ObjectiveTo verify the association between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis by constructing an in vitro co-culture system of testis. MethodsTesticular tissue blocks from 20-25-day-old male rats were placed in an in vitro culture system， and the culture medium was replaced every 2 to 3 days. PCR was used to verify the expression of marker genes of various spermatogenic cells. RNA interference technology was employed to verify the correlation between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis. ResultsThe co-culture system could be continuously cultured for more than 2.5 months in vitro. RT-PCR showed that specific marker genes of spermatogonia， spermatocyte and spermoblast were expressed. The RNA and protein expression of Trib3 and Akt changed after the knocking down of Ddit3 and Trib3， respectively. It demonstrated the existence of Ddit3-Trib3-Akt signaling pathway in rat spermatogenesis. ConclusionThe culture time of more than 2.5 months indicates that the culture system can temporarily maintain the proliferation and differentiation of stem cells， and simultaneously maintain and stabilize spermatogenesis in a simple system. The successful validation of the Ddit3-Trib3-Akt signaling pathway also confirms that this culture system can be used to study possible molecular mechanisms of spermatogenesis in vitro.

ObjectiveTo investigate the mechanisms of Tongnao decoction （TND） in mice with acute ischemic stroke （AIS）. MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group， model group， TND low-dose group （1.86 g·kg^-1）， TND high-dose group （3.72 g·kg^-1）， and butylphthalide （NBP） group （10 mg·kg^-1）， with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis （PT）. The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T₂-weighted imaging （T₂WI） was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin （HE） staining was used to observe histological changes in the cerebral cortex， and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging （LSCI） system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine （BrdU） and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， glycogen synthase kinase-3β （GSK-3β）， and their phosphorylation levels， as well as tight junction-related proteins zonula occludens-1 （ZO-1）， Occludin， and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group， model group， TND low and high dose groups （0.16， 0.32 g·L^-1） and NBP group （10 μmol·L^-1）， with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that， compared with the model group， the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time （P<0.05）. HE staining and Nissl staining showed that， compared with the model group， the drug-treated groups exhibited reduced brain tissue damage， fewer scars， and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group （P<0.01）， promoting angiogenesis. Meanwhile， compared with the model group， the drug-treated groups upregulated the expression levels of p-PI3K， p-Akt， p-GSK-3β， and tight junction proteins ZO-1， Occludin， and Claudin-5 （P<0.05，P<0.01）， and increased the number of intersegmental vessels in zebrafish （P<0.05，P<0.01）. ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway， thereby improving cerebral ischemic injury.

Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

OBJECTIVE To screen a single matrix， prepare dissolving microneedles of Pterocarya hupehensis total flavonoids（PHTF-MN）， and characterize it while evaluating its analgesic effects.METHODS Using microneedle morphology and puncture rate as evaluation indicators， the matrix was screened from polyvinyl alcohol （PVA）， polyvinylpyrrolidone K30 （PVP K30）， PVP K90， and sodium hyaluronate with relative molecular weights of 15 000 and 60 000 （HA 1.5w and HA 6w ）. PHTF-MN was prepared by the layer-by-layer casting method with the selected matrix， and the appearance and morphology， total flavonoid content， mechanical properties， puncture performance， dissolution properties， and drug release behavior of the obtained PHTF-MN were characterized. Using male BALB/c mice as test subjects and aspirin （ASA） as a positive control， the analgesic effects of the microneedles were evaluated using a formalin-induced pain model.RESULTS Blank microneedles prepared with 30% HA 1.5w exhibited optimal surface flatness and the membrane puncture rate （through 4 layers of parafilm membrane） reaching 78%. The PHTF-MNs （with PHTF contents of 10， 20， 30， 40， and 50 mg/g in the matrix） exhibited uniform arrays and intact tips， with RSDs for total flavonoid contents all below 7% （ n ＝8）. The single-needle puncture forces were 1.46 and 1.07 N （with PHTF contents of 30 and 50 mg/g in the matrix， respectively）. The skin penetration rate approached 100%， with visible puncture marks in the stratum corneum and drug residue （with a PHTF content of 50 mg/g in the matrix）. After 30 min of fixation， the needles had almost completely dissolved， and the skin retention rates all exceeded 90% （with PHTF contents of 10， 30， and 50 mg/g in the matrix， respectively）. The cumulative release within 8 h was （134.64±2.03） μg/cm 2 ， and the fit to the first-order kinetic equation （ R 2 ＝0.950 1） was highest （with a PHTF content of 50 mg/g in the matrix）. Low- and high-dose PHTF-MN （containing 85.26 and 145.03 μg of total flavonoids per patch， respectively； 1 patch/day） significantly shortened the cumulative time of phase Ⅱ pain response in mice （ P ＜0.05）， with pain inhibition rates （43.67% and 59.78%） comparable to those of ASA （53.70%）.CONCLUSIONS PHTF-MN using HA 1.5w as a single matrix was successfully prepared. This formulation features a simplified preparation process， uniform drug loading， favorable mechanical properties， resistance to fracture， and rapid dissolution. Its drug release behavior conforms to a first-order kinetic model， and its analgesic effect is comparable to that of ASA.

Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.

ObjectiveTo investigate the independent risk factors for poor prognosis in patients with acute pancreatitis （AP） by analyzing inflammatory factors， lung ultrasound （LUS） scores， and CT scores， to establish a nomogram prediction model， and to provide a basis for early clinical intervention. MethodsA total of 409 patients with AP who were admitted to Changshu Hospital Affiliated to Soochow University from January 2021 to October 2023 were enrolled as subjects， and they were divided into modeling group with 288 patients and validation group with 121 patients using the simple random sampling method at a ratio of 7∶3. According to the prognosis， each group was further divided into poor prognosis group and good prognosis group. The levels of C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） were measured for both groups within 72 hours after admission， and LUS scores， modified CT severity index （MCTSI）， and extrapancreatic inflammation on computed tomography （EPIC） scores were assessed within 48‍ ‍—‍ ‍72 hours after admission. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A LASSO regression analysis was used to screen for the variables that were included in the multivariate logistic regression model to identify the independent risk factors for the poor prognosis of AP， and then a nomogram prediction model was established. The receiver operating characteristic （ROC） curve and the calibration curve were used to assess the discriminatory ability and goodness of fit of the nomogram model， and a decision curve analysis was used to assess the clinical applicability of the model. ResultsAmong the 288 patients with AP in the modeling group， there were 33 （11.46%） in the poor prognosis group and 255 （88.54%） in the good prognosis group； among the 121 patients with AP in the validation group， there were 13 （10.74%） in the poor prognosis group and 108 （89.26%） in the good prognosis group. Compared with the good prognosis group， the poor prognosis group had significantly higher levels of CRP （Z=3.607， P<0.05）， IL-6 （Z=4.189， P<0.05）， and TNF-α （t=2.584， P<0.05）， and significantly higher scores of LUS （t=8.075， P<0.05）， MCTSI （t=5.929， P<0.05）， and EPIC （t=8.626， P<0.05）. The multivariate logistic regression analysis showed that CRP （odds ratio ［OR］=3.592， 95% confidence interval ［CI］： 1.272‍ ‍—‍ ‍10.138， P<0.05）， IL-6 （OR=4.225， 95%CI： 1.468‍ ‍—‍ ‍12.156， P<0.05）， TNF-α （OR=3.540， 95%CI： 1.205‍ ‍—‍ ‍10.401， P<0.05）， LUS （OR=7.094， 95%CI： 2.398‍ ‍—‍ ‍20.986， P<0.05）， MCTSI （OR=7.612， 95%CI： 2.832‍ ‍—‍ ‍20.462， P<0.05）， and EPIC （OR=11.915， 95%CI： 4.007‍ ‍—‍ ‍35.432， P<0.05） were independent risk factor for poor prognosis in patients with AP. A nomogram prediction model was established based on the above 6 indicators， which had an area under the ROC curve of 0.924 （95%CI： 0.883‍ ‍—‍ ‍0.964）， and the Youden index for the optimal cut-off value was 0.670， with a sensitivity of 0.909 and a specificity of 0.761. The calibration curve showed good consistency between the predicted and observed results in both the modeling group and the validation group. The decision curve analysis showed that the predictive model had certain clinical effectiveness. ConclusionThe nomogram model for predicting the risk of poor prognosis in AP patients based on CRP， IL-6， TNF-α， LUS score， MCTSI score， and EPIC score has relatively good predictive performance and can provide important strategic guidance for developing early intensified treatment regimens for AP patients in clinical practice.

Objective: To investigate the effect of a free pit and fissure sealing program for caries prevention on first permanent molars (six-year molars) in Haizhu District, Guangzhou, three years after its implementation in 2019. The study aims to provide a reference for the future development of pit and fissure sealing programs for children’s first permanent molars and the effective prevention and treatment of permanent tooth caries in children. Methods: A random sampling method was used. In 2022 October, 270 sixth-grade primary-school students in Haizhu District, Guangzhou, who had participated in the free pit and fissure sealing program for their first permanent molars in 2019, were placed in the sealant group. Another 223 age-matched students from the same schools who met the criteria for the pit and fissure sealing but did not participate in the program were placed in the control group. The first permanent molars of students in both groups were examined. The retention status of the sealant and the caries status of the first permanent molars were recorded for the sealant group, and the caries status of the first permanent molars was recorded for the control group. The 2022 results were compared with the results of a prior pit and fissure sealing program implemented in Haizhu District in 2011, three years after its implementation. Results: Compared with the control group, the caries rate in the sealant group decreased (15.56% vs. 21.52%, P>0.05), the caries detection rate was significantly lower (6.12% vs. 9.00%, P<0.001), and the mean number of decayed teeth was significantly reduced (0.19 vs. 0.37, P<0.001). Compared with the results of the pit and fissure sealing program in Haizhu District in 2011 (in 2014, the retention rate of the first permanent molar sealant was 65.56%, the intact rate was 42.25%, and the protection rate was 38.34%), the results of the pit and fissure sealing program in Haizhu District in 2019 [in 2022, the retention rate of the first permanent molar sealant was 86.09% (P<0.001), the intact rate was 47.00% (P<0.001), and the protection rate was 51.97%] were improved. Conclusion The quality of the pit and fissure sealing program for the first permanent molars in Haizhu District, Guangzhou in 2019 was good. It reduced the caries detection rate, and the retention rate of the sealant was maintained at a high level. However, the intact rate was less than 50%; therefore, it is necessary to vigorously promote oral-health education and examinations in all age groups, and to be attentive to the re-examination and re-sealing of fissure sealants.

Objective:To explore the RNA expression and alterations in brain structure in individuals who have experienced stressful life events (SLE), as well as the correlation patterns between them and their association with the occurrence of depression.Methods:Prospectively, a total of 80 SLE subjects were recruited from the psychiatry and psychology clinic of the Jiangsu University Affiliated Yixing Hospital between January 2021 and December 2022, with 16 normal controls (NC) enrolled concurrently. The 17 items Hamilton depression scale (HAMD-17) and social readjustment rating scale (SRRS) were used to assess depressive symptoms and stress levels. RNA sequencing information of peripheral blood and imaging data at baseline were collected. Based on whether depression occurred during the 2-year follow-up period, SLE subjects were divided into the SLE-depression group ( n=15) and the SLE-non-depression group ( n=65). Differentially expressed genes (DEGs) were screened using differential analysis and protein-protein interaction (PPI) networks. Fractional anisotropy (FA) of white matter tracts and gray matter volume (GMV) were extracted using tract-based spatial statistics and voxel-based morphometry.Using analysis of variance compared inter-group differences in gene expression, GMV and white matter FA values. Partial correlation analysis was used to explore correlations between DEGs, altered GMV and white matter microstructure. Gene set enrichment analysis (GSEA) was performed on key genes to identify potential biological pathways. Propensity score matching constructed sensitivity subgroups to verify result robustness. Results:The SLE-depression group showed significantly higher SRRS and HAMD-17 scores at baseline and at the end of follow-up compared to the SLE-non-depression group and the NC group ( H=47.773, 35.427, 41.114, all P<0.05). Expression levels of IL-10 (2.12±0.28, 2.43±0.44), EZH2 (2.11±0.43, 2.45±0.51), NCAM1 (3.60±0.30, 3.03±0.39), CD3E (4.95±0.37, 4.57±0.48), CCK (3.29±0.28, 3.02±0.42), and CX3CR1 (5.55±0.40, 5.91±0.34) were significantly different between the SLE-depression group and SLE-non-depression group( F=5.549~28.371, all P<0.05). Compared with the SLE-non-depression group, the SLE-depression group exhibited significantly lower FA values in the genu of the corpus callosum (0.29±0.04, 0.31±0.04) and the left uncinate fasciculus (0.31±0.02, 0.33±0.02), as well as significantly smaller GMV in the right hippocampus (0.29±0.07, 0.33±0.06), bilateral middle frontal gyrus (left: 0.27±0.05, 0.31±0.05; right: 0.28±0.06, 0.32±0.06), right insula (0.36±0.03, 0.38±0.04), and left precentral gyrus (0.19±0.04, 0.24±0.05) ( F=4.593-12.064, all P<0.05, FDR correction). GMV in the right anterior cingulate and paracingulate gyri was significantly larger than that in the SLE-non-depression group (0.34±0.05, 0.29±0.06) ( F=6.704, P=0.034, FDR correction). Partial correlation analysis revealed significantly stronger correlations between hub DEGs and altered brain regions in the SLE-depression group ( r=0.017-0.801) compared to the SLE-non-depression group ( r=0.002-0.382), with a statistically significant difference ( U=629, P<0.001; Cliff's Delta=0.454). GSEA indicated that the aforementioned genes were primarily involved in pathways including the ribosome, spliceosome, ribosome biogenesis in eukaryotes, and neuroactive ligand-receptor interaction. Sensitivity analysis confirmed that the above results remained statistically significant after balancing sample sizes (all P<0.05). Conclusion:The SLE-depression group showed specific RNA expression and brain structure alterations compared to the SLE-non-depression group, and the correlation between RNA and brain structure was significantly enhanced in the SLE-depression group. This suggests that the correlation between genes and brain structure in the SLE population may be related to their susceptibility to depression.