, China during the period from July 2018 to December 2023 were enrolled. All patients underwent colored Doppler ultrasound of the thyroid gland and pathological examination of the thyroid nodules. The pathological examination of the thyroid nodules served as a gold standard to evaluate the value of colored Doppler ultrasound for the differential diagnosis of benign and malignant thyroid nodules. In addition, the value of different ultrasound image features for differential diagnosis of benign and malignant thyroid nodules was evaluated. Results With the pathological examination of the thyroid nodules as a gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the colored Doppler ultrasound were 100.00%, 95.87%, 85.29%, 95.87%, and 96.67% for the differential diagnosis of benign and malignant thyroid nodules. For differential diagnosis of benign and malignant thyroid nodules, a > 1 ratio of longitudinal to transverse diameters of thyroid nodules, irregular margin, and microcalcification showed a 100.00% sensitivity, irregular acoustic halos showed a 100.00% specificity, and microcalcification had the highest accuracy (98.00%). Conclusion Colored Doppler ultrasound has a high value for the differential diagnosis of benign and malignant thyroid nodules. A > 1 ratio of longitudinal to transverse diameters of thyroid nodules, irregular margin, and microcalcification provide valuable insights into the differentiation between benign and malignant thyroid nodules.