BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Objective : To investigate the effect and mechanism of sex-determining region Y-box transcription factor 4(SOX4) on autophagy in small cell lung cancer(SCLC) cells. Methods : Human SCLC cell line NCI-H446 was transfected with small interfering RNA(siRNA) to knockdown SOX4. RT-qPCR and Western blot were used to verify the transfection efficiency. NCI-H446 cells were divided into control group, si-SOX4 group, si-SOX4+oe-Beclin1 group and oe-Beclin1 group. Western blot analysis was performed to detect the ratio of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ expression and the expression of Beclin1 and p62 in different groups of cells. The transcriptional regulation of Beclin1 by SOX4 was detected by dual luciferase reporter assay and chromatin immunoprecipitation PCR(ChIP-PCR) assay. CCK-8 assay was used to detect the proliferation ability of NCI-H446 cells in different groups. Flow cytometry was used to detect the apoptosis rate of NCI-H446 cells in different groups. Transwell assay was performed to determine the cell migration and invasion ability in different groups. Results: Compared with the control group or the si-NC group, the relative mRNA and protein expression level of SOX4 in si-SOX4 group were down-regulated(P<0.05), and the ratio of LC3-Ⅱ/LC3-Ⅰ protein expression and the relative protein expression level of Beclin1 in si-SOX4 group decreased(P<0.05), the relative protein expression of p62 increased(P<0.05). The relative luciferase activity of Beclin1 WT in the si-SOX4 group was lower than that in the si-NC group(P<0.05); the relative enrichment of Beclin1 promoter in the Anti-SOX4 group was higher than that in the Anti-Ig G group( P<0. 05). Compared with control group,cell proliferation activity decreased,cell apoptosis rate increased,migration number and invasion number decreased in si-SOX4 group( P<0. 05). Compared with the si-SOX4 group,the ratio of LC3-Ⅱ/LC3-Ⅰ protein expression and the relative protein expression of Beclin1 increased in si-SOX4 + oe-Beclin1 group,while the relative protein expression of p62 decreased,cell proliferation activity increased,apoptosis rate decreased,migration number and invasion number increased( P<0. 05). Conclusion Down-regulation of SOX4 can inhibit autophagy,decrease proliferation activity of NCI-H446 cells,and inhibit cell migration and invasion by inhibiting Beclin1 expression.

Hemolymphangioma is an extremely rare lymphatic and vascular malformation, recognized as a benign lesion notable for its prolonged clinical course. The digestive tract mainly occurs in the esophagus and colorectum, the small intestine is rarely reported. Here, we report a case of small intestinal hemangiolymphangioma primarily manifesting as gastrointestinal bleeding, with the aim of providing a reference for clinical diagnosis and treatment.

With the deepening understanding of small intestinal diseases and the improvement of the disease spectrum, diseases related to small intestinal villous atrophy have been gradually recognized and diagnosed in recent years. Most patients with villous atrophy present with small intestinal malabsorption syndrome, such as diarrhea, bloating, abdominal pain, and weight loss. However, due to the lack of specificity of clinical symptoms and the fact that endoscopic findings only involve the villi, milder lesions are easily overlooked, leading to missed diagnosis or misdiagnosis. This article summarizes the endoscopic manifestations, examination methods, differential diagnosis, and treatment approaches for small intestinal villous atrophy in recent years, aiming to improve the standardized diagnosis and treatment of diseases related to small intestinal villous atrophy.

The research of damp-heat syndrome in modern TCM mainly focuses on inflammatory response, water metabolism, lipid metabolism, hemorheology, intestinal flora and so on. Modern omics techniques such as metabolomics and genomics provide a new perspective for the exploration of the micro-mechanism of damp-heat syndrome. The study found that the abnormal expression of aquaporin is closely related to the formation of "dampness" in damp-heat syndrome, and the release of inflammatory factors reflects the pathological characteristics of "heat". Damp-heat syndrome is often accompanied by dyslipidemia, hemorheological changes and intestinal flora imbalance, showing characteristic changes in urine, blood and saliva metabolomics, and there are differences in gene expression between damp-heat constitution and gentleness constitution. In the future, the pertinence and systematicness of research should be strengthened, the relationship between indicators should be deeply explored, build a biomarker system should be built, the immune-metabolic regulation mechanism should be explored, the multi-target mechanism of heat-clearing and dampness-removing Chinese materia medica should be clarified to further improve the damp-heat syndrome system, and provide theoretical support for clinical treatment.

Hemolymphangioma is an extremely rare lymphatic and vascular malformation, recognized as a benign lesion notable for its prolonged clinical course. The digestive tract mainly occurs in the esophagus and colorectum, the small intestine is rarely reported. Here, we report a case of small intestinal hemangiolymphangioma primarily manifesting as gastrointestinal bleeding, with the aim of providing a reference for clinical diagnosis and treatment.

With the deepening understanding of small intestinal diseases and the improvement of the disease spectrum, diseases related to small intestinal villous atrophy have been gradually recognized and diagnosed in recent years. Most patients with villous atrophy present with small intestinal malabsorption syndrome, such as diarrhea, bloating, abdominal pain, and weight loss. However, due to the lack of specificity of clinical symptoms and the fact that endoscopic findings only involve the villi, milder lesions are easily overlooked, leading to missed diagnosis or misdiagnosis. This article summarizes the endoscopic manifestations, examination methods, differential diagnosis, and treatment approaches for small intestinal villous atrophy in recent years, aiming to improve the standardized diagnosis and treatment of diseases related to small intestinal villous atrophy.

Objective To investigate the clinical characteristics,diagnosis,treatment,and prognosis of descending necrotizing mediastinitis(DNM)to provide a reference for the early diagnosis and timely treatment of DNM.Methods Data on DNM in China was electronically retrieved from the core databases and comprehensively reviewed from June 2012 to June 2023.The infection,pathogenic microorganisms,main symptoms,comorbidities and treatment methods of DNM were analyzed.Results The data of a total of 781 DNM patients,with an average age of(52.97±5.64)years,were retrieved,including 554 males and 227 females.Odontogenic source,tonsillitis,pharyngeal abscess,sialoadenitis,upper respiratory tract infection,foreign body injury,or iatrogenic traumatic procedures are common causes.Among these,odontogenic infection is the most common source.Streptococcus sp.(n=217)and Staphylococcus sp.(n=82)were most isolated,followed by Klebsiella pneumoniae and Pseudomonas aeruginosa(equally n=59).A total of 69.4％(542/781)of DNM patients recruited in this study were discovered to have various comorbidities,and more than one-third of these patients(n=185)had diabetes.Of the broad antibiotics,carbapenem was most frequently used as treatment,and vancomycin was the most frequently coadministered.The mediastinal drainage approach varies widely,and the optimal regimen is still unknown.Seventy-two patients were treated with video-assisted thoracoscopic/mediastinoscopic surgical drainage,22 patients were treated with percutaneous catheter drainage,30 underwent the transcervical approach,and 40 underwent thoracotomy.A total of 617 patients who were selected underwent the appropriate combined operation for surgical drainage according to the specific location of the infected focus.The overall mortality rate of all 781 DNM pa-tients included was 11.2％.Conclusion The most effective diagnosis and treatment of DNM is a high degree of clini-cal vigilance followed by prompt and adequate drainage with intensive care,including hemodynamic monitoring,nutri-tional support,computer tomographic scanning repeated as necessary,and combined use of systemic antibiotics.

Objective:To investigate the correlation between the osseous structure of temporomandibular joint (TMJ) and three different status of anterior disc location, so that it could guide the clinical diagnosis further.Methods:Fifty-two patients [46 females and 6 males, with an age of (27.8±8.3) years] who treated with MRI and cone beam CT, were recruited from the Temporomandibular Joint Specialist Clinic, The First Affiliated Hospital of Xinjiang Medical University, between March 2018 to December 2021. According to the radiographic findings of the level of anterior disc displacement (ADD) in TMJ, patients were divided into three groups: normal articular disc position (NADP, n=28 TMJs), anterior disc displacement with reduction (ADDWR, n=28 TMJs), and anterior disc displacement without reduction (ADDWoR, n=28 TMJs). In the light of the reconstructed three-dimensional model, ten representative morphological parameters including condylar volume (CV), condylar superficial area (CSA), fossa volume (FV), fossa superficial area (FSA), the proportion of the condylar volume in the articular fossa (CV%), the proportion of the condylar superficial area in the articular fossa (CSA%), superior joint space (SJS), anterior joint space (AJS), posterior joint space (PJS), and medial joint space (MJS), were measured respectively under one-way analysis of variance (ANOVA), Kruskal-Wallis Htest and receiver operator characteristic curve(ROC curve) analyses. Results:CV and CSA values varied significantly in the pathological progression from normal location to irreversible anterior displacement in TMJ. For CV value, NADP group [(1 834.90±667.67) mm 3]>ADDWR group [(1 747.34±369.42) mm 3]>ADDWoR group [(1 256.29±418.27) mm 3] [ t=4.31, P(NADP-ADDWoR)<0.001; t=3.66, P(ADDWR-ADDWoR)<0.001], for CSA value, NADP group [(859.27±216.01) mm 2]>ADDWR group [(838.23±118.82) mm 2]>ADDWoR group [(669.14±150.26) mm 2] [ t=4.27, P(NADP-ADDWoR)<0.001; t=3.80, P(ADDWR-ADDWoR)<0.001]. The difference of SJS value in NADP group [(2.22±0.88) mm], ADDWR group [(1.94±0.64) mm] and ADDWoR group [(1.45±0.57) mm], was statistically significant [ t=4.11, P(NADP-ADDWoR)<0.001; t=2.63, P(ADDWR-ADDWoR)=0.010]. The results of MJS in NADP group [(5.03±1.41) mm], ADDWR group [(3.86±1.32) mm], and ADDWoR group [(4.91±1.65) mm] were significantly different [ t=3.00, P(NADP-ADDWR)=0.004; t=2.63, P(ADDWR-ADDWoR)=0.009]. As calculated by the ROC curve analysis, CV, CSA and SJS showed that (AUC CV=0.77, AUC CSA=0.76; AUC SJS=0.76) for the NADP and ADDWoR groups, and (AUC CV=0.80; AUC CSA=0.80; AUC SJS=0.72) for the ADDWR and ADDWoR groups. While the diagnostic accuracy of MJS for the comparison in NADP versus ADDWR and ADDWR versus ADDWoR was respectively AUC (NADP-ADDWR)=0.73, and AUC (ADDWR-ADDWoR)=0.69. Conclusions:CV, CSA, SJS, and MJS were significantly associated with the different disc displacement status, and the condyle in TMJ ADD exhibited three-dimensionally altered dimensions. They could be considered as promising biometric markers to diagnose the ADD status.

Temporomandibular disorders (TMD) are a heterogeneous group of diseases that affect the temporomandibular joint, chewing muscle system, dental occlusion, and even various structures throughout the body, with significant characteristics of biological-psychological-social pattern. TMD related chronic pain, as the most important clinical symptom, can result in negative emotions seriously affecting patients′ quality of life and physical and mental health. Although a variety of therapies have been previously reported to treat TMD related chronic pain, there is a lack of widely recognized therapies. Professor Jason W Busse (from Michael G DeGroote National Pain Centre, McMaster University, Hamilton ON, Canada) took the lead and collaborated with multiple internationally renowned schools/hospitals of stomatology to develop an international consensus on the management of chronic pain associated with TMD, a clinical practice guideline, which took two years and was published in December 15th, 2023 in a global top journal of clinical research The British Medical Journal. This clinical practice guideline explored the comparative effectiveness of available therapies for chronic pain associated with TMD, conditionally recommended the specific intervention for different treatment or pain relief, proposed a comprehensive, agreed, and standardized clinical practice guideline. This present article describes the methodology and key elements of the clinical practice guideline to help clinicians fully understand and appropriately apply this guidance, which could provide the references for clinical practice of TMD associated chronic pain in China.