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.

ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

The core idea of occupational health risk assessment models is to systematically evaluate occupational health risks according to target hazard characteristics and relevant exposure levels of workers. Occupational exposure assessment is based on concentration, frequency, exposure time, and other indicators that indicate actual exposure of workers to occupational hazards, which is a critical component of health risk assessment. However, the accuracy and comparability of assessment results are affected by differences in parameter assignment for exposure assessment across different studies, as well as insufficient emphasis on multiple occupational hazard exposure. This review aimed to explore the assignment and standardization of exposure assessment parameters for occupational health risk assessment modeling, and systematically sorted out the meaning, assignment methods, and sources of exposure assessment related parameters in commonly used occupational health risk assessment models, with the goal of providing researchers with standardized assessment tools to enhance the scientific rigor and practicality of occupational health risk assessments. Considering the individual differences and temporal fluctuations in occupational exposure, it is recommended that researchers should adopt appropriate sampling strategies, reasonably select sample subjects and time based on the division of similar exposure group (SEG), and conduct statistical inference on the obtained data to derive representative exposure parameters. For combined exposure to chemicals with similar toxic effects, the health risk assessment methods are relatively mature. However, the assessment of combined exposure to hazards with different properties and health effects still lacks scientific authority and needs further research and discussion.

Objective To obtain the protective performance parameters of barium sulfate mortar against positron nuclide γ-rays, provide reference data for precise shielding calculations, and guide the design, evaluation, and construction of radiation shielding. Methods The FLUKA program was used to build a model for simulating the dose equivalent rate variation around points of interest under the irradiation of the most commonly used positron nuclide ¹⁸F with changes in the thicknesses of lead and barium sulfate mortar. The transmission curves of lead and barium sulfate mortar were fitted, and the half-value layer (HVL) and lead equivalence of barium sulfate mortar were calculated based on the fitted curves. Results The ambient dose equivalent rate coefficient of positron nuclide ¹⁸F was 1.339 4×10⁻¹ μSv·m²/MBq·h and the HVL for lead was 4.037 mm, with deviations of 0.043% and 1.53% compared to the values provided in the AAPM Report No. 108, respectively. The HVLs for γ-rays produced by ¹⁸F, using barium sulfate mortar with apparent densities of 4.20, 4.00, and 3.90 g/cm³ mixed with 35.2-grade cement in a 4∶1 mass ratio, were 2.914, 2.969, and 3.079 cm, respectively. The lead equivalences were 0.1385, 0.1360, and 0.1311 mmPb/mm, respectively. Conclusion The three types of barium sulfate mortar can provide good protection against γ-rays in positron imaging locations. As the apparent density of barium sulfate increases, its protective effect improves slightly but remains significantly better than common construction materials like concrete and solid bricks.

Objective To evaluate the efficacy of modified cardiac rehabilitation combined with Xuefu Zhuyu decoction on patients with heart failure of Qi deficiency and blood stasis type,with a focus on analyzing the improvement of galectin-3(Gal-3),soluble suppression of tumorigenicity 2(sST2)levels,cardiac function,traditional Chinese medicine syndromes,and exercise tolerance.Methods 180 patients with heart failure of Qi deficiency and blood stasis type who attended the Department of Rehabilitation Medicine,Huzhou First People's Hospital from October 2021 to March 2023 were selected and randomly divided into treatment group(modified cardiac rehabilitation+Xuefu Zhuyu decoction)and control group(conventional treatment),with a treatment course of 12 weeks.The changes of Gal-3,sST2,left ventricular ejection fraction(LVEF),New York heart association functional classification(NYHA),N-terminal B-type natriuretic peptide(NT-proBNP),traditional Chinese medicine syndrome score and 6-minute walk test(6MWT)were compared between two groups before and after 12 weeks of treatment,and the safety was evaluated.Results After 12 weeks of treatment,Gal-3 and sST2 levels of patients in treatment group were significantly lower than those in control group;LVEF levels of patients in treatment group were significantly higher than those in control group,and the degree of improvement of cardiac function grading in treatment group was significantly better than that in control group;NT-proBNP in treatment group was significantly lower than that in control group;The 6MWT in treatment group was significantly higher than that in control group;The score of traditional Chinese medicine syndrome in treatment group was lower than that in control group;The difference is statistically significant(P＜0.05).After 12 weeks of treatment,the effective rate of treatment group was significantly higher than that of control group(P＜0.05);There was no statistically significant difference in adverse reactions and serious adverse events between two groups of patients(P＞0.05).Conclusion Modified cardiac rehabilitation combined with Xuefu Zhuyu decoction can significantly improve cardiac function,traditional Chinese symptoms,and exercise tolerance in patients with heart failure of Qi deficiency and blood stasis type,reduce Gal-3 and sST2 levels,and has high clinical application value.

Objective To observe the alterations of protein expression of nicotinamide adenine di-nucleotide phosphatase oxidase 4-silent mating type information regulation 2 homolog 1(NOX4-SIRT1)signaling pathway in ApoE-/-mice and C57BL/6J mice induced by high-fat diet.Methods Twenty ApoE-/-mice and 40 C57BL/6J mice,aged of 10 weeks and half male and half female,were randomly divided into a NC group and a HFD group,with 10 mice in each group(ApoE-/-+NC and ApoE-/-+HFD groups,and C57+NC and C57+HFD groups).After 1 week of adaptive feed-ing period,each group was fed with their corresponding diet for subsequent 12 weeks,and then blood samples were collected from the anesthetized orbits and aortic arch tissues were harvested.HE staining and Masson staining were performed to examine the pathological morphology of the aortic arch tissues.The serum levels of TG,TC,HDL-C and LDL-C were measured using an auto-matic biochemical analyzer.The content of ox-LDLC was detected with ELISA,and the contents of ROS,GSH,GPX and NAD+were measured by colorimetry.The expression of SIRT1,p53,p21 and NOX4 was detected by Western blotting.Results Compared with the C57+NC group,the ApoE-/-+NC group showed significant lipid deposition,increased collagen fibers,elevated levels of TC,TG,HDLC,LDL-C,ox-LDL-C and ROS and increased p21 expression level,and obviously decreased contents of GSH,GPX and NAD+(P＜0.05,P＜0.01).Compared with the ApoE-/-+NC group,the ApoE-/-+HFD group showed larger plaque areas,lessened elastic fibers,more col-lagen fibers,increased levels of TC,HDL-C,LDL-C,ox-LDL-C and ROS,and p21 expression level(P＜0.01),and declined expression of GSH,GPX,NAD+and NOX4[6.4±0.8 μmol/L vs 9.6±0.8 μmol/L,242.0±39.0 U/ml vs 362.7±11.1 U/ml,0.61±0.15 nmol/L vs 1.07±0.20 nmol/L,0.26±0.01 vs 0.32±0.03;P＜0.05,P＜0.01[.Conclusion High-fat diet may accelerate vascular aging by elevating lipid and oxidative stress levels,decreasing NAD+and NOX4 expression,ele-vating p21 expression,and thereby activating the NOX4-SIRT1 pathway.

OBJECTIVE To investigate the mechanism of baicalin in alleviating the intestinal mucosal barrier injury in rats with intraperitoneal infection-induced sepsis through the vitamin D receptor(VDR)/nuclear factor E2-relat-ed factor 2(Nrf2)/haemoglobin oxygenase-1(HO-1)signalling pathway.METHODS Twenty-four SD rats were randomly divided into a sham-surgery group,a model group,an ulinastatin group and a baicalin group,with six rats in each group.Sepsis models were established via cecal ligation and puncture(CLP)in rats in each groups ex-cept for the sham surgery group.Six hours after modeling,the sham-surgery and the model groups received intra-peritoneal saline,while the ulinastatin and baicalin groups were administered ulinastatin at 20,000 U/kg and ba-icalin at 100 mg/kg,respectively,via intraperitoneal injection once daily for 5 consecutive days.The histopatho-logical changes in the ileum tissue of rats in each group were observed,and the levels of oxidative stress,inflam-matory factors,and the expression of related mRNA and proteins in the VDR/Nrf2/HO-1 signalling pathway were compared.RESULTS Compared with the sham-surgery group,the model group showed disordered villus ar-rangement,severe intestinal mucosal atrophy and inflammatory cell infiltration,with necrotic epithelial cell shed-ding.Additionally,in the model group,the total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and glutathione peroxidase(GSH-PX)levels reduced,while the levels of tumor necrosis factor-α(TNF-α),inter-leukin(IL)-6,and IL-1βsignificantly increased,and the expression of VDR mRNA,Nrf2 mRNA,HO-1 mR-NA,and VDR,Nrf2,and HO-1 proteins were downregulated(P<0.05).Compared with the model group,the ulinastatin group and the baicalin group showed that villus arrangement,intestinal mucosal atrophy and inflamma-tory cell infiltration got improved,the levels of T-AOC,SOD,and GSH-PX elevated,the levels of TNF-α,IL-6,and IL-1βdecreased,and expressions of VDR mRNA,Nrf2 mRNA,HO-1 mRNA,and VDR,Nrf2,and HO-1 proteins were upregulated.Moreover,all indicators in the baicalin group were superior to those in the ulinastatin group(P<0.05).CONCLUSION Baicalin can inhibit the expression of inflammatory factors and regulate the bal-ance of oxidative stress in vivo by up-regulating the VDR/Nrf2/HO-1 signaling pathway,thereby alleviate the in-testinal mucosal barrier dysfunction caused by intraperitoneal infection-induced sepsis.

Objective:To explore the effect of supervised home-based pulmonary rehabilitation by wearable devices on moderate chronic obstructive pulmonary disease(COPD).Method:A total of 70 patients with moderate COPD in the stable stage who visited the Respiratory Rehabilita-tion Center of Beijing Rehabilitation Hospital of Capital Medical University from January 2020 to October 2021 were randomly divided into a control group and a study group,with 35 cases in each group.The inter-vention lasted for 10 weeks.Cardiopulmonary exercise tests(FEV1,FEV1/FVC％,FEV1％pred,VO2max,VO2AT,maximum power),COPD Assessment Test(CAT),St.George's Respiratory Questionnaire(SGRQ)and modified Medical Research Council dyspnea scale(mMRC)were compared between the two groups before and after rehabilitation.After the study was completed,the compliance of the two groups was compared.Result:A total of 15 subjects dropped out of 70 cases,and finally 27 cases were included in the control group and 28 cases in the study group.There was no significant improvement in FEV1,FEV1/FVC％,and FEV1％pred after rehabilitation in the two groups(P＞0.05).After rehabilitation,VO2max,VO2AT,maximum power,SGRQ,CAT and mMRC[(14.2±2.2vs.18.4±1.6)and(13.9±2.4vs.17.7±1.9),(10.6±1.3vs.11.9±1.6)and(10.3±1.3vs.11.9±1.4),(69.9±7.5vs.88.3±8.4)and(68.6±9.0vs.86.4±9.7),(45.4±9.9vs.35.4±7.5)and(45.3±12.1vs.36.3±8.4),(19.2±3.4vs.12.8±3.5)and(19.5±3.7vs.13.3±3.7),(2.5±0.9vs.1.5±0.6)and(2.6±1.0vs.1.8±0.7)]were significantly improved(P＜0.01),but there were no significant differences between the groups(P＞0.05).The stop training rate of the control group was significantly higher than that of the study group(37％vs.11％,P＜0.05).However,there was no significant difference between the two groups in the proportion of peo-ple who did not reach the target time and target intensity[(15％vs.21％)and(15％vs.29％)](P＞0.05).Conclusion:There is no significant difference between home-based pulmonary rehabilitation and traditional out-patient pulmonary rehabilitation in improving exercise capacity,symptoms and quality of life,but the compli-ance is better.

Objective:To investigate effect of SenkyunolideⅠ(Sen Ⅰ)on function of astrocytes induced by lipopolysaccharide(LPS)and its mechanism.Methods:Rat neural astrocytes were induced by LPS,and the damaged cell model was constructed.Normal and injured astrocytes were treated with different concentrations of Sen Ⅰ(20,50,100,200 μmol/L),respectively.Cell proliferation was detected by CCK-8,cytotoxicity was detected,and the optimal concentration of Sen Ⅰ was determined.Astrocytes were divided into control group,LPS group,LPS+Sen Ⅰ group and LPS+Sen Ⅰ+ML385[nuclear factor E2 associated factor 2(Nrf2)inhibitor]group.Cell proliferation was detected by CCK-8 assay,expression of glial fibrillary acidic protein(GFAP)was detected by immunofluorescence assay and Western blot,mRNA and protein expression of Nrf2 was detected by qRT-PCR and Western blot,contents of TNF-α and IL-1β in supernatant of cells were detected by ELISA,and expression of glial cell line-derived neurotrophic factor(GDNF)in cells was detected by Western blot.Results:Low concentrations of Sen Ⅰ(20,50 μmol/L)were not toxic to astrocytes,while high concentra-tions(100,200 μmol/L)significantly inhibit astrocyte proliferation.The optimal concentration of Sen Ⅰ was 50 μmol/L.Compared with control group,cell proliferation ability,contents of TNF-α and IL-1β in cell supernatant,and expression of GFAP in cells were significantly increased in LPS group(P<0.01),while Nrf2 mRNA and protein level and GDNF protein level in cells were significantly decreased(P<0.01);compared with LPS group,cell proliferation ability,contents of TNF-α and IL-1β in cell supernatant,and ex-pression of GFAP in LPS+Sen Ⅰ group were significantly decreased(P<0.05),while Nrf2 mRNA and protein level and GDNF protein level in cells were significantly increased(P<0.05);compared with LPS+Sen Ⅰ group,LPS+Sen Ⅰ+ML385 group could reverse the above effects(P<0.05).Conclusion:Sen Ⅰ can inhibit the over-activation and inflammatory injury of astrocytes,and the mechanism may be related to the activation of Nrf2 pathway.