Objective To analyze the clinical and cardiac magnetic resonance(CMR)characteristics of patients with Fabry disease(FD)and evaluate the application value of CMR in the early diagnosis of cardiac involvement in FD.Methods This retrospective study involved nine patients with FD confirmed by renal biopsy pathology and genetic testing at our hospital between January 2021 and October 2024.Their clinical baseline data,laboratory test reuslts,and CMR images were collected.CMR images were analyzed using CVI42 software to generate functional,morphological,and structural parameters.Results In this study,78％of the patients were male,and a high proportion(67％)had a family history of FD.Electrocardiographic abnormalities were observed in eight patients(89％),while 33％reported acroparesthesia and 22％exhibited cornea verticillata,a characteristic ocular manifestation of FD.Left ventricular hypertrophy was present in four patients,with one case also showing right ventricular hypertrophy.Late gadolinium enhancement(LGE)was positive in one patient,presenting as intermural enhancement.The mean left ventricular ejection fraction(LVEF)was within the normal range.T1 mapping demonstrated that both global and segmental native T1 values in the left ventricular myocardium were below 1 200 ms.Conclusion Multimodal CMR imaging provides crucial imaging evidence for the diagnosis of FD,with native T1 mapping showing significant clinical potential for disease staging.

Ischemic stroke is a disease resulting from the cerebral ischemia and hypoxia caused by the blockage of brain vessels in the brain,and is characterized by the focal neurological signs.Pathologically,neuronal necrosis in the infarcted area and the neuronal degeneration or delayed death of neurons in the ischemic penumbra,contribute to the morphological basis of the disease.Ischemic stroke is regulated by multiple processes,including ferroptosis,apoptosis,and autophagy.Ferroptosis,a type of iron-dependent cell death,is closely associated with ischemic stroke.Nuclear factor erythroid 2-related factor 2(Nrf2),a key transcription factor,plays a critical role in maintaining cellular redox balance and regulating inflammatory responses.Nrf2 promotes the expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),thereby activating the Nrf2 signaling pathway to counteract ferroptosis and protect cells from damage.This article reviews and analyzes recent experimental studies on traditional Chinese medicine(TCM)therapy targeting the Nrf2/SLC7A11/GPX4 pathway to suppress ferroptosis.The studies have found that TCM therapy with herbal compounds,Chinese patent medicines,single herbal components and their active ingredients,and acupuncture and moxibustion can inhibit ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway,which will provide novel strategies for the TCM intervention of ischemic stroke.

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

Objective To analyze the clinical and cardiac magnetic resonance(CMR)characteristics of patients with Fabry disease(FD)and evaluate the application value of CMR in the early diagnosis of cardiac involvement in FD.Methods This retrospective study involved nine patients with FD confirmed by renal biopsy pathology and genetic testing at our hospital between January 2021 and October 2024.Their clinical baseline data,laboratory test reuslts,and CMR images were collected.CMR images were analyzed using CVI42 software to generate functional,morphological,and structural parameters.Results In this study,78％of the patients were male,and a high proportion(67％)had a family history of FD.Electrocardiographic abnormalities were observed in eight patients(89％),while 33％reported acroparesthesia and 22％exhibited cornea verticillata,a characteristic ocular manifestation of FD.Left ventricular hypertrophy was present in four patients,with one case also showing right ventricular hypertrophy.Late gadolinium enhancement(LGE)was positive in one patient,presenting as intermural enhancement.The mean left ventricular ejection fraction(LVEF)was within the normal range.T1 mapping demonstrated that both global and segmental native T1 values in the left ventricular myocardium were below 1 200 ms.Conclusion Multimodal CMR imaging provides crucial imaging evidence for the diagnosis of FD,with native T1 mapping showing significant clinical potential for disease staging.

Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.

Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.

Objective To investigate the clinical outcomes of suture anchors and knotless anchors in the repair of anterior talofibular ligament.Methods A total of 187 patients with chronic ankle instability caused by anterior talofibular ligament injury admitted to First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2021 were included and divided into the suture anchor group(97 cases)and the knotless anchor group(90 cases)according to the treatment methods.Patients in the suture anchor group were repaired with suture anchor,and patients in the knotless anchor group were repaired with knotless anchor.The postoperative follow-up was conducted for 24 to 48 months,the American Foot and Ankle Association(AOFAS)scores,visual analogue scale(VAS)scores and Cumberland ankle instability tool(CAIT)scores before and after surgery were compared between the two groups,and the ankle MR was performed 12 months after surgery to evaluate the recovery of patients.The complications of patients after surgery were observed.Results There was no significant difference in the VAS score,AOFAS scores or CAIT scores before surgery and at the end of follow-up between the two groups(P>0.05).At the end of follow-up,the VAS scores of the two groups were significantly lower than those before surgery,and the AOFAS scores and CAITs score were significantly higher than those before surgery,with significant differences(P<0.05).The sutures loosing or knots that irritated the surrounding soft tissues was not found in the patients of the suture anchor group,and the signs of knotless anchor loosening was not found in the patients of the knotless suture group.Postoperative complications such as infection and thrombosis were not found in all patients.The local skin numbness at the back of the foot in the early postoperative period was found in 3 patients of the suture anchor group and 2 patients of the knotless suture group,which disappeared at 6 months of follow-up.One patient in the suture anchor group reported subcutaneous discomfort on the operative side after 12 months of follow-up,which was suspected knot irritation,but no obvious abnormality was found in MR examination.Conclusion The clinical outcomes of suture anchors or knotless anchors in patients with chronic ankle instability are similar in the repair of anterior talofibular ligament,which can significantly improve the postoperative stability of the ankle after surgery.

Objective    To summarize the surgical strategy of reoperative aortic root replacement after prior aortic valve replacement (AVR), and analyze the early and mid-term outcomes. Methods    From April 2013 to January 2020, 75 patients with prior AVR underwent reoperative aortic root replacement in Fuwai Hospital. There were 54 males and 21 females with a mean age of 56.4±12.7 years. An emergent operation was performed in 14 patients and an elective operation in 61 patients. The indications were aortic root aneurysm in 38 patients, aortic dissection involving aortic root in 30 patients, root false aneurysm in 2 patients, prosthesis valve endocarditis with root abscess in 2 patients, and Behçet's disease with root destruction in 3 patients. The survival and freedom from aortic events during the follow-up were evaluated with the Kaplan-Meier survival curve and the log-rank test. Results    The operative procedures included prosthesis-sparing root replacement in 45 patients, Bentall procedure in 26 patients, and Cabrol procedure in 4 patients. Operative mortality was 1.3% (1/75). A composite of adverse events occurred in 5 patients, including operative death (n=1), stroke (n=1), and acute renal injury necessitating hemodialysis (n=3). The follow-up was available for all 74 survivors, with the mean follow-up time of 0.5-92.0 (30.3±25.0) months. Four late deaths occurred during the follow-up. The survival rate at 1 year, 3 years and 6 years was 97.2%, 91.4% and 84.4%, respectively. Aortic events developed in 2 patients. The rate of freedom from aortic events at 1 year, 3 years, and 6 years was 98.7%, 95.0% and 87.7%, respectively. There was no difference in rate of survival or freedom from aortic events between the elective patients and the emergent patients. Conclusion    Reoperative aortic root replacement after prior AVR can be performed to treat the root pathologies after AVR, with acceptable early and mid-term outcomes.

Objective:To investigate the feasibility of establishing a canine model of lumbar intervertebral disc degeneration through the application of cumulative axial load and a six-phase combined motion on the vertical sitting dog's lumbar spine.Methods:Twenty adult female grass dogs, each weighing 10.0±0.5 kg, were randomly divided into two groups, with 10 dogs in each group. In the model group, dogs were secured to an exercise machine in a vertical position, and six phases of lumbar spine movement (flexion and extension, left and right lateral flexion, left and right rotation, 45° each) were combined with a specific number of cycles under continuous axial load (245 N). In the control group, dogs were secured to the exercise machine in a vertical position without any intervention. Radiographic examinations were performed before and after 20,000, 50,000, 100,000, and 150,000 compound exercises in the model group. The disc height index (DHI) was measured through lateral X-ray, and MRI T2-mapping was used for quantitative analysis of intervertebral disc degeneration. When intervertebral disc degeneration was evident on MRI T2-weighted imaging (modified Pfirrmann system > Grade V), the combined motion was halted. Micro-CT quantitative analysis of bone mineral density (BMD) in the upper and lower endplates, trabecular bone structure, and histological staining (HE staining, "O" staining, Sirius red staining) were employed to verify and assess the degree of intervertebral disc degeneration.Results:After 50,000 compound exercises, mild degeneration of the intervertebral discs at L 6-7 and L 7S 1 was observed on T2-weighted imaging. With the accumulation of exercise load, the degree of degeneration progressively increased, reaching a moderate degree of degeneration after 100,000 composite exercises, and DHI began to decrease. Mild degeneration was also observed in the upper L 5-6 intervertebral disc. When the cumulative exercise volume reached 150,000 repetitions, the height of intervertebral spaces in the L 5-6, L 6-7, and L 7S 1 segments further decreased, and the intervertebral discs exhibited severe degeneration (improved Pfirrmann grading system Grades IV-VI). The upper L 4-5 intervertebral discs also displayed mild degeneration. Histological scores were as follows: L 5-6 (8.2±0.8), L 6-7 (9.5±0.7), and L 7S 1 (10.3±0.5), indicating a degree of degeneration in the order of L 5-6

ObjectiveTo investigate the long-term safety of triptolide ferulic acid ethosome gel in percutaneous administration. MethodWe mixed triptolide with ferulic acid to make liposomes gel in different doses and then administrated the gel to SD rats of both sexes with intact skin and damaged skin for 12 weeks. The daily dosages calculated based on triptolide for the low-， middle-， and high-dose groups were 63.75， 127.50， 255.00 μg·kg^-1， respectively. The body weight of each rat was measured weekly. The rats were sacrificed in the last week for the determination of serum biochemical parameters and organ indexes as well as the observation of histopathology. The toxicity was assessed based on the body weight and all the parameters and indexes. ResultAfter long-term administration， the body weight and serum biochemical parameters did not show significant difference between the gel-treated groups and the blank group with intact skin， which indicated that the percutaneous administration of triptolide and ferulic acid ethosomes gel was relatively safe. However， the rats in the high-dose group showed sparse hair and were easy to die in the case of unhairing with chloral hydrate at the late stage of the study. Comprared with the female rats with intact skin in the blank control group， the female rats with damaged skin in the middle-dose group showed decreased heart index （P<0.05）， which indicated certain cardiotoxicity. Moreover， damage appeared in skin and lung， which may be influeneced by dosage， sex， and skin state. ConclusionFerulic acid in combination with triptolide is relatively safe for percutaneous administration， whereas there are some risks of skin and lung damage in the case of long-term administration. Individualized administration scheme should be developed according to liver and kidney function and skin conditons to ensure the safety of clinical medication.