ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

Objective: To observe the distribution characteristics of sex differences in physical growth among children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024, so as to provide clues for improving growth assessment standards and promoting the health of children and adolescents. Methods: Using publicly available height and weight data for children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024 released by the statistics agency of the Taiwan education authorities, sex difference indices were analyzed. Growth curve charts and Pearson correlation were used to analyze the correlation between height/weight and year, as well as trends of change with age and year. These were compared with data from the 8th National Survey on Students Constitution and Health in 2019, covering Han and ethnic minority groups aged 6-15 years in mainland China. Results: The sex difference index for height among children and adolescents in Taiwan, China ranged from -1.20% to 6.67%, showed a trend of decreasing first and then increasing with age. The sex difference index for weight ranged from 3.76% to 19.15%, exhibited an age related trend of a slight initial increase, followed by a decrease, and then an increase. The sex difference indices for height in the 12-15 age groups and for weight in the 15-year-old group were positively correlated with the year ( r =0.74, 0.66, 0.61, 0.92 ; 0.63), while the sex difference indices for weight in the 6-8 age groups were negatively correlated with the year ( r =-0.71, -0.77, -0.53) (all P <0.05). In 2024, the height of children and adolescents in Taiwan, China increased gradually with age, but the growth rate for girls slowed down after age 12. A "two crossover" was observed in height between boys and girls, with boys being taller than girls in the 6-9 age range and after age 12. Weight for both sexes gradually increases with age, but boys have greater weight than girls at all ages. In 2019, the sexual differences in body size among children and adolescents in the Taiwan region, China (the sex difference indices for height:-0.96% to 6.49%；the sex difference indices for weight:4.69%-17.89%) fell within the variation ranges of counterparts in mainland China (the sex difference indices for height:-5.43% to 7.69%；the sex difference indices for weight:-10.12% to 21.56%). Conclusion The sex differences in physical growth among children and adolescents in Taiwan, China are dynamically changing with age and over the long term.

Objective To investigate the relationship between the comorbidity of dyslipidemia, hypertension and diabetes and lifestyle of adult residents in Hebei Province in 2018, and to provide reference for the development of chronic diseases prevention measures. Methods Using data from the surveillance of chronic diseases and their risk factors among adults in Hebei in 2018, 7 711 permanent residents aged ≥18 years were selected as the research subjects. Multivariate logistic regression analysis was used to analyze the relationship between the comorbidity of dyslipidemia, hypertension, and diabetes and lifestyle in adult residents. Results A total of 7 711 subjects aged ≥18 years were included in 2018. The comorbidity rates of hypertension and dyslipidemia, diabetes and dyslipidemia, and hypertension and diabetes were 16.88%, 7.91%, and 8.13%, respectively. The comorbidity rate of hypertension, diabetes, and dyslipidemia was 22.65%. These comorbidity rates increased with age and BMI. Multivariate logistic regression results showed that male, age, overweight/obesity, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep problems were risk factors for the comorbidity of the "three highs". Conclusion The prevalence of the "three highs" comorbidities is relatively high in Hebei Province, and there are multiple common risk factors. Maintaining a healthy lifestyle and implementing comprehensive prevention and control measures are the key to improving the health level of residents.

Objective To investigate the influencing factors of stroke patients with hypertension and their compliance with antihypertensive drugs, and to provide targeted intervention measures for stroke prevention in hypertensive patients.  Methods Using the method of multi-stage cluster sampling, a total of 59,434 permanent residents aged 40 and above were selected from 48 monitoring sites in 9 cities of Hebei Province from December 2019 to December 2020. Unconditional logistic regression analysis was used to explore the influencing factors of stroke complicated with hypertension and the compliance of patients with antihypertensive drugs.  Results Among the 59 434 subjects, the prevalence rate of stroke was 4.33% and the prevalence rate of stroke complicated with hypertension was 82.47%. The results of univariate analysis showed that the proportion of women, rural areas, dyslipidemia, diabetes, obesity, and people with family history of stroke was higher in stroke patients with hypertension, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that rural areas, dyslipidemia, diabetes, obesity, and family history of stroke significantly increased the risk of stroke, and the OR (95%CI) values were 1.29 (1.03-1.62), 1.39 (1.12-1.72), 1.58 (1.25-1.99), 1.61 (1.22-2.12) and 1.60 (1.26-2.04), respectively. Among stroke patients with hypertension, 92.71% of patients took antihypertensive drugs. It was found that women's compliance with antihypertensive drugs was good, with an OR (95%CI) value of 1.46 (1.01-2.09).  Conclusion The prevalence rate of stroke complicated with hypertension is high in people aged 40 and above in Hebei Province. Hypertensive people should lower blood lipids, control blood glucose, and lose weight as soon as possible to prevent the occurrence of stroke.

Objective: To evaluate the impact of comprehensive nursing based on the behavioral goal attainment model on the clinical intervention effect among elderly female patients with stress urinary incontinence (SUI), so as to provide a basis for optimizing the nursing strategies for patients with SUI and improving their quality of life. Methods: A total of 190 elderly female patients with SUI who were treated in the Department of Gynecology of the First Hospital of Jilin University from January 2023 to August 2024 were selected and randomly divided into the intervention group and the control group. The control group received routine nursing care, while the intervention group received comprehensive nursing based on the behavioral goal attainment model. The 1-hour pad test was used to assess urinary incontinence symptoms. The bio-electrical stimulation feedback instrument was employed to detect the electromyogram (EMG) values in the pre-resting stage and slow-muscle stage for evaluating pelvic floor function. The bladder function scale was utilized to evaluate bladder function. The Chinese version of urinary incontinence ego-efficacy rating scales and incontinence quality of life assessment scale (IQOL) were used to assess self-efficacy and quality of life. The data on intervention compliance and nursing satisfaction were collected by a questionnaire survey. The differences between the two groups before and after the intervention were compared using the analysis of variance for repeated-measures data to evaluate the intervention effect. Results: There were 95 cases in the control group and 95 cases in the intervention group, with median ages were 64.00 (interquartile range, 23.50) and 64.50 (interquartile range, 19.50) years, respectively. The proportion of patients with cesarean section as the last delivery method was 21.05% in the control group and 12.63% in the intervention group. The proportion of patients with moderate disease severity was 67.36% in the control group and 58.95% in the intervention group. There were no statistically significant differences in age, body mass index, number of pregnancies, number of deliveries, marital status, educational level, mode of last delivery and severity of the disease between the two groups of patients (all P>0.05). The analysis of variance of repeated-measures data showed that there were significant interactions between time and group for the urine leakage volume in the 1-hour pad test, the EMG values in the pre-resting stage, the EMG values in the slow-muscle stage, the scores of the bladder function, the self-efficacy scores, and the IQOL scores (all P<0.05). After 12 weeks of intervention, the EMG values in the slow-muscle stage, the scores of the bladder function, the self-efficacy scores, the IQOL scores in the intervention group were higher than those in the control group, while the urine leakage volume in the 1-hour pad test and the EMG values in the pre-resting stage in the intervention group were lower than those in the control group (all P<0.05). The good compliance rate of intervention and the satisfaction rate of nursing in the intervention group were higher than those in the control group (83.16% vs. 60.00%, 90.53% vs. 75.79%, both P<0.05). Conclusion Comprehensive nursing based on the behavioral goal attainment model can improve urinary incontinence symptoms, pelvic floor function, bladder function, self-efficacy, quality of life, and intervention compliance of elderly female patients with SUI.

Objective Genetic testing and prenatal diagnosis were conducted in 18 congenital insensitivity to pain with anhidrosis(CIPA)families,laying the foundation for reducing the incidence of CIPA.Methods Genetic testing was performed using whole-genome sequencing and/or PCR-Sanger sequencing to identify candidate patho-genic vari-ants in the probands.For deep intronic variants,the pathogenicity was validated through minigene assays,RT-PCR,Sanger sequencing,and co-segregation analysis.DNA extracted from chorionic villus or amniotic fluid cells was analyzed by PCR and Sanger sequencing to determine the genotype of the fetuses.Maternal DNA contamination was excluded by microsatellite allele genotyping.Additionally,multiplex ligation-dependent probe amplification(MLPA)was employed to detect common chromosomal aneuploidies.Results A total of 21 NTRK1 variants were identified across 18 CIPA pedigrees,including 9 missense variants,2 nonsense variants,5 frameshift variants,and 5 deep intronic variants.Among them,3 were novel pathogenic variants.Prenatal genetic diagnosis was performed in 20 high-risk fetuses,revealing 2 normal fetuses,12 carriers,and 6 affected with CIPA.Microsatellite genotyping confirmed the absence of maternal DNA contamination in fetal samples.Moreover,MLPA analysis excluded common chromosomal aneuploidies associated with syndromic conditions in all tested fetuses.Conclusions This study achieved a 100%molecular diagnosis rate in CIPA families,identified three novel pathogenic variants,and enabled the simultaneous prevention of CIPA and common chromosomal syndromes through integrated prenatal ge-netic testing,thereby providing critical insights for genetic counseling.

Objective To explore the predictive value of combined serum soluble hemoglobin scavenger receptor 163(sCD163),hypersensitive C-reactive protein(hs-CRP),and procalcitonin(PCT)for stroke-associated pneumonia(SAP).Methods A total of 100 patients with acute ische-mic stroke admitted to the First Hospital of Zhangjiakou from October 2021 to January 2023 were se-lected as the study subjects.According to whether they developed SPA within 7 days of admission,they were divided into SAP group(n=64)and non-SAP group(n=36).Based on pneumonia se-verity index(PSI),patients in the SAP group were further divided into mild SAP group and severe SAP group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum levels of sCD163,hs-CRP,and PCT.The clinical data of the patients were collected and compared.Pearson's method was used to analyze the correlation between the PSI score and the serum levels of sCD163,hs-CRP,and PCT in SAP patients.Multivariate Logistic regression analysis was employed to screen for factors influencing the occurrence of SAP.Receiver operating characteristic(ROC)curve analy-sis was used to evaluate the predictive efficacy of serum sCD163,hs-CRP,and PCT for the occur-rence of SAP.Results The proportion of patients with dysphagia and the National Institutes of Health Stroke Scale(NIHSS)score in the SAP group were significantly higher than those in the non-SAP group(P＜0.05).The serum levels of sCD163,hs-CRP,and PCT in the SAP group were significantly higher than those in the non-SAP group(P＜0.05).The serum levels of sCD163,hs-CRP,and PCT in the severe SAP group were significantly higher than those in the mild SAP group(P＜0.05).Pearson's correlation analysis showed that the PSI score was positively correlated with the serum levels of sCD163,hs-CRP and PCT in SAP patients(r=0.356,0.413,0.391,P＜0.001).Logistic regression analysis revealed that serum sCD163,hs-CRP,PCT,NIHSS score,and dysphagia were all influencing factors for the occurrence of SAP(P＜0.05).The areas under the curve(AUC)for predicting SAP using serum sCD163,hs-CRP,PCT and their combina-tion were 0.842,0.924,0.866 and 0.973,respectively,with sensitivities of 73.44％,84.37％,67.19％and 90.62％,and specificities of 88.89％,83.33％,97.22％and 94.44％,respectively.The predictive value of the combined detection was superior to that of the individual detection of ser-um sCD163,hs-CRP and PCT(P＜0.05).Conclusion The serum levels of sCD163,hs-CRP,and PCT are elevated in SAP patients,and their changes are closely related to the severity of the disease.The combined detection of these three indicators has a high value in predicting the occur-rence of SAP and may serve as auxiliary markers for predicting early SAP.

ObjectiveTo improve the efficiency of drug delivery, a mannose vinyl stearate mannose ligand (Man ligand) with active liver-targeting properties was synthesized.MethodsNon-aqueous enzymatic synthesis was used to modify the structure of mannose. Glycyrrhetinic acid-tanshinone lipid nanoparticles (GT-LN) and liver-targeted glycyrrhetinic acid-tanshinone mannose-modified lipid nanoparticles (GT-MLN) were prepared. The physicochemical properties and release profiles of both formulations were evaluated, and their pharmacokinetic behavior and tissue distribution were investigated.ResultsThe average particle sizes of GT-LN and GT-MLN were 190.20 ± 1.35 and 204.83 ± 3.86 nm, respectively, with corresponding surface Zeta potentials of −28.0 ± 1.68 and −30.24 ± 2.10 mV. The drug release profile of GT-LN conformed to the Higuchi equation, whereas that of GT-MLN followed both the first-order kinetic and Ritger–Peppas equations. Both formulations significantly enhanced the gastrointestinal stability of the drug. In vivo studies in mice demonstrated that hepatic GA and TSN concentrations in both groups were significantly higher than those in the original drug suspension group (P = .01). Notably, the concentrations in the GT-MLN group were significantly higher compared to the GT-LN group (P = .01).ConclusionMan ligand was formed via the linkage of vinyl stearate with the hydroxyl group at C-6 in mannose. The Man ligand endowed these lipid nanoparticles with obvious active liver-targeting properties. Our results provide an efficient and stable route of drug delivery to the liver with improved drug availability.

Objective: To investigate the effect of intraarticular hemorrhage on extending knee joint contracture model in rats . Methods: 18 mature male SD rats were divided into 3 groups by random number table method . The control group ( group C) was not immobilized and was killed after 4 weeks of feeding . In the simple fixation group( M1 group) , the left lower limb knee joint was immobilized in straight position for 4 weeks . The blood fixationgroup (M2 group) was injected into the knee cavity with body blood and immobilized in a straight position for 4 weeks . The knee joint motion of each group was measured by the joint motion measuring instrument under a stand⁃ard torque . The contracture degree was calculated by the joint range of motion of the knee joint before and after muscles separation . HE staining and Masson staining were used to detect the number of cells and collagen deposi⁃tion in the anterior joint capsule . The protein expressions of transforming growth factor 1 (TGF⁃ β1) , wingless⁃type MMTV integration site family , member 1 ( Wnt1) and beta⁃catenin ( β⁃catenin) in the anterior articular capsule were detected by Western blotting . Results: Compared with group C , total knee contracture and arthrogenic con⁃tracture of rats in M1 and M2 groups increased , and the difference was statistically significant (P < 0. 05) . At the same time , the degree of total contracture and arthrogenic contracture in M2 group was higher than that in M1 group , and the difference was statistically significant (P < 0. 05) . Compared with group C , the number of anterior joint capsule cells and collagen deposition in M1 and M2 groups increased , and the difference was statistically sig⁃group were higher than those in M1 group , and the difference was statistically significant (P < 0. 05) . Compared with group C , the protein expressions of TGF⁃ β1 , Wnt1 and β ⁃catenin in the anterior articular capsule of rats in M1 expressions of TGF⁃ β1 , Wnt1 and β ⁃catenin in the anterior articular capsule of the knee joint in M2 group were sig⁃nificantly higher than those in M1 group , with statistical significance (P < 0. 05) . Conclusion Joint immobiliza⁃ tion can lead to joint contracture , and joint bleeding aggravates the degree of joint capsule fibrosis induced by im⁃mobilization .