ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

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*

Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
Myocardial Infarction/genetics* ; Proteomics/methods* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Protein Disulfide-Isomerases/genetics* ; Male ; Two-Dimensional Difference Gel Electrophoresis/methods* ; Humans ; Rats ; Rats, Sprague-Dawley ; Electrophoresis, Gel, Two-Dimensional

Background and objective Pembrolizumab(PEM)has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer(NSCLC),but clinical trials were based on cohorts of patients selected on specific criteria,and whether the findings are consistent with real-world patients is debatable.The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data.Methods A retro-spective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted.Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy.Results Among 450 matched patients,the incidence rates of any-grade adverse events were 79.87％in the PEM group and86.71％inthe chemotherapy group,while the incidence rates of grade＞3 adverse events were 4.03％and 7.31％,respectively.The objective response rates were 48.63％for PEM and 36.00％for chemotherapy(P=0.011).The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy(P＜0.001),and the median overall survival was not reached for PEM and 26.2 months for chemotherapy(P＜0.001).Conclusion PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Objective To compare the cortical activation characteristic in the healthy subjects and hemiplegia patients during execut-ing treadmill walking with visual feedback(TWVF). Methods From August to November,2021,eight stroke patients with right hemiplegia(patient group)and eight healthy subjects(healthy group)in Fifth Hospital of Xiamen were recruited.Both groups wore functional near-infrared spectroscopy(fNIRS)caps and executed TWVF,respectively.Experimental block design for walking modes in-cluded the preparation period(10 s)and task period(five cycles of"step 30 s-rest 30 s").The cortical activation(β values)were measured.The regions of interest(ROI)included the pre-motor cortex(PMC),supplementary motor area(SMA),primary motor cortex(M1),primary somatosensory cortex(S1)and sensorimotor cortex(SMC,M1+S1). Results No activation in bilateral M1,and some significant activation(P<0.05)in the left hemisphere SAM,PMC and S1,were found during walking in the healthy group.M1 was activated more in the unaffected(right)hemisphere than in the affected(left)hemisphere during walking in the patient group(P<0.05),and less PMC activation was found(P<0.05).M1 in bilateral hemispheres,SMA in the unaffected hemisphere and PMC in the affected hemi-sphere were activated more in the patient group than in the healthy group(P<0.05). Conclusion The locomotor network of SMC-PMC-SMA are activated more in the hemiplegic patients than in the healthy pepole during walking.M1 are almost not activated in the healthy people during walking,and compensa-torily activated in M1 of the unaffected side in the hemiplegic patients.

Objective To explore the value of the prediction model based on diffusion weighted imaging(DWI)radiomic features and apparent diffusion coefficient(ADC)values in the assessment of p53 gene mutation status in endometrial cancer(EC).Methods The DWI data of 22 p53 wild-type and 60 p53 mutant EC patients were analyzed retrospectively.The DWI radiomic features of the primary lesions were extracted,and the ADC values were calculated.The prediction model was constructed based on support vector machine(SVM)algorithm.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the performance of the prediction model.Internal validation was conducted using Bootstrap.Results The ADC value of p53 mutant EC was significantly lower than that of p53 wild-type EC(P=0.002).When comparing the ADC value and radiomics model,the combined ADC-radiomics model demonstrated the highest diagnostic efficacy,achieving an AUC of 0.924,sensitivity of 86.67％,and specificity of 90.91％.In Bootstrap-based validation,the combined ADC-radiomics model also showed high performance with an AUC of 0.904.The calibration curve and clinical decision curve analysis(DCA)showed that the combined ADC-radiomics model not only had better agreement between predicted and actual observed values but also provided better net benefits for the patients concerned.Conclusion The combined ADC-radiomics model achieved a more efficient assessment of p53 status in EC patients.

Objective:To assess the safety and efficacy of single metal clip traction-assisted endoscopic submucosal dissection (ESD) for the treatment of duodenal lesions.Methods:Data of 45 patients with duodenal lesions who underwent ESD in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between April 2021 and October 2022 were retrospectively recruited. Among them, 19 patients received single metal clip traction- assisted ESD while 26 patients received traditional ESD. The incidence of complications, dissection speed, en bloc resection rate and R0 resection rate of the two groups were mainly observed. Secondary observation indexes included specimen longer diameter, shorter diameter and area.Results:All 45 procedures were successfully completed, with the procedure time of 44.0 (27.0, 67.0) min for the single metal clip traction- assisted ESD group and 34.0 (24.0, 43.5) min for the traditional ESD group ( Z=-1.678, P=0.093). In the single metal clip traction-assisted ESD group, 2 cases (10.5%) had complications, including 1 intraoperative perforation and 1 postoperative bleeding (approximately 20 mL). There were three cases (11.5%) of complications in the traditional ESD group, including 1 case of postoperative bleeding (approximately 50 mL) and 2 cases of postoperative perforation, with no significant intergroup variation ( P=1.000). The dissection speed of the single metal clip traction-assisted ESD group was 16.0 (11.0, 25.8) mm 2/min, significantly larger than that of the traditional ESD group [5.3 (2.2, 21.1) mm 2/min, Z=-2.287, P=0.022]. The en block resection rate and R0 resection rate of the single metal clip traction-assisted ESD group were both 100.0% (19/19). Additionally, the specimen longer diameter, shorter diameter and area of the single metal clip traction-assisted ESD group were 34.0 (22.0, 45.0) mm, 25.0 (20.0, 34.0) mm, and 745.8 (380.0, 1 342.4) mm 2, respectively, significantly larger than those of the traditional ESD group of 20.0 (12.8, 30.3) mm ( Z=-3.119, P=0.002), 14.0 (8.8, 21.3) mm ( Z=-3.417, P=0.001), 190.4 (84.0, 498.7) mm 2 ( Z=-3.275, P=0.001). Conclusion:Single metal clip traction is safe and effective for duodenal ESD, demonstrating a notable improvement in the dissection speed, especially suitable for large duodenal lesions.

The accurate location of root canals is essential for the treatment of various endodontic diseases,including negotiation of calcified root canals,treatment of canal abnormality,removal of fiber posts and apical surgeiy.However,traditional root canal treat-ment has numerous drawbacks,such as being time-consuming,high risk of iatrogenic complications and strong dependence on the expe-rience of operators.With the progress of technology,the application of digital RCT guides based on CBCT and intraoral scanning,3D printing technology is gradually used worldwide,providing an accurate and predictable alternative for the treatment of endodontic disea-ses.This article reviews the clinical procedures,applications,indications,advantages,limitations and the latest technical progress of this technology,in order to provide guidance for clinical work.

Objective To study the influence of ANGPTL8 in lipopolysaccharide(LPS)-induced hepatic lipid deposition.Methods Male wild-type(WT)and ANGPTL8 knockout mice at 6-8 weeks were used to induce sepsis models by intrabitoneal injection of LPS(10 mg/kg).qPCR and immunofluorescence were used to detected the mRNA and protein expression of ANGPTL8 in liver tissue and HepG2 cells respectively;The contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and the triglyceride(TG)and malondialdehyde(MDA)in liver homogenate were detected by kits;the histopathological changes of liver tissue were analyzed through HE staining.Lipids accumulation in liver were detected by oil red O staining.The apoptosis of liver was determinated by TUNEL staining.RNA-seq was used to analyzing the differentially expressed genes in the liver tissue of WT and ANGPTL8 KO mice,and the qPCR and Western Blot were used to verify the differential expressed genes.Results The expression of ANGPTL8 in the liver was significantly upregulated at 48 hours after LPS stimulation.Compared with WT mice,the hepatic lipid deposition,steatosis,and apoptosis were significantly alleviated in liver of ANGPTL8 KO mice,the ALT and AST levels in serum and the TG and MDA content in liver homogenate of ANGPTL8 KO mice were also reduced significantly.The expression of caveolin-1(CAV1)in liver of ANGPTL8 KO mice was significantly higher than that of WT mice.Conclusions LPS promoted the expression and secretion of ANGPTL8 in liver tissue,and ANGPTL8 increased hepatic lipid deposition and peroxidation by inhibiting the expression of CAV1.