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 investigate the effects of Qiangxin decoction on myocardial mitochondrial and energy metabolism in rats with chronic heart failure （CHF） based on mitophagy. METHODS Male SD rats were collected to establish CHF model by ligating the left anterior descending branch of coronary artery. The successful modeling rats were divided into model group， Qiangxin decoction group [12.25 g/（kg·d）， calculated by crude drug]， captopril group [10.38 mg/（kg·d）]， and Qiangxin decoction+captopril group （the same usage and dosage as single drug group） according to a random number table method， with 8 rats in each group. Another 8 normal rats were selected and received threading in the left anterior descending branch of the coronary artery without ligation as the sham operation group. Starting from the second day after successful modeling， the rats in administration groups were given relevant drug intragastrically， twice a day， for consecutive 28 days. After the last medication， the levels of adenosine triphosphate （ATP）， adenosine monophosphate （AMP） and free fatty acid （FFA） in infarcted myocardial tissues were detected， the pathological changes and mitochondrial morphology of the infarcted myocardial tissue were observed， as well as the protein expressions of B cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax）， TANK-binding kinase 1 （TBK1）， p62 were detected in each group. RESULTS Compared with the sham operation group， the infarcted myocardial tissue fibrosis was changed evidently， with a large number of mitochondrial swelling and fusion， and internal cristae rupture； the levels of AMP and FFA， the protein expressions of Bax and p62 were all increased or up-regulated significantly in infarcted myocardial tissue， while the level of ATP， and the protein expressions of Bcl-2 and TBK1 were all decreased or down-regulated significantly （P＜0.05）. Compared with the model group， the pathological changes of infarcted myocardial tissue and mitochondrial swelling had been improved； the levels of AMP and FFA， and the protein expressions of Bax and p62 in infarcted myocardial tissue were significantly decreased or down-regulated in administration groups， while the level of ATP， and the protein expressions of Bcl-2 and TBK1 were increased or up-regulated significantly （P＜0.05）. And the effect of Qiangxin decoction+captopril group was better than that of single drug group. CONCLUSIONS Qiangxin decoction can alleviate myocardial fibrosis and mitochondrial swelling in CHF rats， and improve their myocardial energy metabolism， which may be related to regulating the expression of Bcl-2， Bax， TBK1 and p62 proteins and promoting myocardial mitophagy.

The methodological framework for interventional clinical research of Chinese medicine （CM） under the research mode of syndrome dominating disease provides a set of technical principles and methods to design， evaluate， and implement of this kind. It consists of three main parts including general principles， research points and key design elements， with a total of 25 items. This methodological framework proposes implementing requirements and recommendations in a variety of aspects， including basic norms to be followed in relevant studies， perspectives for selecting research topics， as well as the technological details on study population （P）， intervention （I） and comparison（C）， outcome measurement （O）， time frame （T） of treatment and follow-up， sample orientation （prospective versus retrospective）， study design （S） format and type. To provide practical guidance for future studies， this article clearly explains each items of the methodological framework through some supportive cases.

Objective:To construct a multi-dimensional surgical equipment management and control platform based on artificial intelligence and Internet of Things(AIoT)to assist with the refinement and intelligent management medical equipment in hospital operating rooms.Methods:A multi-dimensional surgical equipment control platform based on AIoT was established by integrating the Internet of Things(IoT),big data analysis,indoor positioning technology,artificial intelligence(AI)technology and other technologies to collect real-time process data of surgical equipment such as endoscopy and electrosurgical,and to open up the relationships among information systems relating to surgical equipment,such as hospital information system(HIS),laboratory information system(LIS),radiology information system(RIS)and operation anesthesia management system(OAMS),so as to provide technical support for efficiency analysis,benefit analysis and assets management of surgical equipment.The platform was composed of 3 layers:data extraction layer,data engine layer and AI data analysis layer,including 4 functional modules:automatic data acquisition,deep data fusion,data mining and analysis and data visualization.Results:This platform was launched in Shanghai Municipal Hospital of Traditional Chinese Medicine in June 2022,and had realized achieving intelligent daily management such as indoor positioning of operating room equipment,one click inventory.A set of performance analysis method based on IoT and integrated with information systems was established to automatically count the utilization efficiency and cost-effectiveness of key surgical equipment to realize intelligent service,intelligent management,and digital operation.Conclusion:The construction and application of this platform improved the efficiency of medical equipment in operating rooms,reduced the cost and increased the efficiency,assisted in the refinement and intelligent management of hospital surgical equipment,and provided data support for scientific decision-making of hospital managers.

Objective To explore the correlation between serum residual lipoprotein cholesterol(RLP-C)and triglyceride glucose(TyG)index in postmenopausal type 2 diabetes(T2DM)patients.Methods A total of 389 postmenopausal T2DM patients who attended Ruili People's Hospital from May 2019 to May 2023 were included.RLP-C and TyG index were calculated,and the study subjects were divided into the low TyG index group(n=194)and the high TyG index group(n=195)based on the median of TyG index(9.23).Differences in general clinical data and metabolism-related indexes between the two groups of patients were compared,and Spearman rank correlation was performed to explore their correlation.Single-factor and multivariate Logistic regressions were used to explore their influencing factors,and ROC curve was used to analyze their diagnostic value.Results Compared with the low TyG index group,the history of hypertension(79.49%vs 70.62%),hyperlipidemia(22.05%vs 13.40%),hemoglobin(Hb)(120.34±19.96g/L vs 114.97±21.32g/L),fasting blood glucose(FBG)[3.97(3.03,5.10)mmol/L vs 3.64(2.99,4.74)mmol/L],total cholesterol(TC)[5.00(4.40,5.95)mmol/L vs 4.36(3.78,5.30)mmol/L],triacylglycerol(TG)[2.11(1.60,3.00)mmol/L vs 1.20(0.91,1.54)mmol/L],low-density lipoprotein(LDL-C)[[2.99(2.43,3.93)mmol/L vs 2.71(2.13,3.38)mmol/L],non-high-density lipoprotein(nonHDL-C)[3.94(3.22,4.82)mmol/L vs 3.15(2.53,3.94)mmol/L]and RLP-C concentration[0.76(0.52,1.08)mmol/L vs 0.44(0.29,0.59)mmol/L]of the high TyG index group were higher,while high-density lipoprotein(HDL-C)concentration was lower,and the differences were statistically significant(x2=4.09,4.99;t=-2.56;Z=-2.34,-5.15,-12.08,-3.04,-6.23,-9.15,-3.99,all P<0.05).Spearman correlation analysis showed that TyG in all samples was positively correlated with TC,TG,LDL-C,RLP-C and nonHDL-C(r=0.304,0.769,0.179,0.386,0.571,all P<0.001),but was negatively correlated with HDL-C(r=-0.306,P<0.001).The correlations between TyG and TC,LDL-C in the high TyG index group were not significant(all P>0.05).Single-actor logistic regression analysis showed that history of hypertension,hyperlipidemia,HDL-C,LDL-C,and RLP-C were the factors influencing TyG levels[OR(95%CI)=1.61(1.01～2.57),1.83(1.07～3.12),0.28(0.14～0.54),1.21(1.02～1.43),17.58(8.11～38.11),all P<0.05],while the multivariate regression analysis showed that only RLP-C was an independent risk factor for elevated TyG[OR(95%CI)=13.17(5.71～30.37),P<0.001).ROC curves showed that the AUC(95%CI)for the diagnosis of TyG index elevation by RLP-C was 0.768(95%CI:0.721～0.816),with the cutoffvalue of 0.59 mmol/L.The sensitivity and specificity were 69.71%and 75.77%,respectively.Conclusion RLP-C is an independent risk factor for elevated TyG in postmenopausal T2DM patients,which has some clinical value in predicting insulin resistance.

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.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

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: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.