OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

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*

AIM: To provide references for the non-clinical evaluation of therapeutic targets or drugs for retinoblastoma, fluorescently labeled Y79 cells are injected into the vitreous body of BALB/c-nu mice to establish a retinoblastoma model, and the Melphalan treatment group is used as a positive control, which is verified by fluorescence imaging technology.METHODS: BALB/c-nu mice were intravitreous injected with GFP transfected Y79 cells(1.0×107 cell/mL, 3 μL)to establish the model. On the 27th day, the mice were randomly divided into model control group and different doses of Melphalan groups(1, 3, 10 μg/eye groups)according to the fluorescence value of in vivo imaging, with vitreous body single administrated and ocular symptoms observed daily. Slit-lamp examination was performed at 12, 20, 29, 35, 42, 48, 55, 76, and 83 d after modeling. In vivo imaging was performed on 12, 20, 27, 41, 48, 55, 62, 69, 76, and 83 d. At the last treatment, the eyeball, brain and cerebellum tissues were removed for histopathological examination.RESULTS: From the sixth day of modeling, cloud-like substances could be seen in the eyes of the animals, and the cloud-like substances occupied the whole eyeball of the mice in the model control group at the later stage, accompanied by irregular growth of blood vessels. After 27 days of modeling, the fluorescence value was detected in all the animals, and the fluorescence value continued to increase with the extension of modeling time. The fluorescence value of the tumor reached the peak after 69-83 days of modeling. Histological examination showed severe proliferation of intraocular tumor cells in the model control group, and tumor cells were observed in the brain of 1 model animal. In the 10 μg/eye Melphalan group, the fluorescence value was significantly decreased at 17 d after administration. The fluorescence value of the 3 μg/eye Melphalan group was significantly inhibited at 59 d after administration. No tumor cells were found in the brain tissue of animals in all Melphalan groups.CONCLUSION: After vitreous injection of Y79/pCDH-LUC-copGFP cells in BALB/c-nu mice, significant ocular lesions and proliferation of tumor cells were observed in the eyes. Meanwhile, Melphalan intervention significantly inhibited tumor cells in a dose-dependent manner, indicating that the mouse model of retinoblastoma was successfully constructed.

Objective:To investigate the effect of a new method of utilizing frontalis sling with polypropylene non-absorbable sutures for the treatment of senile ptosis.Methods:A retrospective analysis was conducted on the clinical data of senile patients with blepharoptosis who were treated with frontalis sling surgery with polypropylene non-absorbable sutures at the Department of Plastic Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine between January 2022 and December 2023. The palpebral fissure height and margin reflex distance (MRD1) of the upper eyelid margin were measured and recorded before and after the operation, and the operation time and postoperative detumescence time were recorded. Postoperative complications and recurrence of ptosis were followed up. Patients’ satisfaction with the postoperative effect was investigated and divided into three levels: very satisfied, satisfied, and dissatisfied. Normal distribution measurement data were expressed as Mean±SD; counting data were expressed as frequency.Results:A total of 8 patients were enrolled, including 3 males and 5 females, with an age of (68.8±6.1) years. Six patients underwent bilateral ptosis correction surgery, and two underwent unilateral ptosis correction surgery. The ptosis was graded as follows: 1 case was mild, 2 cases were moderate, and 5 cases were severe. There were 2 cases of aponeurotic ptosis, 3 cases of congenital ptosis and 3 cases of traumatic ptosis (1 of which was prosthetic eye). The operative time of 8 patients (14 eyes) with unilateral ptosis was (43.9±4.9) min. The swelling resolved in (9.4±1.7) days. One patient still had symptoms of lagophthalmos and corneal irritation 7 days after the operation. The symptoms gradually relieved after wearing corneal protective goggles and applying eye ointment. The postoperative follow-up lasted from 2 to 15 months (mean 6.3 months). Palpebral cleft height [(9.8±0.6) mm vs. (3.3±1.2) mm] and MRD1[(4.1±0.5) mm vs. (-1.1±0.8) mm] in 8 patients (14 eyes) after surgery were significantly higher than those before the operation( P<0.01). There was no recurrence of ptosis after the operation. There were 2 cases of upper eyelid hysteresis, of which 1 case was mild upper eyelid hysteresis, and the other case had relatively obvious upper eyelid hysteresis on prosthetic side. Satisfaction survey showed that 7 patients were very satisfied with the result of the operation, and 1 patient was satisfied. Conclusion:Frontal muscle suspension with polypropylene non-absorbable suture is a feasible method for the treatment of ptosis in elderly patients with simple operation, little tissue damage, positive effect, rapid postoperative recovery and acceptable complications.

Objective To observe the value of whole-brain CT perfusion(CTP)parameters at different time and clinical data for predicting delayed cerebral ischemia(DCI)and 3-month poor prognosis in patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods Totally 127 aSAH patients were retrospectively enrolled.Clinical and CTP data within 24 h of symptom onset and during DCI time window(DCITW)were collected.The patients were divided into DCI group(n=34)and non-DCI group(n=93)based on DCI occurred or not during hospitalization,also into poor outcome group(modified Rankin scale[mRS]≥3,n=36)and good outcome group(mRS≤2)based on 3-month's follow-up.Multivariate logistic regression was performed to select independent predictive factors among variates being significantly different between groups.Then receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the predictive performance of logistic regression model.Results Patients'age,modified Fisher score(mFS),subarachnoid hemorrhage early brain edema score(SEBES)and mean flow extraction product(mFEP)within 24 h of onset were all identified as independent predictive factors of DCI,and the AUC of their combination for predicting DCI during hospitalization was 0.817.Patients' age and mFS within 24 h of onset,alternatively,World Federation of Neurosurgical Societies(WFNS)grade and mFEP during DCITW were all independent predictive predictors of 3 months' prognosis,and the combination of the latter two showed better predictive performance(AUC=0.922)tahn the former two(AUC=0.822,P＜0.05).Conclusion Whole-brain CTP parameters combined with clinical data within 24 h of onset of aSAH could be used to predict the occurrence of DCI during hospitalization,whole-brain CTP parameters during DCITW could be used to predict 3 months'poor prognosis.

Juvenile idiopathic arthritis(JIA)is the most prevalent joint disease in childhood.The disease is defined as arthritis of unknown etiology,involving one or more joints,with onset before the age of 16 years and symptomatic duration of more than 6 weeks.Temporomandibular joint(TMJ)arthritis is a common manifestation of JIA,but it often develops insidiously.Failing to diag-nose and treat it promptly may lead to maxillofacial dysfunction and dentofacial deformity,and negatively affect the patient's quality of life.Therefore,early diagnosis and disease management of TMJ arthritis are crucial.This article reviews the occurrence of JIA-TMJ arthritis and its progress in clinical diagnosis and disease treatment in recent years,aiming to provide some reference for den-tists in the clinical diagnosis and treatment of JIA.

Objective This study aims to evaluate the safety and efficacy of internal carotid artery(ICA)embolization for the resection of head and neck tumors invading the ICA.Methods A retrospective analysis was conducted on eight patients with ICA-invading head and neck tumors treated between August 2022 and June 2024 in Beijing Tongren Hospital,Capital Medical University.All patients underwent a preoperative balloon occlusion test(BOT),which yielded negative results before undergoing ICA embolization.Parameters from BOT,technical success rates of embolization procedures,perioperative complications,and follow-up outcomes were recorded.Results During BOT assessments,the mean reflux pressure was found to be 75.4％±10.3％of the pre-occlusion pressure.Patency of both anterior and posterior communicating arteries was observed in three cases;four cases exhibited patency solely in the anterior communicating artery,while one case showed patency only in the posterior communicating artery.The technical success rate of embolization was 100％.One patient experienced acute cerebral infarction following embolization treatment,while two patients had migraine attacks post-procedure.All patients achieved complete tumor resection without new-onset neurological deficits.Conclusion For patients with head and neck tumors invading the ICA who are negative on BOT,preoperative ICA embolization is a safe and feasible approach that enhances surgical safety during tumor resection.

Objective To systematically investigate the effects of Dangmu extract syrup on the growth and development of 4-day-old(postnatal day 4,PND4)Sprague-Dawley(SD)rats and its toxic reactions.Methods According to the whole litter design method,128 young mice(PND2)were randomly divided into negative control group and low,medium and high dose groups.From PND4,the animals were orally given pure water,31 g/kg,93 g/kg and 280 g/kg(calculated as raw herb material)of Dangmu extract syrup,respectively,once daily for 18 consecutive days,with a 15 d of recovery phase.During the study period,the general state,growth and development,nerve reflex function,spontaneous behavior,hematology,coagulation,blood biochemistry,immune function,growth hormone and histopathology of the animals in each group were observed or examined.Results After 18 d of continuous administration,compared with the negative control group,GLU(male and female)in the medium and high dose groups increased(P＜0.05 or P＜0.01),LDH(male and female)and AST(male)in the medium and high dose groups,ALT,AST(female)in the high dose group decreased(P＜0.05 or P＜0.01),RET and percentage of RET(male and female)in the low and high dose groups,RET(male)in the medium dose group increased(P＜0.05 or P＜0.01),spleen mass and the organ-to-body mass ratio(male and female)in the low and high dose groups and female in the medium dose group increased(P＜0.05 or P＜0.01).Splenic nodule structures were formed in all dose groups with large size and number,and there was a dose relationship in the degree of changes.After 15 d recovery period,compared with the negative control group,GLU(female)in the low dose group increased(P＜0.05),ALT,AST,ALP,TG(female)in the medium and high dose groups,GGT,TG,TCHO(male)in the medium dose groups,AST,ALP,TG,LDH(male)in the high dose group decreased(P＜0.05 or P＜0.01),RET(female)and percentage of RET(male)in the high dose group increased(P＜0.05).compared with the 18 d of continuous administration,the spleen structures of the animals in each group were more completely developed and the splenic nodule structures were obvious,but no significant difference was noted in the comparison between groups.No significant drug-related changes were observed in other test result.Conclusions Dangmu extract syrup advanced the development of complete spleen structure in 4-day-old SD rats,accompanied by the enhancement of its hematopoietic function,and at the same time,it caused the animals,blood glucose to rise,the enhancement of glucose metabolism function led to the increase of related enzyme consumption,and led to the decrease of some liver function parameters,and showed a dose correlation.There was no gender difference in the changes,which were reversible after stop administration,and the mechanism of the changes needs to be further explored and confirmed.In the clinical trials,attention should be paid to the control of the dose of the test article,and regular monitoring of the spleen and related blood and clinical chemistry parameters.

Bone defect repair is an urgent problem in the field of orthopedics,and numerous researchers are working to develop more effective treatment plans.The accurate evaluation of bone repair after surgery is a crucial step.In line with the development of computed tomography(CT)imaging,dual-energy CT imaging has shown significant advantages in analyzing bone composition and reducing metal artifacts.This article reviews the application of dual-energy CT imaging for the evaluation of bone repair in animals.

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.