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.

Alzheimer’s disease (AD) is pathologically characterized by cerebral amyloid β‑protein (Aβ) aggregation, neurofibrillary tangles and progressive cognitive deterioration. There is an urgent clinical demand for targeted therapeutic agents against AD, whereas the blood-brain barrier (BBB) acts as a critical physical barrier that blocks over 98% small-molecule drugs and nearly all biomacromolecules from entering brain parenchyma. Nanomedicine-based drug delivery systems (NDDSs) with tunable physicochemical properties can cross the BBB via multiple transcytosis pathways including adsorptive-mediated, receptor-mediated and transporter-mediated routes, opening a promising avenue for targeted AD treatment. A core academic viewpoint proposed herein is that robust in vitro endothelial penetration of nanocarriers cannot guarantee effective accumulation in brain target cells. Comprehensive evaluation of BBB-crossing delivery efficiency should not merely rely on in vitro permeability tests, but cover the full multi-step transcytosis cascade, cellular tropism in brain tissues and in vivo therapeutic outcomes. This review systematically sorts out diverse nanoplatforms applicable to BBB penetration for AD intervention. Inorganic nanomaterials such as gold and ceria nanoparticles possess large specific surface areas and intrinsic antioxidant capacity, which eliminate reactive oxygen species and hinder Aβ fibrillization. Liposomal formulations and solid lipid nanoparticles exhibit superior biocompatibility with biomimetic phospholipid bilayer architectures, capable of co-loading hydrophilic nucleic acids for Tau regulation and lipophilic Aβ inhibitors; relying on receptor-mediated transcytosis, they achieve sustained drug retention in the brain. Polymeric nanocarriers including nanogels and polyamidoamine dendrimers enable multi-target combinatorial therapy, and can be engineered to release cargo in response to inflammatory microenvironments, thereby suppressing excessive microglial activation and protecting neuronal mitochondria. Beyond conventional nanocarriers, this work elaborates two cutting-edge BBB-crossing delivery platforms: biomimetic nanosystems and metal-organic frameworks (MOFs). Biomimetic nanoparticles camouflaged with erythrocyte, platelet or macrophage membranes, as well as natural exosomes, evade immune clearance, prolong systemic circulation and inherently home to inflammatory lesions. Serving as “nano-decoys”, they neutralize Aβ neurotoxins and remodel cerebral inflammatory microenvironments simultaneously. MOFs feature high porosity and customizable pore channels for co-delivery of multiple therapeutics, and can be integrated with near-infrared photothermal and photooxidation modalities to facilitate focal brain lesion therapy. This review highlights a transformative paradigm shift in the field of BBB-targeted AD therapy: research focus has shifted from simply maximizing cerebral drug penetration toward active modulation and functional restoration of the BBB. Impaired BBB transporters intrinsically impede endogenous Aβ clearance. Accordingly, BBB-regulating nanocarriers are designed to remodel the low-density lipoprotein receptor-related protein 1 (LRP1) trafficking cascade, redirecting endocytic vesicles from lysosomal degradation to non-degradable transcytosis and restoring the intrinsic Aβ efflux capacity of the BBB. Distinct from conventional strategies that only exert local lesion inhibition, this systemic clearance strategy eliminates cerebral Aβ deposits by accelerating peripheral excretion.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To address the inefficiency, safety hazards, and resource wastage in traditional medical laboratory management, this study proposes a digital laboratory information management system (LIMS) based on Total Quality Management (TQM) principles. The LIMS has been implemented at the National Center for Geriatric Medicine (Huashan) affiliated with Fudan University.Methods:Centered on the principles of " all-staff participation, whole-process control, and comprehensive management", a multidimensional management framework was developed to integrate personnel, equipment, reagents, and safety protocols. The system incorporated IoT, digital twin, and artificial intelligence (AI) technologies to achieve end-to-end digital control. A layered architecture (physical layer, data layer, model layer, etc.) was designed to integrate functional modules such as full lifecycle equipment management, dual-authentication for hazardous chemicals, and intelligent resource scheduling. A 3D digital twin model was deployed to visualize real-time laboratory operations.Results:Post-implementation, equipment reservation frequency and usage duration at the National Center increased by 114% and 124%, respectively, with no safety incidents reported. Equipment sharing utilization reached 85%, and reagent expiration waste decreased by 30%.Conclusions:The system transforms laboratory management from experience-driven to data-driven by breaking data silos and optimizing collaboration mechanisms. It provides a replicable technical pathway and practical insights for the healthcare industry′s digital transformation. However, further improvements are needed in mobile support and system scalability.

Purpose To investigate the clinicopathological features and prognostic factors of follicular dendritic cell carcinoma(FDCS).Methods Hospital records of 23 patients diagnosed with FDCS were retrospectively re-viewed.The morphological,immunohistochemical features,including the detection of CD21,CD23,and CD35 using the EnVision method,and in-situ hybridization for Epstein-Barr virus encoded nuclear RNA(EBER)were evaluated.Clinicopathological characteristics were analyzed for the evaluation of prognosis.Results The median age of all 23 pa-tients was 50 years(range:27 to 72)and the female to male ratio was 1.3.The median maximum diameter of tumor was 7.0 cm(range:0.5 to 20.0 cm).One case was located in cervical lymph node,while another 22 were discovered in extranodal sites.20 cases were single organ and 3 cases were multiple organs involvement.Microscopically,tumor cells exhibited spindle,oval,or markedly pleomorphic morphology,accompanied by variable lymphoplasmacytic infil-tration in the stroma.CD21,CD35 and CD23 were positive in 22 of 23(95.6％),23 of 23(100.0％)and 4 of 15(26.7％)patients,respectively.EBER in-situ hybridization was positive in 9 of 23 patients(39.1％).The median follow-up time was 84.0(95％CI:50.7-117.3)months,and the 5-year survival rate was 80.2％(95％CI:62.8-97.6).Twelve(52.2％)patients were alive,5(21.7％)were dead,and 6(26.1％)were lost of follow-up.We es-tablished a pathological scoring system containing 5 indexes,i.e.,tumor maximum diameter,mitotic figures,tumor necrosis,cellular pleomorphism and histologic types.Patients with greater than 4 points had a significant poor progno-sis.Conclusion FDCS features a broad spectrum of histologic appearances and behavior.Combined morphological observations(HE staining),applications of a panel of follicular dendritic cell markers and EBER in-situ hybridization are helpful for accurate diagnosis.FDCS poses risks for recurrence,metastasis and death,and those with greater than 4 points in the scoring system have a significant poor prognosis.Long-term follow up is needed.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.