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were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study.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.

Objective: To explore the clinical manifestations, diagnosis, differential diagnosis, and treatment of granulomatous cheilitis complications after treatment in patients with upper lip venous malformations, as well as to provide a reference for their clinical diagnosis and treatment. Methods: This report provides details on the clinical manifestations, diagnosis, differential diagnosis, and treatment of a case of granulomatous cheilitis after the treatment of upper lip venous malformation, and then analyzes granulomatous cheilitis alongside the related literature. The patient, a 30-year old male, was first seen in the dermatology department of another hospital with bright red spots on his lips, diagnosed with allergic dermatitis and received symptomatic treatment, and the erythema did not improve. He was diagnosed with ‘cavernous hemangioma’ and was treated with polydocanol and bleomycin injections. The bright red spots on his lips improved, but the swelling worsened for more than half a year. He then sought treatment at the oral mucosal department of our hospital. At the time of consultation, the swelling of the upper lip and perilabial skin was obvious, and there was a red patch on the right side of the upper lip, that was congested with blood. The upper lip was tough, with hard nodules, unclear borders, and poor mobility. Pathological examination showed epithelial hyperplasia of the upper lip mucosa, surface hyperkeratosis, subepithelial fibrous tissue hyperplasia, and chronic inflammation of the mucosa and minor salivary glands. Focal histiocyte, lymphocyte, and plasma cell infiltration was seen in the submucosal layer, with granulomatous inflammatory manifestations. Based on the patient's medical history, clinical manifestations, and histopathological manifestations, the diagnosis of granulomatous cheilitis was made. Tretinoin 0.3 mL (40 mg/mL, 1 mL/vial) was injected into the deep layer of the mucosa of the right and left upper lips for local block treatment. Prednisone acetate tablets (10 mg/Qd) were taken orally, and after 1 week of follow-up, the symptoms improved, so the original treatment was continued. After 2 weeks of follow-up, the swelling of the lips improved significantly, and the oral prednisone acetate tablets were adjusted to 5 mg/Qd. After 4 weeks of follow-up, the shape of the lips was largely back to normal, and the color and suppleness of the lips had improved significantly. The local block treatment and oral medication were stopped, and the patient was instructed to apply the topical tretinoin ointment Bid on the upper lip. Results: The patient had a follow-up visit 8 weeks later, at which their lip color, shape, and texture remained normal, and the patient was instructed to stop the medication and follow up. A review of the literature suggests that the etiology of granulomatous cheilitis is unknown and that it is associated with genetic predisposition, odontogenic infections, allergic factors, microbial infections, and immunological factors. It needs to be clinically differentiated from diseases such as lip venous malformations, lip angioneurotic oedema, Crohn's disease, and tuberculosis. At present, the clinical treatment of granulomatous cheilitis is still based on local glucocorticoid block therapy or a combination of oral glucocorticoid drugs. In this case, the area of erythema on the lips decreased in size, but swelling occurred and continued to worsen after polydocanol and bleomycin injection treatment. Pre-existing venous malformation should be considered as a complication associated with injectable drugs that can produce granulomatous cheilitis. Conclusion The injection-based treatment of lip venous malformation may be complicated by granulomatous cheilitis, and in the process of clinical diagnosis and treatment, it is necessary to be aware to the existence of drug-related factors in the occurrence and development of granulomatous diseases.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective To explore the effect of M2 polarization of macrophages on intestinal metaplasia(IM)of gastric mucosa and its therapeutic target,so as to provide new ideas and directions for the prevention and treatment of IM with traditional Chinese medicine.Methods The data sets related to IM and macrophage M2 polarization were downloaded from the public database,and the correlation between IM and macrophage M2 polarization was further expounded by immune infiltration analysis,gene correlation analysis,functional enrichment analysis,protein interaction network and experimental verification.Finally,the obtained hub genes were mapped with Coremine Medical platform to predict the effective traditional Chinese medicine and treatment of IM.Results Immunoinfiltration and immunofluorescence analysis showed that the expression of macrophage M2 polarization markers CD68+CD163+(P=0.0394)and CD68+CD206+(P=0.002)in IM group was significantly higher than that in normal group,and the infiltration level of M2 macrophages in IM group was significantly higher than that in normal group(P＜0.05).IM related marker genes(CDX1,MUC2,TFF3)were positively correlated with macrophage M2 polarization markers(CD209,ARG1,MSR1,STAT3,IL32,SELENOP)(P＜0.05).Functional enrichment analysis showed that the differential genes co-expressed by IM and macrophage M2 polarization were closely related to molecular biological functions such as carboxylic acid transmembrane transporter activity and organic acid transmembrane transporter activity.Finally,7 pivotal differential genes co-expressed by IM and macrophage M2 were screened,which were TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA,respectively.According to the prediction of traditional Chinese medicine,23 kinds of traditional Chinese medicine for IM were predicted,which could be classified into 14 categories according to their efficacy,among which heat-clearing antidote appeared most frequently,followed by drugs for tonifying qi and painkillers for promoting blood circulation drugs.Conclusion Macrophage M2 polarization may be involved in the pathogenesis and development of IM through exocrine pathway.IM and seven hub genes co-expressed by macrophage M2 polarization(TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA)and IM specific molecules CDX1,MUC2 and TFF3 may be associated with each other and participate in the progression of IM.The therapeutic method of Jianpi Huayu Jiedu is the core treatment of IM in traditional Chinese medicine.Starting from the M2 polarization of macrophages,it is expected to become a new direction and breakthrough in clinical prevention and treatment of IM.

Objective To explore the effect of M2 polarization of macrophages on intestinal metaplasia(IM)of gastric mucosa and its therapeutic target,so as to provide new ideas and directions for the prevention and treatment of IM with traditional Chinese medicine.Methods The data sets related to IM and macrophage M2 polarization were downloaded from the public database,and the correlation between IM and macrophage M2 polarization was further expounded by immune infiltration analysis,gene correlation analysis,functional enrichment analysis,protein interaction network and experimental verification.Finally,the obtained hub genes were mapped with Coremine Medical platform to predict the effective traditional Chinese medicine and treatment of IM.Results Immunoinfiltration and immunofluorescence analysis showed that the expression of macrophage M2 polarization markers CD68+CD163+(P=0.0394)and CD68+CD206+(P=0.002)in IM group was significantly higher than that in normal group,and the infiltration level of M2 macrophages in IM group was significantly higher than that in normal group(P＜0.05).IM related marker genes(CDX1,MUC2,TFF3)were positively correlated with macrophage M2 polarization markers(CD209,ARG1,MSR1,STAT3,IL32,SELENOP)(P＜0.05).Functional enrichment analysis showed that the differential genes co-expressed by IM and macrophage M2 polarization were closely related to molecular biological functions such as carboxylic acid transmembrane transporter activity and organic acid transmembrane transporter activity.Finally,7 pivotal differential genes co-expressed by IM and macrophage M2 were screened,which were TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA,respectively.According to the prediction of traditional Chinese medicine,23 kinds of traditional Chinese medicine for IM were predicted,which could be classified into 14 categories according to their efficacy,among which heat-clearing antidote appeared most frequently,followed by drugs for tonifying qi and painkillers for promoting blood circulation drugs.Conclusion Macrophage M2 polarization may be involved in the pathogenesis and development of IM through exocrine pathway.IM and seven hub genes co-expressed by macrophage M2 polarization(TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA)and IM specific molecules CDX1,MUC2 and TFF3 may be associated with each other and participate in the progression of IM.The therapeutic method of Jianpi Huayu Jiedu is the core treatment of IM in traditional Chinese medicine.Starting from the M2 polarization of macrophages,it is expected to become a new direction and breakthrough in clinical prevention and treatment of IM.

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.

Objective: To observe the clinical effects of auricular point therapy on burning mouth syndrome (BMS) and its effect on the psychological state of patients and plasma β-endorphin. Methods : A total of 105 patients diagnosed with BMS were randomly divided into an auricular acupoint application group (50 cases) and a drug treatment group (55 cases). The treatment course lasted one month. The patients in the auricular acupoint application group selected 3 points on their tongue, heart and Shenmen through traditional Chinese medical dialectics used for patients with BMS. Wangbuliu seeds were applied, two ears were pressed alternately and one ear was applied each time. The patient was instructed to press the treatment site three times a day, 1-2 min each time, until the auricle skin became reddish and hot. The patients in the drug treatment group took vitamin E 100 mg+oryzanol 10 mg+vitamin B2 10 mg orally three times a day. Before and after treatment, the pain intensity and mental and psychological state of the patients were evaluated. The patient's plasma was detected before and after β-endorphin treatment. Results: The pain sensation intensity of the two groups decreased after treatment (P<0.001). After treatment, the scores of somatization (t = 2.118, P = 0.037), fear (t = 2.084, P = 0.039) and diet and sleep (t = 2.047, P = 0.043) in the auricular acupoint application group were significantly improved compared with the level before treatment. The level of β-endorphin in plasma was increased, and the difference was statistically significant (t = 2.247, P = 0.027) in the auricular acupoint application group after treatment. Conclusion Auricular point therapy is an effective method for patients with BMS, improving psychological state and promoting the synthesis of plasma β-endorphin may be one of its mechanisms.