BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

This study explores the role and underlying molecular mechanisms of fucoidan sulfate(FPS) in regulating heme oxygenase-1(Hmox1)-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy(DCM) through in vivo and in vitro experiments and network pharmacology analysis. In vivo, a DCM rat model was established using a combination of "high-fat diet feeding + two low-dose streptozotocin(STZ) intraperitoneal injections". The rats were randomly divided into four groups: normal, model, FPS, and dapagliflozin(Dapa) groups. In vitro, a cellular model was created by inducing rat cardiomyocytes(H9c2 cells) with high glucose(HG), using zinc protoporphyrin(ZnPP), an Hmox1 inhibitor, as the positive control. An automatic biochemical analyzer was used to measure blood glucose(BG), serum aspartate aminotransferase(AST), serum lactate dehydrogenase(LDH), and serum creatine kinase-MB(CK-MB) levels. Echocardiography was used to assess rat cardiac function, including ejection fraction(EF) and fractional shortening(FS). Pathological staining was performed to observe myocardial morphology and fibrotic characteristics. DCFH-DA fluorescence probe was used to detect reactive oxygen species(ROS) levels in myocardial tissue. Specific assay kits were used to measure serum brain natriuretic peptide(BNP), myocardial Fe~(2+), and malondialdehyde(MDA) levels. Western blot(WB) was used to detect the expression levels of myosin heavy chain 7B(MYH7B), natriuretic peptide A(NPPA), collagens type Ⅰ(Col-Ⅰ), α-smooth muscle actin(α-SMA), ferritin heavy chain 1(FTH1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), 4-hydroxy-2-nonenal(4-HNE), and Hmox1. Immunohistochemistry(IHC) was used to examine Hmox1 protein expression patterns. FerroOrange and Highly Sensitive DCFH-DA fluorescence probes were used to detect intracellular Fe~(2+) and ROS levels. Transmission electron microscopy was used to observe changes in mitochondrial morphology. In network pharmacology, FPS targets were identified through the PubChem database and PharmMapper platform. DCM-related targets were integrated from OMIM, GeneCards, and DisGeNET databases, while ferroptosis-related targets were obtained from the FerrDb database. A protein-protein interaction(PPI) network was constructed for the intersection of these targets using STRING 11.0, and core targets were screened with Cytoscape 3.9.0. Molecular docking analysis was conducted using AutoDock and PyMOL 2.5. In vivo results showed that FPS significantly reduced AST, LDH, CK-MB, and BNP levels in DCM model rats, improved cardiac function, decreased the expression of myocardial injury proteins(MYH7B, NPPA, Col-Ⅰ, and α-SMA), alleviated myocardial hypertrophy and fibrosis, and reduced Fe~(2+), ROS, and MDA levels in myocardial tissue. Furthermore, FPS regulated the expression of ferroptosis-related markers(Hmox1, FTH1, SLC7A11, GPX4, and 4-HNE) to varying degrees. Network pharmacology results revealed 313 potential targets for FPS, 1 125 targets for DCM, and 14 common targets among FPS, DCM, and FerrDb. Hmox1 was identified as a key target, with FPS showing high docking activity with Hmox1. In vitro results demonstrated that FPS restored the expression levels of ferroptosis-related proteins, reduced intracellular Fe~(2+) and ROS levels, and alleviated mitochondrial structural damage in cardiomyocytes. In conclusion, FPS improves myocardial injury in DCM, with its underlying mechanism potentially involving the regulation of Hmox1 to inhibit ferroptosis. This study provides pharmacological evidence supporting the therapeutic potential of FPS for DCM-induced myocardial injury.
Animals ; Ferroptosis/drug effects* ; Rats ; Diabetic Cardiomyopathies/physiopathology* ; Male ; Rats, Sprague-Dawley ; Polysaccharides/pharmacology* ; Heme Oxygenase-1/genetics* ; Myocytes, Cardiac/metabolism* ; Myocardium/pathology* ; Humans ; Cell Line ; Heme Oxygenase (Decyclizing)

The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective:To investigate the MRI characteristics of ductal lesions with microcalcifications detected by mammography,and to evaluate the value of MRI in the differential diagnosis of benign and malignant ductal lesions.Methods:The clinical data of 112 patients with pathologically confirmed ductal lesions with microcalcifications detected by mammography in our hospital from January 2022 to June 2024 were retrospectively analyzed.All patients underwent mammography and MRI examinations.MRI morphological features,dynamic enhancement characteristics,diffusion-weighted imaging(DWI)findings,and apparent diffusion coefficient(ADC)values were analyzed and compared with pathological results.The diagnostic performance of various MRI features was analyzed using ROC curves.Results:Among the 112 patients,there were 47 benign lesions and 65 malignant lesions.Malignant lesions were more likely to present with irregular morphology,heterogeneous T2 signal,lobulation,and spiculation(P＜0.05),while benign lesions were more likely to present with round or oval shapes and homogeneous T2 signal(P＜0.05).Malignant lesions predominantly showed fast rise-fast washout(Washout type)enhancement curves(58.5％),while benign lesions predominantly showed persistent rise(Progressive type)enhancement curves(55.3％).The ADC values of malignant lesions(0.92±0.21× 10-3 mm2/s)were significantly lower than those of benign lesions(1.45±0.28× 10-3 mm2/s)(P＜0.001).The combined application of morphological features,dynamic enhancement curves,and ADC values had the highest diagnostic performance,with a sensitivity of 92.3％,specificity of 89.4％,and accuracy of 91.1％.Conclusion:Multi-parameter MRI can comprehensively evaluate ductal lesions with microcalcifications detected by mammography.The combined application of morphological features,dynamic enhancement curve types,and ADC values can effectively improve the accuracy of differential diagnosis between benign and malignant lesions,providing important basis for clinical treatment decisions.

Objective:Analyze the risk factors for acute lung injury of postoperative acute lung injury(ALI)in patients with Stanford type A aortic dissection(STAAD),and construct a nomogram predictive model.Methods:A retrospective cohort study design was adopted.A total of 112 patients with STAAD who underwent surgical treatment in our hopital from January 2021 to August 2024 were included.They were divided into two groups according to the occurrence of ALI after the surgical:non-ALI group(73 cases)and ALI group(39 cases).Clinical data were collected from both groups of patients.The influencing factors of postoperative ALI in patients with STAAD were analyzed by multivariate logistic regression.Established nomogram prediction model based on influencing factors and validated.Results:Among 112 patients with STAAD who underwent surgical treatment,39 case postoperative ALI occurred,with an incidence rate of 34.82％.Age,preoperative creatinine,body mass index(BMI),preoperative white blood cell count,preoperative lactate and other aspects compared,The difference were statistically significant(P＜0.05).The length of stay in the intensive care unit(ICU)of the ALI group was longer than that of the non ALI group(P＜0.05).The intraoperative red blood cell transfusion volume and extracorporeal circulation time in the ALI group were higher than those in the non ALI group(P＜0.05).Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count were risk factors for postoperative ALI(P＜0.05).The receiver operating characteristic(ROC)curve analysis results show that,the Area under the curve(AUC)of the nomogram prediction model was 0.871.When the optimal critical value was 0.472,its sensitivity and specificity wew 0.887 and 0.776,respectively.The internal validation results of Bootstrap show that,the C-index of the column chart prediction model was 0.862,with an absolute error of 0.032.The calibration curve is close to the ideal curve and the original curve,with a slope close to 1.Conclusions:Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count are independent risk factors for postoperative ALI in patients with STAAD.The nomogram model constructed based on the above risk factors can effectively evaluate the risk of postoperative ALI in patients with STAAD.

Objective:Analyze the risk factors for acute lung injury of postoperative acute lung injury(ALI)in patients with Stanford type A aortic dissection(STAAD),and construct a nomogram predictive model.Methods:A retrospective cohort study design was adopted.A total of 112 patients with STAAD who underwent surgical treatment in our hopital from January 2021 to August 2024 were included.They were divided into two groups according to the occurrence of ALI after the surgical:non-ALI group(73 cases)and ALI group(39 cases).Clinical data were collected from both groups of patients.The influencing factors of postoperative ALI in patients with STAAD were analyzed by multivariate logistic regression.Established nomogram prediction model based on influencing factors and validated.Results:Among 112 patients with STAAD who underwent surgical treatment,39 case postoperative ALI occurred,with an incidence rate of 34.82％.Age,preoperative creatinine,body mass index(BMI),preoperative white blood cell count,preoperative lactate and other aspects compared,The difference were statistically significant(P＜0.05).The length of stay in the intensive care unit(ICU)of the ALI group was longer than that of the non ALI group(P＜0.05).The intraoperative red blood cell transfusion volume and extracorporeal circulation time in the ALI group were higher than those in the non ALI group(P＜0.05).Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count were risk factors for postoperative ALI(P＜0.05).The receiver operating characteristic(ROC)curve analysis results show that,the Area under the curve(AUC)of the nomogram prediction model was 0.871.When the optimal critical value was 0.472,its sensitivity and specificity wew 0.887 and 0.776,respectively.The internal validation results of Bootstrap show that,the C-index of the column chart prediction model was 0.862,with an absolute error of 0.032.The calibration curve is close to the ideal curve and the original curve,with a slope close to 1.Conclusions:Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count are independent risk factors for postoperative ALI in patients with STAAD.The nomogram model constructed based on the above risk factors can effectively evaluate the risk of postoperative ALI in patients with STAAD.

Objective:To investigate the MRI characteristics of ductal lesions with microcalcifications detected by mammography,and to evaluate the value of MRI in the differential diagnosis of benign and malignant ductal lesions.Methods:The clinical data of 112 patients with pathologically confirmed ductal lesions with microcalcifications detected by mammography in our hospital from January 2022 to June 2024 were retrospectively analyzed.All patients underwent mammography and MRI examinations.MRI morphological features,dynamic enhancement characteristics,diffusion-weighted imaging(DWI)findings,and apparent diffusion coefficient(ADC)values were analyzed and compared with pathological results.The diagnostic performance of various MRI features was analyzed using ROC curves.Results:Among the 112 patients,there were 47 benign lesions and 65 malignant lesions.Malignant lesions were more likely to present with irregular morphology,heterogeneous T2 signal,lobulation,and spiculation(P＜0.05),while benign lesions were more likely to present with round or oval shapes and homogeneous T2 signal(P＜0.05).Malignant lesions predominantly showed fast rise-fast washout(Washout type)enhancement curves(58.5％),while benign lesions predominantly showed persistent rise(Progressive type)enhancement curves(55.3％).The ADC values of malignant lesions(0.92±0.21× 10-3 mm2/s)were significantly lower than those of benign lesions(1.45±0.28× 10-3 mm2/s)(P＜0.001).The combined application of morphological features,dynamic enhancement curves,and ADC values had the highest diagnostic performance,with a sensitivity of 92.3％,specificity of 89.4％,and accuracy of 91.1％.Conclusion:Multi-parameter MRI can comprehensively evaluate ductal lesions with microcalcifications detected by mammography.The combined application of morphological features,dynamic enhancement curve types,and ADC values can effectively improve the accuracy of differential diagnosis between benign and malignant lesions,providing important basis for clinical treatment decisions.

Objective To study the activity of ten kinds of antipyretic-antidotal traditional Chinese medicine(TCM),including radix tinosporae.herb of blin conyza and turmeric,against extensively drug-resistant Acineto-bacter baumannii(XDR-AB)infection,screen out the extracts of antipyretic-antidotal TCM which have in vivo anti-infection activity,provide a research basis for the discovery of novel antimicrobials against XD-RAB infection.Methods Ten antipyretic-antidotal TCM were extracted with water,50％ethanol and 95％ethanol respectively,and TCM extracts with different concentrations were prepared,which were co-incubated with the model of XDR-AB-infected Caenorhabditis elegans previously optimized by the research group.The in vivo activity of antipyretic-antidotal TCM against XDR-AB infection was judged through the survival rate of Caenorhabditis elegans.Results With the increase of concentration of turmeric and cortex pseudolaricis extracts,the survival rate of XDR-AB-infec-ted nematodes continued to improve.The water extract,50％ethanol extract,and 95％ethanol extract of turmeric at a concentration of 1 000 μg/mL could increase the survival rates of XDR-AB-infected Caenorhabditis elegans to 54.2％(compared to the negative control group,P＜0.001),18.8％,and 13.3％,respectively.The water ex-tract,50％ethanol extract,and 95％ethanol extract of cortex pseudolaricis at a concentration of 1 000 μg/mL could increase the survival rates of XDR-AB-infected Caenorhabditis elegans to 47.4％(compared to the negative control group,P＜0.001),23.8％,and 15.8％,respectively.Conclusion The water extracts of turmeric and cortex pseudolaricis have good activity against XDR-AB infection,and their main chemical components can be tested for in vitro antimicrobial efficacy to discover novel antimicrobial agents against XDR-AB infection.

Objective:To investigate the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of pediatric pancreaticobiliary maljunction (PBM).Methods:Data of 40 pediatric patients under 14 with PBM diagnosed and treated by ERCP at Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from November 2012 to September 2022 were collected. PBM types, ERCP-related diagnosis and treatment, adverse events and prognosis were retrospectively analyzed.Results:Nineteen cases were P-B type (joining of common bile duct with pancreatic duct), 17 were B-P type (joining of pancreatic duct with common bile duct), and 4 were complex type. Forty children with PBM underwent 50 ERCP-related operations, among which 48 procedures succeeded. One case failed during cannulation of ERCP, replaced by rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP) afterwards. There were no serious postoperative adverse events such as bleeding, perforation or death. Thirty-four patients (85%) were followed up successfully, among which 14 underwent further surgery and 20 continued conservative treatment.Conclusion:ERCP is the golden standard to diagnose pediatric PBM, and it is also safe and effective treatment for PBM.