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

Objective To investigate the effects of goal-directed fluid therapy(GDFT)based on pulse pressure variation(PPV)on postoperative cognitive function in patients undergoing Da Vinci robot-assisted radical resection of gynecological malignancies.Methods A total of 60 patients who underwent robot-assisted radical resection of gynecological malignancies were randomly divided into control group and observation group using a random number table method,with 30 patients in each group.The control group received conventional fluid replacement regimen,while the observation group received GDFT regimen based on PPV.The surgical conditions,hemodynamic indices[heart rate(HR),mean arterial pressure(MAP),PPV],cerebral oxygen saturation(rSO2),gastrointesti-nal function,renal function,cognitive function[Mini-Mental State Examination(MMSE)score],and postoperative conditions of the two groups were compared.Results The amount of crystalloid fluid and urine output in the observation group were less than those in the control group,while the amount of colloid fluid was more than that in the control group,with statistically significant differences(P＜0.05).Five minutes after anesthesia induction,the levels of MAP,HR and rSO2 in the observation group were higher than those in the control group,with statistically significant differences(P＜0.05).Five minutes after anesthesia induction,1 hour after the Trendelenburg position,and imme-diately after the end of surgery,the PPV levels in the observation group were lower than those in the control group,with statistically significant differences(P＜0.05).After surgery,the levels of lactic acid and urea nitrogen in both groupswere higher than those before surgery,but those in the observa-tion group were lower than those in the control group,with statistically significant differences(P＜0.05).After surgery,the creatinine levels in both groups were lower than those before surgery,but those in the observation group were higher than those in the control group,with statistically signifi-cant differences(P＜0.05).The time to first flatus in the observation group was earlier than that in the control group,with a statistically significant difference(P＜0.05).On days 3,7 and 30 after surgery,the MMSE scores in the observation group were higher than those in the control group,with statistically significant differences(P＜0.05).The drainage tube indwelling time and hospital stay in the observation group were shorter than those in the control group,with statistically significant differences(P＜0.05).There was no statistically significant difference in the overall incidence of postoperative complications between the two groups(P＞0.05).Conclusion GDFT based on PPV can stabilize the hemodynamic status and rSO2 in patients undergoing Da Vinci robot-assisted radical resection of gynecological malignancies and reduce postoperative cognitive impairment.

To evaluate the effectiveness and safety of 8-ring assisted traction in endoscopic submucosal dissection (ESD), a total of 13 patients with 15 gastric lesions who underwent 8-ring traction-assisted ESD in Nanjing Drum Tower Hospital from July 2021 to January 2022 were included in the retrospective cohort study. All patients successfully completed the operation. The median procedure time was 56 min, and the dissected area per unit time was 0.20±0.02 cm 2/min. The en bloc resection rate, the complete resection rate and the curative resection rate were 93.3% (14/15), 80.0% (12/15) and 80.0% (12/15), respectively. There were no ESD-related complications, such as delayed bleeding or intraperative and postoperative perforation. No deaths occurred. As a novel internal traction technology, 8-ring traction method is simple to operate, providing a good field of vision during ESD to improve the dissection efficiency and reduce complications, which is worthy of further clinical research and promotion.

Objective To analyze the quality of 22 batches of Fritillariae thunbergii bulbus Formula Granules from 12 different manufacturers by using water-extraction reference substance of Fritillariae thunbergii bulbus(ZBM ERS ST)and water-extraction reference substance of Fritillariae hupehensis bulbus(HBBM ERS ST)as references.Methods Ethyl acetate-methanol-triethylamine-water(17∶1∶1∶0.5)was used as the developing solvent for high-performance thin-layer chromatography(HPTLC)fingerprint analysis.The high-performance liquid chromatography(HPLC)fingerprint analysis was performed on a Agilent Eclipse XDB-C18 column(4.6 mm×250 mm,5 μm)with the gradient mobile phase consisted of acetonitrile-0.03%diethylamine solution.The column temperature was set at 25℃and evaporative light-scattering detector was used.The determination was conducted according to standard test method for measurement of Fritillariae thunbergii bulbus Formula Granules(Guangdong PFKL00117).Results The results of HPTLC and HPLC analysis showed that there are significant differences among the 22 batches of Fritillariae thunbergii bulbus Formula Granules.There were 4 batches of Fritillariae thunbergii bulbus Formula Granules from 3 manufacturers among them showed fingerprint characteristics of Fritillariae hupehensis bulbus.The total amount of peimine and peiminine in the remaining 18 batches of Fritillariae thunbergii bulbus Formula Granules was 0.291-3.179 mg·g-1,which were quite different.Conclusion Currently,the quality of Fritillariae thunbergii bulbus Formula Granules on the market varies greatly.Standardized water-extract reference substance has better applicability for the analysis of the quality of Fritillariae thunbergii bulbus Formula Granules than the control medicinal materials.

Objective:To investigate the trend of radiological diagnostic examination frequency and the related influencing factors in a general hospital in recent four years.Methods:The hospital information system and the radiology information system were used to collect the information on the numbers of the outpatients, the emergency patients, and the inpatients and the radiology examination information from 2019 to 2022. The examination frequency and proportion of various imaging equipment were counted by using the perspective table of data, and the examination items and the proportion of the radiological diagnostic examinations were calculated. The positive rates of the radiological examinations were measured from 2019 to 2022. The gender and age distribution of the patients were analyzed. Spearman correlation analysis was used to analyze the relationships between the numbers of the patients undergoing radiological examinations and the numbers of the outpatients, emergency patients and the inpatients.Results:The annual frequency of radiological diagnostic examinations from 2019 to 2022 were 307 306, 245 418, 317 250 and 325 625, respectively, with a total of 1 195 599. Among them, the proportions of CT, X-rays, bedside X-rays, bone density, gastrointestinal imaging and mammography were 59.74%, 38.04%, 1.39%, 0.42%, 0.21% and 0.19%, respectively. In each year, the proportion of CT in all radiological diagnostic examinations was 49.58%, 63.40%, 60.40% and 65.20%, respectively. The frequency of emergency CT and emergency chest CT was correlated with the number of emergency patients( r =0.63, 0.61, P<0.05), and the frequency of non-emergency CT was correlated with the number of outpatients and inpatients ( r =0.61, 0.66, P<0.05). The positive rates of the CT examinations were higher than 80% except the lowest of 79.95% in 2021. Conclusions:Radiological examinations especially CT examinations have increased significantly, and played an important role in the diagnosis of diseases. However, attention should be paid to the Justification of the CT examinations. Timely statistical analysis of radiological examination information can provide data supports and references for scientific management of radiological examinations.

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.

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.