1.EZH2 protein expression in predicting malignant transformation of oral leukoplakia: a prospective cohort study
MEI Nianrou ; LIU Limin ; YANG Jingwen ; XU Siming ; LI Chenxi ; GE Shuyun ; ZHOU Haiwen
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(10):862-872
Objective:
To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice.
Methods:
This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed.
Results:
There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134).
Conclusion
High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.
2.Research progress on dedifferentiated fat cells and their application in oral and maxillofacial bone tissue engineering
SHEN Yingyi ; CAO Ximeng ; XU chun
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(3):223-228
The identification of suitable seed cells represents a critical scientific problem to be solved in the field of oral and maxillofacial bone tissue regeneration. The application of adipose-derived stem cells (ASCs) in tissue and organ repair and regeneration has been studied extensively. In recent years, dedifferentiated fat (DFAT) cells have also shown broad application prospects in the field of bone tissue engineering. DFAT cells express stem cell-related markers and have the potential to differentiate into adipocytes, osteoblasts, chondrocytes, nerve cells, cardiomyocytes and endothelial cells. In addition, DFAT cells also have the advantages of minimally invasive acquisition, strong proliferation and high homogeneity. Currently, all studies involving the application of DFAT cells in scaffold-based and scaffold-free bone tissue engineering can confirm their effectiveness in promoting bone regeneration. However, cytological research still faces some challenges, including relatively low cell culture purity, unclear phenotypic characteristics and undefined dedifferentiation mechanisms. It is believed that with the continuous development and improvement of isolation, culture, identification and directional induction of osteogenic differentiation methods, DFAT cells are expected to become excellent seed cells in the field of oral and maxillofacial bone tissue engineering in the future.
3.Relationship between zinc finger protein A20, CTGF and FibroScan and fibrosis in chronic hepatitis B patients
Song ZHANG ; Zilong ZHAO ; Qian HU ; Jian LI ; Xiaojing WANG ; Huijie GENG ; Haiyan KANG ; Dianxing SUN ; Zhengrong GUO
Journal of Public Health and Preventive Medicine 2024;35(3):133-136
Objective Studies on the expression and location of zinc finger protein A20 (A20) and connective tissue growth factor (CTGF) in liver tissues of patients with chronic hepatitis B were conducted, and the relationship between them and liver fibrosis was determined by FibroScan. Methods Studies on A20 and CTGF in liver tissues of 160 patients with chronic hepatitis B were conducted in accordance with the stage of pathological fibrosis and inflammation of the liver, and quantitative immunohistochemistry test was conducted, and statistical analysis was conducted by FibroScan. Results The expressions of A20 and CTGF in liver tissues increased with the aggravation of liver pathological fibrosis and inflammation, and there were significant differences between each stage and the control group (P<0.05), and there were significant differences between adjacent groups (P<0.05). Studies have shown that FibroScan increases along with pathological fibrosis and inflammation in the liver. There are significant differences between the stage and the control group (P<0.05), and no significant differences between the adjacent groups (P>0.05). There was positive correlation between liver A20 and CTGF, r=0.796 (P<0.05). Conclusions In patients with chronic hepatitis B, A20, CTGF and FibroScan are positively correlated with the degree of liver fibrosis, and A20 and CTGF are also positively correlated with the degree of liver inflammation, which can be used as indicators to evaluate the degree of liver inflammation and fibrosis, and further guide the anti-inflammatory and anti-fibrosis treatment of patients.
4.Research progress on m6A-modified circRNA in oral diseases
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(2):137-141
N6-methyladenosine (m6A) modification is the most abundant RNA modification in eukaryotes and is widely involved in the regulation of RNA nuclear export, splicing, translation and degradation. Increasing evidence shows that m6A methylation modification of circular RNA (circRNA) has great potential in metabolism, immunity and benign and malignant diseases. Here, we review the research status of circRNA m6A methylation modification in physiological processes, malignant tumors and oral diseases. It has been shown that m6A methylation can regulate circRNA by regulating circRNA translation, promoting circRNA nuclear output, and promoting circRNA degradation; M6A-modified circRNA plays a regulatory role in immunity, the reproductive system, myogenesis and development, and malignant tumors; and the M6A methyltransferase METTL3 promotes the occurrence of oral squamous cell carcinoma (OSCC) through m6A modification mediated by YTHDF1. The high expression of METTL14 can effectively reduce the proliferation, migration and invasion of OSCC. There is little research on circRNA m6A methylation modification in the oral cavity, which is limited to preliminary research in ameloblastoma and oral implant bone absorption. It has broad research prospects in the treatment of major oral diseases (such as potential oral malignant diseases and OSCC).
5.Research progress on selective tooth agenesis caused by LRP6 gene mutation
JIANG Cailing ; ZHAO Bin ; WU Yiqun
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(3):223-228
Selective tooth agenesis (STA) is an abnormal number of teeth due to genetic factors or the environment and is most commonly observed for permanent teeth. LRP6 is one of the common causative genes of STA and is inherited by an autosomal dominant mechanism, leading to non-syndrome tooth agenesis (NSTA) or syndrome tooth agenesis (STA). NSTA is only involved in tooth number and appearance abnormalities, whereas STA caused by LRP6 gene mutation results abnormal ear development, oral-facial clefting, sparse hair and hypohidrosis. In this paper, we review the phenotype and gene mutation traits of selective STA caused by LRP6 gene mutation identified in recent years and describe 38 patients with tooth agenesis from 24 mutation sites of LRP6 gene. We analyzed the percentage of missing teeth and found that the lateral incisor in the maxilla and the second premolar in the maxilla and mandible were most commonly lost, whereas all central incisors in the maxilla remained. LRP6 gene plays a major role in tooth development via the WNT/β-catenin signaling pathway, and LRP6 gene mutation can lead to a series of abnormal manifestations due to the disruption of the signaling pathway. The literature showed that LRP6 gene mutations occurred mostly at the E1 or E2 subdomain, meaning that STA due to the mutants extracellularly disturbed the WNT/β-catenin signaling pathway. However, mature treatments for selective congenital tooth loss are lacking.
6.Advances in comprehensive multidisciplinary treatment for burning mouth syndrome
LU Chenghui ; LUO Wenhai ; LI Xin ; DU Guanhuan ; TANG Guoyao
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(4):290-294
Burning mouth syndrome (BMS) is a chronic oral and facial pain disorder characterized by burning pain in the oral mucosa, with multiple pathogenic factors including psychosocial, neuropathological, endocrine, and immune factors. There is still a lack of effective treatment options that have been demonstrated to work. With the development of research on the pathogenesis and treatment of BMS, multidisciplinary comprehensive treatment has gradually been introduced and become a new trend of diagnosis and treatment. Before multidisciplinary treatment, it is necessary to go through a full and comprehensive diagnosis and analysis, select the best comprehensive treatment plan, take the diagnosis and treatment of stomatology as the basis and premise, and apply other multidisciplinary combined treatment, including the treatment of concurrent diseases, psychological interventions, correction of bad habits, etc. A combination of laser therapy and psychological intervention is a more effective treatment method among the current treatment methods, with high comfort and good acceptance by patients. If necessary, mecobalamin tablets, clonazepam α-lipoic acid and other drugs can be used to nourish nerves and provide symptomatic treatment. The comprehensive multidisciplinary treatment of BMS is expected to become a new trend and provide a new strategy for improving the therapeutic effect.
7.Epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae infection in adult inpatients
Journal of Public Health and Preventive Medicine 2023;34(5):95-98
Objective To analyze the epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) in adult inpatients, and to provide a theoretical basis for the diagnosis and treatment of CRKP. Methods A total of 753 hospitalized patients with Klebsiella pneumoniae (KPN) infection in our hospital from 2017 to 2021 were selected as the investigation subjects. According to the sensitivity to carbapenem drugs, the patients were divided into carbapenem sensitive Klebsiella pneumoniae (CSKP) group (n=638) and CRKP group (n=115). The age, gender, department distribution, underlying diseases, length of hospital stay, use of antibiotics and other clinical data of all subjects were analyzed by self-made survey scale of our hospital. Univariate analysis and logistic regression analysis were used to analyze the risk factors of CRKP nosocomial infection in adult inpatients. Results Among of 753 KPN patients, 115 cases (15.27%) were detected with CRKP, including 87 males and 28 females. The detection rate of CRKP in different age groups was significantly different (P<0.05). The detection rate of CRKP in the age group of >60 years was significantly higher than that in the age group of 41-60 years, 21-40 years, and 16-20 years (P<0.05). The detection rate of CRKP increased year by year from 2017 to 2021, and the difference was statistically significant (P<0.05). There was no significant difference between the detection rate of CRKP in spring and winter (66/459) and that in summer and autumn (49/294) (χ2 value =0.725, P>0.05). CRKP strains were mainly isolated from oral and maxillofacial surgery (19.13%), infection department (15.65%), geriatric department (15.65%), and ICU (14.78%). The detection rate of CRKP in different pathogenic bacteria samples was different, including sputum (19.40%), urine (15.43%) and blood (12.58%), with statistically significant difference (P<0.05) The respiratory tract sputum specimens were all expectoration. There were significant differences in age, gender, use of carbapenems ≥7 days, invasive procedures, use of antibiotics ≥2 kinds, use of antibiotics ≥14 days, and use of enzyme inhibitors ≥7 days between the CSKP group and the CRKP group (P<0.05). Antimicrobial application time ≥14 days (OR=5.412), invasive operation (OR=6.431), and carbapenem use ≥7 days (OR=5.417) were the risk factors for CRKP nosocomial infection in adult inpatients (P<0.05). Conclusion Nosocomial infection of CRKP occurs mostly in elderly ICU patients. Intervention measures should be given to adult inpatients who have used antibiotics for ≥14 days, invasive procedures, and carbapenem antibiotics for ≥7 days, which can reduce the risk of CRKP infection in inpatients.
8.Simultaneous innervated and vascularized iliac bone flap for reconstructing mandible and nerve defects
WANG Lei ; The Ninth People' ; s Hospital of Shanghai Jiaotong University School of Medicine - School of Stomatology, Oral and Maxillofacial-Head and Neck Oncology Department ; National Clinical Medical Research Center for Oral Diseases ; Shanghai Laboratory of Stomatology ; Shanghai Institute of Stomatology Jingcun
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(9):609-617
The functional reconstruction of large maxillofacial defects is a major issue in oral and maxillofacial surgery, and autologous bone transplantation is the main method. However, bone is readily absorbed following an autologous bone transplant. Even with vascular anastomosis, spontaneous osteoporosis of transplanted bone is still serious, which affects dental implantation and functional recovery. Therefore, osteoporosis of the grafted bone has become one of the main complications of jaw reconstruction, and there is no preventive measure. The problem that autologous bone with sufficient blood supply cannot avoid osteoporosis suggests that systemic factors such as nerves, which have been neglected in traditional methods, may regulate the internal environment of the transplanted bone. Based on previous studies on the regulation of mesenchymal stem cells by the neural microenvironment, we initiated a new surgical procedure for innervated and vascularized iliac bone flaps based on animal model and cadaver studies. In the innervated and vascularized iliac bone flap, vascular microanastomosis was performed in conjunction with microneuronal anastomosis between the simultaneously harvested ilioinguinal nerve (which innervates the iliac bone and is usually sacrificed and neglected in the conventional vascularized iliac bone flap) and the inferior alveolar nerve proximally and with the mental nerve distally. By conducting clinical retrospective studies and prospective randomized controlled trials, we proved that the novel method of simultaneous innervated iliac bone transplantation can not only prevent bone resorption but also restore the sensation of adjacent soft tissues such as the lip. This may solve the key problems of sensory loss and osteoporosis after mandibular reconstruction, ensure the success of dental implant dentures, and put forward the new concept of "blood supply + innervation" bi-system bone transplantation.
9.Preliminary study of familial nonsyndromic tooth agenesis caused by ectodysplasin A mutation
WANG Huihui ; WU Qing ; XU Bin ; LING Qi ; WU Yiqun
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(11):768-773
Objective:
To explore the pathogenic genes in a Chinese family affected by nonsyndromic tooth agenesis so as to study the pathogenesis of oligodontia.
Methods :
Hospital ethical approval and informed consent of the patients and family members were obtained. Clinical data of the proband and close family members were collected, peripheral venous blood was collected, and DNA was extracted. Gene sequencing was performed through whole-exome sequencing, and then the screened pathogenic genes were verified by Sanger sequencing. The three-dimensional structure of the mutant proteins was analyzed and compared with the wild-type using bioinformatics tools.
Results:
The two patients with congenital majority tooth loss in this family were cousins, and there were no other patients with congenital majority tooth loss in the family. Besides congenital multiple tooth loss, the two patients had no obvious hair abnormalities, finger/toe abnormalities, sweating abnormalities or other abnormal manifestations of ectodermal tissue. We found a mutant gene that in this family by carrying out gene sequencing of the patients and their close family members. A novel EDA (ectodysplasin A) missense mutation c.983C>T (p. Pro328Leu) was identified, which changed the encoded amino acid from proline (Pro) to leucine (Leu). Analysis of the mutation site showed that the site was highly conserved, and three-dimensional structure modeling also found that it changed the structure of EDA.
Conclusion
A novel EDA missense variant (c.983C>T, p.Pro328Leu) was first identified in a Chinese family with nonsyndromic tooth agenesis, extending the mutation spectrum of the EDA gene.
10.Co-expression of circRNA in oral leukoplakia and oral lichen planus
YANG Jingwen ; SONG Yuhan ; XU siming ; GE Shuyun ; ZHOU Haiwen
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(11):774-781
Objective:
To find any differentially expressed circRNAs in oral leukoplakia (OLK) and oral lichen planus (OLP), to investigate the possible role of circRNAs in the pathogenesis of these two diseases.
Methods:
This study obtained hospital ethical approval. High-throughput sequencing was used to detect differentially expressed circRNAs in OLK, OLP, oral squamous cell carcinoma and normal oral mucosal tissues. CircRNAs were verified by qRT-PCR, enzyme tolerance assays and Sanger sequencing. GO functional analysis and KEGG pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted miRNAs and mRNAs of circRNAs, and ceRNA networks were mapped.
Results:
A total of 49 circRNAs were differentially expressed in OLK and OLP together, including 30 upregulated and 19 downregulated circRNAs. The five circRNAs confirmed with RT-qPCR, including circHLA-C, circRNF13, circTTN, circSEPN2 and circALDH3A2, were all abnormally expressed in OLK and OLP, among which circHLA-C was a key circRNA with trans splice sites, which was validated by expanding the sample size. ROC curve analysis showed that the area under the circHLA-C curve for predicting OLK was 0.955, and the area under the circHLA-C curve for predicting OLP was 0.988. GO functional analysis showed enrichment of many biological processes related to the immune process. The KEGG pathway with the highest enrichment score was "Natural killer cell mediated cytotoxicity". HLA-C was significantly enriched in these processes/pathways. CeRNA network analysis showed that circHLA-C interacted with a variety of miRNAs, such as hsa-miR-26a-5p, hsa-miR-129-5p, and hsa-miR-29a-3p.
Conclusion
Many circRNAs were differentially expressed in both OLK and OLP, circHLA-C being the most elevated. CircHLA-C is valuable for the early diagnosis of OLK and OLP and may serve as a potential biomarker for the diagnosis and prognosis of OLK and OLP.


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