ObjectiveA middle cerebral artery occlusion (MCAO) mouse model is established by electrocoagulation of the middle cerebral artery. The study examines the mechanism by which exosomes (EXO) derived from human amniotic mesenchymal stem cells (hAMSCs) improve ischemic stroke and regulate neural ferroptosis-related injury. MethodsThirty-two SPF-grade male C57BL/6J mice aged 6 - 8 weeks were randomly divided into four groups (n=8 per group): sham group (Sham), model group (MCAO), MCAO plus normal saline group (MCAO+NaCl), and MCAO plus exosome group (MCAO+EXO). The mouse MCAO model was established by electrocoagulation of the middle cerebral artery. Mice in the Sham group underwent exposure of the middle cerebral artery without electrocoagulation. Twenty-four hours before MCAO induction, mice in the MCAO+EXO group received a tail vein injection of 100 μL of exosomes derived from the culture supernatant of hAMSCs at a concentration of 9.5×10¹¹ particles/mL. Mice in the MCAO+NaCl group were injected with an equal volume of normal saline via the tail vein. Twenty-four hours after model establishment, neurological deficits were evaluated using the Longa neurological deficit scoring system. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin and eosin (HE) staining was performed to evaluate morphological changes of neurons in the ischemic brain regions. The contents of ferrous iron (Fe²⁺), malondialdehyde (MDA), total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) in the infarct core and peri-infarct regions were determined using microcolorimetric assays to evaluate differences among groups. The mRNA expression levels of ferroptosis-related factors, including nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the infarct core and peri-infarct regions were measured by real-time quantitative PCR. Protein expression levels of NRF2, SLC7A11, and GPX4 in the infarct and peri-infarct regions of each group were analyzed by Western blotting. ResultsCompared with the MCAO group, the Longa neurological deficit score was significantly reduced in the MCAO+EXO group (P<0.01). Prominent cerebral infarction was observed in the MCAO group, whereas the infarct volume ratio was markedly decreased in the MCAO+EXO group compared with the MCAO group (P<0.001). Histopathological analysis revealed that mice in the MCAO group exhibited obvious neuronal damage, including cytoplasmic vacuolar degeneration, nuclear pyknosis and fragmentation, unclear nuclear structure, and disorganized neuronal arrangement, compared with the Sham group. In contrast, neurons in the MCAO+EXO group showed relatively preserved morphology, with intact cellular structures and large, regular nuclei located centrally within the cells. Biochemical analysis demonstrated that Fe²⁺ and MDA levels in the infarct core and peri-infarct regions were significantly increased in the MCAO group compared with the Sham group (P<0.001). These levels were significantly reduced in the MCAO+EXO group compared with the MCAO group (P<0.01). In addition, total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) levels were markedly decreased in the MCAO group relative to the Sham group (P<0.01). Compared with the MCAO group, the MCAO+EXO group exhibited significantly increased levels of total GSH and GSH (P<0.001), while no significant change was observed in GSSG levels (P>0.05). Furthermore, both mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were significantly downregulated in the MCAO group compared with the Sham group (P<0.01, P<0.001). In contrast, both mRNA and protein expression levels of NRF2, SLC7A11, and GPX4 were significantly upregulated in the MCAO+EXO group compared with the MCAO group (P<0.05). ConclusionIn the mouse MCAO model, tail vein injection of exosomes derived from hAMSCs can improve motor function, reduce infarct area, protect neuronal cell morphology, and reduce the degree of nerve injury. Exosomes may exert a protective effect by activating the NRF2/SLC7A11/GPX4 pathway and reducing ferroptosis in neuronal cells of MCAO model mice.

Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

ObjectiveTo explore the mechanism of Yishen Qubi Tongluo Formula （益肾祛痹通络方， YQTF） in the treatment of rheumatoid arthritis（RA）. MethodsNetwork pharmacology was employed to retrieve and screen the active components and potential targets of YQTF as well as RA-related targets using databases including TCMSP， BATMAN， ETCM and GEO. The intersection of targets related to active components and RA-related targets was identified， and a protein-protein interaction （PPI） network was constructed. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed， and a drug-active component-common target network of YQTF in the treatment of RA was established. The core components of YQTF were molecularly docked with key targets. Human rheumatoid arthritis synovial fibroblast cell line MH7A was divided into blank group， model group， methotrexate group and YQTF group. The blank group was cultured with 10% fetal bovine serum， while the other three groups were stimulated with 10 μg/L of recombinant human tumor necrosis factor-α （TNF-α） for 24 h to establish the RA cell model. On this basis， the methotrexate group was treated with methotrexate suspension at a concentration of 20 μmol/L， and the YQTF group was treated with 10% YQTF-medicated serum. After 48 h of intervention， the levels of TNF-α and interleukin-17A（IL-17A）contents in cell supernatants were detected by enzyme-linked immunosorbent assay （ELISA）， and mRNA expressions of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（AKT） and mammalian target of rapamycin（mTOR） were detected by real-time quantitative polymerase chain reaction （RT-qPCR）. ResultsNetwork pharmacological analysis identified 209 active components and 583 potential target genes of YQTF， as well as 818 RA-related targets. A total of 29 common targets were obtained from the intersection of drug-related targets and RA-related targets. Quercetin，β-sitosterol， kaempferol， stigmasterol and luteolin were the core active components of YQTF for the treatment of RA， while matrix metalloproteinase-9 （MMP9）， prostaglandin-endoperoxide synthase 2 （PTGS2）， Toll-like receptor 4 （TLR4）， tumor protein p53 （TP53） and transcription factor AP-1 subunit JUN were the key targets. The GO and KEGG pathway enrichment analysis showed that the involved biological processes and pathways were mainly associated with antioxidant responses， PI3K-AKT signaling pathway and Toll-like receptor （TLR） signaling pathway. Molecular docking results showed that MMP9 and PTGS2 exhibited high binding affinities with quercetin， β-sitosterol， kaempferol， stigmasterol and luteolin； TLR4 exhibited high binding activities with β-sitosterol， stigmasterol and luteolin； and TP53 showed high binding affinity with luteolin. The results of cell experiments showed that compared with the control group， the contents of TNF-α and IL-17A as well as the mRNA expressions of AKT and mTOR in the model group significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， all the above indicators significantly decreased in the YQTF group， while the contents of TNF-α and the mRNA expression of AKT significantly decreased in the methotrexate group （P＜0.05 or P＜0.01）. ConclusionThe mechanism of YQTF in the treatment of RA may be associated with reducing inflammatory cytokine secretion and inhibiting the activation of the PI3K-AKT-mTOR signaling pathway.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD. Methods: This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared. Results: Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001). Conclusions Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.

Objective:To evaluate the short-term and long-term outcomes of patients with locally advanced low rectal cancer who achieved clinical complete response (cCR) or near-clinical complete response (near-cCR) after neoadjuvant chemoradiotherapy (nCRT) and then underwent local excision.Methods:This was a descriptive case series study. Clinical data of patients with low rectal cancer who received neoadjuvant therapy, achieved cCR or near-cCR, underwent local excision, and had complete postoperative follow-up data were retrospectively analyzed. The study period was from May, 2015 to October, 2024, and the patients were treated at Fujian Medical University Union Hospital. Indications for local excision in this study were as follows: pathologically confirmed rectal adenocarcinoma, with the lower edge of the tumor ≤ 6 cm from the anal verge; maximum diameter of the lesion ≤ 2 cm after nCRT; no regional lymph node metastasis detected by transrectal endoscopic ultrasound (ERUS), pelvic magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT) after nCRT; MRI showing fibrosis of the primary lesion with a small amount of high signal on diffusion-weighted imaging (DWI), consistent with ymrT0-1 stage; serum carcinoembryonic antigen level within the normal range (< 5 μg/L) after nCRT; complicated with severe underlying diseases such as cardiovascular and cerebrovascular diseases and assessed as unable to tolerate radical surgery through comprehensive evaluation; and signed informed consent for local excision. The contraindications were: colonoscopic pathology indicating poorly differentiated adenocarcinoma or signet ring cell carcinoma; suspected lateral lymph node metastasis before neoadjuvant therapy; patients with residual lesions exceeding 3 cm in range after treatment. A total of 153 patients were included in this study, including 84 males and 69 females. The median age was 62 years, and the median distance from the tumor to the anal verge after neoadjuvant therapy was 4.0 cm. The short-term efficacy indicators of this study included postoperative complications of local excision and postoperative pathological results, and the long-term efficacy indicators included oncological prognosis (3-year cumulative local recurrence rate, 3-year cumulative distant metastasis rate, 3-year progression-free survival, and 3-year overall survival) and anal function at 1 year after surgery evaluated using the Low Anterior Resection Syndrome (LARS) scale where the total score is 42 points such that 0-20 points indicate no LARS, 21-29 points indicate mild LARS, and 30-42 points indicate severe LARS.Results:Postoperative pathology showed 122 cases (79.7%) of ypT0 stage, 10 cases (6.5%) of ypT1 stage, 18 cases (11.8%) of ypT2 stage, and 3 cases (2.0%) of ypT3 stage. The incidence of surgery-related complications was 42.5% (65/153), and the main complications included perianal pain (39.9%, 61/153), intestinal wall incision dehiscence (21.6%, 33/153), and intestinal wall incision infection (18.3%, 28/153). The proportion of patients who received hypofractionated radiotherapy before surgery and developed intestinal wall incision dehiscence was 65.2% (15/23), which was higher than that in the conventional long-course (13.6%, 16/118) and short-course radiotherapy groups (16.7%,2/12) (χ 2=30.55, P<0.001); of the 20 patients who received additional immunotherapy before surgery, 13 developed intestinal wall incision dehiscence was 65.0%, which was higher than that in the group without additional immunotherapy [15.0%(20/133),χ 2=25.66, P<0.001]. The median follow-up time of the entire group was 35.4 months. During the follow-up period, there were 9 cases of postoperative local recurrence, with a 3-year cumulative local recurrence rate of 7.9% and 5 cases of distant metastasis, with a 3-year cumulative distant metastasis rate of 5.0%. The 3-year progression-free survival rate was 89.0%, and the 3-year overall survival rate was 95.9%. At 1 year after surgery, 10 cases (10.5%, 10/95) had severe anal dysfunction, and the median LARS score of the entire group was 5.0 (range: 0-41.0) points. Conclusions:For patients with locally advanced low rectal cancer who achieve cCR or near-cCR after neoadjuvant therapy, local excision results in favorable oncological prognosis and anal function preservation effects; however, the incidence of complications is relatively high.

Objective To explore the effect of accelerated intermittent theta burst stimulation(aiTBS)on post-stroke depression(PSD).Methods From July,2021 to July,2023,48 PSD patients in Beijing Bo'ai Hospital were randomly assigned to control group(n=16),high-frequency repetitive transcranial magnetic stimulation(HF-rTMS)group(n=16)and aiTBS group(n=16).aiTBS group received left-sided aiTBS treatment at dorsolateral prefrontal cortex(DLPFC),HF-rTMS group received left-sided 10 Hz rTMS treatment at DLPFC,and the control group received left-sided sham stimulation treatment,for three weeks.They were evaluated with the Hamilton Depression Rating Scale(HAMD),Hamilton Anxiety Rating Scale(HAMA)and Beck Depression Inventory(BDI)before and after treat-ment,and one month of follow-up.Results One case dropped down in each group.The inter-group effect,intra-group effect and interaction effect of HAMD,HAMA and BDI scores were all significant(F>3.235,P<0.05).The post-hoc test results showed that the scores of HAMD,HMMA and BDI were lower in HF-rTMS group and aiTBS group than in the control group(P<0.05),and no significant difference was found between HF-rTMS group and aiTBS group(P>0.05).There was significant difference in the effective rate of depression improvement among three groups(χ2=7.834,P=0.019),the effective rate was higher in aiTBS group than in the control group(P<0.017),and no significant dif-ference was found between HF-rTMS group and aiTBS group(P>0.017).Conclusion aiTBS can improve the depression and anxiety symptoms of patients with PSD,with shorter treatment time,compared with HF-rTMS.

AIM To establish the HPLC characteristic chromatograms for Yixin Fumai Granules,and to determine the contents of sodium danshensu,protocatechualdehyde,chlorogenic acid,calycosin-7-O-β-D-glucoside,ferulic acid,rosalinic acid,salvianolic acid A,salvianolic acid B,schisandrol A.METHODS The analysis was performed on a 35 ℃ thermostatic Acutfex PA-C18 column(4.6 mm ×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 210,250,280,320 nm.Subsequently,cluster analysis and principal component analysis were performed.RESULTS There were 11 characteristic peaks in the characteristic chromatograms for 15 batches of samples with the similarities of more than 0.980.Nine constituents showed good linear relationships within their own ranges(r≥0.999 6),whose average recoveries were 97.60％-107.02％with the RSDs of 0.78％-1.87％.Various batches of samples were clustered into 4 categories,2 principal components demonstrated the accumulative variance contribution rate of 89.454％.CONCLUSION This sensitive and reproducible method can provide a reference for the quality evaluation and control of Yixin Fumai Granules.

Objective To investigate the feasibility of parallel capillary bundle arrays for physiomimetic impedance modeling and establish a parametric quantification framework,thereby providing a customizable impedance characterization methodology for diverse in-vitro mock circulation researches.Methods Based on the parallel flow resistance and Poiseuille equation,a tube resistance element with multiple parallel-aligned capillary glass tubes was designed and fabricated.The resistance values of the capillary-bundle and a ball valve were measured through constant flow experiments analogous to electrical resistance measurement method.Moreover,a simple lumped-parameter mock circulation loop was constructed and the pressure and flow rate for each node of the loop were measured under different input flow waveforms.An 0D-Windkessel model corresponding to the experiment was developed.The impedance and compliance were adjusted to match the simulated and experimental pressure and flow waveforms.The accuracy of the capillary bundle impedance in pulsatile experiments was verified by using the computational resistance values.Results The constant-flow impedance calibration experiments revealed that the capillary bundle impedance remained unaffected by flow rate variations over a wide flow range.When the capillary bundle impedance was integrated into the pulsatile circulatory system and the same impedance value obtained from the constant-flow calibration was applied in the computational model,the resulting pressure and flow waveforms showed good agreement with those measured in the pulsatile experiments.However,when the ball valves with nominally identical impedance values were inserted in the pulsatile system,the calculated impedance exhibited a two-fold difference,and significant discrepancies were observed between the simulated and experimental terminal flow waveforms.Conclusions The capillary bundle impedance maintains a constant value regardless of flow rate variations.Once the calibrated resistance value is determined through constant flow experiments,it can be directly applied to pulsatile systems.This approach can provide quantitative pulsatile flow conditions for testing various medical devices.

Objective A non-targeted metabolomics analysis of vitreous fluid from patients with proliferative diabetic retinopathy(PDR)is conducted to explore the"metabolic map"of PDR.This approach aims to deepen the understanding of the disease,identify potential biomarkers.Methods From 35 PDR patients and 30 fresh rhegmatogenous retinal de-tachment(RRD)patients,10 PDR patients with vitreoretinal abnormal adhesions were selected as the experimental group(PDR group),and 10 fresh RRD patients were chosen as the control group(RRD group).Using ultra-high-performance liq-uid chromatography-mass spectrometry non-targeted metabolomics technology,the metabolic profiles of vitreous fluid were analyzed to obtain metabolic spectra.One-dimensional and multidimensional statistical methods were used to analyze the differences in metabolites and metabolic pathways between the PDR and RRD groups.Results A total of 165 differential metabolites were identified in the vitreous humor samples of patients in the PDR and RRD groups,these differential metab-olites were significantly enriched in 21 metabolic pathways(P＜0.05),Among these pathways,those with at least 5 differ-ential metabolites include:methionine and cysteine metabolism;glycine,serine,and threonine metabolism;ascorbic acid and aldose metabolism;amino acid biosynthesis;and central carbon metabolism in cancer.Pyruvate,serine,D-2-phospho-glycerate,threonine,phosphoserine,and high serine are present in multiple metabolic pathways,the areas under the curve are 0.96,0.82,0.85,0.78,0.40,and 0.31,respectively.Conclusion There are 21 significantly different metabolic pathways between PDR and RRD patients.Pyruvate stands out in multiple pathways,potentially serving as a biomarker for PDR diagnosis.