Nanomaterials can be used in drug delivery systems to enhance drug targeting and efficacy, and reduce adverse reactions. At the same time, they can also be used in tissue engineering and regenerative medicine to promote bone tissue repair and regeneration. Nanozymes are special nanomaterials with the catalytic activity of biological enzymes, which can mediate efficient biochemical reactions and provide a new strategy for the diagnosis and treatment of orthopaedic diseases. In the treatment of tendon-related diseases, the enzymatic nanohybrid encapsulated by extracellular vesicles can effectively mimic catalase to remove reactive oxygen species, continuously release zinc ions, and induce immune regulation through extracellular vesicles. It can significantly promote functional recovery and matrix reconstruction, restore tendon morphology, and inhibit scar formation and adhesion around the tendon. In the treatment of bone and joint diseases, photothermal nanozymes with bionic characteristics can generate thermal energy under near-infrared radiation, enhance joint lubrication performance, reduce cartilage wear in early osteoarthritis, effectively remove reactive oxygen species and reactive nitrogen species, increase the production of hyaluronic acid inside and outside the cells, and help to restore the lubrication and function of articular cartilage. Hollow Prussian blue nanoenzyme prepared by template-free hydrothermal synthesis can inhibit osteoclast formation and bone resorption, inhibit intracellular reactive oxygen species production and mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways, thereby improving osteoporosis. In the treatment of spinal diseases, Prussian blue nanozymes can not only remove excessive reactive oxygen species, maintain the normal Redox level of nucleus pulposus cells, but also escape lysosomal phagocytosis, achieve more effective mitochondrial targeting, and effectively alleviate intervertebral disc degeneration.

Objective To investigate the efficacy and safety of Linggui Qihua No.2 Prescription(LGQH2)in patients with heart failure with preserved ejection fraction(HFpEF).Methods Totally 60 HFpEF patients were randomly divided into experimental group and control group according to random number table method,with 30 patients in each group.On the basis of standardized treatment for heart failure,the experimental group was given LGQH2 granules,13 g/time,twice a day,orally;the control group was given placebo granules of LGQH2,with the same administration method as the experimental group.The treatment course for both groups was 4 weeks.6-minute walking distance(6MWD),Kansas City Cardiomyopathy Questionnaire(KCCQ)score,TCM syndrome score and serum NT-proBNP levels.Echocardiography was used to detect the ratio of early diastolic blood flow velocity(E)at the mitral valve to early diastolic myocardial motion velocity(e')at the mitral annulus,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD)and interventricular septal thickness(IVST).Adverse reactions and events were also recorded.Results Compared with before treatment,both groups showed significant improvement in 6MWD,KCCQ score,TCM syndrome score,serum NT proBNP,and E/e'after treatment(P<0.05),and there was no statistical significance in LAD,LVEDD and IVST between the two groups(P>0.05);after treatment,the experimental group showed better improvement in 6MWD,KCCQ score,TCM syndrome score and E/e'compared to the control group(P<0.05).During the research process,neither group of patients experienced any adverse reactions or events.Conclusion LGQH2 Prescription can effectively enhance exercise tolerance and cardiac function of HFpEF patients,alleviate symptoms,improve quality of life,and inhibit diastolic dysfunction of the heart,without notable adverse reactions.

Objective:Exploring the efficacy and safety of the combination of programmed cell death protein 1 (PD-1) inhibitors with chemotherapy for the treatment of local recurrence at the primary tumor site of esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy.Methods:Seventy-six patients with local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy, who were treated at the Cancer Hospital Affiliated with Nanjing Medical University from January 2019 to January 2024. All patients received treatment with a PD-1 inhibitor combined with chemotherapy, and the short-term efficacy, long-term efficacy, and adverse reactions were observed. Univariate and multivariate Cox regression models were employed to identify the factors influencing overall survival (OS) and after-recurrence survival (ARS).Results:Among the 76 patients, 7 achieved partial response, 35 had stable disease, and 34 experienced progressive disease. The objective response rate was 9.2% (7/76), and the disease control rate was 55.3% (42/76). With a median follow-up time of 23.1 months, 33 out of 76 patients died. The median survival time was 38.5 months (95% CI: 29.6-47.3 months); the 1-year, 2-year, and 3-year OS were 94.5%, 66.6%, and 51.7%, respectively. The median ARS was 14.7 months (95% CI: 10.4-19.1 months); the 6-month, 12-month, and 24-month ARS were 85.8%, 59.6%, and 25.7%, respectively. Univariate analysis showed that the initial radiation dose, the Eastern Cooperative Oncology Group (ECOG) performance status of patients after recurrence, the recurrence-free interval (RFI), and the approach to chemotherapy treatment following local esophageal recurrence were factors affecting OS and ARS ( P＜0.05). Multivariate analysis showed that initial radiotherapy dose ( HR=0.268, 95% CI: 0.100-0.720), the ECOG performance status after recurrence ( HR=4.106, 95% CI: 1.228-13.728), and RFI ( HR=0.248, 95% CI: 0.106-0.582) were independent prognostic factors for OS. Additionally, the initial radiation dose ( HR=0.289, 95% CI: 0.098-0.853) and the ECOG performance status after recurrence ( HR=5.143,95% CI:1.404-18.838) were independent prognostic factors for ARS. The incidence of treatment-related adverse-reactions was 85.5% (65/76). Grade 3 or higher treatment-related adverse reactions primarily included anemia in 4 cases, leukopenia in 8 cases, neutropenia in 9 cases, thrombocytopenia in 2 cases, liver function abnormalities in 4 cases, and elevated troponin T in 2 cases. There were no cases of treatment-related mortality. Conclusions:The combination of PD-1 inhibitors with chemotherapy is safe and effective for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy and can provide survival benefits for patients. This approach can be considered as a therapeutic option for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy.

Objective To develop a core outcome set(COS)for clinical effectiveness trials of heart failure with preserved ejection fraction(HFpEF).Methods Outcome measures were collected through database literatures search,clinical experts questionnaire survey and semi-structured patients interview.Then,the outcome measures pool was constructed and domains were divided.Candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,a consensus meeting was held to determine COS and reach a consensus.Results A total of 317 outcome measures which could be divided into 6 domains were collected through literature research,questionnaire survey and semi-structured interview.15 candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,the consensus meeting reached consensus on a COS with 6 entries.Conclusion In this study,a COS for clinical effectiveness trials of HFpEF was developed,which is conducive to the standardization of efficacy evaluation.

Nanomaterials can be used in drug delivery systems to enhance drug targeting and efficacy, and reduce adverse reactions. At the same time, they can also be used in tissue engineering and regenerative medicine to promote bone tissue repair and regeneration. Nanozymes are special nanomaterials with the catalytic activity of biological enzymes, which can mediate efficient biochemical reactions and provide a new strategy for the diagnosis and treatment of orthopaedic diseases. In the treatment of tendon-related diseases, the enzymatic nanohybrid encapsulated by extracellular vesicles can effectively mimic catalase to remove reactive oxygen species, continuously release zinc ions, and induce immune regulation through extracellular vesicles. It can significantly promote functional recovery and matrix reconstruction, restore tendon morphology, and inhibit scar formation and adhesion around the tendon. In the treatment of bone and joint diseases, photothermal nanozymes with bionic characteristics can generate thermal energy under near-infrared radiation, enhance joint lubrication performance, reduce cartilage wear in early osteoarthritis, effectively remove reactive oxygen species and reactive nitrogen species, increase the production of hyaluronic acid inside and outside the cells, and help to restore the lubrication and function of articular cartilage. Hollow Prussian blue nanoenzyme prepared by template-free hydrothermal synthesis can inhibit osteoclast formation and bone resorption, inhibit intracellular reactive oxygen species production and mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways, thereby improving osteoporosis. In the treatment of spinal diseases, Prussian blue nanozymes can not only remove excessive reactive oxygen species, maintain the normal Redox level of nucleus pulposus cells, but also escape lysosomal phagocytosis, achieve more effective mitochondrial targeting, and effectively alleviate intervertebral disc degeneration.

Objective To develop a core outcome set(COS)for clinical effectiveness trials of heart failure with preserved ejection fraction(HFpEF).Methods Outcome measures were collected through database literatures search,clinical experts questionnaire survey and semi-structured patients interview.Then,the outcome measures pool was constructed and domains were divided.Candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,a consensus meeting was held to determine COS and reach a consensus.Results A total of 317 outcome measures which could be divided into 6 domains were collected through literature research,questionnaire survey and semi-structured interview.15 candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,the consensus meeting reached consensus on a COS with 6 entries.Conclusion In this study,a COS for clinical effectiveness trials of HFpEF was developed,which is conducive to the standardization of efficacy evaluation.

Objective To investigate the efficacy and safety of Linggui Qihua No.2 Prescription(LGQH2)in patients with heart failure with preserved ejection fraction(HFpEF).Methods Totally 60 HFpEF patients were randomly divided into experimental group and control group according to random number table method,with 30 patients in each group.On the basis of standardized treatment for heart failure,the experimental group was given LGQH2 granules,13 g/time,twice a day,orally;the control group was given placebo granules of LGQH2,with the same administration method as the experimental group.The treatment course for both groups was 4 weeks.6-minute walking distance(6MWD),Kansas City Cardiomyopathy Questionnaire(KCCQ)score,TCM syndrome score and serum NT-proBNP levels.Echocardiography was used to detect the ratio of early diastolic blood flow velocity(E)at the mitral valve to early diastolic myocardial motion velocity(e')at the mitral annulus,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD)and interventricular septal thickness(IVST).Adverse reactions and events were also recorded.Results Compared with before treatment,both groups showed significant improvement in 6MWD,KCCQ score,TCM syndrome score,serum NT proBNP,and E/e'after treatment(P<0.05),and there was no statistical significance in LAD,LVEDD and IVST between the two groups(P>0.05);after treatment,the experimental group showed better improvement in 6MWD,KCCQ score,TCM syndrome score and E/e'compared to the control group(P<0.05).During the research process,neither group of patients experienced any adverse reactions or events.Conclusion LGQH2 Prescription can effectively enhance exercise tolerance and cardiac function of HFpEF patients,alleviate symptoms,improve quality of life,and inhibit diastolic dysfunction of the heart,without notable adverse reactions.

Objective:Exploring the efficacy and safety of the combination of programmed cell death protein 1 (PD-1) inhibitors with chemotherapy for the treatment of local recurrence at the primary tumor site of esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy.Methods:Seventy-six patients with local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy, who were treated at the Cancer Hospital Affiliated with Nanjing Medical University from January 2019 to January 2024. All patients received treatment with a PD-1 inhibitor combined with chemotherapy, and the short-term efficacy, long-term efficacy, and adverse reactions were observed. Univariate and multivariate Cox regression models were employed to identify the factors influencing overall survival (OS) and after-recurrence survival (ARS).Results:Among the 76 patients, 7 achieved partial response, 35 had stable disease, and 34 experienced progressive disease. The objective response rate was 9.2% (7/76), and the disease control rate was 55.3% (42/76). With a median follow-up time of 23.1 months, 33 out of 76 patients died. The median survival time was 38.5 months (95% CI: 29.6-47.3 months); the 1-year, 2-year, and 3-year OS were 94.5%, 66.6%, and 51.7%, respectively. The median ARS was 14.7 months (95% CI: 10.4-19.1 months); the 6-month, 12-month, and 24-month ARS were 85.8%, 59.6%, and 25.7%, respectively. Univariate analysis showed that the initial radiation dose, the Eastern Cooperative Oncology Group (ECOG) performance status of patients after recurrence, the recurrence-free interval (RFI), and the approach to chemotherapy treatment following local esophageal recurrence were factors affecting OS and ARS ( P＜0.05). Multivariate analysis showed that initial radiotherapy dose ( HR=0.268, 95% CI: 0.100-0.720), the ECOG performance status after recurrence ( HR=4.106, 95% CI: 1.228-13.728), and RFI ( HR=0.248, 95% CI: 0.106-0.582) were independent prognostic factors for OS. Additionally, the initial radiation dose ( HR=0.289, 95% CI: 0.098-0.853) and the ECOG performance status after recurrence ( HR=5.143,95% CI:1.404-18.838) were independent prognostic factors for ARS. The incidence of treatment-related adverse-reactions was 85.5% (65/76). Grade 3 or higher treatment-related adverse reactions primarily included anemia in 4 cases, leukopenia in 8 cases, neutropenia in 9 cases, thrombocytopenia in 2 cases, liver function abnormalities in 4 cases, and elevated troponin T in 2 cases. There were no cases of treatment-related mortality. Conclusions:The combination of PD-1 inhibitors with chemotherapy is safe and effective for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy and can provide survival benefits for patients. This approach can be considered as a therapeutic option for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy.

Objective:To investigate whether Lycopi Herba can serve as a viable alternative to Alismatis Rhizoma in the treatment of heart failure (HF) through network pharmacology and molecular docking techniques.Methods:TCMSP database was used to filter active components of Lycopi Herba and Alismatis Rhizoma. SwissTargetPrediction database was used to predict potential targets. HF-related targets were collected from databases such as GeneCards, OMIM, and DisGeNET. Venny 2.1.0 was used to draw a Venn diagram illustrating the intersection of targets between Lycopi Herba and Alismatis Rhizoma and HF. A protein-protein interaction (PPI) network was established using the String database, and key targets for the treatment of HF with Lycopi Herba and Alismatis Rhizoma were selected using Cytoscape 3.9.1 software to construct a component-intersection target network. The intersection targets were then analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using Metascape. Molecular docking techniques were used to evaluate the affinity between active components and key targets.Results:Lycopi Herba primarily targeted pivotal proteins such as HMGCR and CYP27B1, while Alismatis Rhizoma had a broader target spectrum, including PPARA, JAK2, among others. Shared key targets between the two included HMGCR and ESR1, which were primarily involved in cholesterol synthesis and steroid hormone biosynthesis. Enrichment pathway analysis showed similarities in steroid metabolism between the two; Alismatis Rhizoma, however, was more likely to act through protein phosphorylation regulation and modulating the PI3K-Akt signaling pathway for HF treatment. A unique target for Lycopi Herba in treating HF was CHRM4, indicating its potential for blood pressure regulation and myocardial protection.Conclusions:Both Lycopi Herba and Alismatis Rhizoma exhibit certain commonalities in the treatment of HF, but Alismatis Rhizoma has a wider range of targets and signaling pathways, implying more extensive therapeutic potential. However, considering the nephrotoxicity of Alismatis Rhizoma, Lycopi Herba could be considered as an alternative treatment for HF, especially in patients with renal insufficiency or in the early stages of HF.

Objective To evaluate the characteristics of a rat model of heart failure with a preserved ejection fraction(HFpEF)induced by combined factors,and to investigate the correlation of myocardial strain parameters to myocardial hypertrophy and fibrosis.Methods Eight WKY rats and eight spontaneously hypertensive rats(SHR)served as control groups and were fed normal feed until the end of the experiment.Thirty-two SHR rats were equally divided into SHR+S,SHR+F,SHR+SF,and SHR+Combined groups,and fed high-salt,high-fat,high-salt-fat,or high-salt-fat-sugar feed,respectively,in combination with intraperitoneal injection of streptozotocin for 30 weeks.After modeling,the heart weight/body weight(HW/BW)ratio,systolic blood pressure(SBP),and diastolic blood pressure(DBP)were measured.Echocardiography was performed to measure the left ventricular(LV)end-diastolic internal diameter(LVIDd),LV anterior wall thickness(LVAWd),LV posterior wall thickness(LVPWd),LV ejection fraction(LVEF),isovolumetric diastolic time(IVRT),and peak early diastolic passive filling velocity(E)/early diastolic mitral annular velocity(e').Speckle tracking echocardiography was conducted to determine the global longitudinal strain(GLS)and strain rate(GLSr),global radial strain(GRS)and strain rate(GRSr),as well as the global circumferential strain(GCS)and strain rate(GCSr).Serum was collected and analyzed for triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),glucose(GLU),and glycated serum protein(GSP).ELISA were used to measure serum B-type brain natriuretic peptide(BNP),angiotensin Ⅱ(AngⅡ),and galectin-3(Gal-3).Myocardial tissue was subjected to HE and Masson staining for cardiomyocytes and myocardial fibrosis,and the cardiomyocyte cross-sectional area(CSA)and collagen volume fraction(CVF)were calculated.Additionally,the correlation of myocardial strain parameters to CSA and CVF was analyzed.Results Compared with the control group,in model groups,especially the SHR+combined group,HW/BW,SBP,DBP,serum indexes(TC,TG,LDL-C,GLU,GSP,BNP,AngⅡ,and Gal-3)and echocardiographic parameters(LVIDd,LVAWd,LVPWd,IVRT,and E/e')were significantly up-regulated.Absolute values of speckle-tracking echocardiographic parameters(GLS,GLSr,GRS,GRSr,GCS,and GCSr)were decreased considerably.HE and Masson staining of myocardial tissues suggested marked cardiomyocyte hypertrophy and fibrosis,and significant increases were observed in CSA and CVF(P＜0.05).Correlation analysis showed that GLSr,GCS,and GCSr were strongly linked to CSA,and GLS,GLSr,and GCSr were strongly linked to CVF(P＜0.01).Conclusions A rat model of HFpEF induced by hypertension and dysregulation of glucolipid metabolism replicated the basic characteristics of HFpEF in terms of etiology,clinical features,and myocardial pathological changes,and might be a reliable animal model of metabolic syndrome-related HFpEF.Moreover,myocardial strain indices were closely related to myocardial hypertrophy and fibrosis and might indirectly reflect subtle myocardial lesions and dysfunction.