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*

Objective:To investigate the effect of combined use of midazolam and remifentanil without muscle relaxant on tracheal intubation in female patients undergoing breast surgery.Methods:A retrospective analysis was performed on 40 female patients with breast disease who underwent tracheal intubation and general anesthesia at The First Affiliated Hospital of Zhengzhou University between January 2023 and June 2023. These patients were divided into a control group ( n = 20) and an observation group ( n = 20) based on whether muscle relaxants were applied at the time of intubation. The control group received intravenous rocuronium bromide, whereas the observation group did not use muscle relaxants. Both groups were intravenously administered midazolam (0.1 mg/kg) and remifentanil (4 μg/kg) prior to tracheal intubation. The intubation conditions were evaluated based on factors such as the ease of inserting the laryngoscope and the patient's response to intubation, including coughing. Results:There were no statistically significant differences in age, height, and body mass between the two groups (all P > 0.05). The excellent rate of intubation conditions was significantly lower in the observation group compared with the control group [45% (9/20) vs. 85% (17/20), χ2 = 7.03, P = 0.008). The good rate of intubation conditions was significantly higher in the observation group compared with the control group [40% (8/20) vs. 5% (1/20), χ2 = 7.03, P < 0.05]. There was no statistically significant difference in the excellent and good rates of intubation conditions between the observation and control groups [85% (17/20) vs. 90% (18/20), χ2 = 0.23, P > 0.05]. No significant difference in intraoperative awareness score was observed between the observation and control groups [(2.59 ± 0.44) points vs. (2.61 ± 0.31) points, P > 0.05]. None of the patients in either group exhibited any episodes of arrhythmias. Furthermore, no adverse reactions such as muscle stiffness, nausea, vomiting, or skin itching were observed in either group following the surgical procedure. Conclusion:Without the use of muscle relaxants, intravenous administration of midazolam at 0.1 mg/kg and remifentanil at 4 μg/kg for tracheal intubation in female patients undergoing breast surgery can offer excellent intubation conditions, ensuring that the patient remains unconscious throughout the surgical procedure.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective:To build a nursing care plan decision-making support system based on the hospital's nursing information system and evaluate its effects in newly hired nurses.Methods:This study adopted a non-synchronous pre-post control design. Totally 181 newly hired nurses recruited by Beijing Tiantan Hospital, Capital Medical University, were selected by convenience sampling. The control group consisted of 85 new nurses hired in August 2021, while the intervention group consisted of 96 new nurses hired in August 2022. The control group received traditional training methods, while the intervention group received training through the nursing care plan decision-making support system in addition to the traditional methods. The nursing decision-making ability and the quality of specialty nursing care were compared between the two groups.Results:Finally, 81 nurses were included in the control group, and 93 nurses were included in the intervention group. The nursing decision-making ability score in the intervention group was (80.15±4.59), which was significantly higher than the (78.62±5.13) in the control group ( t=-2.080, P=0.039). The intervention group also had a significantly higher qualified rate of specialty nursing care compared to the control group (χ 2=6.626, P=0.036) . Conclusions:The application of the nursing care plan decision-making support system in the standardized training of newly hired nurses can improve their nursing decision-making abilities and the quality of specialty nursing care.

Objective:To study the diagnostic value of artificial intelligence B-ultrasound image computer-aided diagnosis system (hereinafter referred to as intelligent ultrasound system) in adult goiter.Methods:In June 2022 and March 2023, two phases of thyroid disease survey were carried out in 4 cities in Anhui Province. One village was selected in each city, and 250 adults were selected as survey subjects in each village. Adult bilateral thyroid area was scanned by both intelligent ultrasound system and conventional ultrasound scanning equipment, and the effectiveness of intelligent ultrasound system in the diagnosis of goiter was analyzed based on the results of conventional ultrasound examination. Receiver operating characteristic (ROC) curve was drawn, and Kappa test was used to analyze the consistency between intelligent ultrasound system and conventional ultrasound examination in the diagnosis of goiter. At the same time, Spearman correlation analysis and Bland-Altman method were used to evaluate the consistency of the two methods in measuring thyroid volume.Results:After screening and removing outliers and missing values, a total of 910 adults were included, including 253 males (27.80%) and 657 females (72.20%). The age was (45.92 ± 10.20) years old, ranging from 18 to 60 years old. The sensitivity, specificity, and accuracy of the intelligent ultrasound system for diagnosing adult goiter were 80.00%, 99.67%, and 99.56%, respectively. The area under the ROC curve (AUC) was 0.996, which was consistent with the results of conventional ultrasound examination for diagnosing goiter ( κ = 0.67, P < 0.001). After controlling for variables such as gender, thyroid function, and thyroid nodules, the intelligent ultrasound system showed good consistency with conventional ultrasound examination in the diagnosis of goiter in females, adults with thyroid dysfunction, and adults without thyroid nodules ( κ = 0.66, 0.80, 0.80, P < 0.001). The consistency in the diagnosis of goiter in adults with thyroid nodules was moderate ( κ = 0.56, P < 0.001). Spearman correlation analysis showed a highly positive correlation between the measurement results of adult thyroid volume by intelligent ultrasound system and conventional ultrasound examination ( r = 0.88, P < 0.001). The Bland-Altman method results showed that only 4.62% (42/910) of points in adults were outside the 95% consistency limit, indicating good consistency between intelligent ultrasound system and conventional ultrasound examination in measuring thyroid volume (< 5%). The proportion of points outside the 95% consistency limit in males, adults with thyroid dysfunction, and adults with thyroid nodules was 6.72% (17/253), 5.83% (12/206), and 6.45% (12/186), respectively. Conclusions:The intelligent ultrasound system has certain diagnostic value for adult goiter and has good consistency with conventional ultrasound examination for thyroid volume measurement. However, the accuracy of diagnosis for males and adults with thyroid nodules still needs to be improved.

Objective To investigate the preoperative predictive value of clinical-radiomics nomogram on N1-N2 lymph node metastasis in patients with stage Ⅰ to Ⅲ A primary lung adenocarcinoma(PL A).Methods A total of 164 PLA patients were divided into a training set(n=114)and an validation set(n=50).Three logistic regression models were created separately and the predictive efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve and area under the curve(AUC)respectively.The AUC difference between models was tested by the DeLong test.The calibration degree was evaluated by the calibration curve.Decision curve analysis was performed to evaluate the benefits of clinical application.Results The radiomics model consisted of 8 imaging features[Radiomics score(Radscore)].The clinical model was composed of tumor type(central or peripheral)and tumor size.The tumor type,tumor size and Radscore formed the nomogram model.In the training set,the prediction of the nomogram model was more effective(AUC=0.909)than the clinical model(AUC=0.748)and the radiomics model(AUC=0.814),while the differences in AUC were statistically significant(P＜0.05).In the validation set,the prediction of the nomogram model was more effective(AUC=0.875)than the clinical model(AUC=0.682),and the difference in AUC was statistically significant(P＜0.05).The prediction of the nomogram model was also more effective than the radiomics model(AUC=0.799),but the difference in AUC was not statistically significant(P＞0.05).The calibration curve showed that the clinical-radiomics nomogram had a high level of calibration and the decision curve analysis showed good benefits from clinical application.Conclusion The clinical-radiomics nomogram is proven to be more effective than radiomics or clinical factors alone in the preoperative prediction of stage Ⅰ to Ⅲ A PLA N1-N2 lymph node metastasis.

Objective:To evaluate the risk factors for the complexity and surgical prognosis in patients with proliferative diabetic retinopathy (PDR).Methods:A historical cohort study of the CONCEPT trial, including 97 patients (97 eyes) who were diagnosed with PDR and requiring three-channel 23-gauge transconjunctival pars plana vitrectomy (PPV) from June 2017 to January 2018 at the First Affiliated Hospital of Nanjing Medical University.All patients received preoperative intravitreal injection of 0.5 mg conbercpet.Based on the PDR complexity score, patients were divided into >3 group or ≤3 group, and the systematic risk factors were compared between the two groups.The influence of sex, age, hypertension, renal insufficiency, duration of diabetes mellitus, and hemoglobin A1c level on the PDR complexity score was evaluated by multivariate logistic regression analysis.Based on age, patients were divided into <45 years group, 45-<60 years group, and ≥60 years group, and the differences in mean operative time, incidence of intraoperative hemorrhage, surgically induced lacrimation and silicone oil filling, and incidence of hemorrhage on color fundus photos and macular edema by optical coherence tomography at postoperative months 1 and 6 were analyzed among different age groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (No.2017-SR-283).Written informed consent was obtained from each subject.Results:The age of patients with PDR complexity score >3 was 46.5(36.0, 51.8) years, which was less than 54.0(45.5, 61.5) years for PDR complexity score ≤3, and the difference was statistically significant ( Z=1.835, P=0.002).Among the factors predicting PDR complexity score >3, logistic regression analysis indicated that only age was statistically significant ( P=0.005).For each 1-year increase in age, the risk of PDR complexity score >3 would increase by 7.4%( OR: 0.929, 95% CI: 0.883-0.977).Among the systemic factors, there were significant differences in age, history of diabetes, proportion of patients with hypertension and renal insufficiency among the three age groups (all at P<0.05).Among the ocular factors, there were significant differences in the proportion of patients with history of retinal laser treatment, fibrovascular membrane and complexity score >3 among the three groups (all at P<0.05).The proportion of patients with fibrovascular membrane and complexity score >3 in the <45 years group was significantly higher than that in the 45-<60 and ≥60 years groups (all at P<0.05).There were significant differences in the proportion of patients with intraoperative bleeding and silicone oil filling in the three age groups (all at P<0.017).The proportion of intraoperative bleeding and silicone oil filling in <45 years group was significantly higher than that in 45-<60 and ≥60 years groups (all at P<0.05).The macular edema on postoperative month 1 in the <45 years old group was significantly higher than that in the 45-<60 and ≥60 years groups (both at P<0.05). Conclusions:Among systemic factors, age has a significant impact on the increased PDR complexity and contributes to the poor prognosis of patients.There is a higher percentage of intraoperative complications and early postoperative macular edema in patients in the younger age group compared to the older age group.

Objective To study the proteomic profiling of lung and colon during lung injury induced by lipopolysaccharide(LPS).Methods Mice were divided into four groups:the control,LPS,LPS+ Platycodonis Radix(PR)and LPS+ Rhei Radix et Rhizoma(RRR).LPS was injected into the lungs through trachea,and the drugs were given by intragastric injection.The mice were weighed,the faeces of each mouse were determined,and the lungs and colon were isolated for analysis of pathophysiological changes and proteomics.Results ①After 7 days of LPS,the weight of mice decreased,the lung showed inflammatory changes,and the faeces increased.Both PR and RRR can improve the inflammation.②There are lot of proteins was increased in lung mainly involved in gene transcription and in colon mainly involved in mitochondrial,endoplasmic reticulum and metabolism,etc.The up-regulated proteins shared by both lung and colon were involved in myoprotein contraction.PR can inhibit the up-regulated protein more than RRR in lung.③There are large number of proteins were down-regulated in lung involved in cell membrane and in colon involved in nucleic acid binding and ATP binding.The down-regulated proteins shared by both lung and colon were involved in endoplasmic reticulum,nucleic acid binding and cell membrane,etc.The down-regulated proteins in lung by PR are more than those by RRR,which is involved in endoplasmic reticulum,cell membrane,etc.Conclusion LPS-induced lung injury can cause changes in the expression of protein in lung and colon proteins,and the increase in the expression of myoprotein contraction genes may be one of the molecular mechanisms related to lung and colon.

Sodium dichloroacetate (DCA) is a small molecule drug usually administered orally. It has therapeutic effects against several diseases, such as metabolic syndrome, cardiovascular and cerebrovascular diseases, and several solid tumors. In this review, the research progresses of DCA in mechanism of action, pharmacological action and toxicological studies were summarized from the recent literatures on the pharmacological actions of DCA.