ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

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*

Ankylosing spondylitis (AS) is linked to an increased prevalence of myocardial infarction (MI). However, research dedicated to elucidating the pathogenesis of AS-MI is lacking. In this study, we explored the biomarkers for enhancing the diagnostic and therapeutic efficiency of AS-MI. Datasets were obtained from the Gene Expression Omnibus database. We employed weighted gene co-expression network analysis and machine learning models to screen hub genes. A receiver operating characteristic curve and a nomogram were designed to assess diagnostic accuracy. Gene set enrichment analysis was conducted to reveal the potential function of hub genes. Immune infiltration analysis indicated the correlation between hub genes and the immune landscape. Subsequently, we performed single-cell analysis to identify the expression and subcellular localization of hub genes. We further constructed a transcription factor (TF)-microRNA (miRNA) regulatory network. Finally, drug prediction and molecular docking were performed. S100A12 and MCEMP1 were identified as hub genes, which were correlated with immune-related biological processes. They exhibited high diagnostic value and were predominantly expressed in myeloid cells. Furthermore, 24 TFs and 9 miRNA were associated with these hub genes. Enzastaurin, meglitinide, and nifedipine were predicted as potential therapeutic agents. Our study indicates that S100A12 and MCEMP1 exhibit significant potential as biomarkers and therapeutic targets for AS-MI, offering novel insights into the underlying etiology of this condition.
Humans ; Spondylitis, Ankylosing/complications* ; Systems Biology/methods* ; Myocardial Infarction/diagnosis* ; Biomarkers/metabolism* ; MicroRNAs/genetics* ; Gene Regulatory Networks ; Gene Expression Profiling ; Machine Learning

Objective To investigate the mechanism of abdominal massage for treating chronic fatigue syndrome(CFS).Methods Thirty clean-grade female Sprague-Dawley rats were randomly divided into the normal control,model control,and abdominal massage groups(n=10 rats per group).The CFS rat model was established through cold water swimming combined with the chronic restraint method in the model control and abdominal massage groups.The rats in the abdominal massage group were treated with the core techniques of Jingu zang-fu massage,namely layer press"Guanyuan"(CV4)for 8 min and Tuanmo"Zhongwan"(CV12)for 12 min as the primary intervention techniques,once a day for 14 consecutive days.The rats in the two control groups did not receive intervention;however,they were bound to the experimental bench when the experimental group was massaged.After the intervention,the indexes of the main organs of the hypothalamic-pituitary-adrenal(HPA)axis and hippocampal cell apoptosis in each group were measured.The morphology of hippocampal cells in each group was observed using Nissl staining of hippocampal tissue and transmission electron microscopy of hippocampal neurons.Results The index of each organ in the model control group was upregulated(P<0.01)compared to that of the normal control group.In contrast,the index of each organ in the abdominal massage group was downregulated(P<0.01)compared with that of the model control group.Compared to the normal control group,the index of each organ in the abdominal massage group was upregulated;however,the difference was not significant.Compared to the normal control group,the cell nuclei in the model control group were significantly consolidated,the nuclear membrane structure was ruptured,and the margins were irregular.Most of the cell morphology in the abdominal massage group was normal compared with that of the model control group,and a small number of nuclear membrane structures were unclear.Compared to the normal control group,the hippocampal neuronal cell in the other two groups was significantly damaged,and the hippocampal neuronal cell in the abdominal massage group was in good condition compared to the model control group.The degree of neuronal apoptosis in the model control group was significantly higher than that in the normal control group(P<0.01).The degree of neuronal apoptosis in the abdominal massage group decreased compared to that of the model control group(P<0.01),which was slightly higher than that in the normal control group but not significant.Conclusion Cold water swimming combined with chronic restraint can simulate CFS in rats,and abdominal massage can reduce the organ index of the hypothalamus,pituitary gland,and adrenal gland,increase hippocampal cell activity,reduce hippocampal tissue damage,inhibit hippocampal cell apoptosis,and maintain the normal physiological function of hippocampal neurons.

Objective:To observe any effect of intermittent theta burst stimulation (iTBS) of a cerebellar hemisphere on the walking of stroke survivors with lower limb dysfunction, and to explore its possible mechanism.Methods:Thirty stroke survivors with walking dysfunction were randomly divided into an experimental group and a control group, each of 15. Before their daily routine rehabilitation, the control group received fake iTBS while the experimental group was given 600 pulses of iTBS over 200s. The experiment continued 5 days a week for 3 weeks. The Berg Balance Scale (BBS), the Fugl-Meyer lower extremity assessment (FMA-LE), the Modified Barthel Index (MBI) and Functional Ambulation Categories (FAC) were used before and after the treatment to evaluate the subjects′ balance, lower extremity motor function, walking and ability in the activities of daily living. Gait analysis was also performed. The amplitude of motor evoked potentials (MEPs) and the cortical silent period (CSP) were also noted to assess corticospinal excitability.Results:After the treatment, the average BBS, FMA-LE and MBI scores, FAC grading, stride length, stride speed, stride frequency, and the percentage of swing period in the walking cycle, as well as MEP amplitude and latency had improved significantly in the experimental group. All were then significantly better, on average, than in the control group. The control group also demonstrated significant improvement in all of the outcomes except the percentage of swing period in the walking cycle.Conclusion:iTBS of the cerebellum can improve the walking of stroke survivors with lower limb dysfunction. The mechanism may be related to the cerebellar regulation of spinal cord excitation of the cerebral cortex.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Objective:To conduct a visual analysis of the related literature on hydrogel materials that promote wound healing, and to explore the research status, hotspots and future development trends in this field, in order to provide a reference for future research and development.Methods:The Web of Science Core Collection database was searched to obtain relevant literature on the promotion of wound healing by hydrogel materials from January 1, 2010 to October 1, 2023. Bibliometrics method were used to integrate the year, author, publication, number of national and institutional publications, cumulative citation and co-citation frequency and key words of the included literatures. VOSviewer 1.6.19 and CiteSpace 6.2.R4 were used for the literature’s visualization analysis and mapping.Results:A total of 3 863 literatures were included, involving 18 921 authors, and the number of publications in this field showed a significant increasing trend from 2010 to 2023. Zhao YJ, the researcher with the most publications, published 38 articles. There were 557 journals that had collected relevant literatures, and the International Journal of Biological Macromolecules had published the most literature, with a total of 286 publications. A total of 92 countries and 3 307 institutions had conducted research in related fields, with China publishing the most papers. Research institutions mainly come from China and the United States. The literature with the highest cumulative citation frequency was "Alginate: properties and biomedical applications", which reached 4 737 times. The highest cumulative co-citation frequency was the literature published by Qu J, et al in 2018, with a total of 404 times. Keyword co-occurrence, clustering, time line and emergence analysis showed that the early research in this field mainly focused on the process of wound healing and the cellular mechanism at the molecular level, and later gradually focused on the development of precise controlled release function of nanoparticles and antibacterial compounds in hydrogel scaffolds. Conclusion:Research on the application of hydrogel materials in wound healing is attracting increasing international attention. According to the changes of hot words, the future research trend in this field is to develop intelligent hydrogels with regulatory capabilities, wound monitoring, controlled drug delivery and diversified functions.