Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Osteoporosis and cardiovascular calcification,two major age-related chronic diseases that China is confronting today,pose serious threats to public health.Previous studies have reported overlapping connections in the pathological processes and molecular mechanisms of these two diseases,particularly concerning inflammation,oxidative stress,and dysregulation of mineral metabolism,and that these two diseases tend to share common pathogenic factors.However,research exploring the comorbidity mechanisms of the two diseases remains limited in both depth and scope,largely due to the lack of widely accepted comorbidity animal models.Herein,we analyzed the latest research findings on the comorbidity mechanisms of vascular calcification and osteoporosis,focusing on summarizing the animal disease models currently in extensive use and the relevant evaluation criteria.We aim to provide new references for comorbidity research models and offer scientific evidence for future studies on pathological mechanisms and the development of new therapeutic strategies.

Objective To systematically characterizes the temporal changes in urokinase-type plasminogen activator(uPA)over the course of neoplastic progression using a mouse oral squamous cell carcinoma(OSCC)model induced by 4-nitroquinoline-1-oxide(4-NQO).Methods A total of 65 wild-type C57BL/6 mice of 5 weeks old were randomly assigned to two groups,a 4-NQO group(n=50),which received daily administration of 100 μg/mL 4-NQO in drinking water,and a control group(n=15),which received sterile water.At 12,16,20,22,and 24 weeks,10 mice from the 4-NQO group and 3 from the control group were randomly selected,weighed,and sacrificed.Tongue tissues were collected for hematoxylin-eosin(HE)staining to preliminarily assess OSCC development,and for immunofluorescence staining and quantitative real-time PCR to evaluate dynamic uPA expression in tongue tissues during OSCC progression.Results After 16 weeks of exposure,4-NQO-treated mice exhibited significantly lower body mass compared with that of the controls(P<0.05)and the weight loss became increasingly more pronounced over time.Histopathological changes in tongue tissues progressed in a clearly time-dependent manner—hyperplasia and mild dysplasia emerged at week 12,while moderate-to-severe dysplasia and carcinoma were observed by week 22,yielding a tumorigenic rate of 25%,which escalated to 70%by week 24.Immunofluorescence and qPCR analyses demonstrated a pronounced,progressive up-regulation of uPA expression in lesional tissues as OSCC progressed(P<0.000 1).Conclusion This study not only confirmed the uniqueness of the 4-NQO model in OSCC research,but also revealed the changes in uPA during tumor invasion.These findings provide a theoretical foundation for the development of early diagnosis and precision treatment strategies,holding significant potential clinical value and research importance for improving patient prognosis.

Objective:To analyze the values of platelet transforming growth factor-β (TGF-β) and SMAD family member 2 (Smad2) in patients′ peripheral platelets for CRC diagnosis and staging.Methods:Retrospective case-control study. Tumor tissues, paratumor tissues and peripheral blood samples were collected from 248 CRC patients (147 males, 101 females; age 21-93 years) diagnosed in the First Hospital of Jilin University from October 10th, 2020, to March 10th, 2025. Peripheral blood samples were also collected from 40 colorectal adenomatous polyp patients (21 males, 19 females; age 22-74 years) and 75 healthy individuals (43 males, 32 females; age 18-81 years) during the same period. Tissue homogenates and platelets were isolated using tissue disruption and gradient centrifugation, respectively. Total RNA was respectively extracted from tissues and platelets, and the expression levels of TGF-β and Smad2 were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) expressed as relative quantity 2 -ΔΔCt. Differences of TGF-β and Smad2 expression were compared between CRC tissues and adjacent tissues, as well as among CRC patients, polyp patients, and healthy controls. The relationship of platelet TGF-β and Smad2 expression with pathological features includingtumor stage, pathological type, and metastasis were analyzed. The efficiency of platelet TGF-β, Smad2, and their combination in diagnosing CRC was evaluated using receiver operating characteristic (ROC) curves. Results:The expression levels of TGF-β and Smad2 in CRC tumor tissues[1.09 (0.45, 2.00), 2.93 (0.78, 6.73)] were significantly higher than those in adjacent tissues[0.81 (0.27, 1.50), 1.29 (0.40, 2.63)] ( Z TGF-β=4.54, Z Smad2=6.67, both P<0.001). The expression levels of TGF-β and Smad2 in platelets of CRC patients[2.73(1.53, 4.38), 3.16 (1.58, 4.38)] were significantly higher than those in the colorectal polyp group[1.23(0.70, 2.54), 1.16(0.78, 2.27)] and the healthy control group[0.96(0.51, 1.88), 0.92 (0.55, 1.88)] ( H TGF-β=59.71, H Smad2=78.74, both P<0.001). Platelet TGF-β expression increased progressively with tumor stage (stage 1-4) ( P<0.05), while platelet Smad2 levels were higher in metastatic CRC compared with non-metastatic cases ( P<0.05). ROC curve analysis showed that the area under the curve (AUC) for diagnosing CRC when combining platelet TGF-β and Smad2 was 0.81[95%Confidence interval( CI) 0.77—0.86], which was 0.90 (95% CI 0.86—0.93) if adding serum carcinoembryonic antigen (CEA). Conclusion:Platelet TGF-β and Smad2 expression correlates with the diagnosis and staging of CRC, demonstrating potential as liquid biopsy biomarkers for colorectal malignancies.

Objective To explore the communication preferences for advance care planning(ACP)among elderly hospitalized patients and to provide references for improving the ACP implementation rate.Methods Convenience sampling was used to select elderly hospitalized patients from a tertiary hospital in Wenzhou City between April and November 2023.Face-to-face surveys were conducted using a general data collection form and a self-designed questionnaire on ACP communication preferences.Mixed Logit Model,willingness-to-pay analysis,relative importance analysis,and subgroup analysis were employed to explore preferences.Results 204 questionnaires were distributed and 200 valid questionnaires were recovered,with a valid questionnaire response rate of 98.04％.The Mixed Logit Model analysis indicated that key attributes-communication timing,communication form,family participation in ACP communication,legal validity of ACP documents,and out-of-pocket costs-significantly influenced preferences(P＜0.05).Willingness-to-pay analysis showed that changes in communication timing,communication form,and family participation altered patients' willingness to pay.Relative importance analysis ranked the top 3 attributes as commu-nication timing,communication form,and family participation.Subgroup analysis revealed that gender,education level,and residence location affected preferences(P＜0.05).Conclusion Key attributes of ACP communication affect elderly hospitalized patients' preferences and willingness to pay,with variations across subgroups.Healthcare professionals should develop optimal communication programs based on patient preferences and individual characteristics.

Objective:To systematically evaluate the current status and methodological quality of guideline and consensus in ovarian stimulation for in vitro fertilization (IVF), and to provide reference for the development of future guidelines and research. Methods:A systematic search was conducted in databases including PubMed, Embase, CNKI, Wanfang, Sinomed and relevant guideline websites from inceptions to October 2024. Data were extracted from the literature that met the inclusion criteria, and methodological quality was assessed using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) tool. Descriptive analysis was performed with results presented in visual data charts.Results:A total of 23 studies were included, with 8 guidelines and 15 consensus. Totally 21 (91.3%) studies focused on the selection of ovarian stimulation protocols, with the majority concentrating on protocols for patients undergoing IVF treatment for the first cycle, and 12 (52.2%) studies focused on the selection of gonadotropin starting dosage. In terms of methodology, the average standardized scores in the 6 assessment domains of the AGREE Ⅱ tool were as follows: scope and purpose (85.1%), stakeholder involvement (66.6%), rigour of development (36.5%), clarity of presentation (70.1%), applicability (36.4%), and editorial independence (46.2%).Conclusion:Current recommendations in ovarian stimulation for IVF exhibit inconsistencies, and the methodological quality varies, which partially hinders the translation of evidence into clinical practice. Future research should further focus on the selection of ovarian stimulation protocols and gonadotropin starting dosage, promoting the update and refinement of guidelines and consensus to guide the precise treatment of ovarian stimulation.

Objective:To systematically evaluate the current status and methodological quality of guideline and consensus in ovarian stimulation for in vitro fertilization (IVF), and to provide reference for the development of future guidelines and research. Methods:A systematic search was conducted in databases including PubMed, Embase, CNKI, Wanfang, Sinomed and relevant guideline websites from inceptions to October 2024. Data were extracted from the literature that met the inclusion criteria, and methodological quality was assessed using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) tool. Descriptive analysis was performed with results presented in visual data charts.Results:A total of 23 studies were included, with 8 guidelines and 15 consensus. Totally 21 (91.3%) studies focused on the selection of ovarian stimulation protocols, with the majority concentrating on protocols for patients undergoing IVF treatment for the first cycle, and 12 (52.2%) studies focused on the selection of gonadotropin starting dosage. In terms of methodology, the average standardized scores in the 6 assessment domains of the AGREE Ⅱ tool were as follows: scope and purpose (85.1%), stakeholder involvement (66.6%), rigour of development (36.5%), clarity of presentation (70.1%), applicability (36.4%), and editorial independence (46.2%).Conclusion:Current recommendations in ovarian stimulation for IVF exhibit inconsistencies, and the methodological quality varies, which partially hinders the translation of evidence into clinical practice. Future research should further focus on the selection of ovarian stimulation protocols and gonadotropin starting dosage, promoting the update and refinement of guidelines and consensus to guide the precise treatment of ovarian stimulation.

Objective:To visualize and analyze the literature on the application of negative-pressure wound therapy (NPWT) in the field of wounds in the Web of Science core collection, and to explore the current status, frontiers, and trends of related research.Methods:The Web of Science core collection was used as the data source, and the search time period was from June 30, 2019 to June 30, 2024. Visual bibliometric analysis of the included literature was performed using VOSviewer 1.6.20 and CiteSpace 6.2.R4 for the number of publications, country and institution of publication, and keywords.Results:A total of 941 papers were included, with an increasing and then decreasing trend in the number of publications. The country with the largest number of publications was the United States (245), and although China ranked 2nd in the number of publications (208), the average number of citations in the literature was low. There was no strong cooperation network among publishing institutions. The proportion of articles published by core authors was 47.61% (448/941), with no significant core group of authors. In the past 5 years, research on NPWT in the field of wounds focused on chronic wound nursing and treatment, acute surgical incision complications and their prevention, wound closure and skin reconstruction, and risk factors for NPWT.Conclusions:The clinical application scope of NPWT has been expanded from simple wounds to complex wounds, tissue regeneration, and other fields. Researchers can carry out multi-center, large-sample, high-quality randomized controlled studies, enhance inter-institutional cooperation, and focus on interdisciplinary intersections and the formulation of NPWT care plans.

Objective To explore the communication preferences for advance care planning(ACP)among elderly hospitalized patients and to provide references for improving the ACP implementation rate.Methods Convenience sampling was used to select elderly hospitalized patients from a tertiary hospital in Wenzhou City between April and November 2023.Face-to-face surveys were conducted using a general data collection form and a self-designed questionnaire on ACP communication preferences.Mixed Logit Model,willingness-to-pay analysis,relative importance analysis,and subgroup analysis were employed to explore preferences.Results 204 questionnaires were distributed and 200 valid questionnaires were recovered,with a valid questionnaire response rate of 98.04％.The Mixed Logit Model analysis indicated that key attributes-communication timing,communication form,family participation in ACP communication,legal validity of ACP documents,and out-of-pocket costs-significantly influenced preferences(P＜0.05).Willingness-to-pay analysis showed that changes in communication timing,communication form,and family participation altered patients' willingness to pay.Relative importance analysis ranked the top 3 attributes as commu-nication timing,communication form,and family participation.Subgroup analysis revealed that gender,education level,and residence location affected preferences(P＜0.05).Conclusion Key attributes of ACP communication affect elderly hospitalized patients' preferences and willingness to pay,with variations across subgroups.Healthcare professionals should develop optimal communication programs based on patient preferences and individual characteristics.

Objective:To visualize and analyze the literature on the application of negative-pressure wound therapy (NPWT) in the field of wounds in the Web of Science core collection, and to explore the current status, frontiers, and trends of related research.Methods:The Web of Science core collection was used as the data source, and the search time period was from June 30, 2019 to June 30, 2024. Visual bibliometric analysis of the included literature was performed using VOSviewer 1.6.20 and CiteSpace 6.2.R4 for the number of publications, country and institution of publication, and keywords.Results:A total of 941 papers were included, with an increasing and then decreasing trend in the number of publications. The country with the largest number of publications was the United States (245), and although China ranked 2nd in the number of publications (208), the average number of citations in the literature was low. There was no strong cooperation network among publishing institutions. The proportion of articles published by core authors was 47.61% (448/941), with no significant core group of authors. In the past 5 years, research on NPWT in the field of wounds focused on chronic wound nursing and treatment, acute surgical incision complications and their prevention, wound closure and skin reconstruction, and risk factors for NPWT.Conclusions:The clinical application scope of NPWT has been expanded from simple wounds to complex wounds, tissue regeneration, and other fields. Researchers can carry out multi-center, large-sample, high-quality randomized controlled studies, enhance inter-institutional cooperation, and focus on interdisciplinary intersections and the formulation of NPWT care plans.