Objective:To investigate the effects of lipopolysaccharide (LPS)-activated stimulator of interferon genes (STING) signaling on the biological behavior of periodontal ligament cells and its mechanism of action.Methods:Human periodontal ligament cells (hPDLC) were divided into the PBS group and the LPS group by stimulated with phosphate-buffered saline (PBS) and LPS derived from Porphyromonas gingivalis (ATCC 33277) for 12 hours, respectively. The intracellular distribution of 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA damage, and the activation level of STING signaling were detected by immunofluorescence. The source of intracellular double-stranded DNA was detected by live-cell probes. The levels of osteogenic-related proteins, such as special protein 7 (SP7), bone morphogenetic protein 2 (BMP2), cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), and STING were detected by Western blotting. The cell supernatants of the PBS group and the LPS group were collected, and the levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and interferon (IFN)-β, were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). A total of 12 cgas knockout mice and 12 littermate wild-type mice were constructed. The maxillary second molars of the mice were ligated with silk or sham surgery, respectively. After 7 days of modeling, the mice were divided into littermate control sham surgery group, littermate control periodontitis group, cgas knockout sham surgery group, and cgas knockout periodontitis group, with 6 mice in each group. Micro-CT was used to collect image data, and three-dimensional reconstructions were performed on the maxillary samples of each group. The distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC), bone volume fraction (BV/TV), and bone mineral density (BMD) in the model area were statistically analyzed using CTAn and CTVOX software. Frozen sectioning was used to obtain sections of the maxillary molars of each group of mice, and the signal intensities of cGAS and STING proteins were detected by immunofluorescence. Results:Immunofluorescence results showed that the fluorescence signal intensity of 8-OHdG outside the nucleus in the LPS group (4.09±0.24) was significantly higher than that in the PBS group (1.00±0.10) ( t=20.33, P<0.001). The co-localization signal of mitochondrial marker TOM20 and 8-OHdG (8.56±0.53) were significantly higher than that of PBS group (1.00±0.09) ( t=24.37, P<0.001). Live cell DNA probe detection showed that the signal intensity of double-stranded DNA in LPS group (3.23±0.12) was significantly stronger than that in PBS group (1.00±0.17) ( t=18.30, P<0.001). Immunofluorescence demonstrated a significant increase in STING expression in hPDLC of the LPS group ( t=6.42, P<0.001), and it was colocalized with the Golgi marker GM130. ELISA results showed that the abundance of IL-6, IFN-β, and IL-1β in the supernatant of the LPS group were higher than those of the PBS group ( t=12.44, t=11.38, t=9.48, all P<0.001). Animal experiments confirmed that compared with the sham operation group [(207.61±38.09) and (238.97±45.90) μm], the CEJ-ABC in the periodontitis group [(420.31±35.32) and (405.16±35.51) μm] were increased ( P<0.01), while the CEJ-ABC in the cgas knockout periodontitis group [(295.11±35.43) and (309.15±32.22) μm] were significantly lower than those in the control periodontitis group of the same litter ( P<0.01). Compared with the sham operation group (45.84±6.41), the STING fluorescence signal in the periodontitis group (152.44±6.86) was significantly increased ( P<0.001). Compared with the control periodontitis group of the same litter, the STING signal in the cgas knockout periodontitis group was significantly reduced (88.31±9.70) ( P<0.001). Conclusions:LPS stimulation can activate the STING signal by generating mitochondrial-derived double-stranded DNA, stimulating hPDLC to secrete inflammatory cytokines and impairing osteogenic differentiation potential. Suppressing STING activation in animal models can reduce bone destruction in periodontitis.

Objective To investigate the correlation among constipation symptom and clinical features and peripheral immunity of patients with Parkinson's disease(PD).Methods A total of 135 PD patients who were admitted to the Department of Neurology in our hospital from September 2019 to October 2021 were included in this study.Their relevant data were collected,and they were divided into the PD-non-constipation group and the PD-constipation group based on the assessment of constipation in the non-motor symptom scale(NMSS)of PD.The clinical features and peripheral immune cell subsets were compared between the two groups.In the PD-constipation group,the correlation between the constipation score and each factor was analyzed.Finally,the independent risk factors of the constipation score were determined by multivariate Logistic regression analysis.Results Compared with the PD-non-constipation group,the PD-constipation group was older in terms of age and age onset,with higher scores in non-motor symptoms,lower weight,body mass index,cognitive scores and fewer neutrophils and basophils in peripheral blood,the differences of which were all statistically significant(all P＜0.05).The constipation score was negatively correlated with the number of total T cells(CD4 T,CD8 T)in peripheral blood,and positively correlated with the number of NK cells(all P＜0.05).The constipation was lighter in PD patients with higher weight,body mass index,education level,and cognitive scores;while it was heavier in PD patients with older age,age onset,higher non-motor symptoms and anxiety scores(all P＜0.05).Logistic regression indicated that scales for outcomes in PD-autonomic(OR=1.108,95％CI:1.013-1.212,P=0.025)and NMSS scores(OR=1.026,95％CI:1.002-1.050,P=0.034)were independent risk factors for the constipation score.Conclusions Compared with PD-non-constipation group,PD-constipation group has the clinical features of overall older age,lighter weight,more severe cognitive and non-motor symptoms.The peripheral blood T cell population is decreased,while the number of NK cells is increased with worse constipation.Among them,autonomic dysfunctions and non-motor symptoms are risk factors for the severity of constipation.

Objective:To investigate the effects of lipopolysaccharide (LPS)-activated stimulator of interferon genes (STING) signaling on the biological behavior of periodontal ligament cells and its mechanism of action.Methods:Human periodontal ligament cells (hPDLC) were divided into the PBS group and the LPS group by stimulated with phosphate-buffered saline (PBS) and LPS derived from Porphyromonas gingivalis (ATCC 33277) for 12 hours, respectively. The intracellular distribution of 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA damage, and the activation level of STING signaling were detected by immunofluorescence. The source of intracellular double-stranded DNA was detected by live-cell probes. The levels of osteogenic-related proteins, such as special protein 7 (SP7), bone morphogenetic protein 2 (BMP2), cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), and STING were detected by Western blotting. The cell supernatants of the PBS group and the LPS group were collected, and the levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and interferon (IFN)-β, were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). A total of 12 cgas knockout mice and 12 littermate wild-type mice were constructed. The maxillary second molars of the mice were ligated with silk or sham surgery, respectively. After 7 days of modeling, the mice were divided into littermate control sham surgery group, littermate control periodontitis group, cgas knockout sham surgery group, and cgas knockout periodontitis group, with 6 mice in each group. Micro-CT was used to collect image data, and three-dimensional reconstructions were performed on the maxillary samples of each group. The distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC), bone volume fraction (BV/TV), and bone mineral density (BMD) in the model area were statistically analyzed using CTAn and CTVOX software. Frozen sectioning was used to obtain sections of the maxillary molars of each group of mice, and the signal intensities of cGAS and STING proteins were detected by immunofluorescence. Results:Immunofluorescence results showed that the fluorescence signal intensity of 8-OHdG outside the nucleus in the LPS group (4.09±0.24) was significantly higher than that in the PBS group (1.00±0.10) ( t=20.33, P<0.001). The co-localization signal of mitochondrial marker TOM20 and 8-OHdG (8.56±0.53) were significantly higher than that of PBS group (1.00±0.09) ( t=24.37, P<0.001). Live cell DNA probe detection showed that the signal intensity of double-stranded DNA in LPS group (3.23±0.12) was significantly stronger than that in PBS group (1.00±0.17) ( t=18.30, P<0.001). Immunofluorescence demonstrated a significant increase in STING expression in hPDLC of the LPS group ( t=6.42, P<0.001), and it was colocalized with the Golgi marker GM130. ELISA results showed that the abundance of IL-6, IFN-β, and IL-1β in the supernatant of the LPS group were higher than those of the PBS group ( t=12.44, t=11.38, t=9.48, all P<0.001). Animal experiments confirmed that compared with the sham operation group [(207.61±38.09) and (238.97±45.90) μm], the CEJ-ABC in the periodontitis group [(420.31±35.32) and (405.16±35.51) μm] were increased ( P<0.01), while the CEJ-ABC in the cgas knockout periodontitis group [(295.11±35.43) and (309.15±32.22) μm] were significantly lower than those in the control periodontitis group of the same litter ( P<0.01). Compared with the sham operation group (45.84±6.41), the STING fluorescence signal in the periodontitis group (152.44±6.86) was significantly increased ( P<0.001). Compared with the control periodontitis group of the same litter, the STING signal in the cgas knockout periodontitis group was significantly reduced (88.31±9.70) ( P<0.001). Conclusions:LPS stimulation can activate the STING signal by generating mitochondrial-derived double-stranded DNA, stimulating hPDLC to secrete inflammatory cytokines and impairing osteogenic differentiation potential. Suppressing STING activation in animal models can reduce bone destruction in periodontitis.

Objective To investigate the correlation among constipation symptom and clinical features and peripheral immunity of patients with Parkinson's disease(PD).Methods A total of 135 PD patients who were admitted to the Department of Neurology in our hospital from September 2019 to October 2021 were included in this study.Their relevant data were collected,and they were divided into the PD-non-constipation group and the PD-constipation group based on the assessment of constipation in the non-motor symptom scale(NMSS)of PD.The clinical features and peripheral immune cell subsets were compared between the two groups.In the PD-constipation group,the correlation between the constipation score and each factor was analyzed.Finally,the independent risk factors of the constipation score were determined by multivariate Logistic regression analysis.Results Compared with the PD-non-constipation group,the PD-constipation group was older in terms of age and age onset,with higher scores in non-motor symptoms,lower weight,body mass index,cognitive scores and fewer neutrophils and basophils in peripheral blood,the differences of which were all statistically significant(all P＜0.05).The constipation score was negatively correlated with the number of total T cells(CD4 T,CD8 T)in peripheral blood,and positively correlated with the number of NK cells(all P＜0.05).The constipation was lighter in PD patients with higher weight,body mass index,education level,and cognitive scores;while it was heavier in PD patients with older age,age onset,higher non-motor symptoms and anxiety scores(all P＜0.05).Logistic regression indicated that scales for outcomes in PD-autonomic(OR=1.108,95％CI:1.013-1.212,P=0.025)and NMSS scores(OR=1.026,95％CI:1.002-1.050,P=0.034)were independent risk factors for the constipation score.Conclusions Compared with PD-non-constipation group,PD-constipation group has the clinical features of overall older age,lighter weight,more severe cognitive and non-motor symptoms.The peripheral blood T cell population is decreased,while the number of NK cells is increased with worse constipation.Among them,autonomic dysfunctions and non-motor symptoms are risk factors for the severity of constipation.

Aim To investigate the serum levels of thrombin-antithrombin complex(TAT),tissue type plas-minogen activator-inhibitor complex(t-PAIC)and thrombomodulin(TM)in patients with intracranial atherosclerotic steno-sis(ICAS),and their correlations with the degree of stenosis.Methods A total of 196 ICAS patients(ICAS group)who underwent treatment in Cangzhou People's Hospital from January 2021 to February 2023 were enrolled as research sub-jects.Based on the degree of vascular stenosis,they were separated into three groups:mild group(n=78),moderate group(n.=64),and severe group(n=54).A group of 196 healthy outpatient with similar clinical basic data to ICAS patients was selected as controls.The serum levels of TAT,t-PAIC,and TM in each group were compared;Spearman method was applied to analyze the correlation between serum levels of TAT,t-PAIC,TM and stenosis severity in ICAS pa-tients;Multivariate Logistic regression was applied to analyze the influencing factors of severe stenosis in ICAS patients;ROC curve was applied to analyze the predictive value of serum TAT,t-PAIC,TM and total cholesterol(TC)levels for se-vere stenosis in ICAS patients.Results Compared with the control group,the serum levels of TAT,t-PAIC,and TM were significantly increased in the ICAS group(P＜0.05);the levels of serum TAT,t-PAIC,TM,and TC in the mild,moderate,and severe groups increased accordingly(P＜0.05).Spearman analysis showed that the serum levels of TAT,t-PAIC,and TM in ICAS patients were positively correlated with the degree of stenosis(r=0.574,0.695,0.628;all P＜0.05).Multivariate Logistic regression analysis showed that TAT,t-PAIC,TM,and TC were independent risk factors for severe stenosis in ICAS patients(P＜0.05).The ROC curve showed that the AUC of severe stenosis in ICAS patients predicted by combination of TAT,t-PAIC,TM,and TC was 0.927,with a sensitivity of 83.33％and a specificity of 86.62％,which was superior to the independent prediction of TAT,t-PAIC,TM and TC(Zcombined detection-TAT=4.617,Zcombined deteetion-t-PAIC=4.024,Zcombined detection-TM=4.004,Zcombined detection-TC=7.078,all P=0.000).Conclusion The ser-um levels of TAT,t-PAIC,and TM in the ICAS group were significantly increased,and were positively correlated with the severity of stenosis.The combination of the three and TC has a high predictive value for the occurrence of severe stenosis in ICAS patients.

Objective:To investigate the agreement of ultrasound derived fat fraction (UDFF) with magnetic resonance imaging proton density fat fraction (MRI PDFF) on evaluating hepatic steatosis, and the performance of UDFF on diagnosing metabolic dysfunction associated steatotic liver disease (MASLD).Methods:One hundred and twenty-five volunteers and one hundred and seven inpatients who underwent abdominal ultrasound examination in Zhongda Hospital Southeast University from November 2023 to February 2024 were prospectively enrolled.UDFF and MRI PDFF were applied to evaluate hepatic steatosis. Spearman correlation test and Bland-Altman plot were applied to analyze the agreement of UDFF and MRI PDFF. Receiver operating characteristic curve (ROC) was applied to calculate the performance of UDFF on diagnosing MASLD.Results:In our participants, compared to individuals without hepatic steatosis, patients with MASLD had higher body mass index (BMI), waist-to-hip ratio, prevalence of diabetes mellitus, levels of alanine transaminase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), triglyceride, and UDFF (all P<0.05). The percentage of hepatic steatosis measured by UDFF and MRI PDFF was strongly correlated[ρ=0.873(95% CI=0.837-0.901), P<0.001]. UDFF performed excellent for diagnosing MASLD with an area under the curve (AUC) of 0.983(95% CI=0.956-0.995, P<0.001), and was better than semi-quantitative assessment based on two-dimensional ultrasound as well as ultrasound attenuation parameter. The optimal cut off value of UDFF to diagnose MASLD was ≥6%. Conclusions:The percentage of hepatic steatosis measured by UDFF and MRI PDFF agrees with each other, and UDFF obtains an excellent performance on diagnosing MASLD, so that UDFF should be considered a reliable imaging technique for quantitively evaluating hepatic steatosis and diagnosing MASLD.

Purpose/Significance Based on the concepts of healthy cities and smart cities,the paper introduces a new concept-smart healthy cities.It explores the definition,scope,function,challenges,and strategic responses associated with the concept.Meth-od/Process Through literature review and case study analysis,the theoretical foundations,characteristics,objectives,and implementa-tion strategies of healthy cities and smart cities are compared,revealing differences and points of convergence,proposing the origins,def-initions,and delineations of smart healthy cities,and exploring the relationships among healthy cities,smart cities,and smart healthy cit-ies.Result/Conclusion Smart healthy cities enhance urban health governance and the well-being of residents through technological in-novation.Effective integration of advanced technologies with urban governance policies is essential,alongside the implementation of di-verse strategies to drive progress.Future urban development should focus more on the theoretical and practical collaborative development within the smart healthy cities framework.

Purpose/Significance To explore the technical key points and implementation paths of relevant policies,and provide ref-erence for the planning and construction of future smart healthy cities.Method/Process It reviews and analyzes domestic and internation-al policy progress in the field of smart healthy cities,deeply analyzes policy documents,reveals the evolution trajectory,core elements,and driving effects on urban health development.Result/Conclusion Establishing a framework for health informatization,resource net-working,intelligent services,and integrated supervision can effectively address urban health challenges,provide efficient health services,and improve residents'quality of life and hygiene level.Policies such as optimizing the allocation of medical resources,promoting coordi-nation and cooperation among medical institutions,and expanding the health industry will jointly promote the sustained progress of urban health ecosystems.

Background::High body mass index (BMI) results in decreased fecundity, and women with high BMI have reduced rates of clinical pregnancy and live birth in in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI). Meanwhile, ovarian responses show great heterogeneity in patients with a high BMI. This study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian response. Methods::We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive Center of Peking University Third Hospital, with 3530 (23.3%) in the overweight group and 1380 (9.1%) in the obese group, who had a normal ovarian response (5-15 oocytes retrieved) and underwent fresh embryo transfer (ET) cycles from January 2017 to December 2018, followed by linked frozen-thawed embryo transfer (FET) cycles from January 2017 to December 2020. Cumulative live birth rate (CLBR) was used as the primary outcome. Furthermore, a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the outcomes. We used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI outcomes.Results::High BMI was associated with poor IVF/ICSI outcomes, both in cumulative cycles and in separate fresh ET or FET cycles. In cumulative cycles, compared with the normal weight group, obesity was correlated with a lower positive pregnancy test rate (adjusted odds ratio [aOR]: 0.809, 95% confidence interval [CI]: 0.682-0.960), lower clinical pregnancy rate (aOR: 0.766, 95% CI: 0.646-0.907), lower live birth rate (aOR: 0.706, 95% CI: 0.595-0.838), higher cesarean section rate (aOR: 2.066, 95% CI: 1.533-2.785), and higher rate of large for gestational age (aOR: 2.273, 95% CI: 1.547-3.341). In the generalized additive model, we found that CLBR declined with increasing BMI, with 24 kg/m 2 as an inflection point. In the decision tree, BMI only made a difference in the population aged ≤34.5 years, with anti-Mullerian hormone >1.395 ng/mL, and the first time for IVF. Conclusions::High BMI was related to poor IVF/ICSI outcomes in women with a normal ovarian response, and CLBR declined with increasing BMI, partly due to suppressed endometrial receptivity. A high BMI had the most negative effect on young women with anticipated positive prognoses.