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 compare the effectiveness of posterior axillary edge approach and arthroscopic assisted reduction in the treatment of Ideberg type Ⅰ and Ⅱ glenoid fracture of the scapula. METHODS: The clinical data of 26 patients with fresh Ideberg type Ⅰ and Ⅱ scapular fractures admitted between June 2021 and September 2024 who met the selection criteria were analyzed retrospectively. The patients were divided into two groups according to different treatment methods. Ten cases in the posterior axillary edge group were fixed by open reduction plate through the posterior axillary edge approach, and 16 cases in the arthroscopy group were treated with suture anchor fixation under arthroscopy. There was no significant difference in baseline data between the two groups ( P>0.05), such as gender, age, surgical side, Ideberg type, cause of injury, time from injury to operation, rotator cuff injury, and superior labrum anterior posterior (SLAP) injury, etc. The operation time and fracture healing time were recorded and compared between the two groups, and the shoulder pain was evaluated by visual analogue scale (VAS) score at 1 week, 1 month, and 3 months after operation. At 3 and 6 months after operation, the range of motion of shoulder joint in anteflexion, abduction, external rotation, internal rotation, and backward extension was evaluated, the upper limb dysfunction was evaluated by the Disability Assessment Scale of Arm, Shoulder, and Hand (DASH), and the shoulder joint function was evaluated by the Constant-Murley score. The differences between 6 months and 3 months after operation (changes) were statistically analyzed. RESULTS: Patients in both groups were followed up 11-13 months, with an average of 12.5 months. The operation time and fracture healing time in the posterior axillary edge group were significantly shorter than those in the arthroscopy group ( P<0.05). There was no complication such as wound infection, vascular and nerve injury, loss of reduction, bone nonunion, or glenohumeral instability in both groups. At 1 week after operation, the VAS score in the posterior axillary edge group was significantly higher than that in the arthroscopy group ( P<0.05); there was no significant difference in the VAS score between the two groups at 1 and 3 months after operation ( P>0.05). At 6 months after operation, the changes of shoulder joint in anteflexion, internal rotation range of motion and DASH scores in the posterior axillary edge group were significantly lower than those in the arthroscopy group ( P<0.05), while the changes of abduction, external rotation, backward extension range of motion and Constant-Murley scores were not significantly different between the two groups ( P>0.05). CONCLUSION For Ideberg type Ⅰ and Ⅱ glenoid fracture of the scapula, the posterior axillary edge approach for internal fixation has a short operation time, fast fracture healing, and is beneficial for early functional recovery; arthroscopic assisted reduction has minimal trauma and can handle joint injuries simultaneously. Both surgical procedures are safe and effective, and individualized selection should be made based on soft tissue conditions and combined injuries.
Humans ; Arthroscopy/methods* ; Scapula/surgery* ; Male ; Female ; Retrospective Studies ; Adult ; Fracture Fixation, Internal/instrumentation* ; Fractures, Bone/surgery* ; Middle Aged ; Treatment Outcome ; Bone Plates ; Suture Anchors ; Fracture Healing ; Range of Motion, Articular ; Young Adult ; Shoulder Joint/surgery* ; Operative Time

Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

Objective To investigate the predictive value of combining polygenic risk score(PRS)with the National Institutes of Health Stroke Scale(NIHSS)socre for the development of deep venous thrombosis(DVT)in patients with ischemic stroke.Methods A total of 150 patients with ischemic stroke who were hos-pitalized in Jilin Provincial People's Hospital from December 2023 to May 2024 were selected as study sub-jects.After excluding patients who did not meet the criteria,139 patients were successfully followed up and di-vided into two groups based on whether DVT occurred.PRS strategy and fluorescence in situ hybridization(FISH)technology were used to detect the mutation of the gene loci associated with the risk of venous throm-boembolism(VTE).Based on these genotype data and the effect size of single nucleotide polymorphism(SNP)loci,the PRS score of patients was calculated through the model formula.The degree of neurological impairment was evaluated by NIHSS score.Receiver operating characteristics(ROC)curve was used to ana-lyze the efficacy of PRS score,NIHSS score and their combination in predicting ischemic stroke with lower limb DVT,and clinical data related to VTE formation were collected.Results There were no statistically sig-nificant differences between the two groups in terms of gender,age,body mass index(BMI),smoking,alcohol consumption,hypertension,diabetes,D-dimer(D-D),total cholesterol(TC),triglycerides(TG),and lipopro-tein(a)[(LP(a)]levels(P＞0.05).The PRS score,NIHSS score,and Barthel index in the DVT group were significantly higher than those in the non-DVT group,and the proportion of patients with bed rest exceeding 72 h and homocysteine(Hcy)levels were also relatively higher,with statistical significance(P＜0.05).Logis-tic regression analysis showed that PRS score＞2.55,NIHSS score ≥-3 and Barthel index＜60 were inde-pendent risk factors for lower limb DVT after ischemic stroke(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of PRS score,NIHSS score and combined prediction of ischemic stroke combined with lower limb DVT were 0.655,0.747 and 0.763,respectively,and the AUC of combined predic-tion was higher than that of single prediction(P＜0.05).Conclusion PRS score combined with NIHSS score has good predictive efficacy for ischemic stroke complicated with DVT.

【Objective】 To observe the effects of early postnatal immune activation (EPIA) on social behaviors of male and female mice, and to explore the possible role of the functional state of astrocytes and microglia in this process. 【Methods】 Using lipopolysaccharide (LPS) induced EPIA mice as study subjects, mice were divided into the male-control, male-model, female-control, and female-model groups, each containing 10 mice (n=10). Behavioral tests were performed at 25 - 32 days of age, and the social behavior ability of mice was evaluated by open field test, three-chamber sociability test, and marble burying test. The expression levels of GFAP, IBA-1, TLR4, and NFκB p65 in the cortex and hippocampus were detected by Western blot (n=3). 【Results】 In behavioral tests, social index significantly decreased in LPS treatment group (F=14.907, P<0.05). The interaction effect between treatment and sex was significant in the residence time (F=5.260, P<0.05) and the number of buried marbles (F=7.788, P<0.05). LPS treatment decreased the retention time of the central region in male mice (F=4.261, P<0.05), and increased the number of buried marbles in males (F=20.645, P<0.05). Western blot results showed that LPS treatment increased the expression of GFAP protein in the hippocampus (F=50.443, P<0.05) and cortex (F=30.116, P<0.05), as well as the expression of IBA-1 protein (F=21.844. P<0.05) and TLR4 protein (F=6.215, P<0.05) in the cortex. The results of NFκB p65 showed a significant interaction between treatment and sex in the cortex (F=6.558, P<0.05), and LPS increased the expression of NFκB p65 protein in the cortex in female mice (F=16.317, P<0.05). 【Conclusions】 EPIA is sufficient to induce sex-specific autism spectrum disorder (ASD)-like behavior and enhance astroglial and microglial reactivity in mice. ASD-like behavior induced by EPIA may be related to the TLR4/NFκB signaling pathway in the cortex.

Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.

Objective To evaluate the utility of the gray zone results of syphilis-specific antibody detection by chemiluminescent microparticle immunoassay(CMIA)with S/CO values of 1-10 in routine screening for syphilis infection.Methods A total of 119 907 patients who underwent CMIA for syphilis in the hospital were retrospectively analyzed.Among them,602 patients with S/CO values of 1-10 in the evaluation results ob-tained with CMIA method for two times were included in the study.Treponema pallidum particle agglutina-tion(TPPA)test was adopted as the confirmatory test and rapid plasma reagin(RPR)was performed to as-sess the disease activity.The patients were divided into three groups(CMIA method S/CO 1-3 group 399 ca-ses,CMIA method S/CO＞3-6 group 136 cases,CMIA method S/CO＞6-10 group 67 cases)according to different intervals of S/CO values obtained with CMIA method.Then the patients were divided into two groups(0-3 years old group 399 cases,＞3 years old group 136 cases)according to their ages.The general da-ta and test results of the patients were compared between groups to analyze the differences.Results Among 119 907 patients with syphilis CMIA detection,a total of 602 cases with S/CO values of 1-10 were confirmed in the two initial screening results with CMIA method and the positive detection rate was 5.02‰.Among them,in TPPA retest,the number of cases with positive results was 186(30.9％)and 16 cases(2.7％)were suspected to be weak positive.In RPR test,the number of cases with positive was 7(1.20％).In the grouping statistics based on S/CO values of CMIA method,the positive rate of CMIA method S/CO 1-3 group in TP-PA retest was significantly lower than that of CMIA method S/CO＞3-6 group and CMIA method S/CO＞6-10 group(P＜0.05).The RPR positive rate also showed CMIA method S/CO 1-3 group significantly lower CMIA method S/CO＞6-10 group(0.3％vs.3,4.5％,P＜0.05).The S/CO of CMIA in 0-3 years old group were lower than those in＞3 years old group[1.53(1.27,2.24)vs.2.30(1.48,4.15),P＜0.05],and the positive rate of TPPA in 0-3 years old group was lower than that in＞3 years old group[0.7％vs.40.0％,P＜0.05].Conclusion The specificity of routine screening of syphilis-specific antibody in CMIA method S/CO 1-3 group is low,so TPPA is recommended to assist diagnosis.In CMIA method S/CO＞6-10 group,more than 10.0％false positives are still confirmed by TPPA reexamination,so it is suggested that the TPPA reexamination cut-off value should be 10.0-3 years old group CMIA method S/CO value is low,the TPPA positive rate is low.