The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.

OBJECTIVE: To explore the effectiveness of posterior single-level osteotomy with 360° release and correction for the treatment of osteoporotic vertebral compression fractures (OVCF) complicated with moderate to severe kyphosis. METHODS: A retrospective analysis was conducted on 11 patients with OVCF complicated with moderate to severe kyphosis between January 2022 and March 2023. There were 4 males and 7 females with an average age of 57 years ranging from 47 to 69 years. The disease duration ranged from 3 to 15 months, with an average of 7 months. Fracture segments included T ₁₁ in 3 cases, T ₁₂ in 5, L ₁ in 2, and L ₂ in 1. The T value of lumbar spine bone density was -5.0 to -2.0, with an average of -3.5. The preoperative neurological function was grade E according to Frankel grading. The Pfirrmann classification of the intervertebral disc above the injured vertebra was grade Ⅲ in 8 cases and grade Ⅳ in 3 cases. All patients underwent posterior single-level osteotomy with 360° release and correction. The operation time, intraoperative blood loss, hospital stay, and postoperative complications were recorded. Thoracolumbar local kyphosis Cobb angle, the mean height of the functional spinal unit (FSU), the sagittal vertical axis (SVA), and the sagittal index (SI) were measured. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were used to evaluate the improvement of pain and function before operation, at 1 month after operation, and at last follow-up. RESULTS: The operation successfully completed in all patients, and there was no obvious complication. The operation time ranged from 100 to 190 minutes, with an average of 153 minutes, and the intraoperative blood loss ranged from 200 to 800 mL, with an average of 468 mL. The length of hospital stay was 8-14 days (mean, 12 days). All patients were followed up 6-24 months, with an average of 12.4 months. At last follow-up, all the 11 patients had bony fusion in the osteotomy area, and there was no displacement or subsidence of the Cage, no complication such as internal fixation failure or pseudarthrosis formation was found. The Cobb angle of local thoracolumbar kyphosis, the mean height of FSU, SVA, and SI significantly improved immediately after operation and at last follow-up when compared with preoperative ones, and the VAS score and ODI also significantly improved at 1 month after operation and at last follow-up ( P<0.05); there was no significant difference in above indexes between the two time points after operation ( P>0.05). CONCLUSION Posterior single-level osteotomy with 360° release and correction is an effective surgical method for treating OVCF complicated with moderate to severe kyphosis, with definite early effectiveness.
Humans ; Kyphosis/etiology* ; Male ; Female ; Osteotomy/methods* ; Middle Aged ; Retrospective Studies ; Aged ; Spinal Fractures/diagnostic imaging* ; Fractures, Compression/diagnostic imaging* ; Osteoporotic Fractures/complications* ; Treatment Outcome ; Lumbar Vertebrae/injuries* ; Thoracic Vertebrae/injuries* ; Operative Time ; Fracture Fixation, Internal/methods*

OBJECTIVE: To investigate the short-to-medium-term clinical efficacy of total hip arthroplasty(THA) with Pinnacle ES constrained liner in the treatment of femoral neck fractures(FNF) associated with lower limb neuromuscular disorders. METHODS: A retrospective analysis was conducted on 16 patients who underwent primary THA using Pinnacle ES constrained liner for FNF with lower limb neuromuscular disorders and had complete follow-up data, treated between January 2020 and January 2023. There were 7 males and 9 females, with a mean age of (68.42±3.58) years old ranging from 61 to 75 years old. Among them, 10 cases had left-sided fractures and 6 had right-sided fractures;based on the Garden classification, 11 cases were type Ⅲ and 5 cases were type Ⅳ. The affected limbs were complicated with sequelae of poliomyelitis (2 cases), Parkinson's disease (2 cases), and sequelae of cerebral infarction (12 cases). All operations were performed via a posterolateral approach. Prosthesis position was evaluated using imaging data. Hip function was assessed by the Harris hip score(HHS) and Merle D'Aubigne hip score. During the follow-up period, the occurrence of complications such as prosthetic dislocation, loosening, and infection was recorded. RESULTS: One patient died of advanced tumor 2 years after surgery, and the remaining 15 patients were followed up for 24 to 64 months with a mean of (34.8±5.5) months. The operation time ranged from 50 to 90 minutes with a mean of (75.56±8.15) minutes, and the blood loss ranged from 150 to 200 ml with a mean of (170.32±12.56) ml. All patients achieved primary wound healing after surgery. Intraoperatively, femoral calcar splitting occurred in 2 cases, which were treated with titanium cable binding;no neurovascular injuries were observed in any case. The mean HHS increased from (18.95±2.25) preoperatively to (88.02±2.42) at the last follow-up, and the mean Merle D'Aubigne Score increased from (3.05±0.06) preoperatively to (16.65±0.93) at the last follow-up. Postoperative follow-up X-rays showed good prosthetic position, and no complications such as dislocation, prosthetic loosening, periprosthetic fracture, or deep infection occurred during the follow-up period. CONCLUSION Total hip arthroplasty with Pinnacle ES constrained liner is effective in the treatment of femoral neck fractures associated with lower limb neuromuscular disorders. It can significantly improve hip function, reduce the postoperative prosthetic dislocation rate, provide good initial stability, and achieve satisfactory short-to-medium-term clinical efficacy.
Humans ; Male ; Female ; Middle Aged ; Aged ; Arthroplasty, Replacement, Hip/methods* ; Femoral Neck Fractures/complications* ; Retrospective Studies ; Neuromuscular Diseases/surgery* ; Lower Extremity ; Treatment Outcome

OBJECTIVE: To evaluate the efficacy and safety of DCAG (decitabine, cytarabine, anthracyclines, and granulocyte colony-stimulating factor) regimen in the treatment of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). METHODS: The clinical data of 64 R/R AML patients received treatment at Chinese PLA General Hospital from January 1st, 2012 to December 31st, 2022 were retrospectively analyzed. Primary endpoints included efficacy measured by overall response rate (ORR) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). The patients were followed from enrollment until death, or the end of last follow-up (June 1st, 2023), whichever occurred first. RESULTS: Sixty-four patients who failed prior therapy were enrolled and completed 1 cycle, and 26 and 5 patients completed 2 and 3 cycles, respectively. Objective response rate was 67.2% ［39: complete remission (CR)/CR with incomplete hematologic recovery (CRi), 4: partial remission (PR)］. With a median follow-up of 62.0 months (1.0-120.9), the median overall survival (OS) was 23.3 and event-free survival was 10.6 months. The median OS was 51.7 months (3.4-100.0) in responders (CR/CRi/PR) while it was 8.4 months (6.1-10.7) in nonresponders ( P <0.001). Grade 3-4 hematologic toxicities were observed in all patients. Four patients died from rapid disease progression within 8 weeks after chemotherapy. CONCLUSION The DCAG regimen represents a feasible and effective treatment for R/R AML.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Cytarabine/administration & dosage* ; Granulocyte Colony-Stimulating Factor/administration & dosage* ; Retrospective Studies ; Male ; Female ; Decitabine ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anthracyclines/administration & dosage* ; Middle Aged ; Adult ; Treatment Outcome ; Aged ; Recurrence

Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Aim To investigate the targeting mechanism of miR-23b on PINKl/Parkin pathway in transdifferentiation of NRK-52E cellsinduced by TGF-β1, and to elucidate the intervention mechanism of Qingshen granules drug-containing serum on NRK-52E cell transdifferentiation. Methods Ultra-high performance liquid chromatography ( UPLC ) fingerprinting method was used to analyze Qingshen granules. The NRK-52E transdifferentiation model induced by TGF-β1 was constructed. The NRK-52E cells were divided into simulated no-load control group, miR-23b-5p simulated group, inhibitor no-load control group, and miR-23b-5p inhibitor group, after transfection with siRNA, and the effect of miR-23b-5p on PINK1 expression was ob-served. The NRK-52E cells were then divided into normal group, TGF-(31 group, Qingshen granule group, miR-23 b-mimic group, miR-23 b-mimic group, and miR-23b-mimic + Qingshen granule group. Western blot was used to detect the expression of Pinkl, Parkin, LC3 n, Beclin-1, P62 and a-SMA proteins, and RT- PCR was used to detect the expression of miR-23 b-5p, Pinkl, Parkin, Beclin-1 and a-SMA mRNA in NRK- 52E cells. Dual-Luciferase Reporter gene experiment was used to detect the targeting relationship between miR-23b-5p and PINKL Results UPLC fingerprinting method found 11 active components in Qingshen granules. After overexpression of miR-23b-5p, the expression of PINkl mRNA significantly increased (P < 0. 05). And after silencing of miR-23 b-5 p expression, the expression of PINkl mRNA also significantly decreased (P < 0. 05 ). Dual-Luciferase Reporter Assay showed that Rno-miR-23b-5p could significantly down- regulate the luciferase activity of Rno-PINKl-WT (P < 0. 05 ), but could not down-regulate the luciferase activity of mutant Rno-PINKl -mut ( P > 0. 05 ). The experimental results showed that the expressions of miR- 23b-5p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 II/ I ratio in TGF-β1 group were significantly lower than those in normal group, but the expressions of P62 and a-SMA were significantly higher than those in normal group ( P <0.05). The expressions of miR-23 b-5 p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 11/ I ratio in Qingshen granule group and miR-23 b-mimic group were significantly higher than those in TGF-β1 group, and the expressions of P62 and a-SMA were significantly lower than those in TGF-β1 group (P < 0. 05 ). The performance of miR-23 b-mimic + Qingshen granule group was better than that of miR-23 b-mimic group (P < 0. 05 ). Conclusions Qingshen granules can up- regulate the expression of miR-23b-5p in NRK-52E cellsand inhibit the transdifferentiation process of NRK- 52E cells by enhancing the mitochondrial autophagy activity mediated by PINKl/Parkin pathway.