Objective To investigate the impact of minocycline(MC)on myocardial cell damage in rats with chronic heart failure(CHF)by regulating the hypoxia-inducible factor 1α(HIF-1α)/B-cell lymphoma-2/adenovirus E1B 19-kDa interacting protein(BNIP3).Methods All rats were randomly divided into Sham,CHF,positive drug(LP),low dose MC,high dose MC(HMC),and HMC+HIF-1α activator(DMOG)groups.Cardiac function was detected using echocardiography.HE staining,transmission electron microscopy,and TUNEL assay were used to evaluate myocardial pathology and apoptosis.Enzyme-linked immunosorbent assay was applied to quantify tumor necrosis factor α(TNF-α),interleukin-1β,superoxide dismutase(SOD),and malondialdehyde(MDA).Quantitative real-time PCR was used to detect the mRNA levels of Bcl-2 and Bcl-2-related X protein(Bax),while Western blotting was applied to detect the expres-sion of HIF-1α,BNIP3,Beclin-1,and microtubule-associated protein 1 light chain 3(LC3)proteins.Results Compared to rats in the sham group,rats from the CHF group exhibited increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),cell apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,and LC3Ⅱ/Ⅰwith decreased left ventricular ejection fraction(LVEF),left ventricular shortening fraction(LVFS),SOD,and Bcl-2 levels(P<0.05).Compared with CHF group,rats from LP group,LMC group and HMC group exhibited decreased levels of LVEDD,LVESD,apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,LC3Ⅱ/Ⅰ,and increased levels of LVEF,LVFS,SOD and Bcl-2(P<0.05).DMOG attenuated the protective effect of high-dose MC on myocardial cell damage in rats of the CHF group(P<0.05).Conclusion MC improves myocardial cell damage in rats of CHF group by inhibiting the HIF-1α/BNIP3 signaling pathway.

Objective To investigate the impact of minocycline(MC)on myocardial cell damage in rats with chronic heart failure(CHF)by regulating the hypoxia-inducible factor 1α(HIF-1α)/B-cell lymphoma-2/adenovirus E1B 19-kDa interacting protein(BNIP3).Methods All rats were randomly divided into Sham,CHF,positive drug(LP),low dose MC,high dose MC(HMC),and HMC+HIF-1α activator(DMOG)groups.Cardiac function was detected using echocardiography.HE staining,transmission electron microscopy,and TUNEL assay were used to evaluate myocardial pathology and apoptosis.Enzyme-linked immunosorbent assay was applied to quantify tumor necrosis factor α(TNF-α),interleukin-1β,superoxide dismutase(SOD),and malondialdehyde(MDA).Quantitative real-time PCR was used to detect the mRNA levels of Bcl-2 and Bcl-2-related X protein(Bax),while Western blotting was applied to detect the expres-sion of HIF-1α,BNIP3,Beclin-1,and microtubule-associated protein 1 light chain 3(LC3)proteins.Results Compared to rats in the sham group,rats from the CHF group exhibited increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),cell apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,and LC3Ⅱ/Ⅰwith decreased left ventricular ejection fraction(LVEF),left ventricular shortening fraction(LVFS),SOD,and Bcl-2 levels(P<0.05).Compared with CHF group,rats from LP group,LMC group and HMC group exhibited decreased levels of LVEDD,LVESD,apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,LC3Ⅱ/Ⅰ,and increased levels of LVEF,LVFS,SOD and Bcl-2(P<0.05).DMOG attenuated the protective effect of high-dose MC on myocardial cell damage in rats of the CHF group(P<0.05).Conclusion MC improves myocardial cell damage in rats of CHF group by inhibiting the HIF-1α/BNIP3 signaling pathway.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective:s To investigate the risk factors for delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) in patients with acute carbon monoxide poisoning (ACOP) and to develop predictive models based on machine learning algorithms.Methods:Patients with ACOP hospitalized at the First Affiliated Hospital of Zhengzhou University from August 2019 to October 2024 were included, with the occurrence of DEACMP as the outcome measure. The dataset was randomly divided into training and validation sets at a ratio of 7:3. Lasso regression was used to select features influencing the outcome in training sets. Nine machine learning models—including Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM)—were constructed. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) calculated for each model. Calibration curves were used to assess accuracy, and decision curve analysis (DCA) was applied to evaluate clinical utility. The SHapley Additive exPlanations (SHAP) method was employed to visualize and interpret the best-performing model.Results:A total of 264 ACOP patients were included, of whom 54 (20.5%) developed DEACMP. Lasso regression identified eight key feature variables. Based on these factors, predictive models were constructed, showing good AUC stability across the nine machine learning models in both training (0.92–0.99) and validation sets (0.85–0.91). The RF model performed best, with an AUC of 0.99 in the training set and 0.90 in the validation set; its calibration curve and DCA curve also demonstrated excellent performance. SHAP analysis of the RF model revealed the importance ranking of factors from highest to lowest as follows: Glasgow Coma Scale (GCS) score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, diastolic blood pressure (DBP), and drinking history.Conclusions:The RF model exhibited the highest predictive performance for DEACMP occurrence in ACOP patients. The influencing factors, ranked in order of importance from highest to lowest, are as follows: GCS score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, DBP, and drinking history.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Chronic wounds, defined as persistent failure to heal due to specific etiological factors, remain a major clinical challenge. Current standard interventions such as negative pressure wound therapy are limited by complications like hypergranulation and poor patient compliance, while emerging stem cell-based therapies carry potential tumorigenic risks. Consequently, identifying strategies to safely and effectively accelerate wound healing continues to be a critical focus in contemporary clinical research. Platelet-rich plasma derived extracellular vesicles (PRP-EVs) are extracellular vesicles released by platelets after activation. They have the characteristics of autologous origin, higher safety, and more mild and convenient clinical application. Studies have shown that PRP-EVs are rich in bioactive molecules such as lipids, proteins and RNA, which have outstanding performance in regulating wound inflammation, promoting angiogenesis, enhancing cell migration and proliferation, and are expected to become an effective tool for the treatment of chronic wounds. This review discusses the methods, mechanisms of action, and challenges associated with the use of PRP-EVs in chronic wound management, providing a foundation for future research and clinical applications in this field.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Chronic wounds, defined as persistent failure to heal due to specific etiological factors, remain a major clinical challenge. Current standard interventions such as negative pressure wound therapy are limited by complications like hypergranulation and poor patient compliance, while emerging stem cell-based therapies carry potential tumorigenic risks. Consequently, identifying strategies to safely and effectively accelerate wound healing continues to be a critical focus in contemporary clinical research. Platelet-rich plasma derived extracellular vesicles (PRP-EVs) are extracellular vesicles released by platelets after activation. They have the characteristics of autologous origin, higher safety, and more mild and convenient clinical application. Studies have shown that PRP-EVs are rich in bioactive molecules such as lipids, proteins and RNA, which have outstanding performance in regulating wound inflammation, promoting angiogenesis, enhancing cell migration and proliferation, and are expected to become an effective tool for the treatment of chronic wounds. This review discusses the methods, mechanisms of action, and challenges associated with the use of PRP-EVs in chronic wound management, providing a foundation for future research and clinical applications in this field.

Objective:By observing the loss(LORR)and recovery of righting reflex(RORR)in mice after anes-thesia and the exploration of Y-maze,explore the role of oxytocin(OXT)in promoting arousal in mice.Methods:The expression of oxytocin receptor(OXTR)in the cell bodies and tyrosine hydroxylase(TH)positive immunoreactive neu-rons in locus coeruleus(LC)was verified by immunofluorescence staining.Using the function of intraperitoneal injec-tion anesthesia and gas anesthesia,and intraperitoneal injection,intrathecal injection,and right LC single tube catheter administration,OXT or saline given as experimental group and control group,respectively,explored the time needed in the induction anesthesia period and anesthesia recovery period of mice after administration,and conducted Y-maze test on groups with statistically different anesthesia results,then explored the exploration of novel arm in Y-maze after 6,9,18 and 24 hours of RORR.Results:In LC,TH and OXTR positive neurons had double labeling.There was no differ-ence in the time of RORR after intraperitoneal injection and intrathecal injection of OXT and saline respectively,and no difference in the time of LORR and RORR after single-tube cannula administration of OXT and saline with intraperitone-al anesthesia and gas anesthesia.Compared with the control group,the recovery time of mice in the experimental group under gas anesthesia given OXT with single cannula was reduced(P＜0.05).In this group,the exploration activities of Y-maze novel arm increased after 9 hours of anesthesia recovery(P＜0.05),but there was no significant statistical difference in the exploration activities of Y-maze novel arm at 6,18 and 24 hours.Western Blot showed that compared with the control group,the expression of TH in LC in the experimental group increased significantly within 9 hours after anesthesia(P＜0.05),and then began to decrease after 9 hours(P＜0.01).Conclusion:OXT can promote the arousal of mice,and the cognitive degree of mice given OXT recovered better after waking up for 9 hours after anesthe-sia.