Spinal cord stimulation (SCS) is a commonly used treatment for refractory zoster-associated pain (ZAP). The conventional open-loop regulation mode mainly relies on patients' subjective feedback for manual parameter adjustment, whereas the clinical application of closed-loop SCS regulation remains immature and requires further optimization. Previous studies have shown that SCS can influence electroencephalography (EEG) functional connectivity. This study aims to investigate whether a support vector machine (SVM) based on EEG functional connectivity features can effectively identify different neuromodulation states of SCS. A total of 21 patients with ZAP who underwent SCS treatment were retrospectively included. Visual Analogue Scale (VAS) scores were recorded before SCS implantation, at discharge, and at 1, 3, and 6 months postoperatively. EEG data lasting 5-10 minutes were collected under SCS-on and SCS-off conditions. The EEG data were randomly divided into a training set and a test set at a ratio of 7∶3. Pearson correlation coefficient (PCC) and coherence (COH) between EEG feature channels were extracted to construct an SVM-based classification model. Model performance in distinguishing SCS-on and SCS-off EEG states was evaluated using accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). Shapley additive explanations (SHAP) were used to interpret the SVM model by analyzing the contribution and direction of each EEG feature to the model prediction. SCS effectively alleviated pain in patients with ZAP. Compared with baseline, VAS scores were significantly reduced at discharge and at 1, 3, and 6 months after SCS treatment (all P<0.001). The classification performance of SVM with different kernel functions for identifying SCS neuromodulation states showed that the radial basis function kernel SVM achieved an accuracy of 0.912, sensitivity of 0.927, specificity of 0.893, and AUC of 0.972, whereas the linear kernel SVM achieved an accuracy of 0.677, sensitivity of 0.714, specificity of 0.665, and AUC of 0.744. SHAP analysis showed that the top 20 most influential features contributing to the classification results were all COH features. In the beta frequency band, the COH between electrode pairs O2-F8 and FP2-F7 contributed most strongly to the model prediction, and increases in these values were positively associated with the SCS-on state. In contrast, the COH of the P4-P8 electrode pair in the theta frequency band was closely associated with the SCS-off state. The SVM model based on EEG functional connectivity features can effectively identify different neuromodulation states of SCS in patients with ZAP. These findings suggest that SCS may induce alterations in brain functional connectivity and provide a basis for future studies on EEG-based closed-loop SCS regulation.

In recent years, the phenomenon of "hollow heart syndrome" has become increasingly prevalent among college students, characterized by persistent inner emptiness, lack of motivation, and a diminished sense of meaning. Even when external achievements are attained, individuals often fail to experience a sense of fulfillment and satisfaction. Such students may appear successful outwardly but remain trapped in confusion and meaninglessness, and may even frequently experience suicidal ideation. As a critical stage of psychological development, the college period involves the transition from identity diffusion to identity formation. Establishing a stable and clear self-identity during this stage is essential for developing a sustained sense of meaning in life. Therefore, this study aims to examine the relationship between self-concept clarity and meaning in life among college students using a longitudinal design, and to further investigate the moderating role of depressive symptoms in this relationship, thereby providing theoretical support for promoting meaning in life and empirical evidence for improving psychological crisis prevention and intervention systems. A longitudinal design was employed. A total of 387 college students from a comprehensive university were assessed twice at a four-week interval, with the two time points denoted as T1 and T2. The instruments included the Self-Concept Clarity Scale (SCCS), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Meaning in Life Questionnaire (MLQ). Cross-lagged analysis was conducted to examine the bidirectional relationship between self-concept clarity and meaning in life, and standardized regression coefficients (β) were calculated. Based on this, a two-step multiple regression analysis was used to test the moderating effects of depressive symptoms on the pathways from self-concept clarity to meaning in life and from meaning in life to self-concept clarity. For paths showing significant moderation, simple slope analyses were further conducted to explore the moderating patterns at different levels of depressive symptoms. Self-concept clarity at T1 significantly and positively predicted meaning in life at T2 (β=0.214, P<0.001), and meaning in life at T1 significantly and positively predicted self-concept clarity at T2 (β=0.211, P<0.001). Depressive symptoms significantly moderated only the predictive effect of self-concept clarity on meaning in life (P=0.035). Simple slope analysis showed that the effect sizes were 0.400 and 0.245 in the high and low depressive symptom groups, respectively. However, the moderating effect of depressive symptoms on the pathway from meaning in life to self-concept clarity was not significant (P=0.258). This is a reciprocal and mutually reinforcing relationship between self-concept clarity and meaning in life. Depressive symptoms play a moderating role in this relationship, such that higher levels of depressive symptoms strengthen the predictive effect of self-concept clarity on meaning in life. Therefore, in mental health education and intervention among college students, it is important to emphasize the coordinated development of self-concept and meaning construction, and to utilize the moderating role of depressive symptoms to optimize intervention strategies. For students with depressive tendencies, priority should be given to assessing and improving their identity status, promoting self-acceptance, integration, and identity consolidation. For students with unclear self-concept, timely assessment of depressive symptoms and early psychological intervention are recommended to reduce the negative cycle between self-concept and meaning in life and to promote psychological adaptation and healthy development.

The prognostic nutritional index (PNI) is a composite indicator reflecting nutritional and immune status; however, its association with incident hyperuricemia (HUA) remains unclear. This large-scale retrospective cohort study aims to investigate the relationship between PNI and the risk of developing HUA, providing evidence for early screening and nutritional intervention strategies. A total of 22 551 individuals who underwent baseline health examinations in 2012 were included. Participants were categorized into quartiles according to PNI levels (Q1, <52.4; Q2, 52.4-<55.1; Q3, 55.1-<57.9; Q4, ≥57.9). Cox proportional hazards models were used to evaluate the association between PNI and incident HUA, with progressive adjustment for age, sex, body mass index (BMI), hypertension, diabetes, dyslipidemia, and renal function. Using Q1 as the reference group, hazard ratios (HR) for Q2-Q4 were estimated. Restricted cubic spline models were applied to assess the dose-response relationship between continuous PNI and HUA risk. Additionally, Q1-Q3 were combined as the low-PNI group (PNI<57.9) and Q4 as the high-PNI group (PNI≥57.9) for subgroup analyses and interaction testing. The numbers of participants in Q1-Q4 were 5 468, 5 658, 5 680, and 5 745, respectively. During a median follow-up of 10.5 years, 5 247 incident HUA cases were identified. In the fully adjusted model, participants in Q4 had an 18.4% higher risk of HUA compared with Q1 [HR=1.184, 95% confidence interval (CI) 1.089 to 1.287, P<0.001]. When treated as a continuous variable, each 1-unit increase in PNI was associated with a 1.4% increase in HUA risk (HR=1.014, 95% CI 1.007 to 1.020, P<0.001), demonstrating a significant dose-response relationship (Ptrend<0.001). Restricted cubic spline analysis indicated a linear positive association between PNI and HUA risk after full adjustment (Ptrend<0.05). Subgroup analysis revealed that the high-PNI group had a 16.2% higher risk of HUA compared with the low-PNI group (HR=1.162, 95% CI 1.092 to 1.237, P<0.001); however, this association was attenuated among individuals with hypertension (Pinteraction=0.010). Elevated PNI (≥57.9) is an independent risk factor for incident HUA in a general health examination population, and this association is significantly modified by hypertension status. As a readily available composite marker, PNI may facilitate early identification of individuals at high risk for HUA and support personalized screening and intervention strategies.

The incidence and mortality of colorectal carcinoma (CRC) continue to rise globally, highlighting the need to identify modifiable risk factors for early detection and prevention. Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines; however, due to limitations in study design and potential confounding factors, the causal relationships remain unclear. This study aims to investigate the causal relationships between inflammatory cytokines, serum metabolites, and CRC risk, providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets. A two-sample Mendelian randomization (MR) design was applied using summary statistics from genome-wide association studies (GWAS). Instrumental variables (IVs) were derived from: 1) metabolomics GWAS data of 1 400 serum metabolites (n=8 299); 2) cytokine GWAS data of 91 inflammatory factors (n=14 824); and 3) CRC risk data from the FinnGen consortium (6 847 cases and 314 193 controls). The primary analysis was conducted using the inverse-variance weighted (IVW) method, with sensitivity analyses performed using MR Egger regression and the weighted median method. Effect estimates including odds ratios (OR), 95% confidence intervals (CI), and false discovery rates (FDR) were calculated. MR analysis indicated that higher levels of axin-1 (AXIN1) (OR=0.841 95% CI 0.714 to 0.991) and Fms-related tyrosine kinase 3 ligand (Flt3L) (OR=0.916, 95% CI 0.844 to 0.994) were associated with a reduced risk of CRC. In contrast, higher levels of Delta/Notch- like epidermal growth factor-related receptor (DNER) (OR=1.119, 95% CI 1.009 to 1.241) and vascular endothelial growth factor A (VEGF-A) (OR=1.078, 95% CI 1.011 to 1.150) were associated with an increased risk of CRC (all P<0.05). Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines (FDR<0.05), suggesting that they may regulate CRC risk through inflammatory pathways. Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC. These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.

Cardiac fibrosis is a common pathological feature during the progression of various cardiovascular diseases and is characterized by excessive deposition of extracellular matrix (ECM) in the myocardial interstitium, accompanied by alterations in cardiac structure and function. MicroRNAs (miRNAs) play important roles in the regulation of cardiac fibrosis. Previous studies have suggested that miR-34a is involved in fibrotic processes; however, its in vivo effects on cardiac fibrosis and cardiac function, as well as its relationship with mitochondrial tumor suppressor 1 (MTUS1), remain unclear. This study aimed to investigate the effects of miR-34a targeting MTUS1 on cardiac fibrosis and cardiac function in rats through in vivo intervention. Healthy adult male Sprague-Dawley (SD) rats were used to establish a myocardial fibrosis model by subcutaneous injection of isoproterenol (ISO) at a dose of 10 mg/(kg·d) for 14 consecutive days (model group), while the control group received equal volumes of normal saline. Transthoracic echocardiography (TTE) was performed to evaluate cardiac structural and functional changes. Left ventricular tissues were collected and paraffin sections were prepared. Hematoxylin-eosin (HE) staining was used to observe histological changes in myocardial tissue, and Masson staining was used to assess collagen deposition. Real-time polymerase chain reaction (real-time PCR) and Western blotting were performed to detect the expression levels of miR-34a, MTUS1, and fibrosis-related proteins including α-smooth muscle actin (α-SMA) and collagen I. Bioinformatics analysis was used to predict potential binding sites between miR-34a and MTUS1. A dual-luciferase reporter assay was performed to verify the targeting relationship between miR-34a and MTUS1. Furthermore, adeno-associated virus (AAV) was used in vivo to downregulate the expression of miR-34a and MTUS1, and the effects on cardiac function and myocardial fibrosis were evaluated. ISO-treated rats exhibited pronounced myocardial fibrotic changes. HE staining revealed disorganized myocardial fibers and widened interstitial spaces, and Masson staining demonstrated increased collagen deposition. TTE analysis showed that left ventricular ejection fraction was reduced in the model group compared with the control group (P<0.05). Compared with control rats, ISO-treated rats showed increased miR-34a expression and decreased MTUS1 expression in myocardial tissues, accompanied by elevated protein levels of α-SMA and collagen I (all P<0.05). Dual-luciferase reporter assays demonstrated that miR-34a directly bound to the 3' untranslated region of MTUS1 and suppressed its expression. AAV-mediated downregulation of miR-34a attenuated myocardial fibrosis, reduced collagen deposition, and improved cardiac functional parameters compared with the model group; these effects were correspondingly altered when MTUS1 expression was concurrently modulated. In an ISO-induced rat model of cardiac fibrosis, miR-34a participates in the regulation of myocardial fibrosis and cardiac functional alterations by targeting MTUS1. The in vivo AAV intervention results suggest that the miR-34a-MTUS1 regulatory axis is associated with the progression of cardiac fibrosis.

Zoster-associated pain (ZAP) is an acute and chronic neuropathic pain condition caused by reactivation of varicella-zoster virus in sensory ganglia, which can severely impair patients' quality of life. Nerve block is one of the most commonly used interventional techniques in clinical practice and is often combined with various adjunctive agents to enhance therapeutic efficacy. However, these agents differ in mechanisms of action and levels of evidence, and due to differences in the pathological mechanisms at different stages of ZAP, there is currently a lack of systematic evaluation based on disease staging, resulting in insufficient precision in clinical decision-making. This study aims to systematically evaluate the clinical evidence for different adjunctive agents and clarify their application value at different stages of the disease course, thereby providing a reference for individualized treatment. Relevant literature published up to December 31, 2025, was systematically searched in PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform. Inclusion criteria were: 1) Patients diagnosed with acute herpes zoster (AHZ) or postherpetic neuralgia (PHN); 2) interventions involving drugs used as adjuncts in nerve blocks or local injections; 3) randomized controlled trials (RCT), prospective cohort studies, or case-control studies. Two reviewers independently performed literature screening and data extraction. Extracted data included first author, publication year, sample size, type of nerve blocks or local injections, type and dosage of adjunctive agents, and main outcome measures. The level of evidence was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria, and adjunctive agents were graded according to the highest level of evidence. A total of 29 clinical studies were included. Based on the level of evidence, adjunctive agents were categorized into level A and level B evidence groups. Among level A evidence agents, glucocorticoids relieve pain through potent anti-inflammatory effects, while botulinum toxin type A exerts analgesic effects by inhibiting the release of pain mediators and modulating neural signaling. Among level B evidence agents, platelet-rich plasma promotes nerve repair by releasing growth factors; medical ozone exerts effects through anti-inflammatory action and improvement of circulation; methylene blue provides long-term analgesia by ameliorating reversible demyelinating nerve injury; and vaccinia virus-inoculated rabbit inflammatory skin extract (Neurotropin) may regulate pain by activating descending inhibitory pathways. Based on disease stage, anti-inflammatory treatment (e.g., glucocorticoids) is recommended in the acute phase, whereas neuromodulation and nerve repair (e.g., botulinum toxin type A, platelet-rich plasma) are emphasized in the chronic phase. All adjunctive agents require careful consideration of their specific potential serious adverse events. The use of adjunctive agents in nerve blocks/local injections provides a multi-mechanistic and stage-specific therapeutic strategy for ZAP. Glucocorticoids and botulinum toxin type A have the highest level of supporting evidence. However, challenges remain, including heterogeneity in evidence levels and lack of standardized protocols. Future high-quality, large-scale randomized controlled trials, especially those comparing different adjunctive agents across disease stages, are needed to further optimize clinical treatment strategies.

Internet addiction and depressive symptoms are common comorbid mental health problems among adolescents. This study aims to employ a cross-lagged panel network (CLPN) model to examine the longitudinal dynamic interactions between adolescent internet addiction and depressive symptoms at the symptom level, and to explore gender-specific patterns. A total of 1 138 adolescents from a middle school in a northern city were followed for 5 months with two waves of assessment. Internet addiction and depressive symptoms were measured using the Internet Addiction Test (IAT) and the Patient Health Questionnaire-9 (PHQ-9), respectively. CLPN was conducted using R software version 4.4.0 to estimate out-expected influence (out-EI) and in-expected influence (in-EI). The cross-lagged effects of depressive symptoms on internet addiction were stronger than the reverse effects. In the overall sample, feelings of worthlessness showed the highest out-EI. Gender-specific CLPN results indicated that, in males, suicidal ideation had significant negative cross-lagged effects on salience, neglect of work, and anticipation in internet addiction. In females, excessive internet use and lack of control showed significant positive cross-lagged effects. Depressive symptoms are key drivers of internet addiction in adolescents, with notable gender differences in symptom pathways. Future research and interventions should consider gender sensitivity and target specific symptom pathways to develop precise prevention and intervention strategies.

Prevention and treatment of perioperative acute kidney injury (AKI) remain a major focus in clinical practice. This study aims to investigate the role and underlying mechanism of sestrin2 (SESN2) in Erastin-induced ferroptosis of renal tubular cells and AKI in ICR mice. For in vitro experiments, human renal proximal tubular epithelial cells (HK-2) stably transfected with lentivirus were divided into three groups: control group, Erastin model group, and SESN2 intervention group. The control group was transfected with empty vector lentivirus (LV-Con). The Erastin model group was transfected with LV-Con and then treated with 10 μmol/L Erastin for 24 h. The SESN2 intervention group was transfected with SESN2-overexpressing lentivirus (LV-SESN2) followed by Erastin treatment. For in vivo experiments, after confirming successful establishment of the Erastin-induced AKI mouse model by measuring serum creatinine (SCr) and blood urea nitrogen (BUN), 18 healthy adult male ICR mice were randomly divided into three groups (n=6 per group): control group, Erastin model group, and SESN2 intervention group. The control group received tail vein injection of control virus (AAV9-Con). The Erastin model group received AAV9-Con followed by intraperitoneal injection of Erastin (30 mg/kg) after 4 weeks. The SESN2 intervention group received tail vein injection of SESN2-overexpressing virus (AAV9-Sesn2), followed by Erastin injection at the same dose after 4 weeks. Serum and renal tissues were collected 24 h after modeling. Enzyme-linked immunosorbent assay (ELISA) was used to measure lactate dehydrogenase (LDH), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels in cell and tissue supernatants. Reactive oxygen species (ROS) levels were assessed using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and dihydroethidium (DHE) fluorescence staining. Malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe2+) levels were determined by colorimetric assays. Cell apoptosis was calculated using Annexin V-FITC/propidium iodide (PI), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and flow cytometry. The mRNA and protein expression levels of SESN2, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and ferroptosis suppressor protein 1 (FSP1) were detected by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) and Western blotting (WB). Compared with the in vitro/in vivo control groups, the Erastin model groups and SESN2 intervention groups showed significantly increased levels of LDH, IL-6, TNF-α, MDA, ROS, and Fe2+, along with significantly decreased GSH levels and increased apoptosis rates (all P<0.001). The mRNA and protein expression levels of GPX4 and FSP1 were significantly decreased, whereas those of SESN2 and Nrf2 were significantly increased (all P<0.001). Compared with the Erastin model groups, the SESN2 intervention groups exhibited significantly reduced levels of LDH, IL-6, TNF-α, MDA, ROS, and Fe2+, increased GSH levels, and decreased apoptosis rates (all P<0.001). In addition, the mRNA and protein expression levels of SESN2, Nrf2, GPX4, and FSP1 were significantly increased (all P<0.001). SESN2 exerts protective effects against Erastin-induced ferroptosis in renal tubular cells and ferroptosis-related AKI by activating the Nrf2 signaling pathway, upregulating ferroptosis-related molecules GPX4 and FSP1, and inhibiting oxidative stress, lipid peroxidation, and inflammatory responses.

Postherpetic neuralgia (PHN) is a severe and distressing complication in elderly patients with herpes zoster and is associated with increased sympathetic nervous system activity. Spinal cord stimulation (SCS) implantation has been shown to effectively relieve PHN. In recent years, heart rate variability (HRV) analysis, as a reliable and objective indicator of autonomic nervous system (ANS) activity, has been widely used in the assessment of chronic pain. This study aims to investigate the clinical effects of SCS implantation on HRV in patients with PHN and its correlation with pain outcomes. A total of 28 patients who met the inclusion criteria and were treated in the Department of Pain Medicine, the Third Xiangya Hospital of Central South University between November 2023 and March 2024 were retrospectively included. All patients underwent SCS implantation. HRV parameters before and after SCS implantation were collected, including the standard deviation of all normal-to-normal intervals over 24 hours (SDNN), root mean square of successive differences (RMSSD), standard deviation of successive differences (SDSD), percentage of adjacent normal-to-normal intervals differing by more than 50 milliseconds (PNN50), low-frequency power (LF), high-frequency power (HF), the LF/HF ratio, and total power (TP) within 5 minutes across all frequency bands. Univariate linear regression analysis was performed to explore the correlations among HRV parameters before and after SCS treatment. After SCS implantation, the HRV time-domain indices SDNN, RMSSD, SDSD, and PNN50, as well as the frequency-domain indices LF, HF, and TP, were significantly increased (all P<0.05), while the change in LF/HF ratio was not statistically significant (P>0.05). SCS treatment also had positive effects on pain relief, improvement of negative emotions, and reduction of psychological stress (all P<0.05). Differences were observed among implantation segments. In patients receiving SCS implantation below the T8 thoracic segment, SDNN, LF, and HF decreased significantly (all P<0.05). Correlation analysis revealed that pain scores were significantly correlated with SDNN. Significant correlations were also observed among the HRV time-domain indices SDSD, RMSSD, and PNN50 (all P<0.05), whereas correlations among frequency-domain indices were relatively weak. The changes in time-domain and frequency-domain HRV indices showed a synergistic trend. Pain outcomes in patients with PHN are accompanied by synchronous changes in autonomic nervous system activity. SCS implantation can improve HRV stability in patients with PHN and contribute to better cardiac rhythm regulation. HRV measurement may serve as evidence reflecting ANS activity in patients with PHN.

Pulmonary hypertension (PH) is a progressive disease characterized by elevated pulmonary arterial pressure, and its prognosis is closely associated with right ventricular (RV) function. Echocardiography, as a noninvasive and convenient imaging modality, plays an important role in the diagnosis of PH, etiological screening, assessment of RV function, and risk stratification. In response to the anatomical, physiological, and pathophysiological adaptive changes of the RV caused by PH, echocardiography demonstrates significant value in the detailed evaluation of both systolic and diastolic function. Noninvasive parameters such as the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) have also been confirmed to possess important prognostic value in assessing RV-pulmonary arterial (RV-PA) coupling. In addition, the application of artificial intelligence in echocardiographic analysis provides new tools for the early detection of PH and helps overcome limitations of conventional estimation methods. Current evidence indicates that a noninvasive right heart functional assessment system centered on echocardiography plays a central role in the management of PH. Future studies are required to further validate the performance of multiparametric combined models and to promote deeper integration of artificial intelligence technologies with clinical practice, thereby enabling earlier and more precise individualized diagnosis and treatment.