Objective To explore the clinical efficacy and safety of endoscopic endonasal dorsum sellae and posterior clinoid process resection combined with pituitary hemi-transposition in the treatment of pan-sellar area lesions. Methods Clinical data from 57 patients with pan sellar diseases who underwent endoscopic transnasal resection of the posterior clinoid process combined with lateral pituitary displacement surgery in the neurosurgery department of Zhongshan Hospital, Fudan University from January 2019 to January 2025 were collected, and their clinical surgical characteristics and prognosis were analyed. Results A total of 57 patients with pan-sellar area lesions were included in this study, comprising 27 craniopharyngiomas, 7 giant suprasellar pituitary adenomas, 7 chordomas, 6 chondrosarcomas, 5 diaphragma sellae/dorsum sellae meningiomas, and 5 rare lesions. All procedures were completed successfully, and gross total or near-total resection was achieved in all patients. No new neurovascular complications occurred intraoperatively. The follow-up duration ranged from 3 to 24 months. New postoperative anterior pituitary insufficiency occurred in 3 patients (5.3%), and new posterior pituitary insufficiency requiring long-term hormone replacement therapy occurred in 4 patients (7.0%). No additional pituitary dysfunction was observed in the remaining patients. Cerebrospinal fluid rhinorrhea occurred in 1 patient (1.8%) and was successfully repaired. Intracranial infection occurred in 3 patients (5.3%) and resolved after medical treatment. Conclusion Endoscopic resection of the posterior clinoid process combined with lateral displacement of the pituitary gland can effectively expand the surgical space, while repositioning the pituitary gland can reduce the extent of skull base defects. In addition, the risk of pituitary dysfunction caused by lateral displacement of the pituitary gland is relatively low.

Objective To apply an artificial intelligence (AI) -based pelvic floor optimization training system using human motion analysis technique in patients undergoing pelvic floor rehabilitation, so as to assist clinicians in providing guidance, improving clinical efficiency, and enhancing the efficacy of patients' independent training. Methods A total of 60 patients with overactive bladder (OAB) complicated with urgent urinary incontinence (UUI) treated in our hospital during Sep. 2024 and Dec. 2025 were enrolled and randomly divided into the routine guidance group (n=30) and AI guidance group (n=30). The routine guidance group received conventional pelvic floor optimization training under clinicians' instruction, while the AI guidance group underwent training with the AI-based pelvic floor optimization system using human motion analysis. After 6 weeks of intervention, outcomes were compared between the two groups, including the international consultation on incontinence questionnaire-short form (ICI-Q-SF), incontinence quality of life scale (I-QoL), overactive bladder symptom score (OABSS), patient's perception of bladder condition (PPBC) score, pelvic floor muscle function (myoelectric values in the preresting, post-resting, type Ⅰ muscle, type Ⅱ muscle, and endurance test phases), urine output, average flow rate (Qavg), and maximum flow rate (Qmax). Results After 6 weeks of treatment, the ICI-Q-SF, I-QoL, OABSS, PPBC score, type I muscle myoelectric value, Qavg and Qmax were significantly improved in both groups compared with baseline (P＜0.05). After 6 weeks of intervention, the I-QoL score was significantly higher in the AI guidance group than in the routine guidance group[81.82 (79.55, 84.38) vs.77.84 (75.00, 79.55) ], with significant difference (P＜0.05). Compared with the routine guidance group, the AI guidance group showed significant improvements in myoelectric values in the pre-resting, post-resting, type I muscle and endurance testing phases (P＜0.05). Conclusion The AI-based pelvic floor optimization training system can effectively assist clinicians in guiding patients to complete pelvic floor optimization training, improve rehabilitation efficiency and efficacy of independent exercise, and reduce dependence on specialized clinicians, which exhibits favorable safety.

BackgroundAdverse childhood experiences （ACEs） are strong predictors of psychopathology across the lifespan， exerting extensive adverse effects on physical and mental health during early development. While ACEs increase the risk of childhood psychopathology， sleep quality and impair cognitive function， the early neurobiological mechanisms mediating ACE-induced cognitive impairment remain unclear. ObjectiveTo explore the association between ACEs exposure and the risk of psychopathology， sleep disorders， and cognitive function， and to examine the mediating role of the putamen volume in the relationship between ACEs and cognitive function from a neurodevelopment perspective. MethodsData were obtained from the Adolescent Brain Cognitive Development （ABCD） study， comprising 10 572 children aged 9 to 10. Participants were categorized into five groups based on the cumulative score of ACEs reported by their parents and the children themselves： no-exposure group （0 types of ACEs）， the one-exposure group， the two-exposure group， the three-exposure group， and the high-risk exposure group （≥ 4 types of ACEs）. Logistic regression analysis was employed to evaluate the association between ACEs and psychopathological symptoms ［T score of the Child Behavior Checklist （CBCL） ≥ 65］. Multiple linear regression analysis was ultilized to analyze the correlations between ACEs and the scores of the Sleep Disturbance Scale for Children （SDSC）， the NIH Toolbox Cognition Battery （NIHTB-CB）， as well as the multiple structures in the cerebral cortex and subcortex. The Bootstrap method was applied to test the mediating effect of the putamen volume between ACEs and neurocognitive function. ResultsAfter adjusting for confounders， ACEs cumulative score was correlated with children's psychopathological symptoms in a dose-response manner. Compared with the no-exposed group， the high-risk exposure group had a 2.08-fold （OR=2.080， 95% CI： 1.401–3.088） increased risk of internalizing problems and a 3.13-fold （OR=3.132， 95% CI： 1.703–5.760） increased risk of externalizing problems， and the risk of conduct problems was 4.68 times that of the no-exposed group （OR=4.681， 95% CI： 2.528–8.669）. ACEs cumulative score positively predicted the total score of SDSC （β=0.080， 95% CI： 0.059–0.102）， with relatively stronger predictive effects on sleep-wake transition disorder （β=0.086， 95% CI： 0.063–0.109） and sleep onset and maintenance disorder （β=0.066， 95% CI： 0.043–0.089）. In terms of neurocognition and brain structure， ACEs cumulative score negatively predicted the overall cognitive composite score （β=-0.025， 95% CI： -0.050–-0.001）， the crystallized cognitive composite score （β=-0.035， 95% CI： -0.060–-0.010）， the volume of the left putamen nucleus （β=-0.025， 95% CI： -0.046– 0.003）， and the volume of the right putamen nucleus （β=-0.023， 95% CI： -0.044– 0.003）. The total putamen volume played a partial mediating role between ACEs and the overall cognitive composite score， the effect value was -0.002 （95% CI： -0.004–-0.001）， accounting for 7.49% of the total effect. ConclusionACEs exposure may increase the risk of psychopathological and sleep disturbances in children and may impair neurocognitive function. Reduced putamen volume may serve a potential neurobiological pathway underlying the impact of ACEs on childhood cognition. ［Funded by National Natural Science Foundation of China-Young Scientists Program （number， 82401763）； Sichuan University West China Hospital Full-time Postdoctoral Research and Development Fund Project （number， 2023HXBH084）］

OBJECTIVE: To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

OBJECTIVES: To explore the molecular mechanism of Jiangzhi Huaban Decoction (JZHBD) for improving atherosclerosis through the "qi meridian-blood channels" pathway. METHODS: ApoE^-/- mouse models of atherosclerosis were established by high-fat diet feeding for 8 weeks, with C57BL/6 mice on a normal diet as the controls. Forty ApoE^-/- mouse models were randomized into model group, low-, medium-, and high-dose JZHBD treatment groups, and atorvastatin treatment group (n=8) for their respective treatments for 8 weeks. The changes in body weight and overall condition of the mice were monitored weekly. After the treatments, serum levels of TC, TG, HDL-C, LDL-C, TBA, ALT, and AST of the mice were measured, pathological changes in the liver and aortic root plaques were examined with HE staining, and lipid accumulation in the liver and aortic wall was assessed using Oil Red O staining. The core molecular mechanism was studied through transcriptomics, and the expressions of the key pathway proteins were confirmed using Western blotting and immunohistochemistry. RESULTS: Treatment with JZHBD significantly reduced blood lipid and total bile acid levels, improved liver function and hepatic steatosis, and decreased aortic lipid deposition and plaque area in the mouse models of atherosclerosis. Transcriptomic analysis suggested that the therapeutic mechanism of JZHBD involved reverse cholesterol transport, PPAR signaling, and the inflammatory pathways. In atherosclerotic mice, JZHBD treatment obviously up-regulated hepatic expressions of PPARγ, LXRα, ABCA1, ABCG1, and CYP7A1, down-regulated hepatic expressions of p-p65/p65, IL-6, IL1β in the liver, increased ABCG5 and ABCG8 expressions in the intestines, and decreased ICAM-1 and VCAM-1 expressions in the aortic plaques. CONCLUSIONS JZHBD improves atherosclerotic vascular damage and plaque formation possibly by regulating hepatic reverse cholesterol transport and inflammation via modulating the hepatic PPARγ/LXRα/NF-κB signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Plaque, Atherosclerotic/metabolism* ; Liver/metabolism* ; Mice ; Atherosclerosis/metabolism* ; Cholesterol/metabolism* ; PPAR gamma/metabolism* ; Male ; Diet, High-Fat ; Biological Transport

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.