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*

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.

Objective:To investigate the effects of dictyophora polysaccharides(DIP)on cognitive dysfunction induced by chronic alco-hol exposure in rats.Methods:Sixty male Sprague-Dawley(SD)rats were randomly divided into five groups(n=12):control group(normal saline),DIP group[DIPH,DIP administered by gavage at 300 mg/(kg·d)for 28 consecutive days],alcohol group[EtOH,60%alcohol administered by gavage at 10 mg/(kg·d)for 28 consecutive days],low-dose DIP treatment group[EtOH+DIPL,60%alcohol administered at 10 mg/(kg·d)and DIP administered at 100 mg/(kg·d)by gavage,with an interval of 6 hours between doses,for 28 consecutive days],and high-dose DIP treatment group[EtOH+DIPH,60%alcohol administered at 10 mg/(kg·d)and DIP administered at 300 mg/(kg·d)by gavage,with an interval of 6 hours between doses,for 28 consecutive days].On day 25 of gavage,water maze training was provided for the rats for 4 days.On day 29,a water maze test was performed to determine the memory and learning functions of the rats;HE staining was used to evaluate the edema and inflammation of the liver and brain tissues;presence of inflammatory cells and the expression of myelin basic protein(MBP)in brain tissue were measured using immunohistochemical staining;Western blot was used to measure the expression of 2,2-cyclic nucleotide-3-phosphodiesterase(CNP)in the hippocampal tissue;the structural integrity of the myelin sheath was evaluated using LuxoL fast blue(LFB)staining and transmission electron microscopy.Results:Compared with the control group,the EtOH group showed a significantly increased escape latency,reduced expression of MBP,and decreased density of the myelin sheath.DIP intervention significantly improved cognitive dysfunction in rats,increased the expression of MBP and CNP,and reduced myelin damage.Conclusion:At a dose of 300 mg/kg,DIP may ameliorate cognitive dysfunction induced by chronic alcohol exposure by pro-tecting the structural and functional integrity of myelin sheaths.

Objective:To observe the pathological changes of myocardial tissue under differentdegrees of coronary atherosclerotic le-sions,to measure the expression levels of proteins associated with the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway in coronary arteries,and to investigate the role of cGAS-STING in the development and progression of coronary heart disease.Methods:Eligible cases of coronary heart disease and control cases were selected and divided into control group with normal coronary arteries and grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups.HE staining was used to observe and evaluate the pathological conditions of coronary arteries,Western blotting was used to measure the expression levels of downstream pro-teins of the cGAS-STING pathway in coronary tissue,and ELISA was used to measure the levels of inflammatory factors in coronary tis-sue.A correlation analysis was performed to investigate the correlation of the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors with the development and progression of coronary heart disease.Results:Mi-croscopic examination showed that compared with the control group,the other four groups had varying degrees of pathological changes such as vascular wall thickening and luminal stenosis,with a gradual increase in the degree of stenosis from grade Ⅰ to grade Ⅳ coronary lesions.Compared with the control group,the grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups had significant increases in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors in coronary tis-sue,with a trend of increase from grade Ⅰ to grade Ⅳ coronary le-sions.The expression levels of downstream proteins of the cGAS-STING signaling pathway in coronary tissue were positively correlated with the development and progression of coronary heart disease(cGAS:r=0.927,P<0.001;p-Sting:r=0.889,P<0.001;p-TBK1:r=0.910,P<0.001;p-IRF3:r=0.936,P<0.001;IFN-1:r=0.936,P<0.001;TNF-α:r=0.945,P<0.001;IL-1β:r=0.962,P<0.001;IL-6:r=0.933,P<0.001).Conclusion:There are significant differences in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors,and this signaling pathway may be a potential target for the treatment of coronary heart disease.

Objective::This study aimed to investigate the feasibility, efficacy, and safety of using a miniature mobile integrated cabin-theatre equipped with angiography and surgical operating room capabilities, and to explore its therapeutic scope, effectiveness, and operational mode.Methods::A miniature mobile integrated operating cabin-theatre was deployed across 15 hospitals in 15 cities or counties in China from April 2012 to November 2024. The interventions and outcomes of interventional and minimally invasive surgical procedures were prospectively observed and evaluated; perioperative complications were documented, and the stability, adaptability, and mobility of the integrated system were assessed.Results::A total of 133 procedures were successfully performed, 130 of which were interventional and 3 minimally invasive. The angiography machine showed good imaging performance without any equipment failures, loosening, or damage, with normal chamber unfolding. One patient experienced a fever the day after laparoscopy, while none of the other patients exhibited perioperative complications such as infection, surgical site bleeding/hematoma, or reperfusion arrhythmia. The instrument was easily manipulated, aligning with the needs of clinical intervention and surgery, and was perceived by patients as being a comfortable environment, with no psychological or other obvious discomfort.Conclusions::The miniature mobile integrated cabin-theatre, comprising an angiography machine and an operating room, allows interventional or minimally invasive surgical procedures to be performed smoothly and safely. It can also provide rapid and efficient on-site treatment of acute and critical illnesses across multiple body systems, including the cardiovascular, cerebrovascular, and gastrointestinal systems.

Background:Duodenal papillary adenoma is a benign tumor with relatively low incidence but significant carcinogenesis potential.Despite the minimal invasiveness and low complication rate,endoscopic papillectomy is associated with a definite risk of recurrence for duodenal papillary adenoma.Investigating the driver genes of duodenal papillary adenoma and establishing predictive models for recurrence and malignant progression could facilitate the precision medicine.Aims:To identify the key driver genes for tumor occurrence,carcinogenesis and recurrence in duodenal papillary adenoma by integrating multi-dimensional bioinformatics approaches based on transcriptomics data,and validate clinically.Methods:Expression profiles of duodenal papillary adenoma and adenocarcinoma were obtained from the GEO database(including data sets GSE189035,GSE94919,GSE111156,and GSE102208).Differentially expressed genes(DEGs)between adenomatous and normal tissues were screened.Weighted gene co-expression network analysis(WGCNA)and pseudo-time analysis were combined to identify the core genes exhibiting an"initial rise followed by decline"expression pattern during the dynamic progression from normal tissue to adenoma and adenocarcinoma.Functional annotation,immune microenvironment profiling,and protein-protein interaction network analysis were performed to explore the tumor-promoting mechanisms of these core genes.Clinical validation was conducted using immunohistochemistry to estimate the gene expression level and its relationship with tumor recurrence.Results:A total of 469 common DEGs were identified.WGCNA revealed that the blue module(including 1 051 genes)was associated with adenoma development and progression(Cor=-0.29,0.15,and 0.11 for normal tissue,adenoma,and adenocarcinoma,respectively).Intersection with DEGs pinpointed four key genes:SLC12A2,BEST4,SLC37A2,and SOAT2.Pseudo-time analysis demonstrated that only SLC12A2 maintained sustained high expression in both adenoma and adenocarcinoma tissues.KEGG enrichment analysis indicated that SLC12A2 was linked to various malignant pathways(e.g.,PD-1/PD-L1 signaling pathway),and its high expression correlated with the reduced immune cell infiltration(e.g.,γδ T cells,CD8+T cells,etc.).Clinical validation by immunohistochemistry confirmed the trend of initial upregulation and subsequent downregulation of SLC12A2 expression in normal,adenoma,and adenocarcinoma tissues.Patients with tumor recurrence showed higher SLC12A2 expression level(P=0.004);likewise,SLC12A2 high expression was associated with an elevated recurrence risk(P=0.034).Conclusions:SLC12A2 serves as a critical driver of tumorigenesis and progression for duodenal papillary adenoma,and might be a promising biomarker for recurrence prediction.

Objective To investigate the effect of orthosis design parameters on correction of scoliosis and orthosis-trunk interface pressure.Methods A finite element model of scoliosis was constructed to simulate the assembly effect of the orthosis.The orthosis was divided into four loading areas(left rib,right rib,anterior-left and posterior-right area)to simulate six modification conditions.In Models 1,2 and 3,a fixed modification of 20 mm was applied on the anterior left and posterior right areas,while the displacement loads of 20,25 and 30 mm were applied on both the left rib and right rib areas.In Models 4,5 and 6,a fixed modification of 25 mm was applied on left rib and right rib areas,with the displacement loads of 15,20 and 25 mm applied on both anterior left and posterior right areas.The Cobb angle,apical vertebral rotation(AVR)and interface pressure were calculated.Results The correction of Cobb angle in Models 1,2 and 3 was 8.94°,15.62° and 17.91°,respectively,with AVR correction of 7.53°,6.69° and 5.87°,respectively.In Models 4,5 and 6,the correction of Cobb angle was 14.55°,15.62° and 16.09°,with AVR correction of 5.25°,6.69° and 8.63°,respectively.In Model 6,the correction rate of Cobb angle and AVR was 45.48%and 41.22%,respectively,with a maximum pressure of 26.51 kPa on orthosis-trunk interface,achieving the most significant outcome.Conclusions The modification of orthosis has a significant effect on the correction of Cobb and AVR angles.The loading on the left rib and right rib areas mainly affect the Cobb angle,while the loading on the anterior left and posterior right areas mainly affect the spinal axial-rotation.A modification of 25 mm on all loading areas achieves the optimal spinal correction.This study provides the quantitative data for orthosis design.

Objective::This study aimed to investigate the feasibility, efficacy, and safety of using a miniature mobile integrated cabin-theatre equipped with angiography and surgical operating room capabilities, and to explore its therapeutic scope, effectiveness, and operational mode.Methods::A miniature mobile integrated operating cabin-theatre was deployed across 15 hospitals in 15 cities or counties in China from April 2012 to November 2024. The interventions and outcomes of interventional and minimally invasive surgical procedures were prospectively observed and evaluated; perioperative complications were documented, and the stability, adaptability, and mobility of the integrated system were assessed.Results::A total of 133 procedures were successfully performed, 130 of which were interventional and 3 minimally invasive. The angiography machine showed good imaging performance without any equipment failures, loosening, or damage, with normal chamber unfolding. One patient experienced a fever the day after laparoscopy, while none of the other patients exhibited perioperative complications such as infection, surgical site bleeding/hematoma, or reperfusion arrhythmia. The instrument was easily manipulated, aligning with the needs of clinical intervention and surgery, and was perceived by patients as being a comfortable environment, with no psychological or other obvious discomfort.Conclusions::The miniature mobile integrated cabin-theatre, comprising an angiography machine and an operating room, allows interventional or minimally invasive surgical procedures to be performed smoothly and safely. It can also provide rapid and efficient on-site treatment of acute and critical illnesses across multiple body systems, including the cardiovascular, cerebrovascular, and gastrointestinal systems.