BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

Objective:To evaluate the value of peripheral blood systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), D-dimer, and albumin (ALB) alone or their combination in the diagnosis of early-onset colorectal cancer (EOCRC).Methods:From January 1, 2023 to November 30, 2024, 104 patients with EOCRC (EOCRC group) hospitalized at Renmin Hospital of Wuhan University were enrolled. During the same period, by simple random sampling method, 104 patients with benign colorectal polyps (benign polyp group) and 104 healthy individuals for health examinations (healthy control group) from outpatient department were enrolled. The peripheral blood parameters (including neutrophil count, lymphocyte count, CEA, and others) and pathological characteristics of EOCRC (including TNM stage, tumor differentiation grade, and depth of invasion) were collected. The relationship between peripheral blood parameters and EOCRC pathological features were analyzed. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the diagnostic value. Multivariate logistic regression analysis was performed to analyze the peripheral blood parameters which independently correlated with EOCRC and a combined diagnostic model was established. Simple random sampling method was used to divide the subjects in the negative control group (healthy control group + benign polyp group) and positive group (EOCRC group) into a training set (218 cases) and a validation set (94 cases) at a ratio of 7∶3, and the diagnostic performance of the combined diagnostic model in the training and validation sets was assessed. Hosmer-Lemeshow test and calibration curve were used to evaluate the fit and consistency of the model. Independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test were used for statistical analysis. Results:EOCRC group had the highest levels of SII(744.03 (473.01, 1 246.28), 437.77 (342.28, 607.47), 497.31 (385.76, 721.63)×10 9/L), NLR(2.42 (1.76, 3.94), 1.96 (1.54, 2.52), 1.91 (1.55, 2.75)), CEA (3.58 (1.96, 20.85), 1.31 (0.95, 1.93), 1.21 (0.76, 2.11) μg/L) and D-dimer (0.36 (0.20, 0.90), 0.19 (0.12, 0.28), 0.18 (0.12, 0.30) mg/L), and the lowest levels of LMR(3.51±1.56, 4.38±1.37, 4.72±1.84) and ALB(42.40 (39.90, 44.70), 44.57 (42.83, 46.25), 44.95 (43.10, 46.58) g/L) than benign polyp group and healthy control group, and the differences were statistically significant ( H=31.18, 16.21, 76.72 and 47.72, F=15.40, H=34.19; all P<0.001). In EOCRC patients, there were statistically significant differences in SII and LMR between patients with different tumor invasion depth ( Z=-2.48, t=2.31; both P<0.05), in CEA between patients with different TNM stage, with or without lymph node metastasis and distant metastasis( Z=-2.68, -2.50 and -2.65; all P<0.05), in D-dimer between patients with different TNM stage, differentiation grade, invasion depth, and with or without lymph node metastasis and distant metastasis ( Z=-2.50, -2.60, -2.06, -2.14 and -3.33; all P<0.05), and in ALB between patients with or without distant metastasis ( Z=-2.52, P=0.012).The AUC of combination of SII, NLR, LMR, CEA, D-dimer, and ALB in differential diagnosis of the healthy control group and the EOCRC group was 0.914 (95% confidence interval (95% CI): 0.870 to 0.958, P<0.001), and the AUC of the combination in differential diagnosis of the benign polyp group and the EOCRC group was 0.904 (95% CI: 0.857 to 0.950, P<0.001). The results of multivariate logistic regression analysis revealed that SII, NLR, LMR, CEA, and ALB were all independently correlated with EOCRC (all P<0.05). The diagnostic model for EOCRC was established by the combination of SII, NLR, LMR, CEA, and ALB, and the AUC of the model in the training set and validation set was 0.911 and 0.883, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated good model fit ( P=0.437). Calibration curve analysis showed strong consistency between predicted probabilities and actual probabilities, and the mean absolute error was 0.015. Conclusions:SII, NLR, LMR, CEA, D-dimer, and ALB all demonstrate diagnostic value in the diagnosis of EOCRC. The combined diagnostic model based on SII, NLR, LMR, CEA, and ALB demonstrates excellent diagnostic performance, which may serve as an adjunctive diagnostic approach for EOCRC.

To verify a new diagnostic method in traditional Chinese medicine (TCM), we evaluated the function of meridians using thermal sensitivity measurement (TSM), and conducted a comparative study between nephropathy patients and healthy individuals. We also evaluated whether TSM is useful for diagnosing nephropathy. The subjects included nephropathy patients (n = 203) and healthy individuals (n = 826). Heat detection times were measured at the well points on both the left and right sides of the twelve meridians. Multivariate analysis was conducted, with the presence or absence of nephropathy as the objective variable and the heat detection times of each meridian as the explanatory variable. The meridians identified as important for diagnosing nephropathy included the pericardium meridian, the triple energizer (sanjiao) meridian, small intestine meridian, liver meridian, bladder meridian, and kidney meridian. A diagnostic method combining age and the heat detection times of these meridians achieved sensitivity and specificity of over 80%. This method intuitively and quantitatively reflects the sub-heat and sub-cold states of each meridian, and is expected to enrich the diagnostic methods in traditional Chinese and Oriental medicine.

Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase Ⅰ)to gastric precancerous lesions(Phase Ⅱ)and finally to GC(Phase Ⅲ).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases Ⅰ and Ⅱ,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase Ⅰ,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resis-tance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase Ⅱ,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase Ⅲ,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.

Abstract： ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 （GLUT1） on the proliferation， migration， adhesion， and angiogenesis of human umbilical vein endothelial cells （HUVECs） under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment （1% O₂， 5% CO₂， 94% N₂）. The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability， proliferation capacity， and examining the expression changes of GLUT1， HIF-1α， and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further， GLUT1 was overexpressed using plasmid transfection and the proliferation， migration， adhesion， and angiogenic capabilities of HUVECs were evaluated through scratch assays， cell adhesion assays， and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy，and oxygen consumption rate （OCR） was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions， the ischemia-hypoxic environment significantly inhibited the proliferation， cell viability， migration， and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1， HIF-1α and VEGFA proteins were also markedly reduced. However， when GLUT1 expression was upregulated， the migration， adhesion， and angiogenic capabilities of HUVECs were significantly improved， and the protein expression levels of HIF-1α， VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage， while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions， potentially through modulating cellular energy metabolism and signal transduction pathways， thereby affecting cell proliferation， migration， adhesion， and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.

Gastric carcinoma (GC) is a malignancy with multifactorial involvement, multicellular regulation, and multistage evolution. The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa, in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis (Phase I) to gastric precancerous lesions (Phase II) and finally to GC (Phase III). Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa. Intervening in early gastric mucosal lesions, i.e., Phase I and II, will be the key strategy to prevent and treat GC. Natural products (NPs) have been an important source for drug development due to abundant sources, tremendous safety, and multiple pharmacodynamic mechanisms. This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis. In phase I, NPs modulate Helicobacter pylori urease activity, motility, adhesion, virulence factors, and drug resistance, thereby inhibiting H. pylori-induced gastric mucosal inflammation and oxidative stress, and facilitating ulcer healing. In Phase II, NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle, apoptosis, autophagy, and angiogenesis to reverse gastric precancerous lesions. In Phase III, NPs suppress cell proliferation, migration, invasion, angiogenesis, and cancer stem cells, induce apoptosis and autophagy, and enhance chemotherapeutic drug sensitivity for the treatment of GC. In contrast to existing work, we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development, providing new ideas for gastric cancer prevention, treatment, and drug development.

Objective:To evaluate the value of peripheral blood systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), D-dimer, and albumin (ALB) alone or their combination in the diagnosis of early-onset colorectal cancer (EOCRC).Methods:From January 1, 2023 to November 30, 2024, 104 patients with EOCRC (EOCRC group) hospitalized at Renmin Hospital of Wuhan University were enrolled. During the same period, by simple random sampling method, 104 patients with benign colorectal polyps (benign polyp group) and 104 healthy individuals for health examinations (healthy control group) from outpatient department were enrolled. The peripheral blood parameters (including neutrophil count, lymphocyte count, CEA, and others) and pathological characteristics of EOCRC (including TNM stage, tumor differentiation grade, and depth of invasion) were collected. The relationship between peripheral blood parameters and EOCRC pathological features were analyzed. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the diagnostic value. Multivariate logistic regression analysis was performed to analyze the peripheral blood parameters which independently correlated with EOCRC and a combined diagnostic model was established. Simple random sampling method was used to divide the subjects in the negative control group (healthy control group + benign polyp group) and positive group (EOCRC group) into a training set (218 cases) and a validation set (94 cases) at a ratio of 7∶3, and the diagnostic performance of the combined diagnostic model in the training and validation sets was assessed. Hosmer-Lemeshow test and calibration curve were used to evaluate the fit and consistency of the model. Independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test were used for statistical analysis. Results:EOCRC group had the highest levels of SII(744.03 (473.01, 1 246.28), 437.77 (342.28, 607.47), 497.31 (385.76, 721.63)×10 9/L), NLR(2.42 (1.76, 3.94), 1.96 (1.54, 2.52), 1.91 (1.55, 2.75)), CEA (3.58 (1.96, 20.85), 1.31 (0.95, 1.93), 1.21 (0.76, 2.11) μg/L) and D-dimer (0.36 (0.20, 0.90), 0.19 (0.12, 0.28), 0.18 (0.12, 0.30) mg/L), and the lowest levels of LMR(3.51±1.56, 4.38±1.37, 4.72±1.84) and ALB(42.40 (39.90, 44.70), 44.57 (42.83, 46.25), 44.95 (43.10, 46.58) g/L) than benign polyp group and healthy control group, and the differences were statistically significant ( H=31.18, 16.21, 76.72 and 47.72, F=15.40, H=34.19; all P<0.001). In EOCRC patients, there were statistically significant differences in SII and LMR between patients with different tumor invasion depth ( Z=-2.48, t=2.31; both P<0.05), in CEA between patients with different TNM stage, with or without lymph node metastasis and distant metastasis( Z=-2.68, -2.50 and -2.65; all P<0.05), in D-dimer between patients with different TNM stage, differentiation grade, invasion depth, and with or without lymph node metastasis and distant metastasis ( Z=-2.50, -2.60, -2.06, -2.14 and -3.33; all P<0.05), and in ALB between patients with or without distant metastasis ( Z=-2.52, P=0.012).The AUC of combination of SII, NLR, LMR, CEA, D-dimer, and ALB in differential diagnosis of the healthy control group and the EOCRC group was 0.914 (95% confidence interval (95% CI): 0.870 to 0.958, P<0.001), and the AUC of the combination in differential diagnosis of the benign polyp group and the EOCRC group was 0.904 (95% CI: 0.857 to 0.950, P<0.001). The results of multivariate logistic regression analysis revealed that SII, NLR, LMR, CEA, and ALB were all independently correlated with EOCRC (all P<0.05). The diagnostic model for EOCRC was established by the combination of SII, NLR, LMR, CEA, and ALB, and the AUC of the model in the training set and validation set was 0.911 and 0.883, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated good model fit ( P=0.437). Calibration curve analysis showed strong consistency between predicted probabilities and actual probabilities, and the mean absolute error was 0.015. Conclusions:SII, NLR, LMR, CEA, D-dimer, and ALB all demonstrate diagnostic value in the diagnosis of EOCRC. The combined diagnostic model based on SII, NLR, LMR, CEA, and ALB demonstrates excellent diagnostic performance, which may serve as an adjunctive diagnostic approach for EOCRC.

Background and purpose:Long non-coding RNA(lncRNA)LINC01410,with a length of 647 bp,participates in a variety of tumor biological processes.However,the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma(ESCC)remain unclear.This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion,to provide a potential prognostic indicator and therapeutic target for individuals with ESCC.Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas(TCGA).Gene Set Enrichment Analysis(GSEA)was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC.A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected.This project has been approved by the Hospital Ethics Committee(First Affiliated Hospital of Xinxiang Medical College,No.2018036;First People's Hospital of Pingdingshan City,No.2019-018).The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410.Stable transfected cells(EC109/NC,EC109/OE,EC9706/NC and EC9706/KD)were selected in primary cell culture medium containing puromycin.The expression of LINC01410 was detected by RTFQ-PCR.The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and colony formation assays.The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay.T cell factor/lymphoid enhancer factor 1(TCF/LEF1)luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway.The expressions of Wnt/β-catenin and epithelial-mesenchymal transition(EMT)signal pathway related proteins in ESCC cells were detected by Western blot.Results:By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2,we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues(P＜0.05),and high LINC01410 expression was associated with poorer overall survival(OS).RTFQ-PCR assay showed that expressions of LINC01410 were higher in esophageal cancer tissues and esophageal cancer cells(EC109 and EC9706)than in precancerous tissues and HEEC cells(P＜0.05).The expression level of LINC01410 was significantly correlated with invasion range,lymph node metastasis and TNM stage in ESCC patients(P＜0.01).LINC01410 expression was also upregulated in EC109/OE,however the expression of LINC01410 in EC9706/KD was decreased(P＜0.01).MTT assay showed overexpression of LINC01410 increased the viability of EC109 cells,while knockdown of LINC01410 decreased the viability of EC9706 cells(P＜0.01).Colony formation assay indicated that overexpression of LINC01410 enhanced the clonogenic ability of ESCC cells,while knockdown of LINC01410 reduced colony formation(P＜0.01).Transwell migration assay showed that LINC01410 overexpression drastically increased the number of migratory cells,while silencing of LINC01410 suppressed the migration in EC9706 cells(P＜0.01).GSEA revealed that Wnt/β-catenin and EMT pathways were significantly enriched in ESCC samples with a high level of LINC01410.TCF/LEF1 luciferase reporter assay showed higher levels of Wnt-dependent activities were observed in EC109/OE cells,whereas silenced LINC01410 in EC9706 cells led to contrary results(P＜0.01).Western blot analysis showed that overexpression of LINC01410 in EC109 cell significantly increased the expression levels of N-cadherin,β-catenin,cyclin D1,c-Myc and decreased E-cadherin expression,while knockdown LINC01410 resulted in opposite results.Conclusion:LINC01410 promotes proliferation and metastasis of ESCC,which might be caused by activation of Wnt/β-catenin and EMT signaling pathways.

ObjectiveTo assess the microstructural involvement of gray matter in recovered COVID-19 patients using Synthetic MRI. MethodsThis study was conducted in 29 recovered COVID-19 patients， including severe group （SG， n=11） and ordinary group （OG， n=18）. Healthy volunteers matched by age， sex， BMI and years of education were selected as a healthy control group （HC=23 cases）. Each subject underwent synthetic MRI to generate quantitative T₁ and T₂ maps， and the T₁ and T₂ maps were segmented into 90 regions of interest （ROIs） using automatic anatomical labeling （AAL） mapping. T₁ and T₂ values for each ROI were obtained by averaging all voxels within the ROIs. The T₁ and T₂ values of the 90 brain regions between the three groups were compared. ResultsRelative to HC， the SG had significantly higher T2 values in bilateral orbital superior frontal gyrus， bilateral parahippocampal gyrus， bilateral putamen， bilateral middle temporal gyrus， bilateral Inferior temporal gyrus， left orbital superior frontal gyrus， left orbital inferior frontal gyrus， left gyrus rectus， left anterior cingulate and paracingulate gyri， right median cingulate and paracingulate gyri， left posterior cingulate gyrus， and left supramarginal gyrus （P＜0.05）； Relative to OG， SG showed significantly increased T₂ values in the left rectus gyrus， left parahippocampal gyrus， bilateral middle temporal gyrus， and bilateral inferior temporal gyrus （P＜0.05）. Relative to HC， the T₁ values of SG were significantly increased in bilateral orbital superior frontal gyrus， left rectus gyrus， left anterior cingulate and paracingulate gyri， right posterior cingulate gyrus， left parahippocampal gyrus， left lingual gyrus， left putamen， left thalamus（P＜0.05）； Relative to OG， the T₁ values of SG were significantly higher in the right posterior cingulate gyrus， right calcarine fissure and surrounding cortex， and left putamen （P＜0.05）. ConclusionsEven after recovering from COVID-19， patients may still have persistent or delayed damage to their brain gray matter structure， which is correlated with the severity of the condition. SyMRI can serve as a sensitive tool to assess the extent of microstructural damage to the central nervous system， aiding in early diagnosis of the disease.