Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

AIM:Given the uncertain impact of osmotic pressure on embryoid body(EB)differentiation,this study aimed to investigate the effects of increased osmotic pressure on EB differentiation and explore the potential relation-ship between this process and cadherin.METHODS:Polhethylene glycol 300(PEG 300)was used to increase the os-motic pressure of the culture medium used for cultivating EBs under both high osmotic pressure and standard culture condi-tions.The experimental design included a control group,an experimental group(hypertonic group),groups treated with varying concentrations of PEG 300,and an experimental group treated with an inhibitor.Western blot,RT-qPCR,AM/PI staining,CCK-8,and immunocytochemical staining was used to analyze the cell viability and the expression of CDH1 and CDH2 markers of the three germ layers,and pluripotency markers within the EBs.RESULTS:Hypertonicity did not af-fect cell viability.Significant differences were observed in the expression of the cadherin proteins CDH1 and CDH2 in EBs between the experimental and control groups;however,no cleartrend towards an EMT shift was observed.Specifically,CDH2 expression was significantly down-regulated in experimental group,showing a clear correlation with variations in os-motic pressure.Moreover,compared with control group,pluripotency markers in the EBs from experimental group exhibited significantly higher expression levels from the 2nd day to the 5th day.A substantial increase in the expression of mesoder-mal markers was also observed;however,a downward trend was observed for ectodermal markers in experimental group.Intervention using SB431542,which up-regulates CDH2 expression by affecting TGF-β signaling,reversed the expression trend of mesodermal and ectodermal markers in experimental group.CONCLUSION:Elevated osmotic pressure appears to enhance the mesodermal differentiation efficiency in EBs,possibly correlating with CDH1 and CDH2 changes induced by osmotic pressure.Therefore,this study emphasizes the significant role of osmotic pressure in stem cell applications.

ObjectiveTo investigate the acute effects of compound air pollution on children’s respiratory function. MethodsUsing panel group study design， 223 students in five classes of grade 4 from two primary schools （a， b） in Xuhui and Hongkou districts of Shanghai were randomly selected to measure pulmonary function and exhaled nitric oxide （FeNO）. The first three tests were carried out from May to June in 2020， and the fourth test was carried out from September to December in 2021. At the same time， the daily and hourly mean values of PM_2.5， PM₁₀， SO₂， NO₂， O₃ and CO was collected from the nearby air quality monitoring points of the two schools during the same period ， as well as meteorological monitoring data （temperature， humidity， wind speed and atmospheric pressure）. The linear mixed effect model was used to analyze the effects of air pollution on pulmonary function and respiratory inflammation in the summer. ResultsThe results of single pollutant model showed that PM_2.5， PM_10， SO₂ and NO₂ were positively correlated with FeNO， and the effect was reflected in lag0， lag1 and lag3 （P<0.05）. PM_2.5， PM₁₀ and NO₂ were negatively correlated with the changes of lung function FEF_25%， FEF_50%， FEF_75%， FeF_25%-75%， PEF， FVC， FEV1 and FEV1/FVC， and the effect was reflected in lag0 to lag3 days （P<0.05）. The results of the dual pollutant model showed that the concentration changes of SO₂ and NO₂ were significantly correlated with the decrease of FEV1 when combined with O₃ or PM_2.5 （P<0.01）， and the concentration changes of PM_2.5 was significantly correlated with the increase of FeNO when O₃， SO₂ and NO₂ were combined respectively （P<0.01）. The effects of the dual pollutant model were greater than the effect of PM_2.5 single pollutant model. ConclusionThe health effects of different air pollutants on children’s respiratory tract function indexes in summer are different. The combined effects of two pollutants on the lung function of children increased to different degrees. Although air pollution is light in summer， it still has an impact on children’s respiratory tract function index and inflammation index， and the combined effect of dual pollutants is more significant than that of single pollutant.

Endo-periodontal lesions(EPLs)involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing factors.This etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical practice.Furthermore,EPL-affected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy.By compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

Objective To investigate the application of transesophageal echocardiography in the evaluation of left atrial ear volume and function changes in patients with patent foramen ovale and atrial fibrillation. Methods Eighty patients with patent foramen ovale were selected as the study objects, and were divided into atrial fibrillation group (n=44) and non-atrial fibrillation group (n=36), and 30 healthy subjects were selected as control group. Transesophageal echocardiography was performed in three groups. The left atrial appendage volume and changes of function in three groups were compared. Results The left atrial appendage maximum volume (LAAV_max), left atrial appendage minimum volume (LAAV_min), left atrial appendage opening maximum area (MA) and left atrial appendage opening maximum length diameter (MD) in the atrial fibrillation group and non-atrial fibrillation group were significantly higher, and the left atrial appendage maximum emptying velocity (LAAeV) and left atrial appendage maximum filling velocity (LAAfV) were significantly lower than those of the control group (P < 0.05). The LAAV_max, LAAV_min as well as MA and MD of left auricular opening in patients with left auricular spontaneous imaging (SEC) in the atrial fibrillation group were significantly higher than those in the non-atrial fibrillation group, and LAAeV and LAAfV were significantly lower than those in the non-atrial fibrillation group (P < 0.05). After treatment, the incidence of end-point events in the atrial fibrillation was significantly higher than that in the non-atrial fibrillation group (P < 0.05). Conclusion The application of transesophageal echocardiography in the evaluation of left atrial ear volume and function changes in patients with patent foramen ovale and atrial fibrillation is effective. The left atrial appendage function of patients with atrial fibrillation is worse than that of patients without atrial fibrillation.

AIM:To observe the effect of angiotensin-converting enzyme 2(ACE2)deletion on vasoconstric-tion reactivity of aortic segments in ACE2 knockout(KO)mice with tourniquet shock(TS).METHODS:The 8-month-old male mice with C57BL/6 background were divided into wild-type(WT)control group,WT-TS group,KO group and KO-TS group,with 10 mice in each group,of which five were used for determination of vascular reactivity,and the other five for the other assays.The hindlimbs of the mice in WT-TS group and KO-TS group were ligated with tourniquet for 2 h and loosened for 4 h.The mice in WT group and KO group were subjected to the same treatment except for tourniquet liga-tion.The vasoconstriction reactivity of the aorta was measured on tensiometer.The morphological damage of the aorta was evaluated by vascular histopathology.Western blot was used to detect the expression of AT1,MAS,ACE and ACE2 pro-teins in aorta.The serum levels of angiotensin(Ang)Ⅱ and Ang-(1-7)were determined by enzyme-linked immunosorbent assay.RESULTS:Compared with WT group,the mice in WT-TS group had lower vascular reactivity to norepinephrine(NE)and obvious vascular lesions.The expression of ACE protein increased significantly(P＜0.01),while the expres-sion of ACE2 decreased(P＜0.05).The expression of AT1 protein in aorta decreased significantly,the expression of MAS protein increased significantly,and the AT1/MAS ratio decreased(P＜0.01).Serum Ang II level increased,serum Ang-(1-7)level decreased,and Ang Ⅱ/Ang-(1-7)ratio increased(P＜0.05).Compared with WT group,vascular reactivity in KO group increased at low concentration of NE(＜10-7 mol/L),and decreased at high concentration(＞10-7 mol/L)without vascular lesion.The expression levels of aortic AT1,MAS and ACE were all elevated(P＜0.05).The serum level of Ang Ⅱ increased(P＜0.05),but the level of Ang-(1-7)had no obvious change.Compared with KO and WT-TS groups,the aortic reactivity in KO-TS group subtracted apparently(P＜0.05),representing its curve shifting to the right obviously.The morphological damage aggravated slightly,and the expression of AT1 and ACE increased slightly in KO-TS group com-pared with WT-TS group(P＜0.05).However,the expression of MAS increased significantly in vascular tissue(P＜0.01).The serum levels of Ang Ⅱ and Ang-(1-7)further increased and decreased,respectively,and the Ang Ⅱ/Ang-(1-7)ratio increased(P＜0.01).CONCLUSION:Deficiency of ACE2 induces severe aortic hyporeactivity to NE during TS,which may be related to the increased imbalance of renin-angiotensin system in ACE2 gene knockout mice.

BACKGROUND: The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies. METHODS: The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model. RESULTS: The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website ( https://chris-yu.shinyapps.io/hypertension_risk_prediction/ ) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population. CONCLUSION This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.
Adult ; Humans ; Asian People ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Hypertension/epidemiology* ; Nomograms ; Ethnicity

Background Air quality health index (AQHI) has been widely used to quantify the health effects of multiple pollutants observed in population-based epidemiological studies, and can better reflect the widespread linear non-threshold between air pollution and health effects. Objective To explore an AQHI for pediatric respiratory diseases (AQHI_r) in Shanghai and evaluate its feasibility. Methods The daily numbers of hospital outpatient visits for pediatric respiratory diseases from 2015 to 2019 were obtained from five general hospitals in Xuhui, Baoshan, Hongkou, Jinshan, and Chongming Districts of Shanghai. Monitoring data on air pollutants (PM_2.5, PM₁₀, SO₂, NO₂, and O₃), air quality index (AQI), and meteorological variables (temperature, relative humidity, air pressure, and wind speed) were collected from five air quality monitoring sites nearest to selected hospitals. Time-series analysis using generalized additive model (GAM) was conducted to estimate the associations between respiratory-related pediatric outpatient visits and the concentrations of air pollutants. The sum of excess risk (ER) of hospital outpatient visits was used to construct AQHI_r. To assess the predictive power of AQHI_r, the associations of AQHI_r and AQI with the number of pediatric respiratory outpatient visits in three hospitals in Xuhui, Hongkou, and Chongming districts were compared. Results Air pollutants had various effects on respiratory diseases outpatient visits. PM_2.5, NO₂, and O₃ had most significant impacts on lag0 day and the associated ERs of hospital outpatient visits for each 10 μg·m⁻³ increase in pollutant concentration were 1.27% (95%CI: 0.88%-1.66%), 0.75% (95%CI: 0.40%-1.11%), and 0.36% (95%CI: 0.10%-0.62%), respectively. PM₁₀ and SO₂ had most significant impacts on lag3 day and the associated ERs of hospital outpatient visits for each 10 μg·m⁻³ increase in pollutant concentration were 0.81% (95%CI: 0.51%-1.12%) and 5.64% (95%CI: 3.37%-7.96%), respectively. There were significant effects of combinations of two pollutants among PM_2.5, PM₁₀, NO₂, SO₂, and O₃ except for PM₁₀+NO₂, SO₂+PM_2.5, and SO₂+NO₂ (P<0.05). According to the results of single-pollutant and two-pollutant models, PM_2.5, NO₂, SO₂, and O₃ were selected to construct AQHI_r. The comparison showed that for every interquartile range increase in AQHI_r, the ER for pediatric outpatient visits was higher than that for the value corresponding to AQI. Conclusion Air pollutants in Shanghai have an impact on the number of pediatric respiratory outpatient visits. The AQHI_r based on and outpatient visits for pediatric respiratory diseases can be a sensitive index to predict the effects of air pollution on children's respiratory health.

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
Humans ; Citric Acid/adverse effects* ; Prospective Studies ; Sodium Citrate ; Hemorrhage/chemically induced* ; Citrates/adverse effects* ; Anticoagulants/adverse effects* ; Renal Dialysis/adverse effects*