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.

Objective To explore the association between different levels of fluoride exposure and dyslipidemia in elderly people, and to analyze the influencing factors and their interactions. Methods A total of 1 143 elderly people over 60 years old were randomly selected from historical high water fluorosis areas and control areas in Tianjin. Logistic regression model and classification tree model were used to analyze the influencing factors of dyslipidemia, and to analyze the interaction between high fluoride exposure and relevant influencing factors on dyslipidemia. Results The prevalence of elevated low density lipoprotein cholesterol (LDL-C) was 5.69% (65/1 143). There was a significant difference in the prevalence of high LDL-C in different fluoride-exposed areas (2 = 0.092，P = 0.762). Multivariate logistic analysis showed that high fluoride exposure (OR=2.306，95%CI：1.185-4.491) and abdominal obesity (OR=2.274，95%CI：1.299-3.978) were risk factors for high LDL-C, while type B personality (OR=0.529，95%CI：0.308-0.908) was a protective factor for high LDL-C. The results of classification tree model showed that abdominal obesity contributed the most to the prevalence of high LDL-C in the elderly, followed by high fluoride exposure and hyperglycemia. There was a significant multiplicative interaction between high fluoride exposure and abdominal obesity on dyslipidemia (OR=5.191,95%CI：1.609-16.745，P=0.006). Conclusion High fluoride exposure may increase the risk of high LDL-C, and there is a multiplicative interaction between high fluoride exposure and abdominal obesity on dyslipidemia.

Objective: To understand the dose response relationship between urinary fluoride and dental fluorosis among children from drinking water borne endemic fluorosis areas in Tianjin, so as to provide a scientific basis for assessing fluoride exposure risk among children from endemic areas and establishing reference values for urinary fluoride. Methods: From January to December 2024, 83 endemic villages were selected in Tianjin. A total of 2 382 children aged 8-12 years from these villages underwent dental fluorosis examination, along with water fluoride and urinary fluoride testing. Additionally, data from areas where the drinking water fluorosis control target was achieved for more than 12 years (10 villages, 50 people per village) were included as controls. A restricted cubic spline model was used to analyze the relationship between urinary fluoride levels and dental fluorosis prevalence, and benchmark dose (BMD) and benchmark dose lower bound (BMDL), as well as reference dose (RfD), were calculated using the benchmark dose method. Results: The prevalence rates of dental fluorosis among children in drinking water borne endemic fluorosis areas and areas of normal fluoride content in water in Tianjin were 10.58%, 7.60%, with a geometric mean urinary fluoride level of 0.72 and 0.60 mg/L,respectively. There were statistically significant differences in both dental fluorosis prevalence and geometric mean urinary fluoride levels between the drinking water borne endemic fluorosis areas group and the areas of normal fluoride content in water ( χ 2/Z = 4.05 , -7.31, both P <0.05). Across different periods of water source improvement, there were statistically significant differences in overall population, male, and female dental fluorosis prevalence rates and geometric mean urinary fluoride levels ( χ 2/H =44.95, 23.96, 21.05; 168.39, 63.93, 107.50, all P <0.01). Significant differences were also observed across age groups among children from drinking water borne endemic fluorosis areas in terms of dental fluorosis prevalence and geometric mean urinary fluoride levels ( χ 2/H =32.14, 79.73, both P <0.01). The results of the restricted cubic spline model showed that the risk of dental fluorosis in different sex, age and overall children in the drinking water borne endemic fluorosis areas increased significantly with rising urinary fluoride concentration(all P-general trend <0.05). The BMD value for the drinking water borne endemic fluorosis areas was 1.72 mg/L, the BMDL was 1.31 mg/L, and the RfD was 1.31 mg/L. Conclusions The prevalence of dental fluorosis among children in the drinking water borne endemic fluorosis areas in Tianjin has been effectively controlled, but it is still higher than that in the areas of normal fluoride content in water. Moreover, urinary fluoride levels and dental fluorosis prevalence among children from drinking water borne endemic fluorosis areas show a clear dose response relationship.

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 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 investigate the status and the influencing factors of thyroid volume of children aged 8-10 years in Tianjin. Methods Among the 1-2 primary schools were randomly selected from 12 districts in Tianjin. A total of 1 090 children were selected by class cluster sampling method (half male and half female, with a balanced age distribution). A questionnaire survey was conducted. Children’s height, weight and thyroid volume were measured, and their salt iodine content and urinary iodine content were detected. Results I n this study, the median urinary iodine in children was 161.35 µg/L, the mean thyroid volume was 2.56 mL, and the goiter rate was 3.58%. Univariate analysis showed that age, BSA, salt iodine content, urinary iodine content, eating habits, food taste, eating lunch at school, father's work, anxiety and depression, pressure, and different regional grouping were the influencing factors of thyroid volume (P<0.05). Multivariate linear regression showed that BSA, age, food taste, and urinary iodine content had significant independent effects on thyroid volume (P<0.05). Conclusion In Tianjin, the iodine nutrition level of children aged 8-10 years is at an appropriate level. When evaluating the thyroid volume of children, in addition to age factors, other factors such as physical development level and iodine intake should also be considered.

Objective To explore the current situation of evidence-based nursing practice in pain assess-ment by nurses in China to provide the decision-making data for maximizing to relieve the patient pain by car-rying out the pain assessment evidence-based nursing practice.Methods The non-probability sampling meth-od was used to conduct an online anonymous survey in 63 class 3A hospitals in the whole country.The ques-tionnaire included the general information questionnaire and evidence-based nursing practice scale for pain as-sessment.The evidence-based nursing practice scale for pain assessment included the pain screening,compre-hensive pain assessment,exchange with the patients and their households in the pain assessment,pain re-as-sessment,pain assessment tool selection and record.The 5 dimensions were compared by using item equaliza-tion.The data analysis was performed by the SPSS26.0.Results A total of 1 518 questionnaires were recov-ered,in which 1 482 questionnaires were valid with an effective recovery rate of 97.62％.The evidence-based nurse practice of pain assessment by nurse was(108.40±17.96)points,the pain screening was(12.87±2.23)points,the item average score was the highest[(4.29±0.74)points],the communication with the patients and their household was(23.69±4.93)points and the item average score was the lowest[(3.94±0.82)points].The regression analysis showed that whether receiving the pain training and whether distinguishing active pain and resting pain had a positive effect on the practical behavior(P＜0.05).Conclusion The evi-dence-based nursing practice in pain assessment by nurses in the partial class 3A hospitals in China is in the upper medium level.However,the communication between the patients and their families is insufficient.Man-agers should constantly enrich the training content and methods,and guide nurses to strengthen the communi-cation between nurses and the patients.

Objective:To explore the relationship between school bullying and mental sub-health in middle school students and the potential moderating role of resilience in this relationship.Methods:Totally 792 students aged 10 to 14 years from two middle schools in Wuhan were selected.The Chinese version of Olweus Bully/Victim Questionnaire,Multidimensional Sub-health Questionnaire of Adolescents,and Adolescent Psychological Resilience Scale were used to measure school bullying,mental sub-health,and psychological resilience of students,respectively.Results:Being bullied scores were positively associated with mental sub-health scores(β=1.88).The moderating effect of psychological resilience scores between being the scores of bullied and mental sub-health was statistically significant(β=-0.07).Conclusion:The experience of bullying may be associated with mental sub-health problems of middle school students,and psychological resilience may play a moderating role in the relation-ship between being bullied and mental sub-health.