ObjectiveTo investigate whether Shixiaosan can improve neurological function and inhibit ferroptosis in rats with cerebral ischemia-reperfusion injury （CIRI） by regulating the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. MethodsA rat model of CIRI was established using the intraluminal filament method. Briefly， cervical blood vessels were separated， branches of the external carotid artery were ligated， and the common carotid artery and internal carotid artery were clamped. A nylon filament was inserted through the opening of the external carotid artery to the origin of the middle cerebral artery to block blood flow and induce cerebral ischemia. After 60-120 min of ischemia， the filament was withdrawn to restore blood flow， and the external carotid artery incision was ligated. The rats were divided into a CIRI group， a Shixiaosan low-dose （-L） group （intragastric administration of 1.26 g·kg^-1 Shixiaosan）， a Shixiaosan high-dose （-H） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan）， a donepezil hydrochloride tablet （DON） group （intragastric administration of 0.45 mg·kg^-1 DON）， and a Shixiaosan -H + Nrf2 inhibitor （ML385） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan combined with intraperitoneal injection of 30 mg·kg^-1 ML385）. An additional 12 rats underwent cervical artery separation followed by incision suturing and served as the control group. Equal volumes of double-distilled water were administered to the CIRI and control groups. Neurological function impairment was assessed using the modified Garcia JH score. Magnetic resonance imaging was used to determine the cerebral infarct volume ratio. Hematoxylin-eosin （HE） staining and Prussian blue staining were performed to observe neuronal injury and iron accumulation in the ischemic penumbra， respectively. Transmission electron microscopy was used to examine the ultrastructure of neuronal mitochondria in the ischemic penumbra. Commercial kits were used to measure ferrous iron （Fe²⁺）， malondialdehyde （MDA）， reduced glutathione （GSH） content， and reactive oxygen species （ROS） activity in the ischemic penumbra. The BODIPY （581/591） C11 fluorescent probe was used to detect intracellular lipid peroxidation levels. Western blot was performed to detect protein expression levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFRC）， ferritin heavy chain （FHC）， and ferritin light chain （FLC） in the ischemic penumbra. ResultsCompared with the control group， the CIRI group exhibited neuronal injury in the ischemic penumbra， characterized by reduced neuron numbers， nucleolar shrinkage， and interstitial edema. Marked iron accumulation was observed in the tissue. Neuronal mitochondria showed atrophy and rupture， with reduced mitochondrial cristae and increased membrane density. The cerebral infarct volume ratio， Fe²⁺ content， MDA content， ROS activity， and lipid peroxidation levels were increased， whereas the modified Garcia JH score， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC were decreased， and TFRC protein expression was increased （P<0.05）. Compared with the CIRI group， the Shixiaosan -L group， Shixiaosan -H group， and DON group showed attenuated neuronal injury in the ischemic penumbra， reduced iron accumulation， alleviated mitochondrial damage， decreased cerebral infarct volume ratio， Fe²⁺ and MDA contents， ROS activity， and lipid peroxidation levels， as well as increased modified Garcia JH scores， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC， while TFRC protein expression was decreased （P<0.05）. The magnitude of changes in all indicators was greater in the Shixiaosan -H group than in the Shixiaosan -L group （P<0.05）. Compared with the Shixiaosan -H group， all measured indicators in the Shixiaosan -H + ML385 group showed opposite trends （P<0.05）. ConclusionShixiaosan may inhibit ferroptosis and restore neurological function in rats with CIRI by activating the Nrf2/SLC7A11/GPX4 pathway.

Objective The high post-surgery recurrence rate of endometriosis(EMs)has emerged as a challenge in the long-term manaagement of the condition.This study is aimed at investigating the mechanisms of Neiyiting(NYT)decoction in preventing postoperative recurrence of EMs.Methods An animal model of EMs postoperative recurrence and a model of endometrial stromal cells(hEM15A)cocultured with macrophages(RAW 264.7 cell line)were established for both in vivo and in vitro experiments.An autotransplantation method was used to establish a rat model of EMs.The rats were divided into 4 groups(6 rats per group)and received the corresponding treatments:a Model group receiving distilled water,a Gestrinone group receiving gestrinone at 0.325 mg/kg,a low-dose NYT(NYT-L)group receiving NYT decoction at 5.04 g/(kg-d),and a high-dose NYT(NYT-H)group receiving NYT decoction at 10.08 g/(kg-d).The treatment was administered for 3 weeks via intragastric gavage.In addition,6 SD rats were randomly selected for the control group(Control group),and were given distilled water for 3 weeks via intragastric gavage.The sizes and pathological changes of recurrent lesions in EMs rats were observed.Immunohistochemistry and qRT-PCR were performed to assess the expression of M1 macrophage marker CD86 protein and mRNA in vivo.Additionally,immunohistochemistry and qRT-PCR were used to assess the expression of indicator proteins related to the triggering receptor expressed on myeloid cells 1(TREM1)/Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway and mRNA.The proliferation of hEM15A cells in the coculture experiment was observed.Flow cytometry was performed to determine the polarization of RAW264.7 macrophages,and qRT-PCR was used to determine the expression levels of inducible nitric oxide synthase(iNOS)and interleukin 1β(IL-1β)mRNA.Western blot was performed to determine the expression of signaling pathway-related indicator proteins in vitro.ELISA was performed to determine the levels of inflammatory factors in vitro.Results Compared with the Model group,the volume of recurrent lesions in the NYT-H group was reduced(P＜0.01).Findings from the macrophage M1 polarization assessment showed that the expression levels of CD86 protein and mRNA in the recurrent lesions of the Model group were higher than those in the control group(P＜0.01).The expression levels of CD86 protein and mRNA in the recurrent lesions of the NYT-H group were lower than those of the Model group(P＜0.01).In addition,the RAW 264.7 cell experiment further verified that NYT decoction could reduce the number of CD86-positive macrophages induced by plasmids overexpressing TREM1 and reduce the expression of IL-1β and iNOS mRNA(P＜0.01).The results of the hEM15A cell proliferation assay showed that NYT decoction down-regulated KI-67 protein expression in hEM15A cells induced by macrophage M1 polarization(P＜0.01).The results of TREM1/TLR4/NF-κB signaling pathway showed that the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the Model group were higher than those of the control group(P＜0.01).Compared with those in the Model group,the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the NYT-H group were lower(P＜0.01).In addition,the coculture experiment of RAW264.7 and hEM15A cells further confirmed that NYT decoction reduced the expression of TREM1,TLR4,and P-P65 proteins(P＜0.01).Conclusion NYT decoction can inhibit macrophage M1 polarization through the TREM1/TLR4/NF-κB signaling pathway,improve the inflammation level,and inhibit the formation of ectopic endometrial lesions,thereby preventing postoperative recurrence of EMs.

Neuroimaging techniques are tools used to investigate and monitor the activity of the nervous system.This study reviews studies that have attempted to quantify athletes'brain using neuroimaging techniques,and summarizes the specific changes in athletes'brain as evidenced by structural magnetic resonance imaging,functional magnetic resonance imaging,functional near-infrared spectroscopy,transcranial magnetic stimulation and electroencephalography.Open-skill sports have been found to increase the brain volume and resting-state functional connectivity related to athletes'executive control,somatosensory processing,vision,and balance coordination,whereas closed-skill sports may decrease the brain volume and resting-state functional connectivity related to athletes'episodic memory,emotional processing and executive functions.Brain regions associated with executive functions,body awareness,motor learning,and episodic memory exhibit stronger activation during tasks.Athletes demonstrate higher neural excitability and neural efficiency.The association between sports training and the brain should be explored through multimodal neuroimaging techniques,which will play a significant role in athlete selection,real-time status monitoring and long-term training supervision.

Objective: To construct and validate a prognostic model for lung cancer based on acrolein-related genes using bioinformatics methods . Methods: Lung cancer datasets GSE30219 and GSE68465 were obtained from the GEO database , and acrolein-related gene sets were retrieved from the CTD database . Differentially expressed genes (DEGs) between cancer and adjacent tissues were identified in the GSE30219 dataset. The intersection of these DEGs and acrolein-related genes was then used to identify candidate genes . Gene set variation analysis ( GSVA) was performed to assess functional alterations based on the intersection genes . A protein-protein interaction (PPI) network was constructed based on the STRING database to identify core hub genes . Subsequently , support vector machine recursive feature elimination (SVM-RFE) and LASSO-Cox regression analyses were employed to develop a prognostic model based on acrolein-related genes , which was independently validated using the GSE68465 dataset. The CIBERSORT algorithm was applied to evaluate the immune cell infiltration characteristics between high- and low-risk groups , and functional enrichment analysis of DEGs between the two groups was conducted to further ex- plore the potential molecular mechanisms underlying the prognostic model . Results : A total of 361 acrolein-related DEGs were identified in lung cancer , and 7 key genes were selected for model construction . Kaplan-Meier survival analysis revealed that patients in the high-risk group had significantly lower survival rates compared to those in the low-risk group (P < 0. 000 1) . Receiver operating characteristic (ROC) curve analysis demonstrated that the mod- el possessed good predictive performance . Moreover , immune infiltration analysis indicated that the risk score was closely associated with multiple immune cell subsets , suggesting a potential role of acrolein-related genes in modula- ting the lung cancer immune microenvironment. Conclusion The prognostic model for lung cancer based on acro- lein-related genes demonstrates significant application value in predicting the prognosis of lung cancer , providing new insights into the potential mechanisms of acrolein in the onset and progression of lung cancer.

Objective To explore the application value of ultrasound-guided use of bupivacaine for subarachnoid block in hip replacement surgery for elderly femoral neck fractures.Methods A total of 108 elderly patients who underwent hip replacement surgery at Ganzhou Traditional Chinese Medicine Hospital from March 2020 to March 2022 were selected as the study subjects.They were divided into conventional anesthesia group and ultrasound guided anesthesia group by means of random number table,54 cases in each group.Patients in the conventional anesthesia group received routine general anesthesia;Patients in the ultrasound guided anesthesia group received unilateral lumbar anesthesia with bupivacaine under ultrasound-guided guidance.Compare the effectiveness of two anesthesia methods during surgery.Results Compared with the conventional anesthesia group,the anesthesia effect of the ultrasound guided anesthesia group was better(P<0.05);The surgery time,amount of bleeding during surgery,postoperative recovery time,and length of hospital stay in the ultrasound guided anesthesia group were all lower than those in the conventional anesthesia group(P<0.05).The ultrasound guided anesthesia group performed better in terms of hemodynamic stability,with a smaller range of changes,and significantly lower pain scores at different postoperative time points compared to the conventional anesthesia group(P<0.05).Conclusion In elderly patients undergoing hip replacement surgery,using ultrasound-guided bupivacaine for subarachnoid block can achieve ideal anesthesia and analgesic effects compared to traditional general anesthesia,shorten drug onset time,alleviate pain in elderly patients,maintain hemodynamic stability,and have significant clinical application effects.

Objective To investigate the prognostic value of M2 macrophage-related genes(MRG)in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods The transcriptome data of 73 patients with HBV-related HCC were obtained from TCGA database,and the MRG modules were identified by WGCNA.The MRG-based risk scoring model was constructed by LASSO regression analysis and validated using an external dataset.The correlation of the risk score with immune cell infiltration and drug sensitivity of HCC were analyzed with CIBERSORT and R.pRRophetic.The signaling pathways of the differential genes between the high-and low-risk groups were investigated using GSVA and GSEA enrichment analyses,and MRG expressions at the single cell level were validated using R.Seurat.The cell interaction intensity was analyzed by R.Cellchat to identify important cell types related to HCC progression.MRG expression levels were detected by RT-qPCR in THP-1 cells with HCC-conditioned medium-induced M2 polarization and in HBV-positive HCC cells.Results A high M2 macrophage infiltration level was significantly correlated with a poor prognosis of HCC,and 5 hub MRG(VTN,GCLC,PARVB,TRIM27,and GMPR)were identified.The overall survival of HCC patients was significantly lower in the high-risk than in the low-risk group.The high-and the low-risk groups showed significant enrichment of M2 macrophages and na?ve B cells,respectively,and were sensitive to BI.2536 and to AG.014699,AKT.inhibitor.Ⅷ,AZD.0530,AZD7762,and BMS.708163,respectively.The proliferation-related and metabolism-related pathways were enriched in the high-risk group,where monocytes showed the most active cell interactions during HCC progression.VTN was significantly upregulated in HCC cell lines,while GCLC,PARVB,TRIM27,and GMPR were upregulated in M2 THP-1 cells.Conclusion The MRG-based risk scoring model can accurately predict the prognosis of HBV-related HCC and reveal the differences in tumor microenvironment to guide precision treatment of the patients.

Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts,often misdiagnosed due to its similarity to many infectious and non-infectious diseases.This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics,including methotrexate,leflunomide,and infliximab,leading to recurrent joint pain,poorly controlled rheumatoid arthritis activity,and persistent elevation of white blood cell counts.Abdominal CT revealed a pelvic mass and right ureteral dilation.Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules,indicating actinomycosis.The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide,hydroxychloroquine sulfate,and tofacitinib,resulting in improved joint symptoms and normalized white blood cell counts.After 2 years of follow-up,the patient remained stable with no recurrence.This case highlights the importance of clinicians being vigilant for infections,particularly chronic,occult infections from rare pathogens,in rheumatoid arthritis patients on potent immunosuppressants and biologics,advocating for early screening and diagnosis.

This report describes a case of maturity-onset diabetes of the young(MODY)type 3(MODY3)complicated with type 5(MODY5),including the patient's clinical features,diagnosis,and treatment,and reviews relevant literature.Using next-generation sequencing of MODY(types 1-14)gene exons and Sanger sequencing for verification,the patient and her mother were assessed.Based on the clinical phenotype and genetic test results,the patient was diagnosed as MODY3 combined with MODY5.Treatment included insulin and linagliptin,with monitoring of blood glucose changes.Clinicians should enhance their understanding of MODY clinical phenotypes.In adolescents with diabetes who have congenital pancreatic and renal developmental defects,elevated high-density lipoprotein cholesterol,no spontaneous ketosis,insulin secretion defects,negative pancreatic autoantibodies,no significant insulin resistance,and who are not obese,gene testing should be conducted to screen for MODY.Accurate diagnosis and personalized treatment can aid in achieving glycemic control,improving quality of life,and optimizing reproductive planning.

Objective:To investigate the correlation between plasma fibrinogen/serum albumin ratio (FAR) and the degree of cerebral artery stenosis in patients with acute cerebral infarction (ACI).Methods:Clinical data of 189 patients with acute cerebral infarction diagnosed and treated in the Department of Neurology of the First Affiliated Hospital of Hainan Medical College from January 2021 to March 2023 were selected for retrospective analysis. Digital subtraction angiography (DSA) was improved, and they were divided into four groups according to the degree of intracranial vascular stenosis according to NASCET grading method: no stenosis group (47 cases), mild stenosis group (45 cases), moderate stenosis group (39 cases) and severe stenosis and occlusion group (58 cases). The differences of basic data, plasma fibrinogen/serum albumin ratio (FAR) and other inflammatory indicators among all groups were compared, and the correlation between FAR level and the severity of cerebral artery stenosis was analyzed. Multivariate Logistic regression was used to explore the factors influencing to cerebral artery stenosis and ROC curve was used to evaluate the diagnostic value of FAR in the degree of cerebral artery stenosis in cerebral infarction patients.Results:There were significant differences in blood neutrophil (NEU), mean platelet volume (MPV), fibrinogen (FIB), fibrinogen (FIB), albumin (ALB) and FAR among the 4 groups (statistical values were H=11.50, H=8.44, F=5.16, H=30.93, H=40.38; all P<0.05). Correlation analysis showed a positive correlation between FAR and the degree of cerebral artery stenosis ( r=0.455, P<0.05). Multivariate Logistic regression showed that FAR was an independent risk factor for the degree of cerebral artery stenosis ( OR=1.445, 95% CI=1.261-1.655, P<0.001). Conclusion:FAR is an independent risk factor for cerebral artery stenosis in patients with acute cerebral infarction (ACI), and may be a new biomarker for predicting cerebral artery stenosis.

Objective To investigate the prognostic value of M2 macrophage-related genes(MRG)in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods The transcriptome data of 73 patients with HBV-related HCC were obtained from TCGA database,and the MRG modules were identified by WGCNA.The MRG-based risk scoring model was constructed by LASSO regression analysis and validated using an external dataset.The correlation of the risk score with immune cell infiltration and drug sensitivity of HCC were analyzed with CIBERSORT and R.pRRophetic.The signaling pathways of the differential genes between the high-and low-risk groups were investigated using GSVA and GSEA enrichment analyses,and MRG expressions at the single cell level were validated using R.Seurat.The cell interaction intensity was analyzed by R.Cellchat to identify important cell types related to HCC progression.MRG expression levels were detected by RT-qPCR in THP-1 cells with HCC-conditioned medium-induced M2 polarization and in HBV-positive HCC cells.Results A high M2 macrophage infiltration level was significantly correlated with a poor prognosis of HCC,and 5 hub MRG(VTN,GCLC,PARVB,TRIM27,and GMPR)were identified.The overall survival of HCC patients was significantly lower in the high-risk than in the low-risk group.The high-and the low-risk groups showed significant enrichment of M2 macrophages and na?ve B cells,respectively,and were sensitive to BI.2536 and to AG.014699,AKT.inhibitor.Ⅷ,AZD.0530,AZD7762,and BMS.708163,respectively.The proliferation-related and metabolism-related pathways were enriched in the high-risk group,where monocytes showed the most active cell interactions during HCC progression.VTN was significantly upregulated in HCC cell lines,while GCLC,PARVB,TRIM27,and GMPR were upregulated in M2 THP-1 cells.Conclusion The MRG-based risk scoring model can accurately predict the prognosis of HBV-related HCC and reveal the differences in tumor microenvironment to guide precision treatment of the patients.