ObjectiveThe present study aimed to investigate alterations in white matter microstructure and spontaneous neural activity in male college smokers, and to further explore their associations with nicotine dependence. Given that adolescence and early adulthood represent critical periods for brain maturation, particularly for white matter development, understanding the neural correlates of smoking behavior during this stage is of substantial importance for both neuroscience and public health. MethodsA total of 115 male undergraduate students were initially recruited for this study. After quality control and exclusion procedures, 52 male college smokers and 42 demographically matched healthy non-smokers were included in the final analysis. All participants underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI). White matter fiber tracts were reconstructed using the automated fiber quantification (AFQ) method, which enables precise identification and quantification of major fiber bundles. Eighteen major white matter tracts were segmented for each participant. Along the core trajectory of each tract, 100 equidistant nodes were sampled. Fractional anisotropy (FA) was calculated at each node to assess white matter microstructural integrity, while amplitude of low-frequency fluctuation (ALFF) was computed to evaluate spontaneous neural activity within white matter tracts. Between-group differences in FA and ALFF were assessed using two-sample t-tests, with appropriate corrections applied for multiple comparisons. Furthermore, Pearson correlation analyses were conducted to examine the relationships between imaging-derived metrics (FA and ALFF values in regions showing significant group differences) and nicotine dependence severity, as measured by the Fagerström test for nicotine dependence (FTND). ResultsCompared with healthy non-smokers, male college smokers exhibited significantly increased FA values in several white matter tracts, including the left thalamic radiation, right corticospinal tract, forceps major of the corpus callosum, left uncinate fasciculus, and right arcuate fasciculus. These findings suggest altered microstructural organization or increased directional coherence within these pathways. In addition, smokers demonstrated significantly elevated ALFF values in the forceps major, right uncinate fasciculus, and left arcuate fasciculus, indicating enhanced spontaneous neural activity in these white matter regions. Correlation analyses revealed that FA values in the left thalamic radiation and right corticospinal tract were negatively correlated with FTND scores, suggesting that higher levels of nicotine dependence were associated with reduced microstructural integrity or altered fiber organization in these regions. In contrast, ALFF values in the forceps major and right uncinate fasciculus were positively correlated with FTND scores, indicating that greater nicotine dependence was associated with increased spontaneous neural activity in specific white matter pathways. ConclusionThe present study provides evidence that male college smokers exhibit distinct alterations in both white matter microstructure and functional activity. These abnormalities are not uniformly distributed but rather localized to specific fiber tracts implicated in sensorimotor processing, interhemispheric communication, and higher-order cognitive and emotional regulation. Importantly, the observed associations between imaging metrics and nicotine dependence severity suggest that these structural and functional alterations may reflect neurobiological mechanisms underlying addiction. The combination of AFQ-based tract profiling and multimodal MRI offers a sensitive approach for detecting subtle changes along white matter pathways, highlighting its potential utility in identifying neuroimaging biomarkers of nicotine dependence. Overall, these findings indicate that smoking during early adulthood may disrupt ongoing white matter maturation, potentially leading to long-term consequences for brain function. This study provides novel insights into the neural basis of nicotine dependence and underscores the importance of early intervention and prevention strategies targeting young smokers.

Based on the different medical systems and textual contexts within Inner Canon of Yellow Emperor （《黄帝内经》）， this paper argues that "opening， closing， and pivot" in the three yin and three yang theory encompasses both spatial and temporal dimensions. From the spatial perspective， the concepts of opening， closing and pivot are used to describe the dynamic movement of qi within the meridian system. In The Spiritual Pivot·Root and Knot （《灵枢·根结》）， the theory primarily explains the superficial-deep and exterior-interior hierarchy of the meridians， emphasizing the movement of channel qi and the transmission of disease. By contrast， Basic Questions·Treatise on the Separation and Union of Yin and Yang （《素问·阴阳离合论篇》） primarily explains the relationships of separation and union between yin and yang among different regions and orientations on the same body-surface level. From the temporal perspective， the theory also explains the waxing and waning of yin and yang according to seasonal changes throughout the year， and has been applied to clinical practice within the theory of the five circuits and six qi. Therefore， opening， closing， and pivot in the three yin and three yang theory encompasses multiple connotations， including meridian structure， spatial distribution， seasonal qi transformation， and the annual circulation of climatic qi. Clarifying these different levels and their respective scopes of application is essential for accurately understanding the rich connotations of the opening， closing and pivot theory.

The α7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated ion channel characterized by high Ca²⁺ permeability, rapid activation, and rapid desensitization. It is widely expressed in the nervous system and various non-neuronal cell types. α7 nAChR is involved in regulating neuronal excitability, synaptic transmission and plasticity, cognitive function, and inflammatory responses. These properties have made α7 nAChR a potential therapeutic target for neuropsychiatric and inflammatory diseases. In recent years, advances in cryo-electron microscopy have provided structural insights into α7 nAChR gating, ligand recognition, allosteric modulation, and allosteric activation. The receptor mainly undergoes transitions among resting, open, and desensitized states. Recent structural studies have further revealed asymmetric conformational changes and multiple intermediate states during receptor activation and recovery from desensitization. Conformational rearrangements in the extracellular domain-transmembrane domain coupling region and the pore-forming M2 helices are closely associated with channel opening and desensitization. However, structural characterization of the α7 nAChR gating cycle still largely depends on pharmacological stabilization. Open-state structures have been resolved in the presence of PNU-120596 or GAT107, whereas a high-resolution structure of the open state induced by acetylcholine alone remains to be determined. These physiological roles underpin the involvement of α7 nAChR in multiple disease processes. In the hippocampus, α7 nAChR regulates local neuronal circuits, theta oscillations, synaptic transmission, and synaptic plasticity, thereby contributing to learning, memory, attention, and other cognitive processes. In macrophages, microglia, and other immune-related cells, α7 nAChR activation regulates inflammatory responses and oxidative stress. These effects involve several signaling pathways, including Janus kinase 2 (JAK2)/STAT3, phosphoinositide 3-kinase (PI3K)/AKT, and NF-κB signaling, as well as regulation of the NLRP3 inflammasome and IL-1β production. Such anti-inflammatory effects may also contribute to α7 nAChR-mediated neuroprotection. Although several compounds targeting α7 nAChR have entered clinical studies, no α7 nAChR-selective drug has been approved for clinical use. Limited clinical translation may be related to rapid receptor desensitization, inconsistent efficacy across clinical studies, insufficient or variable target engagement, patient heterogeneity, and clinical endpoint selection. TC-5619 showed promising effects on cognitive impairment and negative symptoms in an early exploratory study of schizophrenia, but these effects were not confirmed in a subsequent, larger phase II trial. Encenicline (EVP-6124) also showed cognitive improvement in early studies, whereas two global phase III trials in schizophrenia failed to meet their co-primary cognitive and functional endpoints. Pharmacological strategies targeting α7 nAChR have expanded from orthosteric agonists to positive allosteric modulators (PAMs) and allosteric agonist-positive allosteric modulators (ago-PAMs). Orthosteric agonists directly activate the receptor by binding to the orthosteric site, but their effects are limited by rapid receptor desensitization. Type I PAMs mainly enhance agonist-evoked responses with relatively small effects on desensitization, whereas type II PAMs markedly potentiate receptor responses and reduce or delay desensitization. Ago-PAMs such as GAT107 can directly activate α7 nAChR through an allosteric mechanism while also potentiating responses to orthosteric agonists. Together, these findings have broadened the pharmacological approaches to α7 nAChR regulation. In summary, future drug development should focus on precise regulation of α7 nAChR according to receptor structure and disease mechanisms, rather than simply enhancing receptor activation. Further studies are needed to clarify how candidate ligands affect receptor gating, conformational transitions, recovery from desensitization, and downstream signaling. Pharmacological differences between neuronal and non-neuronal α7 nAChRs, between homomeric α7 and heteromeric α7β2 receptors, and between α7 nAChR and other nAChR subtypes also require further investigation. Integrating structure prediction, artificial intelligence-assisted virtual screening, molecular docking, molecular dynamics simulations, and electrophysiological validation may facilitate the discovery and optimization of new α7 nAChR modulators.

ObjectiveTo explore the long-term dynamic trajectories of fasting blood glucose （FBG） and insulin resistance （IR） in patients with type 2 diabetes mellitus （T2DM） and their influencing factors. MethodsThis retrospective cohort study included 1 896 T2DM patients registered at Tongren Hospital from May 2020 to May 2025. Based on longitudinal follow-up data of FBG and fasting insulin， joint latent class mixed models （JLMM） were applied to identify FBG-IR trajectories. Univariate and multinomial logistic regression was used to examine demographic characteristics， lifestyle， and clinical determinants of trajectory type. ResultsFour distinct FBG-IR trajectories were identified： stable FBG-IR （9.76%）， rising FBG-stable IR （5.01%）， stable FBG-elevated IR （75.90%）， and elevated FBG-IR （9.34%）. Compared with the stable FBG-IR group， age ≥60 years was protective against the elevated FBG-stable IR trajectory （OR=0.55， 95%CI：0.33-0.92， P=0.023）. Highereducation increased the risk of stable FBG-elevated IR （OR=1.40， 95%CI：1.01-1.94， P=0.046）. Abnormal blood pressure was associated with lower risks of stable FBG-elevated IR （OR=0.66， 95%CI：0.48-0.92， P=0.013） and elevated FBG-IR （OR=0.48， 95%CI：0.31-0.74， P=0.001）. Non-drinkers were less likely to belong to the stable FBG-elevated IR trajectory （OR=0.39， 95%CI：0.16-0.95， P=0.038）. ConclusionsThe evolution trajectory of FBG and IR in T2DM patients shows significant heterogeneity. The majority of patients have a deterioration of IR first. Age， education level， blood pressure， and alcohol consumption are the main influencing factors. Joint assessment of FBG and IR is helpful for early identification of high-risk individuals and guiding individualized intervention.

Objective: Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by central sensitivity to pain, and it is universally acknowledged as a recalcitrant disease. A single-blind randomized controlled trial was conducted to assess the effectiveness and safety of the Roujin formula in treating FMS patients with liver depression and spleen deficiency syndrome, aiming to provide more scientific and effective treatment options. Methods: Forty-eight eligible participants were enrolled and randomly assigned to either the Roujin formula group (n = 24) or the placebo group (n = 24). The Roujin formula group received 150 mL of the Roujin formula twice daily, whereas the placebo group was given a tenth of the Roujin formula dosage, twice daily. The treatment lasted for 8 weeks, with a follow-up extending to 12 weeks. The primary outcome was the improvement in the pain Visual Analogue Scale (VAS) score, whereas secondary outcomes included enhancements in the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory-II (BDI-II), Revised Fibromyalgia Impact Questionnaire (FIQR), and 36-item Short-Form Health Survey (SF-36) scores. These measures were assessed at baseline and after 4, 8, and 12 weeks. The Patients’ Global Impression of Change (PGIC) was collected at week 12. Safety assessments were based on routine blood tests, urine tests, and liver and kidney function evaluations. Results: The improvement in the pain VAS score was significantly greater in the Roujin formula group than that in the placebo group at the 4-, 8-, and 12-week follow-ups (p < 0.05). At the 8-week treatment and the 12-week follow-up, improvements in PSQI and FIQR scores were also superior in the Roujin formula group compared with the placebo group (p < 0.05). There were no differences between the 2 groups in the improvement of BDI-II scores, SF-36 physical component summary, and mental component summary scores at any observation time points. At the 12-week follow-up, PGIC ratings were significantly better in the Roujin formula group (p < 0.05). There were 4 adverse events, all of which occurred in the Roujin formula group, including 3 cases of diarrhea and 1 case of stomach pain; no serious adverse events were reported during the study. Conclusion: The Roujin formula can effectively enhance the overall condition of FMS patients, relieve pain, improve sleep quality, and elevate physical and mental well-being. Only mild gastrointestinal reactions were observed. The Roujin formula may be a viable candidate for clinical implementation.

Objective: Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by central sensitivity to pain, and it is universally acknowledged as a recalcitrant disease. A single-blind randomized controlled trial was conducted to assess the effectiveness and safety of the Roujin formula in treating FMS patients with liver depression and spleen deficiency syndrome, aiming to provide more scientific and effective treatment options. Methods: Forty-eight eligible participants were enrolled and randomly assigned to either the Roujin formula group (n = 24) or the placebo group (n = 24). The Roujin formula group received 150 mL of the Roujin formula twice daily, whereas the placebo group was given a tenth of the Roujin formula dosage, twice daily. The treatment lasted for 8 weeks, with a follow-up extending to 12 weeks. The primary outcome was the improvement in the pain Visual Analogue Scale (VAS) score, whereas secondary outcomes included enhancements in the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory-II (BDI-II), Revised Fibromyalgia Impact Questionnaire (FIQR), and 36-item Short-Form Health Survey (SF-36) scores. These measures were assessed at baseline and after 4, 8, and 12 weeks. The Patients’ Global Impression of Change (PGIC) was collected at week 12. Safety assessments were based on routine blood tests, urine tests, and liver and kidney function evaluations. Results: The improvement in the pain VAS score was significantly greater in the Roujin formula group than that in the placebo group at the 4-, 8-, and 12-week follow-ups (p < 0.05). At the 8-week treatment and the 12-week follow-up, improvements in PSQI and FIQR scores were also superior in the Roujin formula group compared with the placebo group (p < 0.05). There were no differences between the 2 groups in the improvement of BDI-II scores, SF-36 physical component summary, and mental component summary scores at any observation time points. At the 12-week follow-up, PGIC ratings were significantly better in the Roujin formula group (p < 0.05). There were 4 adverse events, all of which occurred in the Roujin formula group, including 3 cases of diarrhea and 1 case of stomach pain; no serious adverse events were reported during the study. Conclusion: The Roujin formula can effectively enhance the overall condition of FMS patients, relieve pain, improve sleep quality, and elevate physical and mental well-being. Only mild gastrointestinal reactions were observed. The Roujin formula may be a viable candidate for clinical implementation.

Objective: Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by central sensitivity to pain, and it is universally acknowledged as a recalcitrant disease. A single-blind randomized controlled trial was conducted to assess the effectiveness and safety of the Roujin formula in treating FMS patients with liver depression and spleen deficiency syndrome, aiming to provide more scientific and effective treatment options. Methods: Forty-eight eligible participants were enrolled and randomly assigned to either the Roujin formula group (n = 24) or the placebo group (n = 24). The Roujin formula group received 150 mL of the Roujin formula twice daily, whereas the placebo group was given a tenth of the Roujin formula dosage, twice daily. The treatment lasted for 8 weeks, with a follow-up extending to 12 weeks. The primary outcome was the improvement in the pain Visual Analogue Scale (VAS) score, whereas secondary outcomes included enhancements in the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory-II (BDI-II), Revised Fibromyalgia Impact Questionnaire (FIQR), and 36-item Short-Form Health Survey (SF-36) scores. These measures were assessed at baseline and after 4, 8, and 12 weeks. The Patients’ Global Impression of Change (PGIC) was collected at week 12. Safety assessments were based on routine blood tests, urine tests, and liver and kidney function evaluations. Results: The improvement in the pain VAS score was significantly greater in the Roujin formula group than that in the placebo group at the 4-, 8-, and 12-week follow-ups (p < 0.05). At the 8-week treatment and the 12-week follow-up, improvements in PSQI and FIQR scores were also superior in the Roujin formula group compared with the placebo group (p < 0.05). There were no differences between the 2 groups in the improvement of BDI-II scores, SF-36 physical component summary, and mental component summary scores at any observation time points. At the 12-week follow-up, PGIC ratings were significantly better in the Roujin formula group (p < 0.05). There were 4 adverse events, all of which occurred in the Roujin formula group, including 3 cases of diarrhea and 1 case of stomach pain; no serious adverse events were reported during the study. Conclusion: The Roujin formula can effectively enhance the overall condition of FMS patients, relieve pain, improve sleep quality, and elevate physical and mental well-being. Only mild gastrointestinal reactions were observed. The Roujin formula may be a viable candidate for clinical implementation.

Purpose: This study aimed to evaluate the contrast-enhanced ultrasound with Sonazoid (Sonazoid-CEUS) features of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: In this retrospective study, patients who underwent surgical resection and were histopathologically diagnosed with NAFLD or cirrhosis-related HCC were included. All patients received Sonazoid-CEUS examinations within 1 week prior to hepatic surgery. The enhancement patterns of HCC lesions were evaluated and compared between the two groups according to the current World Federation for Ultrasound in Medicine and Biology guidelines. Multivariate logistic regression analysis was used to assess the correlations between Sonazoid-CEUS enhancement patterns and clinicopathologic characteristics. Results: From March 2022 to April 2023, a total of 151 patients with HCC were included, comprising 72 with NAFLD-related HCC and 79 with hepatitis B virus (HBV) cirrhosis–related HCC. On Sonazoid-CEUS, more than half of the NAFLD-related HCCs exhibited relatively early and mild washout within 60 seconds (54.2%, 39/72), whereas most HBV cirrhosis–related HCCs displayed washout between 60 and 120 seconds (46.8%, 37/79) or after 120 seconds (39.2%, 31/79) (P<0.001). In the patients with NAFLD-related HCC, multivariate analysis revealed that international normalized ratio (odds ratio [OR], 0.002; 95% confidence interval [CI], 0.000 to 0.899; P=0.046) and poor tumor differentiation (OR, 21.930; 95% CI, 1.960 to 245.319; P=0.012) were significantly associated with washout occurring within 60 seconds. Conclusion Characteristic Sonazoid-CEUS features are useful for diagnosing HCC in patients with NAFLD.

Objective:This study aims to initially establish a scoring system for comprehensively reflecting the severity of intracranial atherosclerotic lesions and to explore the correlation between this score and atherosclerotic risk factors as well as stroke events.Methods:This study retrospectively analyzed patients who underwent head and neck computer tomography angiography(CTA)examinations and had head MRI examinations within one month before or after the CTA examination from January 2021 to August 2024 in Beijing Hospital.An intracranial atherosclerosis disease score(ICADS)system was constructed based on the degree and number of vascular stenosis.The relationship between ICADS and atherosclerotic risk factors was explored by grouping patients according to the quartile of ICADS.Patients were divided into acute stroke group and non-acute stroke group to compare differences in ICADS and cerebrovascular disease risk factors between the two groups, and to investigate the correlation between stroke events and ICADS.Results:There were statistically significant differences in the proportions of patients with hypertension and diabetes among different ICADS groups.Multiple linear regression analysis showed that hypertension( B=1.17, 95% CI: 0.20-2.14, P<0.05)and diabetes( B=2.75, 95% CI: 1.85-3.64, P<0.001)were risk factors for higher ICADS.The ICADS was higher in the acute stroke group than in the non-acute stroke group(9 vs.6, P<0.001), and a higher ICADS was identified as a risk factor for stroke( OR=1.10, 95% CI: 1.07-1.14, P<0.001). Conclusions:ICADS can comprehensively reflect the severity of intracranial atherosclerotic lesions and is correlated with stroke events, making it useful for clinical screening of high-risk patients for stroke.

Objective:To investigate the cytopathological features of thyroid tumor with DICER1 mutation.Methods:A retrospective study on the preoperative cell smear was conducted on thyroid tumors with DICER1 gene mutations detected by Sanger sequencing in the Department of Pathology Shanghai Sixth People′s Hospital affiliated to Shanghai Jiaotong University School of Medicine from May 2022 to November 2024.Results:Totally 163 cases with histological features indicating DICER1 mutation related thyroid tumor underwent Sanger sequencing. Fifteen cases were confirmed to harbor DICER1 mutation (15/163,9.2%). Fourteen of 15 patients were female, and only 1 was male; average age 42(31,47) years. Eight cases presented with D1709 hotspot mutation (8/15) and 7 cases with the E1813 hotspot mutation (7/15) and there was no statistical significant difference between mutation rate of different hotspot ( F=0.620， P=0.438). All specimens were stained with hematoxylin-eosin staining. A moderate number of cells were observed for all cases, predominantly with macrofollicular pattern and rare small papillae. The cell nuclei were mainly uniform, small, round and dark, slightly enlarged or medium-sized. Several cases could also present RAS-like nuclear features: 3 cases showed visible nuclear grooves. According to the expert consensus on the cytopathological diagnosis of thyroid fine needle aspiration (version 2023),the cytopathological diagnostic categories were: Ⅱ, 6 cases; Ⅲ, 2 cases; Ⅳ, 6 cases; and Ⅴ, 1 case. Postoperative histological diagnoses included follicular thyroid carcinoma in 2 cases, high-grade differentiated thyroid carcinoma in 1 case, follicular thyroid adenoma in 3 cases, follicular thyroid tumor of undetermined malignant potential in 4 case, and thyroid follicular nodular disease in 5 cases. Conclusions:The morphological features of DICER1-mutated thyroid tumors are predominant macrofollicles, with uniformly small round and dark nuclei. It is difficult to identify typically diagnostic atrophic follicles on cell smear, leading to a preoperative diagnosis of benign non-neoplastic or indeterminate category. Therefore, it is necessary to carefully observe the macro-follicles and small round dark nuclear features, which is necessary to suggest a genetic test of DICER1 gene and to confirm the diagnosis before surgery.