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*

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.

Prone position ventilation(PPV)is an essential therapeutic intervention for patients with refractory hypoxemic respiratory failure.The outbreak of coronavirus disease 2019(COVID-19)has further elevated the significance of PPV in clinical practice.Early enteral nutrition(EN)is considered a crucial measure for improving outcomes in critically ill patients.However,there remains considerable controversy regarding the implementation of EN during PPV.This review summarizes the research progress on the tolerance and safety of EN during PPV before and after the COVID-19 outbreak.It also highlights key strategies to enhance EN tolerance in prone-positioned patients,providing a clinical reference for improving patient management.

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 systematically evaluate the safety and efficacy of percutaneous closure of atrial septal defect (ASD) guided by echocardiography alone versus fluoroscopy. Methods     The databases of PubMed, The Cochrane Library, EMbase, VIP, Wanfang Data and CNKI from January 2000 to October 2021 were searched by computer for relevant research literature. Two reviewers independently screened the literature, extracted the data and evaluated the quality according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Results     A total of 19 cohort studies and 1 randomized controlled study were collected, including 2 825 patients. The Newcastle-Ottawa Scale score for cohort studies was≥7 points. Meta-analysis showed that there was no statistical difference in the operative success rate (RR=1.01, 95%CI 1.00 to 1.02, P=0.17), incidence of occluder displacement/shedding (RR=0.77, 95%CI 0.26 to 2.27, P=0.63), incidence of arrhythmia (RR=0.50, 95%CI 0.21 to 1.14, P=0.10), incidence of pericardial effusion (RR=0.98, 95%CI 0.32 to 2.98, P=0.97), operative time (MD=–0.23, 95%CI –7.56 to 7.10, P=0.95) or cost (SMD=–0.39, 95%CI –1.09 to 0.30, P=0.27) between the two groups. The echocardiography group reduced the incidence of total postoperative complications (RR=0.42, 95%CI 0.30 to 0.60, P<0.001) and residual shunt (RR=0.70, 95%CI 0.50 to 0.98, P=0.04), and shortened length of hospital stay (MD=–0.43, 95%CI –0.77 to 0.09, P=0.01). Conclusion     Compared with traditional fluoroscopy-guided percutaneous closure of ASD, echocardiography guidance alone is equivalent in terms of operative success rate, major postoperative complications, operative time and total cost, but it reduces the incidence of total postoperative complications and residual shunt, and has a shorter length of hospital stay.

Objective:To observe any relationship between corticospinal tract integrity and the upper limb motor function of stroke survivors treated with repetitive transcranial magnetic stimulation (rTMS).Methods:Bilateral corticospinal tracts (CSTs) were reconstructed in ischemic or hemorrhagic stroke survivors with upper limb motor dysfunction using diffusion tensor imaging (DTI). Thirty patients with good CST integrity (rFA>0.5) and 30 with rFA≤0.5 were further divided into a high frequency rTMS group (HF, n=10), a low frequency group (LF, n=10), and a control group ( n=10). All groups were given routine rehabilitation, while the high and low frequency groups were additionally provided with 5Hz and 1Hz rTMS respectively applied over the M1 area of the contralesional hemisphere. Before and after 3 weeks of treatment, all of the subjects were evaluated using the Fugl-Meyer upper extremity scale (F-M UE), the Wolf Motor Function Test (WMFT) and the Modified Barthel Index (MBI). Results:For the high CST integrity group, significant improvement was observed in the average scores of all measurements, with the average FMA-UE, WMFT and MBI scores of the LF group [(38.10±5.71), (43.20±5.32) and (78.00±11.35)] significantly better than those of the other 2 groups. Among the low CST integrity group, the HF subgroup showed greater improvement than the other 2 on average.Conclusions:For patients with good CST integrity, LF-rTMS over the contralesional cortex is superior to HF-rTMS in promoting upper limb motor function, while for patients with low CST integrity HF-rTMS over the contralesional cortex has a better effect than LF-rTMS or sham stimulation in terms of improving upper limb motor function after a stroke.