BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

Objective:To analyze the epidemiological information of oral leukoplakia and explore the relationship between clinical characteristics and different degrees of epithelial dysplasia.Methods:A total of 430 patients with oral leukoplakia confirmed by pathology in the Department of Oral Medicine, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from February 2013 to May 2021 were enrolled. Epidemiological information was recorded, and univariate and multivariate Logistic regression analysis were performed on age, gender, smoking, drinking, lesion size, lesion site and lesion type to evaluate the correlation between the risk factors and the degree of epithelial dysplasia in oral leukoplakia.Results:A total of 430 valid samples were included in this study, among which 23 patients were diagnosed with oral leukoplakia with concurrent cancer. The age of all patients was (52.9±12.9) years (22-85 years); 213 were male and 217 were female. One hundred and seventy-six cases (40.9%) had lesions on the lateral and ventral tongue, and 254 cases (59.1%) had lesions in other locations. Three hundred and two cases (70.2%) had homogeneous lesions, and 128 cases (29.8%) had heterogeneous lesions. The degrees of epithelial dysplasia included none [11.9% (51/430)], mild [51.9% (223/430)], moderate [24.4% (105/430)], severe [6.5% (28/430)], and concurrent cancer [5.3% (23/430)]. Smoking, drinking, and gender were correlated with the degree of epithelial dysplasia in some binary classification systems, while tongue (border and ventral) and non-homogeneous damage were significantly correlated with higher degrees of epithelial dysplasia in all binary classification systems ( P<0.05). Conclusions:Lesions on the lateral or ventral tongue and heterogeneous lesions are significantly associated with higher degrees of dysplasia, suggesting that clinicians should pay more attention to these types of oral leukoplakia during the follow-up monitoring process.

Oral cancer, as one kind of mucosal epithelial tumor, constitutes approximately 2% of all cancers, while the most common type, oral squamous cell carcinoma (OSCC) represents around 90% histopathology of oral cancers. Although the treatment of OSCC has been improved in recent 20 years, its 5-year survival rate has not raised significantly. The crux to improve the survival rate and prognosis of OSCC patients lies in the early diagnosis and intervention of this disease. Hence, exploring new diagnostic and therapeutic strategies for OSCC is therefore an urgent priority. Exosomes, the small membrane vesicles originated from endosomes, have been detected in a wide array of bodily fluids. Exosomes have biological properties of derived cells based on containing a diversity of proteins, lipids, DNA fragments, mRNAs, and non-coding RNAs, including microRNAs, long non-coding RNAs, piRNAs, circular RNAs, tsRNAs, and ribosomal RNAs, which are delivered to neighboring cells or even transported to distant sites. They participate in cellular communication as well as play an important role in many diseases and immune response. Exosomes have been associated with the tumorigenesis of OSCC, promoting the proliferation, colonization, and metastasis of OSCC by transferring their cargos to the target cells. Furthermore, exosomes participate in the regulation of the tumor microenvironment to affect cancer progression in vivo. In this review, we summarize the crucial role of exosomes in the tumorigenesis and progression of OSCC and discuss the potential clinical application of exosomes in OSCC treatment.

Objective:To explore the expression level of Porphyromonas gingivalis, downstream of tyrosine kinase 3 (DOK3) and tumor-associated macrophage (TAM) in the tumor immunomicroenvironment of oral squamous cell carcinoma (OSCC) and the correlation with clinicopathological characteristics and prognosis of patients.Methods:A retrospective case-control study was conducted. The clinical data of 200 OSCC patients with Porphyromonas gingivalis-positive confirmed by 16S rDNA sequencing technology in the First Affiliated Hospital, Xinjiang Medical University between June 2008 and June 2020 were collected. The tumor tissues and the corresponding adjacent normal mucosal tissues of 6 OSCC patients (including 3 cases with Porphyromonas gingivalis -positive and 3 cases with Porphyromonas gingivalis-negative) were selected for high-throughput sequencing to screen differentially co-expressed genes. Immunohistochemistry method was used to detect the expressions of Porphyromonas gingivalis, DOK3, and CD206 (a TAM marker). The median H score of OSCC tissues was used as the threshold to categorize the expression level of Porphyromonas gingivalis, DOK3 and CD206 into low-expression (H score < threshold) and high-expression (H score ≥ threshold) groups. The overall survival (OS) analysis was conducted by using the Kaplan-Meier method, and the log-rank test was employed.Results:The high-throughput sequencing results revealed that DOK3 is a differentially co-expressed gene among normal oral mucosa, Porphyromonas gingivalis-positive, and Porphyromonas gingivalis-negative OSCC. In 200 patients with Porphyromonas gingivalis-positive OSCC, 139 exhibited high expression of Porphyromonas gingivalis (H score ≥ 7 points), while 61 showed low expression (H score < 7 points). There were statistically significant differences in the expression levels of Porphyromonas gingivalis in patients with different survival status, pathological T stage, pathological N stage, clinical stage, tumor diameter, degree of tumor differentiation and recurrence (all P < 0.05). Among the 139 OSCC patients with high expression of Porphyromonas gingivalis, 92 cases showed high expression of DOK3 (H score ≥ 6 points) and 47 showed low expression (H score < 6 points); 78 cases exhibited high expression of CD206 (H score ≥ 6 points), while 61 showed low expression (H score < 6 points). There were statistically significant differences in the DOK3 expression level in the high expression of Porphyromonas gingivalis OSCC patients with different age, survival status, pathological T stage, pathological N stage, and recurrence (all P < 0.05). There were statistically significant differences in the CD206 expression level in the high expression of Porphyromonas gingivalis OSCC patients with different pathological T stage, clinical stage, and degree of tumor differentiation (all P < 0.05). The expression of Porphyromonas gingivalis was positively correlated with the expressions of DOK3 and CD206 (both P < 0.01). At the last follow-up on April 6th, 2024, the median follow-up time was 45 months (3 to 106 month range). The median OS time of the 200 patients was 2 429 d, and the 3-year OS rate was 63.9%. The OS of OSCC patients with high expressions of Porphyromonas gingivalis, DOK3, and CD206 was worse than that in those with low expressions (all P < 0.05). Conclusions:The high expression levels of Porphyromonas gingivalis, DOK3, and TAM are associated with a poor prognosis of OSCC patients, suggesting their potential as key biomarkers for prognostic evaluation.

Objective:To compare the dose-response effects of single-fraction ultra-high dose rate (FLASH) and conventional dose rate (CONV) whole abdominal irradiation (WAI) with X-rays on acute radiation-induced intestinal injury in mice, in order to identify optimal dose parameters and potential mechanisms.Methods:A total of 186 male C57BL/6J mice were randomly assigned to a non-irradiation group ( n=6), FLASH irradiation groups ( n=90), and CONV irradiation groups ( n=90). Acute radiation-induced intestinal injury models were established using single-fraction WAI with 11, 12, 13, 14, and 15 Gy X-rays (200 Gy/s for FLASH and 4 Gy/min for CONV). Changes in body weight, stool characteristics, and disease activity index (DAI) scores were assessed at 9 d post-irradiation. At 7 d post-irradiation at 11, 12, and 13 Gy, the intestines were collected for macroscopic examination and length measurement. The small intestine was selected for HE staining and quantitative analysis of intestinal crypt number and mucosal epithelial thickness. The survival of mice was assessed at 15 d post-WAI across all dose groups. Results:After single-fraction WAI at 11, 12, and 13 Gy, the body weight was higher in the FLASH group than that in the CONV group ( t=10.17, 12.65, 10.16, P<0.05). The DAI scores for the FLASH group were 1.00±1.10, 3.17±0.75, and 2.83±1.17, respectively, which were lower than those of the CONV group (4.33±0.52, 7.00±0.00, 8.60±0.55; t=8.70, 11.71, 14.99, P<0.05). However, after WAI at 14 Gy and 15 Gy, there were no significant differences in body weight and DAI between the FLASH group and the CONV group ( P>0.05). At 7 d after single-fraction WAI at 11, 12, and 13 Gy, mice in the FLASH group exhibited less intestinal congestion, edema, and shortening compared with the CONV group. The difference between the FLASH and CONV groups were statistically significant in small intestine length at 11 and 13 Gy ( t=4.42, 3.78, P<0.05), and in colorectal length at 11 and 12 Gy ( t=3.97, 3.12, P<0.05). Small intestine HE staining revealed superior preservation of intestinal architecture in the FLASH group compared with the CONV group, characterized by longer villi, increased crypt numbers, thicker mucosal epithelium, and enhanced structural integrity. The differences in crypt number and mucosal epithelial thickness were statistically significant ( tcrypt=13.10, 23.80, 11.90; tmucosal=5.75, 2.64, 7.74; P<0.05). At 15 d post-irradiation, the survival rate in the 15 Gy FLASH group was higher than that in the CONV group (50% vs. 10%, χ2=5.39, P<0.05), with a median survival extension of 6 d ( HR=0.340, 95% CI: 0.115 4-0.999 9). No significant survival differences were observed between the FLASH group and the CONV group at 11, 12, 13, and 14 Gy ( P>0.05). Conclusions:FLASH irradiation significantly alleviated acute radiation-induced intestinal injury from medium single-fraction WAI with 11, 12, and 13 Gy X-rays compared with CONV irradiation, and showed potential to improve mouse survival after single-fraction WAI at 15 Gy. This effect is likely associated with the preservation of intestinal crypts and exhibits a dose-dependent relationship.

Objective:To investigate the effect of semaglutide on the metabolomics of obese patients with type 2 diabetes mellitus (T2DM) complicated by metabolic-associated fatty liver disease (MAFLD).Methods:A prospective non-randomized controlled study was conducted. Obese patients with T2DM complicated by MAFLD who attended the Department of Endocrinology of Shijiazhuang People′s Hospital from October 2022 to June 2023 were selected as the semaglutide group, and healthy individuals from the physical examination center were selected as the control group. Clinical data of both groups were collected. The semaglutide group was subcutaneously injected with semaglutide following a basic hypoglycemic regimen (starting dose of 0.25 mg once a week, which was changed to 0.5 mg once a week after 1 week for 12 weeks). Liquid chromatography-tandem mass spectrometry was used for qualitative and quantitative analyses of plasma metabolites, and multivariate analysis methods were used to analyze the metabolomics data.Results:In total, 69 patients in the semaglutide group completed the treatment, with 49 males (71%) and a median age of 46 (36, 54) years, and the healthy control group consisted of 100 individuals, with 38 males (38%) and a median age of 40 (35, 45) years. The body mass index and levels of fasting blood glucose, alanine aminotransferase, and interleukin-6 (IL-6) in the semaglutide group before treatment were significantly higher than those in the control group (all P<0.001). The body mass index [23.65 (22.33, 24.45) vs. 28.72 (27.50, 32.07) kg/m 2], liver stiffness measurement [1.61 (0.91, 2.00) vs. 5.78 (5.51, 6.10) kPa], and homeostasis model assessment of insulin resistance index [5.10 (2.90, 7.95) vs. 9.00 (6.25, 11.80)] in the semaglutide group were significantly lower after treatment than before treatment (all P<0.001), and the blood glucose, blood lipid, liver function indicator, and IL-6 levels all significantly decreased after treatment. Metabolomics analysis revealed that there were 219 differential metabolites (131 up-regulated and 88 down-regulated) between the semaglutide group ( n=27) before treatment and the control group ( n=12), with glycerophospholipids and free fatty acids being significantly up-regulated. The semaglutide group showed 203 differential metabolites (121 up-regulated and 82 down-regulated) after treatment compared with before, with significant down-regulation of long-chain fatty acids and significant up-regulation of metabolites including carnitines, branched-chain amino acids, and taurine. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differential metabolites identified before and after semaglutide treatment were involved in several signaling pathways, such as biosynthesis of unsaturated fatty acids, linoleic acid metabolism, aldosterone synthesis and secretion, and the mTOR signaling pathway, etc. Conclusion:Semaglutide alters the serum metabolite levels in obese patients with T2DM complicated by MAFLD.

Objective To explore the relationship between disease risk perception and objective risk in stroke risk population,and to provide theoretical basis for prevention and control of stroke.Methods From February to May 2023,560 residents who participated in medical examinations in 2 community health service centers of Zhengzhou and Luohe were selected as respondents.The objective risk of stroke was assessed,and the general data questionnaire and Risk Perception Questionnaire for People at High Risk of Stroke were used for investigation.Logistic regression model and restricted cubic spline model were used to analyze the correlation and the dose-response relationship between disease risk perception and objective stroke risk.Results A total of 542 effective questionnaires were collected.The detection rate of stroke high-risk groups was 48.71％.Logistic regression analysis showed that after adjusting confounding factors,the objective risk of stroke in the general population and in different gender stratification decreased first and then increased with the increase of the level of disease risk perception.The results of the restricted cubic spline showed that the disease risk perception and objective risk of stroke in the total population and gender stratification showed a nonlinear dose-response relationship(P nonlinear＜0.05),and the curve showed a"U"type change.The disease risk perception score of 90.0～110.0 was the protective factor of objective risk of stroke.Conclusion The objective risk of stroke decreases first and then increases with the increase of the perceived risk.Medical staff should maintain individual disease risk perception within the appropriate level,and pay attention to the difference in disease risk perception of different gender groups to implement targeted risk communication strategies,so as to promote the development of healthy behaviors and reduce the incidence of stroke.

Triple-negative breast cancer(TNBC)is a highly aggressive and prognostically unfavorable subtype.Tertiary lymphoid structure(TLS)within the tumor microenvironment,comprising dendritic cells,B cells,T cells,and other immune cells,modulate the tumor immune response.The heterogeneity of TLS in TNBC,such as density,structural maturity,and molecular expression patterns,affects the tumor immune microenvironment and,consequently,treatment responses and clinical outcomes.Studies indicate a positive correlation between the density and maturity of TLS and the pathological complete response(pCR)of TNBC patients,with TLS enhancing the quantity of tumor-infiltrating immune cells and improving anti-tumor immune responses,thereby increasing sensitivity to chemotherapy and immunotherapy.Recent research has found that mature TLS are associated with effective immune responses,becoming significant predictors of treatment response.The combination of TLS with immune checkpoint inhibitors has shown promising prospects.Research demonstrates that promoting the formation or enhancing the functionality of TLS can improve anti-tumor immune effects and enhance treatment outcomes for TNBC patients.Targeting TLS may reduce immune evasion and increase the sensitivity to immunotherapy.However,clinical application of TLS still faces challenges,particularly the impact of their heterogeneity on treatment response.Current assessment methods for TLS are not standardized,lacking a uniform standard and diagnostic system,which limits their widespread application.Future research should focus on resolving these issues by developing standardized assessment tools and further exploring the role of TLS in immune escape and resistance mechanisms.This review aimed to summarize and analyze the existing research progress on TLS in TNBC,in order to provide new ideas for the development of personalized immunotherapy strategies.

Objective To explore the challenges faced by online appointment nurses during nasogastric intubation and to provide a reference for improvement of the quality and safety of the services provided by online appointment nursing.Methods A purposive sampling was employed to select 13 online appointment nurses from our hospital who had previously provided home nasogastric intubation services for patients.Semi-structured interviews were conducted with the online appointment nurses.The results acquired from the interviews were analysed using Colaizzi's method.Results Two themes were identified.Theme 1 covered the increased risks of nasogastric intubation due to the patients themselves and home environment,which included 4 sub-themes of difficulties in identification and response due to complex conditions of patient,high risk of a sudden asphyxia with poor resuscitation facility,psychological stress from unfamiliar home environment,and more challenges in risk identification due to limited conditions for performing home-based intubation procedures;Theme 2 covered the coping strategies of online-scheduled nurses,which included the improvement of knowledge and skills in emergency nursing to improve comfidence and judge ability of intubation,the strengthening of nurse-patient communication to build a trust and cooperation,the conduct of thorough assessment to ensure procedural safety,and the use of alternative tools and collaboration with family members.Conclusion Online appointment nurses face challenges and risks from both of the procedures and patients themselves during home based nasogastric intubation.Hospitals and relevant management should actively implement corresponding strategies,provide training and guidance for online appointment nurses,develop relevant regulations,and improve the management mechanisms of the internet platform to ensure the safety of home based nasogastric intubation for online appointment nurses and improve the quality of the"Internet Plus Nursing Services."