The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

Objective To develop an appropriate comprehensive scale for mild cognitive impairment in Parkinson dis-ease(PD-MCI)due to various diagnostic methods for PD-MCI and a lack of consensus on the applicable neuropsychological scales for PD-MCI.Methods A total of 92 non-dementia PD patients with a confirmed diagnosis were enrolled in this study,and all patients were assessed using the comprehensive scale of five cognitive domains recommended by the Chinese version of PD-MCI guidelines and Movement Disorder Society(MDS).Based on the norms of healthy controls assessed by the same scale,the patients were divided into non-cognitive impairment PD group and PD-MCI group.The t-test was used to observe the consistency between groups;the receiver operating characteristic(ROC)curve was used to investigate the cut-off value of each scale with the highest sensitivity and specificity in identifying the impairment in each cognitive domain of PD-MCI;a binary lo-gistic regression analysis was used to determine the specific contents of the comprehensive cognitive domain assessment scale for PD-MCI.Results This study showed that the ten-point comprehensive cognitive domain assessment scale based on long-time memory in Brief Visuospatial Memory Test,Clock Drawing Test,digit span backward test,Trail Making Test A,Verbal Flu-ency Test,Trail Making Test B,Similarities,Boston Naming Test,long-time recall memory in Auditory Verbal Learning Test,and short-time recall memory in Wechsler Memory Scale-IV Logical Memory Test had a significant diagnostic validity in predict-ing PD-MCI,with an area under the ROC curve of 0.971(95%CI 0.941?1.000).Conclusion The recommended cut-off value can be used to perform a subtype analysis of PD-MCI and observe the outcome and clinical specificity of different subtypes of PD-MCI,and therefore,it has a certain clinical significance.

Objective To establish the delimitation norm of cognitive domain assessment scales for Parkinson dis-ease(PD)in Beijing,China,and to investigate the optimal cut-off values for determining abnormal neuropsychological as-sessments.Methods A total of 33 normal middle-aged and elderly individuals in communities and 89 patients with non-dementia PD were included in this study,and all subjects underwent global cognitive function screening and cognitive do-main assessments.According to whether Montreal Cognitive Assessment(MoCA)score was greater than 25 points,the pa-tients with PD were divided into mild cognitive impairment group(PD-MCI group)and normal cognition group(PD-NC group).In order to compare the consistency between PD-related cognitive domain assessment scales and global cognitive function screening in the diagnosis of PD-MCI,different cut-off values below the appropriate norms(i.e.,1.00 standard deviation,1.28 standard deviations,1.64 standard deviations,1.96 standard deviations below the mean)were examined for sensitivity,specificity,positive predictive value,and negative predictive value to obtain the optimal cut-off value.Results The delimitation norm of PD-related cognitive domain assessment scales was established for Beijing,and the re-sults showed that 1.96 standard deviations had the highest consistency in the diagnosis of PD-MCI and PD-NC,with the best sensitivity and specificity.Conclusion This study establishes the delimitation norm of PD-related cognitive domain assess-ment scales and fills the blank of the unbounded value of most domestic PD cognitive impairment assessment scales,and it also proposes the optimal cut-off value of abnormal neuropsychological assessment,which provides a reference standard for the cognitive domain assessment of PD patients in China and helps clinicians to identify cognitive decline in PD patients and adopt intervention measures in the early stage.

Previous studies mainly used β-amyloid and α-synuclein as the biomarkers for the diagnosis of neurodegenerative diseases. In recent years，studies have shown that telomeres at the end of chromosome can be used as an index to measure the degree of biological aging，and telomere length and telomerase activity may also be used as the blood markers to evaluate the risk，progression，and poor prognosis of neurodegenerative diseases in the elderly；however，there is still a lack of consistency between the research findings in China and globally. Understanding the role of telomere-related biomarkers in age-related diseases can help clinicians learn more about the mechanism of disease development and progression. This article reviews the latest research advances in the telomere-telomerase system in neurodegenerative diseases，in order to introduce the influence of telomere length and telomerase activity on neurodegenerative diseases and their potential mechanisms of action.
Telomere ; Telomerase ; Neurodegenerative Diseases ; Alzheimer Disease ; Parkinson Disease

Objective To observe the therapeutic effect of lymphatic plasma therapy(LPE)combined with semi whole blood exchange on patients with moderate to severe anemia caused by severe postoperative infection.Methods Thirty patients who developed severe postoperative infections with moderate to severe anemia and were treated with antibiotics for 48 to 72 hours but failed to meet the criteria were divided into an observation group(LPE combined with semi whole blood replacement surgery and antibiotic treatment,n = 15)and a control group(conventional antibiotic anti infection and blood transfusion treatment,n = 15).Evaluation indicators of infection and anemia between and within two groups before and after treatment,and the treatment effect were compared,respectively.Results There was no statistically significant difference in the observation indicators of infection and anemia between the two groups before treatment(P>0.05);After each treatment,there was a statistically sig-nificant difference in the evaluation and observation indicators of infection and anemia between the two groups(P<0.05);Observation group:There was a statistically significant difference in the observation and evaluation in-dicators of infection and anemia before and after treatment within the group(P<0.05);Control group:Compared within the group before and after treatment,there was no significant decrease in WBC,NEUT,and NEU observation indicators,and CRP and PCT observation indicators showed an upward trend,while RBC,HBG,and HCT did not show a significant increase.The difference was not statistically significant(P>0.05);Conclusions The com-bination of LPE and semi whole blood replacement surgery is superior to the conventional treatment regimen of anti-biotics alone for anti-infection and blood transfusion to improve anemia symptoms in the treatment of postoperative severe anemia.

【Objective】  To study the composition and function of tongue coating (TC) and gastrointestinal tract (GIT) microbiota in participants with yellow-greasy tongue coating (YGTC), and to explore the representative metabolite markers and pathways in this group. 【Methods】  Subjects with YGTC or thin-white tongue coating (TWTC) were recruited from December 1, 2021 to October 30, 2022, and the TC and fecal samples were collected. Samples were subjected to both whole-genome shotgun (WGS), and 16S rRNA gene sequencing. The α-diversity analysis, principal component analysis (PCA), and Spearman correlation analysis were performed for two groups. Ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC–MS/MS) analysis was used to analyze metabolomics and enrichment of metabolic pathways. 【Results】  The results revealed 20 YGTC participates and 19 TWTC participates. At the genus level, the dominant bacterial species of TC flora and intestinal flora in the two groups were roughly the same, but the relative kurtosis difference was marked, and the abundance of potentially pathogenic bacteria in TC and fecal samples of YGTC subjects was higher. There were 9 down-regulated microorganisms in the TC samples, 26 down-regulated microorganisms, and 6 up-regulated microorganisms in YGTC subjects. The α-diversity analysis indicated that the Chao and abundance-based coverage estimator (ACE) indices of TC bacteria in the YGTC subjects showed a decreasing trend, but the difference was not statistically significant (P > 0.05). The α-diversity of fecal samples and the Chao and ACE indices decreased significantly (P < 0.05). PCA showed that the microflora structure of TC and fecal samples were significantly different between the two groups. Spearman correlation analysis showed that there was no correlation between TC and fecal microorganisms at phyla and genus levels in the same subjects (P > 0.05). The metabolomics results demonstrated that fumarate reductase, V/A ATPase, and phosphatidylethanolamine were increased, and glycerate-3p, UDP-glucose, and quinone oxidoreductase metabolites were decreased in YGTC TC samples. Inosine monophosphate (IMP), uridine monophosphate (UMP), and gamma-aminobutyric acid(GABA) were increased in YGTC fecal samples, while the contents of ribo-5P, histidine, biotin,and cobalamin were decreased. Metabolic pathway analysis indicated that the abundance of the TC and fecal samples of the YGTC subjects was relatively low in various metabolic pathways, including amino acid metabolism, carbohydrate metabolism, nitrogen metabolism, and energy metabolism. 【Conclusion】  Structural and functional changes in TC and GIT microbiota or metabolite markers could be potential biological bases of YGTC formation.

Objective To evaluate the early diagnosis value of serum cystatin C in the pediatric intensive care unit (PICU) children with septic acute kidney injury.Methods A total of 196 children in PICU confirmed with sepsis in Hunan Province Children's Hospital was enrolled in this study.Patients were divided into acute kidney injury (AKI) and non-AKI group according to whether accompanied with acute kidney injury.The serum cystatin C and serum creatinine were collected in 2 h,48 h,and 96 h after admission,and the clinical data were collected.The serum Cys C was drawn in receiver operating characteristic (ROC) curve.The sensitivity and specificity of Cys C were evaluated in diagnosis of septic AKI.Results The incidence of septic AKI was 35.20％,higher Cys C levels were risk factors for the onset of AKI,and OR was 26.218 (95％ CI:6.235 ～ 110.232).In AKI group,the serum Cys C level in 2 hours after admission was (2.05 ± 0.90)mg/L,which was higher than 48 hours (1.72 ± 0.72)mg/L and 96 hours (1.62 ±0.95) mg/L(Z =2.169,P =0.030; Z =2.789,P =0.005).In the septic AKI group,cystatin C and creatinine were positive correlation (r =0.582,P =0.000).The area under the ROC curve at 2hours after admission for serum cystatin C in diagnosis of AKI was 0.831.A cutoff point of 1.325 mg/L for 2 hours after admission was identified for cystatin C in the diagnosis of septic AKI,with a sensitivity of 87.1％and specificity of 78.9％.Conclusions Higher level of Cys C was risk factor for the onset of AKI.Compare to creatinine,cystatin C was earlier increased in children with septic AKI and positively correlated with it.It might be a biomarker for early diagnosis of septic AKI in PICU critical ill children.

Objective To analyze the clinical value of continuous veno-venous hemofiltration (CVVH) treatment in children with severe hand-foot-and-mouth disease(HFMD) complicated with cardiopulmonary failure,via the prognostic comparison of the general comprehensive treatment and CVVH add-on treatment.Methods Fifty-one cases of severe HFMD with cardiopulmonary failure were divided into a CVVH group (n =19) and a control group(n =32) based on whether CVVH add-on or not.Their physiological and biochemical indicators were recorded and pediatric critical illness score (PCIS) and pediatric risk of mortality score (PRISM Ⅲ) were calculated within 24 hours,when they were diagnosed with neurogenic pulmonary edema (NPE)/pulmonary hemorrhage.Both groups were treated with endotracheal intubation,mechanical ventilation with high PEEP,corticosteroids,ulinastatin,actively lowering the intracranial pressure,fluid resuscitation,milrinone,dopamine and other vasoactive drugs,high-dose intravenous gamma globulin,the CVVH group were added with CVVH treatment(duration ＞ 12 h).Prognosis difference of CVVH add-on treatment after diagnosed with NPE/pulmonary hemorrhage by tracking indicators of the third day.Survival analysis between two groups were compared by 3-day survival rates,7-day survival rates,28-day survival rates and the finally survival rates.Results (1) The overall conditions of two groups were comparable when diagnosed with NPE/pulmonary hemorrhage.PCIS,PRISM Ⅲ,WBC counting,lactic acid,micro-blood sugar,myocardial enzymes and liver enzymes showed no significant difference between two groups.Three days after treatment,WBC and lactic acid decreased,but there was no significant difference (P ＞ 0.05),the remaining indicators had significantly improved in the CVVH group than those in the control group (P ＜ 0.05).(2) The 3-day survival rate,7-day survival rate,28-day survival rate and the finally survival rates in control group and CVVH group were 40.63 ％ vs.84.21％,37.50％ vs.73.68％,25.00％ vs.63.16％,18.75％vs.52.63％,the survival rate in CVVH group were significantly higher(P ＜0.05).(3)The survival curve indicated that the survival time of CVVH group was significantly longer than that of the control group,the median survival time were 17 d and 2 d,respectively,and the difference was statistically significant (P ＜ 0.05).(4)In the CVVH group,15 cases received CVVH after diagnosed with NPE/pulmonary hemorrhage within 12 hours,of which 10 cases(66.67％) ultimately survived,while the other 4 cases received CVVH after 12 h were all end to death,the difference was statistically significant(P ＜ 0.05).Further analysis of the impact of the timing of blood purification on the prognosis of children showed that the mortality rates of children received CVVH within 6 hours,6 to 12 hours,after 12 hours of diagnosis of NPE/pulmonary hemorrhage,were 2/8,3/7,4/4,respectively.Conclusion Continuous hemofiltration can significantly improve the prognosis of children with severe HFMD,and may be preferable to perform in early stage.