Pulpitis is a common infective oral disease in clinical situations. The regulatory mechanisms of immune defense in pulpitis are still being investigated. Osteomodulin (OMD) is a small leucine-rich proteoglycan family member distributed in bones and teeth. It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells (hDPSCs). In this study, the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated. The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining. Intriguingly, the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens. The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide (LPS)-induced inflammation. A conditional Omd knockout mouse model with pulpal inflammation was established. LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice, whereas OMD administration exhibited a protective effect against pulpitis. Mechanistically, the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB (NF-κB) signaling pathway. Interleukin-1 receptor 1 (IL1R1), a vital membrane receptor activating the NF-κB pathway, was significantly downregulated in OMD-overexpressing hDPSCs. Additionally, the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking. In vivo, excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist. Overall, OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway. OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
Pulpitis/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction ; Humans ; Mice ; Mice, Knockout ; Dental Pulp/metabolism* ; Disease Models, Animal ; Lipopolysaccharides

Objective: To explore the effect of tumor cell perineural invasion on the prognosis of cervical cancer and the early predictive factors of perineural invasion in patients with cervical cancer. Methods: A retrospective a⁃ nalysis was conducted on the clinical , pathological , and survival data of 551 patients with cervical cancer. These patients were categorized into a survival group (n = 477) and a death group (n = 74) . The baseline characteristics of the two groups were compared using independent samples t ⁃tests , Wilcoxon rank⁃sum tests , and chi⁃square tests.Multivariate binary Logistic stepwise regression analysis was employed to identify independent risk factors associated with mortality. In addition , univariate Logistic regression analysis was performed to determine predictive factors for perineural invasion. A predictive model for perineural invasion in cervical cancer was subsequently developed based on the multivariate regression equation , and its predictive accuracy was assessed using the ROC curve. Results: In the basic data of cervical cancer patients , the high level of perineural invasion , lymphatic metastasis and postopera⁃tive pathological stage in pathological data had an impact on the poor prognosis of patients ( P < 0 . 0 5 ) , Lympho⁃vascular space invasion , parametrial involvement , and tumor invasion depth ≥ 1/2 were identified as significant predictors of PNI. The predictive value was the best in the multivariate model ( Area under the curve = 0. 80) . Conclusion Perineural invasion is an independent risk factor for poor prognosis of cervical cancer patients , and the occurrence of perineural invasion can be effectively predicted by the constructed multivariate mode.

Objective: To explore the regulatory effects of ginkgo biloba extract on airway inflammatory injury and Toll⁃like receptor 4(TLR4)/nucleotide⁃binding oligomerization domain⁃containing 3(NLRP3) pathway in rats with vided into four groups : the normal control group , Methods: Thirty⁃six male SD rats were selected and randomly divided into four groups : the normal control group , the model group , the prednisone treatment group , and the ginkgo biloba extract treatment group , with 9 rats in each group. Except for the normal control group , the COPD rat mod⁃els in the other groups was constructed by intratracheal instillation of lipopolysaccharide (LPS) combined with ciga⁃rette smoke exposure. After successful modeling , the rats were continuously administered drugs for 12 weeks , fol⁃lowed by sampling. The general conditions and respiratory symptoms of the rats were observed. The pathological changes of lung tissues were observed by hematoxylin⁃eosin (HE) staining technique ; the mRNA and protein ex⁃pression levels of TLR4 , tumor necrosis factor⁃α (TNF⁃α ) , interleukin⁃1β (IL⁃1β) and NLRP3 in rat lung tissueswere detected by real⁃time quantitative polymerase chain reaction (RT⁃qPCR) and Western blot. Results: Com⁃pared with the normal control group , the lung tissues of rats in the model group were significantly damaged , and the protein and mRNA expression of TLR4 , TNF⁃α , IL⁃1β , and NLRP3 increased ( P < 0. 05 ) . Compared with the model group , lung tissue damage was reduced in the prednisone group and the ginkgo biloba extract group , and TLR4 , TNF⁃α , IL⁃1β , NLRP3 protein and mRNA expression decreased (P < 0. 05) . Conclusion Ginkgo biloba airway inflammatory response by inhibiting the TLR4/NLRP3 signaling pathway.

Objective To investigate the changes of blood lipid and glycosylated hemoglobin (HbA1c) levels in obese type 2 diabetes (T2DM) patients and their relationship with insulin resistance (Homa-IR). Methods A total of 120 cases of T2DM newly diagnosed in Motuo County, Tibet from February to October 2022 were selected as the observation group. According to BMI, the patients were divided into diabetes normal weight group (46 cases), overweight group (43 cases) and obesity group (31 cases); 145 healthy subjects were selected as the control group. The levels of HbA1c, fasting blood glucose (FPG), fasting insulin (FINS), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) were detected in the study subjects, and Homa-IR and Homa-β indices were calculated. The height, weight, and abdominal circumference were measured. The differences in the levels of the above indicators between the observation group patients and the control group, as well as among various subgroups within the observation group were compared. The influencing factors of Homa-IR in obese T2DM patients were analyzed. Results Compared with the control group, a significant increase in BMI, abdominal circumference, blood pressure, HbA1c, FBG, FINS, TC, TG, LDL-C, UA, visceral fat area, and the levels of Home-IR and Home-β was found in the observation group (all P<0.05). There were significant differences in BMI, abdominal circumference, and the levels of FINS, Homa IR, Homa-β, and HbA1c in diabetes patients with different BMI (all P<0.05). Correlation analysis showed that TG levels in obese T2DM patients in the observation group were significantly correlated with HbA1c (r=0.396, P=0.027), Homa-IR (r=0.405, P=0.024), and Home-β (r=-0.401, P=0.025); LDL-C was significantly correlated with Homa-IR (r=0.411, P=0.022) and Homa-β (r=-0.412, P=0.021); HbA1c was significantly positively correlated with BMI (r=0.371, P=0.040). Conclusion Insulin resistance is closely related to TG, LDL-C, and BMI in obese T2DM patients from the Motuo ethnic minority of Tibet, suggesting that these factors may play a role in the occurrence of T2DM.

[摘 要] 目的：探究甘露糖结合凝集素2（LMAN2）在激素受体（HR）阳性乳腺癌组织中的表达水平与乳腺癌患者预后的关系及其对MCF-7 细胞增殖和迁移的影响。方法：通过TCGA、Bc-GenExMiner、GEPIA和Kaplan-Meier Plotter数据库分析LMAN2在乳腺癌组织和正常乳腺组织中的差异性表达及其与患者预后的关系。采用小RNA干扰技术将si-LMAN2#1、si-LMAN2#2及si-NC转染至MCF-7细胞，将过表达LMAN载体（pc-LMAN）及空载体pcDNA3.1阴性对照（pc-NC）转染至MCF-7细胞，实验分为si-LMAN2#1、si-LMAN2#2、si-NC、pc-LMAN2和pc-NC组。通过qPCR和WB实验检测各组细胞中LMAN2 mRNA和蛋白的表达水平，CCK-8、克隆形成、Transwell迁移、WB等实验检测敲低和过表达LMAN 2对MCF-7细胞增殖、克隆形成、迁移及AKT信号通路相关蛋白表达的影响。结果：LMAN2在乳腺癌组织中的表达水平显著高于正常乳腺组织（P<0.001）。HR阳性乳腺癌组织中LMAN2表达水平显著高于HR阴性乳腺癌组织（P<0.001）；LMAN2高表达与HR阳性乳腺癌患者不良预后有关联。敲低LMAN2可显著降低MCF-7细胞的增殖和迁移能力（P<0.01或P<0.001），过表达LMAN2可显著提高MCF-7细胞的增殖和迁移能力（均P<0.001）。敲低LMAN2组MCF-7细胞中PTEN和P21蛋白表达水平均显著升高，p-AKT蛋白表达水平显著降低（均P<0.01）。结论：LMAN2在乳腺癌组织和HR阳性乳腺癌组织中高表达，且与不良预后有关联。LMAN2高表达与MCF-7细胞增殖和迁移有关联，其作用机制可能涉及AKT信号通路。

Objective:To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region.Methods:We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis.Results:The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history ( HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status ( HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits ( HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy ( HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits ( HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy ( HR=5.002, 95% CI: 2.300-10.880) and radiotherapy ( HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade ( HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression ( HR=0.399, 95% CI: 0.168-0.945), HER-2 expression ( HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy ( HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions:The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.

Objective This study aimed to explore the heterogeneity and gene ontology of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells(CNCs)in mice.Methods The embryos of Wnt1-Cre;R26RmTmG and Pax2-Cre;R26RmTmG at embryonic day(E)8.0-E9.25 were collected for histological observation.We per-formed immunostaining to compare green fluorescent pro-tein(GFP)-positive CNCs in Pax2-Cre;R26RAi9 and Wnt1-Cre;R26RAi9 mice at E15.5.Single-cell RNA sequencing(scRNA-seq)was used to analyze the first branchial arch GFP-positive CNCs from Wnt1-Cre;R26RmTmG and Pax2-cre;R26RmTmGmice at E10.5.Real time fluorescence quantitative polymerase chain reaction(q-PCR)was performed to val-idate the differential genes.Results Wnt1-Cre-marked and Pax2-Cre-marked CNCs migrated from the neural plateto first and second branchial arches and to the first branchial arch,respectively,at E8.0.Although Wnt1-Cre-marked and Pax2-Cre-marked CNCs were found mostly in cranial-facial tissues,the former had higher expression in palate and tongue.The results of scRNA-seq showed that Pax2-Cre-marked CNCs specifically contributed to osteoblast differentia-tion and ossification,while Wnt1-Cre-marked CNCs participated in limb development,cell migration,and ossification.The q-PCR data also confirmed the results of gene ontology analysis.Conclusion Pax2-Cre mice are perfect experimen-tal animal models for research on first branchial arch CNCs and derivatives in osteoblast differentiation and ossification.

Objective:To explore the clinicopathological characteristics of primary bladder mucosal-associated lymphoid tissue extranodal marginal zone lymphoma (MALToma).Methods:A retrospective case series study was conducted. The clinicopathological data of 9 primary bladder MALToma patients diagnosed and underwent transurethral resection of bladder tumors at the Fujian Provincial Hospital, Zhangzhou Municipal Hospital, Mindong Hospital of Ningde City, Zhangzhou Second Hospital and Fuzhou Taijiang Hospital from December 2008 to December 2021 were collected. Paraffin-embedded surgical specimens were collected for HE staining, immunohistochemical staining and genetic testing, the clinicopathological characteristics of patients were summarized, and the literature was reviewed.Results:Of the 9 cases, 8 were female and 1 was male, the age was (59± 11) years old (range: 39-74 years old). Two cases had 3 lesions, 3 cases had 2 lesions, and 4 cases had single lesion. The maximum diameter of the mass was (3.2±1.9) cm (range: 0.3-7.0 cm). The follow-up time was 6-127 months, 4 cases lost to follow-up, 4 cases were disease-free survival, and 1 case was survival with tumor. Pathomorphologically, the bladder tissue consisted of diffusely infiltrating small-to-medium sized lymphocytes, with moderate amounts of pale-staining cytoplasm, without obvious nucleoli, some of them were translucent, and the mitosis was rare. Large cell proliferation in some areas was observed in 1 case, with prominent nucleoli and mitotic figures. Tumor cells in all 9 patients expressed CD20; bcl-2, CD43 and CD38 were positive in some cells in 4 cases, and CD138 was positive in a few cells in 2 cases; κ was positive in 4 cases, and scattered positive in 5 cases; λ was positive in 4 cases, and scattered positive in 5 cases. B-cell receptor gene clonal rearrangement was positive in all 8 cases who underwent the assay. No break-apart signal was observed in all 6 cases who underwent the fluorescence in situ hybridization assay with MALT1 gene segregation probe.Conclusions:Primary bladder MALToma is a rare low-grade B-cell lymphoma that is more commonly found in elderly women. There is no abnormal change in MALT1 gene.

Objective:To investigate the clinicopathological features of pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma).Methods:A retrospective case series study was conducted. A total of 41 cases of pulmonary MALToma who were admitted to multiple centers from April 2002 to August 2023 were collected, including 33 cases from Fujian Provincial Hospital, 5 cases from Binzhou People's Hospital, 1 case from the Second Hospital of Zhangzhou, 1 case from the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, and 1 case from Jinjiang Hospital. The results of pathological morphological examination, immunohistochemical examination and genetic testing of patients were summarized, their clinicopathological characteristics were analyzed, and the relevant literature was reviewed.Results:Among the 41 patients, there were 24 males and 17 females, aged (58±13) years (range: 36-81 years). The longest diameter of the tumor under the gross macroscopic examination was (2.8±2.0) cm, with a range of 0.8-9.7 cm. Under the microscope, diffuse, flakelike and nodular patterns of lymphoid tissue were seen in the lung tissue with small- to medium-sized lymphoid cells including small lymphocytes, centrocyte-like cells, mononuclear cells and plasma cells. A small number of activated cells were noted, and the lymphoid cells grew along the alveoli. In some areas, the lymphoid cells invaded the bronchi, and lymphatic follicular implantation was rare; 1 case was accompanied by large cell transformation. Tumor cells expressed CD20, Pax-5, bcl-2, and CD43, with Ki-67 proliferation index of 2%-20%, and 50% in some areas of 1 case. The positive rate of clonal B-cell receptor gene rearrangement was 100.00% (29/29); the positive rate of MALT1 gene was 18.75% (3/16), and the positive rate of API2-MALT1 fusion was 66.67% (2/3). The treatment methods included surgery, anti-inflammatory therapy, radiotherapy, and chemotherapy. Follow-up for 4-143 months showed that 43.90% (18/41) had disease-free survival, 21.95% (9/41) had tumor bearing survival, 9.76% (4/41) died, and 24.39%, (10/41) were lost to follow-up. The progression-free survival of patients aged ≥ 60 years was worse than that of patients aged < 60 years ( χ2 = 5.39, P = 0.020). Conclusions:Pulmonary MALToma belongs to indolent B-cell lymphoma, and its diagnosis requires a combination of clinical imaging, pathology and immunophenotyping. If necessary, genetic testing can be used to assist in the diagnosis. The differential diagnosis should be made from pneumonia, low-grade B-cell lymphoma, and extrapulmonary MALToma with lung involvement. The treatment methods include anti-inflammatory therapy, surgical resection and chemotherapy, and the prognosis is good.

Objective:To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region.Methods:We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis.Results:The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history ( HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status ( HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits ( HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy ( HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits ( HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy ( HR=5.002, 95% CI: 2.300-10.880) and radiotherapy ( HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade ( HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression ( HR=0.399, 95% CI: 0.168-0.945), HER-2 expression ( HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy ( HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions:The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.