ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

OBJECTIVE To investigate the improvement effects and mechanism of Zhichi suanzaoren decoction （ZSD） on hippocampal oxidative stress injury in hippocampal neurons of mice with perimenopausal insomnia. METHODS The potential targets of active ingredients in ZSD were predicted using TCMSP and TCMIP databases； the targets related to insomnia were searched through GeneCards， OMIM and DisGeNET databases； protein-protein interaction network of intersecting targets of ZSD ingredients and insomnia was constructed； Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted on key targets. Sixty mice were divided into sham operation group， model group， ZSD low-， medium-， and high-dose groups （11， 22， and 33 g/kg）， and eszopiclone group （positive control， 1 mg/kg）. Except for sham operation group， the perimenopausal insomnia model was constructed by ovariectomy （OVX） in the other groups. After successful modeling， mice in each group were gavaged with normal saline or the corresponding drug solution， once a day， for three consecutive weeks. The sleep status of mice was evaluated through the pentobarbital sodium sleep synergy experiment， and the pathological changes of hippocampal neurons and the expressions of related genes and proteins in mice were observed by HE staining， immunohistochemistry staining， immunofluorescence staining， transcriptome sequencing technology and Western blot. RESULTS The results of network pharmacology showed that there were 296 intersection targets between ZSD and perimenopausal insomnia. Protein kinase B1 （Akt1） was a key target for treating insomnia with ZSD. After administration of ZSD， the sleep latency of mice was shortened， the sleep duration was prolonged significantly， and the mean optical density value of neuron-specific nuclear protein in the hippocampal CA1 region was significantly increased （P＜0.01）. Additionally， hippocampal neuron damage in OVX mice was significantly alleviated. The results of transcriptome sequencing showed that ZSD significantly upregulated the transcriptional levels of Nfe2l2 gene in hippocampal tissue of OVX mice （P＜0.05）. After administration of ZSD， protein expressions of nuclear factor E2 related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in hippocampal tissue of OVX mice， as well as the phosphorylated Akt level， were increased significantly （P＜0.01）. CONCLUSIONS ZSD can ameliorate hippocampal oxidative stress injury of hippocampal neurons in perimenopausal insomnia mice by activating the Akt/Nrf2/HO-1 signaling pathway.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of tirzepatide for diabetes mellitus type 2 （T2DM） and long-term weight management， and provide evidence-based basis for clinical drug treatment and health insurance policy formulation. METHODS Computer searches were conducted in Embase， PubMed， the Cochrane Library， CNKI and health technology assessment （HTA） official website from their inception to October 1st 2024 to collect HTA report， systematic review/ meta-analysis and pharmacoeconomic study on tirzepatide for the treatment of T2DM or for weight management. After data extraction and quality evaluation， descriptive analysis was performed on the research results. RESULTS Totally 18 papers were included， including 14 systematic reviews/meta-analyses and 4 pharmacoeconomics studies， and no HTA report was retrieved. In terms of efficacy， most results showed that the tirzepatide 10 mg and 15 mg were significantly better than other glucagon-like peptide-1 （GLP-1） receptor agonists in reducing glycosylated hemoglobin， body weight， and waist circumference （P＜0.05）. In terms of safety， compared with other GLP-1 receptor agonists， tirzepatide did not increase the incidence of gastrointestinal-related adverse events （AE）， the incidence of AE of grade ≥3， or the incidence of severe hypoglycemia （P＞0.05）. However， tirzepatide 15 mg may significantly increased the incidence of hypoglycemia and the rate of discontinuation due to adverse reactions （P＜ 0.05）. In terms of cost-effectiveness， based on the background of foreign pharmacoeconomic studies， tirzepatide was more cost- effective compared to semaglutide and liraglutide in the treatment of T2DM or for weight management. CONCLUSIONS Tirzepatide at doses of 10 mg and 15 mg has good efficacy and safety for the treatment of T2DM and for long-term weight management. However， when using the 15 mg dose of tirzepatide， close monitoring is required due to the risk of hypoglycemia and discontinuation due to adverse reactions it may pose. Based on pharmacoeconomic studies conducted abroad results， tirzepatide exhibits economic advantages.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

Objective:To evaluate the diagnostic efficacy of B-type natriuretic peptide(BNP)combined with the Evaluation of Guidelines in Syncope Study(EGSYS)score for cardiogenic syncope(CS), and to provide evidence for rapid clinical identification of high-risk patients.Methods:We retrospectively analyzed 366 patients with syncope hospitalized in the department of cardiovascular medicine of Beijing Hospital from January 1, 2016, to December 31, 2022.Based on the international guideline diagnostic criteria, the patients were categorized into four groups: neutrally mediated reflex syncope(NMS)group, orthostatic hypotension(OH)group, cardiogenic syncope(CS)group, and syncope of unknown origin(US)group.BNP levels were measured at admission and EGSYS scores were calculated.Receiver operating characteristic(ROC)curve analysis was performed to assess the diagnostic efficacy of individual and combined indices for CS.Results:A total of 366 syncope patients were included, among which 70 patients(19.1%)were diagnosed with NMS, 25 patients(6.8%)with OH, 44 patients(12.0%)with CS, and 227 patients(62.0%)with US.Patients in the CS group had significantly higher BNP levels and EGSYS scores compared to those in the NMS, OH, and US groups(all P<0.001). The AUC of EGSYS score for diagnosing CS was 0.783(95% CI: 0.711-0.855), while the AUC of BNP level for diagnosing CS was 0.805(95% CI: 0.727-0.884). When BNP level was combined with EGSYS score, diagnostic performance was significantly improved, with the AUC increasing to 0.855(95% CI: 0.792-0.918). Conclusions:The combination of BNP and EGSYS score significantly can improve the diagnostic accuracy of cardiogenic syncope, providing a practical diagnostic strategy for the early identification of high-risk syncope patients in clinical practice.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

BACKGROUND:Overexpression of the nuclear factor I-C gene in vitro promotes the differentiation of human stem cells from apical papilla,as does the activation of the Wnt/β-catenin signaling pathway.Moreover,nuclear factor I-C regulates the Wnt/β-catenin pathway in mesenchymal stem cells.However,whether nuclear factor I-C can affect cell differentiation by activating the Wnt/β-catenin pathway inhuman stem cells from apical papilla has not been reported.OBJECTIVE:To investigate the role of nuclear factor I-C in the Wnt/β-catenin signaling pathway in regulating the differentiation of human stem cells from apical papilla.METHODS:H uman stem cells from apical papilla were cultured by the slide-covered tissue block method and lentiviral transfection overexpressing the nuclear factor I-C gene.(1)A control group,an empty viral vector group,and an overexpressed nuclear factor I-C gene group were set up.The expression ofβ-Catenin,LRP5,and TCF7L2 was detected by Western blotting.(2)The control group,empty viral vector group,overexpressed nuclear factor I-C gene group,and overexpressed nuclear factor I-C gene+DKK-1(Wnt pathway inhibitor)group were set up.Alkaline phosphatase staining and activity quantification were performed after 7 days of osteogenic induction.qPCR and Western blotting were performed to detect the expression of Runt-related transcription factor 2,dentin salivary phosphoprotein,osteocalcin mRNA,and protein after 14 days of osteogenic induction.Alizarin Red staining was used to observe the formation of mineralized nodules.RESULTS AND CONCLUSION:(1)Compared with the control and empty viral vector groups,the expression of Wnt/β-Catenin pathway-related proteins β-Catenin,LRP5,and TCF7L2 inhuman apical dentin papilla stem cells was significantly increased in the overexpressed nuclear factor I-C gene group(P＜0.01).(2)Compared with the control and empty viral vector groups,the expression of alkaline phosphatase and osteocalcin in human apical dentin papilla stem cells was significantly increased(P＜0.01);the expression levels of Runt-related transcription factor 2,dentin salivary phosphoprotein,osteocalcin mRNA and protein were significantly higher(P＜0.01),and the number of mineralized nodules was significantly increased(P＜0.01)in the overexpressed nuclear factor I-C gene group.(3)Compared with the overexpressed nuclear factor I-C gene group,the alkaline phosphatase activity and the expression of Runt-related transcription factor 2,dentin salivary phosphoprotein,osteocalcin mRNA and protein expression levels were significantly down-regulated(P＜0.05),and the number of mineralized nodules was significantly reduced(P＜0.05)in human stem cells from apical papilla of the overexpressed nuclear factor I-C gene+DKK-1 group.The results show that nuclear factor I-C can activate the Wnt/β-catenin signaling pathway in human stem cells from apical papilla and mediate the osteogenic/odontogenic differentiation of human stem cells from apical papilla.

BACKGROUND:With the aging of the population,the number of joint replacement operations is increasing,and correspondingly,the number of joint revision operations is also increasing.Qualitative and quantitative analysis of the current research status,research hotspots,and research frontiers in the field of joint revision is of great significance. OBJECTIVE:To perform visual analysis of the related literature in the field of joint revision in recent 20 years through bibliometrics,explore the research hot spots and dynamic trends in this field in order to provide a reference for further research. METHODS:Computer searches of CNKI,VIP,and WanFang Data from January 1,2003 to December 31,2022 were conducted to include relevant literature on joint revision.Duplicate data were removed using Note Express(3.9.0.9588)software.The scientific knowledge map was drawn by using CiteSpace(6.2.R6),VOS viewer(1.6.20),and Excel(2016)software on the number of papers published,the cooperative network of authors and institutions,the co-occurrence,emergence and clustering of keywords. RESULTS AND CONCLUSION:(1)A total of 1 806 articles were included.In the past 20 years,the overall trend of the annual publication volume in this field tended to be stable.(2)Analysis of the collaborative network showed that the author with the most publications and the highest intermediary centrality was Zhou Yixin;the institution with the most publications was Beijing Jishuitan Hospital,where Zhou Yixin worked,and the institution with the highest intermediary centrality was the General Hospital of the Chinese People's Liberation Army.(3)Keyword analysis showed that the research focus was mainly on hip joint,infection,rehabilitation nursing,bone defect,and prosthesis loosening.(4)The visual analysis of the literature in the field of joint revision clarifies the context for the research in this field,provides research ideas and methods for many scholars,and reveals the research trend and frontier hot spots in this field.

Objective To investigate the role of long non-coding RNA-small nucleolar RNA host gene 3(lncRNA-Snhg3)and its regulatory mechanism in the hepatic glucose metabolism of mice.Methods Adenovirus Snhg3 was over-expressed by the tail vein injection in db/db mice,and then glucose tolerance and pyruvate tolerance were meas-ured.The mRNA expression of mouse liver gluconeogenesis-related genes phosphoenolpyruvate carboxylase(Pepck)and glucose-6-phosphatase(G6pc)and stress-inducing protein 2(Sestrin2,Sesn2,a gene adjacent to Snhg3)were de-tected by RT-qPCR.The dual luciferase reporter assay was used to detect the effect of Snhg3 on the Sesn2 promoter activity in 293T cells.Results Snhg3 over-expression improved glucose tolerance and pyruvate tolerance in db/db mice.Snhg3 over-expression inhibited the mRNA of gluconeogenesis genes of Pepck(P＜0.05)and G6pc(P＜0.05),while promoted the mRNA of Sesn2(P＜0.01).Meanwhile,Snhg3 over-expression promoted Sesn2 promoter activity in 293T cells(P＜0.05).Conclusions Snhg3 improves glucose metabolism in mice by promoting Sestrin2 expression.