ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

Objective To explore the mechanism of action of Danshen Baoxin Cha(DBC) on depressed mice with coronary heart disease (CHD) based on network pharmacology and NLRP3 inflammatory pathway. Methods (1) TCMSP and BATMAN-TICAM databases were used to screen the DBC active ingredients and targets. The targets of CHD with depression were screened using the OMIM and Genecards databases. The targets of DBC active ingredients and related targets of CHD with depression were imported into Venny 2.1 online platform to obtain the intersection targets,which was the potential target of DBC in the treatment of CHD with depression. Protein-protein interaction (PPI) analysis was performed on the intersection targets using the STRING platform to screen the key targets. A "drug-active ingredients-disease-targets" network was created to select the main active ingredients and core targets of DBC for the treatment of CHD with depression. Thereafter,the primary targets were examined by GO function and KEGG pathway enrichment using the Metascape database.(2)Kunming mice were split into six groups of eight mice each at random:the control group,the model group,the positive control group (metoprolol tartrate 5.14 mg·kg-1+sertraline hydrochloride 10.3 mg·kg-1),and the DBC high-,middle-,and low-dose groups (30.8,15.4 and 7.7 g·kg-1·d-1). Chronic unpredictable mild stimulation (CUMS)and subcutaneous injection of isoprenaline hydrochloride (ISO) were used to induce a mice model of CHD with depression. Mice were treated orally with the corresponding drug once a day for 18 consecutive days. Behavioral experiments involving forced swimming test,tail suspension test,and open-field test were applied to detect depression levels of mice. Histopathological alterations in hippocampus tissues were noted using HE and Nissl staining. qPCR was used to determine the mRNA expression levels of IL-6,TNF-α,NLRP3,IL-1β,IL-10,and Caspase-1 in hippocampus tissues. Results(1) Sixty-five active components in Salvia and seven active components in green tea were screened out. A total of 1042 potential targets and 2116 CHD complicated with depression-related targets were obtained. The intersection of the targets of active components and disease-related targets was performed by Venny 2.1.0 platform to obtain 299 potential targets (common targets) of DBC in the treatment of CHD with depression. The core targets including IL-1β,AKT1,TNF-α,IL-6,VEGFA,CASP3 and IL-10 were screened through PPI network analysis of potential targets. Key active ingredients including vitamin B,luteolin,salvianolic acid,tanshinone ⅡA and catechin,as well as key targets,such as PTGS2、IL-1β、IL-6、TNF-α and IL-10,were obtained by network analysis of "drugs-active ingredients-disease-targets". The potential targets were correlated with biological processes such as inflammation response,regulation of tumour necrosis factor (TNF),glucocorticoid regulation,regulation of nuclear factor kappa B(NF-κB) transcription factor,as well as major pathways including PI3K-Akt signaling pathway,TNF signaling pathway,apoptosis signaling pathway,and NF-κB signaling pathway.(2) Compared with the control group,mice in the model group showed a significant decrease in the total and center distance of the open field (P<0.01) and a significant increase in the time of forced swimming and immobility time of tail suspension test (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β,and Caspase-1 was significantly up-regulated(P<0.01) in the hippocampus tissues,but IL-10 mRNA expression was down-regulated (P<0.05). Compared with the model group,the total and center distance in DBC high-,middle-,and low-dose groups were significantly up-regulated(P<0.05,P<0.01),and the time of forced swimming and immobility time of tail suspension test were significantly down-regulated (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β and Caspase-1 of the DBC high-,middle-,and low-dose groups were significantly down-regulated(P<0.01),IL-10 mRNA expression in mice hippocampus tissue of DBC high-and middle-dose groups was up-regulated (P<0.01). Conclusion The intervention effect of DBC on depressed mice with CHD may be achieved by active ingredients including luteolin,tanshinone,salvianolic acid and catechin acting on the key targets,such as IL-6,TNF-α,IL-1β and IL-10,to regulate the NLRP3 inflammatory signaling pathway.

Objective:To investigate the psychological status of HD nursing staff in hospitals in Guangdong province and its influential factors.Methods:1 630 nursing staff in HD rooms of 71 hospitals or units in Guangdong Province in February and March 2020 were evaluated by using the 10-item Kessler psychological distress scale (Kessler 10), General self-efficacy scale (GSES) and Connor-Davidson resilience scale (CD-RISC) to conduct a questionnaire survey on their psychological status. Insomnia severity index (ISI) and Fatigue scale-14 (FS-14) were used to investigate their degree of insomnia and fatigue. General information on gender, age, educational level, marital status, economic income, professional title, HD working hours, average weekly overtime times and hours, total number of HD patients per day, and whether holding other positions were collected.Results:A total of 1 630 questionnaires were collected, among which 1 629 were valid, with an effective recovery rate of 99.9%. The scores of the three scales were (20.16±7.47), (27.03±4.45) and (58.37±15.75), respectively. According to the Kessler 10, 835 people (51.2%) had mental disorders. Univariate analysis showed that age, educational level, economic income, type of work unit, total number of HD patients per day and living status in recent one week were related with Kessler 10 score (all P<0.05). Economic income, type of work unit, whether holding other positions, total number of HD patients per day and living status in recent one week were related with GSES scores (all P<0.05). Age, marital status, economic income, professional title, type of work unit, whether holding other positions and living status in recent one week were related to CD-RISC score (all P<0.05). Spearman rank correlation analysis showed that the number of HD machines ( r=0.100, P<0.001), the number of nurses ( r=0.082, P=0.001), average weekly overtime times ( r=0.142, P<0.001) and overtime hours ( r=0.136, P<0.001), ISI score ( r=0.572, P<0.001) and FS-14 score ( r=0.635, P<0.001) were correlated with Kessler 10 score. ISI score ( r=-0.311, P<0.001) and FS-14 score ( r=-0.335, P<0.001) were correlated with GSES score. Working years of HD service ( r=0.112, P<0.001), ISI score ( r=-0.289, P<0.001) and FS-14 score ( r=-0.314, P<0.001) were correlated with CD-RISC score. Multiple linear regression analysis showed that the economic income in 5 001-10 000 yuan (with<3 000 yuan as reference, B=-1.603, 95% CI -3.036--0.169, P=0.028) and the total number of HD patients per day >200 (with ≤50 as reference, B=-1.153, 95% CI -2.242--0.065, P=0.038) were negatively correlated with Kessler 10 score, and average weekly overtime times ( B=0.221, 95% CI 0.069-0.374, P=0.004), ISI score ( B=0.518, 95% CI 0.454-0.582, P<0.001) and FS-14 score ( B=1.166, 95% CI 1.066-1.265, P<0.001) were positively correlated with Kessler 10 score. The economic income (with<3 000 yuan as reference) in 3 001-5 000 yuan ( B=1.930, 95% CI 0.847-3.013, P<0.001), 5 001-10 000 yuan ( B=1.949, 95% CI 0.887-3.012, P<0.001), 10 001-15 000 yuan ( B=1.482, 95% CI 0.318-2.647, P=0.013), >20 000 yuan ( B=4.300, 95% CI 2.463-6.136, P<0.001), secondary hospital (with primary hospitals as reference, B= 1.078, 95% CI 0.005-2.152, P=0.049) and holding other positions ( B=0.729, 95% CI 0.277-1.181, P=0.002) were positively correlated with GSES score, and ISI score ( B=-0.169, 95% CI -0.217--0.120, P<0.001) and FS-14 score ( B=-0.403, 95% CI -0.478--0.328, P<0.001) were negatively correlated with GSES score. The economic income (with<3 000 yuan as reference) in 3 001-5 000 yuan ( B=7.631, 95% CI 3.753-11.509, P<0.001), 5 001-10 000 yuan ( B=9.236, 95% CI 5.362-13.110, P<0.001), 10 001-15 000 yuan ( B=9.039, 95% CI 4.735-13.342, P<0.001), 15 001-20 000 yuan ( B=8.639, 95% CI 2.989-14.289, P=0.003), >20 000 yuan ( B=16.101, 95% CI 9.162-23.039, P<0.001) and holding other positions ( B=3.228, 95% CI 1.510-4.945, P<0.001) were positively correlated with CD-RISC score, and ISI score ( B=-0.593, 95% CI -0.765--0.420, P<0.001) and FS-14 score ( B=-1.258, 95% CI -1.525--0.992, P<0.001) were negatively correlated with CD-RISC score. Conclusion:The psychological status of nursing staff in HD rooms of hospitals in Guangdong Province needs to be improved. Effective preventive measures should be taken to provide timely psychological support, counseling and intervention to nursing staff with psychological abnormalities, and encourage them to take the initiative to seek psychological counseling when necessary, so as to promote their physical and mental health.

Ceria nanoparticles(CeO2 NPs)have become popular materials in biomedical and industrial fields due to theirpotential applications in anti-oxidation,cancer therapy,photocatalytic degradation of pollutants,sensors,etc.Many methods,including gas phase,solid phase,liquid phase,and the newly proposed green synthesis method,have been reported for the synthesis of CeO2 NPs.Due to the wide application of CeO2 NPs,concerns about their adverse impacts on human health have been raised.This review covers recent studies on the biomedical applications of CeO2 NPs,including their use in the treatment of various diseases(e.g.,Alzheimer's disease,ischemic stroke,retinal damage,chronic inflammation,and cancer).CeO2 NP toxicity is discussed in terms of the different systems of the human body(e.g.,cytotoxicity,genotoxicity,respiratory toxicity,neurotoxicity,and hepatotoxicity).This comprehensive review covers both fundamental discoveries and exploratory progress in CeO2 NP research that may lead to practical developments in the future.

Regular and adequate use of broad-spectrum sunscreen has been proven to offer significant protection against acute Ultraviolet-induced photodamage, photoaging, immunosuppression, and the development of skin tumors. However, concerns regarding the safety and standardized use of sunscreens persist, including potential allergenicity and irritability of certain organic sunscreens, the impact of systemic absorption on the endocrine system, the effect on vitamin D synthesis and absorption, and environmental implications. Special caution is advised when using small molecule organic sunscreens and nanoparticle inorganic sunscreens, especially for infants, pregnant women, and areas with damaged skin.

Regular and adequate use of broad-spectrum sunscreen has been proven to offer significant protection against acute Ultraviolet-induced photodamage, photoaging, immunosuppression, and the development of skin tumors. However, concerns regarding the safety and standardized use of sunscreens persist, including potential allergenicity and irritability of certain organic sunscreens, the impact of systemic absorption on the endocrine system, the effect on vitamin D synthesis and absorption, and environmental implications. Special caution is advised when using small molecule organic sunscreens and nanoparticle inorganic sunscreens, especially for infants, pregnant women, and areas with damaged skin.

Objective To explore the expression of mocro RNA(miR)-142-5p and suppressor of cytokine signaling 1(SOCS1)mRNA in peripheral blood mononuclear cells(PBMC)of mice and clinical patients with ankylosing spondylitis(AS)and their impact on immune function.Methods The mRNA levels of miR-142-5p and SOCS1 in PBMC of 30 patients with AS(Patient group)and 30 healthy controls(Health group)treated in the First People's Hospital of Shangqiu from January 2022 to March 2023 were measured by quantitative real time PCR(qRT-PCR).AS mice models were induced by bovine proteoglycan combined with complete Freund's adjuvant,and these mice were divided into control group,model group,NC group and antagomir group.Normal saline was injected into tail vein in control group and model group,and NC-antagomir and miR-142-5p-antagomir were injected into tail vein in NC group and antagomir group,respectively.After 2 weeks of treatment,the arthritis symptom scores of mice in each group were evaluated.The morphology of ankle joint was evaluated by hematoxylin eosin(HE)staining.The levels of Th1 cytokine interferon-γ(IFN-γ),Th2 cytokine interleukin-4(IL-4),Th17 cytokine interleukin-17(IL-17)and Treg cytokine forkhead box protein P3(FOXP3)in PBMC of mice were detected by ELISA method.The mRNA and protein expression of miR-142-5p,SOCS1,IFN-γ,IL-4,IL-17 and FOXP3 in PBMC and ankle joints were detected by qRT-PCR and Western blot.Results Compared with Health group,the level of miR-142-5p in PBMC of patient group was increased(1.00±0.21 vs 3.03±0.99,t=10.997,P＜0.001),while the level of SOCS1 mRNA was decreased(1.00±0.18 vs 0.41±0.09,t=15.956,P＜0.001).Compared with control group,miR-142-5p level(1.00±0.04 vs 4.00±0.52)and the mRNA and protein levels of IFN-γ and IL-17 in ankle joint tissue of model group were increased,while the mRNA and protein levels of SOCS1,IL-4 and FOXP3 were decreased,with significant differences(t=23.356,31.420,48.056,47.224,38.035,29.007,54.183,28.123,55.155,26.758,45.346,all P＜0.05).The arthritis symptom score was increased(7.83±0.94 vs 0.00±0.00,t=22.212,P＜0.05),and the ankle joint structure was damaged.Serum IFN-γ,IL-17 levels,IFN-γ/IL-4 ratio(0.81±0.08 vs 2.08±0.33)and IL-17/FOXP3 ratio(0.41±0.03 vs 1.27±0.10)were increased,and the differences were statistically significant(t=15.382,35.779,8.934,35.130,all P＜0.05).Compared with NC group,miR-142-5p level(3.89±0.33 vs 1.47±0.10),the mRNA and protein levels of IFN-γ and IL-17 in ankle joint tissue of antagomir group were decreased,while the mRNA and protein levels of SOCS1,IL-4 and FOXP3 were increased,and the differences were statistically significant(t=18.846,22.969,43.454,32.617,23.259,20.881,41.832,11.994,32.977,15.190,35.834,all P＜0.05).The arthritis symptom score was decreased(7.42±1.24 vs 2.75±0.75,t=13.233,P＜0.05),and the shape of the ankle joint of the rats was improved.Serum IFN-γ,IL-17 levels,IFN-γ/IL-4 ratio(1.22±0.11 vs 1.91±0.19)and IL-17/FOXP3 ratio(0.69±0.05 vs 1.23±0.12)were decreased,and the differences were statistically significant(t=8.688,22.972,3.785,22.007,all P＜0.05).Conclusion MiR-142-5p was highly expressed in AS.Down-regulation of miR-142-5p using antagonists may reduce Th1/Th2 ratio and Th17/Treg ratio through up-regulation of SOCS1,there by improving the immune balance of AS mice and inhibiting the progression of AS.

Objective To investigate the changes of cortical thickness in patients with insomnia disorder(ID).Methods High-resolution MRI data were collected from 32 ID patients(ID group)and 30 healthy controls(HC)(HC group).The cortical thickness of both groups were analyzed using statistical parametric mapping 12(SPM12)software,while considering age,gender,and educational level as covariates.The cortical thickness in brain regions showed statistically significant differences was extracted for Pearson's correla-tion analyses with sleep and mood-related scales.Results Compared with the HC group,the ID group exhibited significantly decreased cortical thickness in brain regions such as the left insula,fusiform gyrus,orbitofrontal lobe,superior temporal gyrus,middle temporal gyrus,lateral occipital lobe and right caudal anterior cingulate gyrus[P＜0.05,family-wise error(FWE)correction].Furthermore,reduced cortical thickness of the cingulate gyrus was negatively correlated with the Pittsburgh sleep quality index(PSQI)score(r=-0.437,P=0.012).Conclusion The cortical thickness of several brain regions associated with sleep and mood are significantly reduced in patients with ID,providing potential neuroimaging evidence for understanding the pathophysiological mechanism of ID.

Objective:To observe the protective effects of Zhiganqing Prescription on the liver of C57BL/6J non-alcoholic fatty liver disease (NAFLD) mice induced by high fat diet and its effects on PI3K/Akt/FoxO1 signaling pathway, insulin resistance (IR) and gluconogenesis.Methods:A total of 48 8-week-old male C57BL/6J mice were divided into control group ( n=8) and modeling group ( n=40) according to random number table method. The control group was fed with ordinary diet, and the model group was fed with high-fat diet. The NAFLD model was established after 8 weeks of feeding. The modeling group was divided into model group, Pioglitazone group, Zhiganqing Prescription low-, medium-, and high-dosage group ( n=8 in each group) according to random number table method, and drug intervention lasted for 8 weeks. The body mass of mice was measured regularly during administration. Fasting blood glucose (FBG) levels were measured at 0 and 8 weeks of administration, and oral glucose tolerance tests (OGTT) were conducted. After the experiment, serum levels of GPT, GOT, TC, TG, LDL-C, HDL-C, FINS and C-P were detected and HOMA-IR was calculated. The pathological morphology of liver was observed by HE and PAS staining. The expression levels of PI3K and p-Akt were detected by IHC staining. The protein expression levels of PI3K, Akt, p-Akt, FoxO1, p-FoxO1, G6PC and PCK1 were detected by Western blot. Results:Compared with model group, the body weight of mice in each administration group decreased at 4, 6 and 8 weeks ( P<0.05 or P<0.01). At the 8th week of administration, the levels of FBG and OGTT AUC in each administration group decreased ( P<0.05 or P<0.01), the levels of GPT, TC, TG and LDL-C decreased ( P<0.01), and the GOT levels in Zhiganqing Prescription medium- and high-dosage groups decreased ( P<0.01). The HDL-C level in Zhiganqing Prescription medium-dosage group decreased ( P<0.05 or P<0.01), and the HOMA-IR level in Zhiganqing Prescription low- and medium-dosage groups decreased ( P<0.05 or P<0.01). The levels of FINS and C-P in each administration group increased ( P<0.05 or P<0.01), and the expressions of PI3K protein and p-Akt/Akt, p-FoxO1 /FoxO1 protein in liver tissues increased ( P<0.05 or P<0.01). The protein expressions of G6PC and PCK1 decreased ( P<0.05 or P<0.01). Conclusion:Zhiganqing Prescription can effectively control the body mass, blood glucose, liver function and blood lipids of NAFLD mice, improve IR and gluconeogenesis, the mechanism of which may be related to the activation of PI3K/Akt/FoxO1 signaling pathway.