BACKGROUND:Oral submucous fibrosis is a chronic progressive disease that is prone to malignant transformation.Traditional treatment methods are not ideal and have limitations.As an emerging discipline,tissue engineering has opened up a new path for the treatment of oral submucous fibrosis.OBJECTIVE:To review the latest progress in the pathogenesis and treatment of oral submucous fibrosis,and to summarize and analyze the role and research progress of mesenchymal stem cells,bioscaffold materials,and tissue-engineered oral mucosa in oral submucous fibrosis,thereby providing ideas for the research and clinical application of tissue engineering in the treatment of oral submucous fibrosis.METHODS:In October 2024,the first author used computers to search for relevant literature from January 1970 to October 2024 in PubMed and CNKI databases.The search terms were"oral submucous fibrosis,tissue engineering,mesenchymal stem cells,bioscaffold materials"in English and Chinese,respectively.A total of 166 articles were finally included for analysis.RESULTS AND CONCLUSION:(1)The pathogenesis of oral submucous fibrosis is complex,and many factors are closely related to oral submucous fibrosis,but ultimately they promote the development of oral submucous fibrosis by promoting collagen deposition and accelerating fibroblast proliferation.(2)Traditional treatment methods for oral submucous fibrosis have problems such as low patient compliance and unsatisfactory results,and new treatment strategies are urgently needed.(3)Mesenchymal stem cells regulate the pathological microenvironment,reduce inflammation and inhibit the process of fibrosis due to their immunomodulatory and antioxidant properties,providing a new idea for the treatment of oral submucous fibrosis.(4)Biomass materials,as drug and cell delivery carriers,regulate the pathological microenvironment and are used in various fibrotic diseases,providing a new solution for the treatment of oral submucous fibrosis.(5)Tissue-engineered oral mucosa can be used as an autologous mucosa substitute to promote tissue repair,and also provides a basis for the establishment of disease models.(6)Tissue engineering treatment strategy has great potential for achieving comprehensive treatment of oral submucous fibrosis,but its role in the treatment of oral submucous fibrosis has not yet been verified.It is of great significance to explore tissue engineering-based treatment strategies for oral submucous fibrosis in the future.

BACKGROUND:Oral submucous fibrosis is a chronic progressive disease that is prone to malignant transformation.Traditional treatment methods are not ideal and have limitations.As an emerging discipline,tissue engineering has opened up a new path for the treatment of oral submucous fibrosis.OBJECTIVE:To review the latest progress in the pathogenesis and treatment of oral submucous fibrosis,and to summarize and analyze the role and research progress of mesenchymal stem cells,bioscaffold materials,and tissue-engineered oral mucosa in oral submucous fibrosis,thereby providing ideas for the research and clinical application of tissue engineering in the treatment of oral submucous fibrosis.METHODS:In October 2024,the first author used computers to search for relevant literature from January 1970 to October 2024 in PubMed and CNKI databases.The search terms were"oral submucous fibrosis,tissue engineering,mesenchymal stem cells,bioscaffold materials"in English and Chinese,respectively.A total of 166 articles were finally included for analysis.RESULTS AND CONCLUSION:(1)The pathogenesis of oral submucous fibrosis is complex,and many factors are closely related to oral submucous fibrosis,but ultimately they promote the development of oral submucous fibrosis by promoting collagen deposition and accelerating fibroblast proliferation.(2)Traditional treatment methods for oral submucous fibrosis have problems such as low patient compliance and unsatisfactory results,and new treatment strategies are urgently needed.(3)Mesenchymal stem cells regulate the pathological microenvironment,reduce inflammation and inhibit the process of fibrosis due to their immunomodulatory and antioxidant properties,providing a new idea for the treatment of oral submucous fibrosis.(4)Biomass materials,as drug and cell delivery carriers,regulate the pathological microenvironment and are used in various fibrotic diseases,providing a new solution for the treatment of oral submucous fibrosis.(5)Tissue-engineered oral mucosa can be used as an autologous mucosa substitute to promote tissue repair,and also provides a basis for the establishment of disease models.(6)Tissue engineering treatment strategy has great potential for achieving comprehensive treatment of oral submucous fibrosis,but its role in the treatment of oral submucous fibrosis has not yet been verified.It is of great significance to explore tissue engineering-based treatment strategies for oral submucous fibrosis in the future.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective To evaluate the effectiveness and feasibility of a remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology.Methods A convenient and elderly-friendly mo-bile application(hereinafter referred to as Yaoshiyi APP)was developed,and a remote medication treatment management team consisting of clinical pharmacists from tertiary hospitals,community pharmacists,and community physicians was formed.Patients from communities were selected for practical research,led by pharmacists.Based on the Yaoshiyi APP,patients were subjected to 6 months of medication treatment management practice,and the effectiveness and feasibility of the practice were evaluated.Re-sults The Yaoshiyi APP can be integrated with a variety of medical-grade wearable devices to realize the functions of automati-cally uploading monitoring data,abnormal value reminding,medication reminding,medication consultation,and medication sci-ence popularization.A total of 302 elderly patients with chronic disease at home completed the study.The results showed that phar-macists have identified and intervened in 695 cases of medication-related problems.According to the classification of medication-related problems,the top three were 247 cases(35.5％)of additional treatment,97 cases(14.0％)of unnecessary drug treat-ment,and 93 cases(13.4％)of medication compliance problems.The patient's medication adherence score(Morisky medication adherence scale-8,MMAS-8)increased from(5.85±1.57)at enrollment to(6.74±1.23)6 months after enrollment(P＜0.01).After 6 months of enrollment,the patient's satisfaction with the pharmacist's work reached a score of(4.99±0.08)out of 5.The average reduction in drug costs for patients caused by pharmacists intervening in irrational medication is(20.9±18.0)％.At the end of follow-up,93.4％of patients were proficient in using the Yaoshiyi APP.Conclusion The remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology constructed in this study can ef-fectively improve patient compliance with disease monitoring and medication,ensure rational drug use,reduce medical resource waste,and receive high patient acceptance.

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

Background Industrial emissions are a well-established major source of urban fine particulate matter (PM_2.5) and associated heavy metals. To improve local air quality, Shanghai No. 1 Iron and Steel Plant in Baoshan District was entirely relocated, with all production lines successively shut down in 2018. Objective To evaluate the trends in PM_2.5 and three heavy metal concentrations - chromium (Cr), mercury (Hg), and thallium (Tl) —in the local atmosphere pre- and post- relocation of the steel plant. Methods Taking the steel plant relocation in 2019 as the intervention cutoff point, this study was divided into two phases: pre-intervention (January 2017 to December 2018) and post-intervention (January 2019 to December 2021). Monthly mean pollutant concentrations were used to construct an interrupted time series (ITS) model, followed by segmented linear regression to assess the pre- and post-intervention trends in ambient PM_2.5 and three heavy metals surrounding thesteel plant. Results The ITS regression analysis revealed that the change in PM_2.5 concentration (b₂) after the intervention was −7.16 μg·m⁻³, while the changes in Cr, Hg, and Tl concentrations (b₂) were −0.46, −0.03, and −0.06 ng·m⁻³, respectively. Prior to the intervention, PM_2.5 mass concentrations exhibited a temporal decline with a slope of b₁ = –0.69 (P<0.05); seasonal adjustment further strengthened the overall significance of the model. Before the intervention, the concentration of Cr increased over time, with a slope of b₁=0.12 (P<0.05). After the intervention, the concentration of Cr showed a gradual downward trend over time, with a slope (b₁ + b₃) of −0.04, and significant seasonal variations were observed. The concentration of Hg decreased over time before the intervention, with a slope of b₁=−0.0029 (P<0.05). After the intervention, the slope was −0.0003, showing a further slow decline in Hg concentration over time. However, no significant seasonal trend was observed for Hg. The mass concentration of Tl decreased after the intervention, and the difference before and after the intervention was statistically significant (P<0.05). PM_2.5, Cr, and Tl better fit to the seasonal model, whereas Hg showed a better fit to the non-seasonal model. Conclusion The steel plant relocation intervention has markedly improved local air quality.

Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer's disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
Humans ; Biomarkers/cerebrospinal fluid* ; Nervous System Diseases/diagnosis* ; Brain Injuries/metabolism* ; Phosphopyruvate Hydratase/cerebrospinal fluid* ; Glial Fibrillary Acidic Protein/blood* ; S100 Calcium Binding Protein beta Subunit/blood* ; tau Proteins/cerebrospinal fluid* ; Ubiquitin Thiolesterase/blood* ; Myelin Basic Protein/cerebrospinal fluid* ; Neurofilament Proteins/blood* ; MicroRNAs/blood* ; Brain Injuries, Traumatic/metabolism*

This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

Objective:To investigate the clinical efficacy of botulinum toxin type A（BTX-A）bladder injection in the treatment of neurogenic detrusor overactivity（NDO）with autonomic dysreflexia（AD）.Methods:The patients with spinal cord injury at or above T6，who were treated at Guangdong Provincial Work Injury Rehabilitation Hospital from January 2018 to December 2022，were included in this study prospectively. Inclusion criteria：①chronic spinal cord injury patients over 18 years old（with no progression of neurological symptoms within 3 months）；② presence of NDO and AD；③ inadequate response or intolerance to oral antimuscarinic agent（M-receptor antagonists or β 3-receptor agonists）④ perform clean intermittent catheterization to empty the bladder. Exclusion criteria：① primary disease in the acute or progressive phase；② previous surgeries that would affect lower urinary tract function，such as transurethral sphincterotomy，bladder neck resection，prostatectomy，or bladder surgery；③ allergy to BTX-A or its adjuvants，or those with allergic predisposition ④ patients who were pregnant，breastfeeding，or planning for pregnancy in the near future；⑤ patients did not accept or were unable to perform intermittent catheterization. Before treatment，all patients were required to maintain 3-5 day urine diary，along with urodynamic studies（UDS），incontinence specific quality of life instrument（I-QOL）and AD symptom severity assessment，and blood pressure monitored. Key UDS parameters recorded included maximum bladder capacity，maximum detrusor pressure during filling phase，changes in maximum systolic blood pressure（SBP）relative to baseline（ΔSBP）during UDS examination，and the frequency of 24-hour blood pressure exceeding baseline by 20 mmHg. After general anesthesia or epidural anesthesia，BTX-A（200 U）was injected into the bladder at 30 points（including the triangle）under the cystoscope using a special injection needle，6.7 U per injection，and then the catheter was kept for 3-5 days after treatment. Three months later，relevant indicators were collected and compared with pre-treatment data. Results:A total of 43 patients were included in this study，including 34 males and 9 females. The age was（39.23±13.17）years old and the disease course was（2.69±3.27）years old. There were 33 cervical and 10 thoracic cases. The American Spinal Injury Association Injury Scale score distribution was as follows：26（60%）A，4（9%）B，9（21%）C，and 4（9%）D. The presence of AD was confirmed in all patients during urodynamic examination（UDS），that was the systolic blood pressure（SBP）suddenly increased and exceeded 20 mmHg（1 mmHg = 0.133 kPa）. Before treatment，The AD symptoms severity score（consist of headache，sweating，goose bumps，anxiety and palpitation）were（14.53±2.51），Bladder-related AD frequency was 10.67 episodes/day. Baseline SBP was（103.51±9.64）mmHg，the maximum SBP was（150.40±22.75）mmHg，and the change in SBP（ΔSBP）from maximum to baseline SBP during UDS examination was（43.83±21.01）mmHg. The UDS indicated that the maximum detrusor pressure during storage phase was（54.95±24.68）cmH 2O，and the bladder capacity was（131.70±75.29）ml. Bladder diary showed the volume of catheterization each time from was（181.16±49.86）ml，and The I-QOL score was（44.07±8.60）. Three months after treatment，the AD symptoms severity score（consist of headache，sweating，goose bumps，anxiety and palpitation）were（11.37±2.39）. The frequency of bladder-related AD episodes was（7.51±2.37）episodes/day，showing statistically significant differences compared to pre-treatment（ P<0.05）.The SBP before UDS examination was（102.12±10.28）mmHg，with no statistically significant difference from baseline（ P = 0.518）. The maximum SBP in perfusion phase and the ΔSBP were（132.84±16.30）mmHg and（28.72 ± 14.02）mmHg，respectively，both demonstrating statistically significant differences（ P < 0.05）. The UDS examination revealed that the maximum detrusor pressure during the storage phase was（29.77±13.72）cmH 2O，showed a significant decrease，and the bladder capacity was（272.63±79.75）ml，which were both statistically different before and after surgery. Bladder diary showed the volume of catheterization each time was（326.74±63.71）ml；I-QOL score was（71.86±11.45），both were significant different after treatment（ P < 0.01）. Conclusion:BTX-A intravesical injection in the treatment of NDO can also alleviate the severity and frequency of bladder related AD.