OBJECTIVE To explore the improvine mechanism of Yifei xuanfei jiangzhuo formula （YFXF） on vascular dementia （VAD） model rats based on the growth factor receptor-bound protein 2 （GRB2）/extracellular signal-regulated kinase （ERK）/cardiolipin synthase 1 （CRLS1） pathway. METHODS VAD rat model was established by permanent bilateral common carotid artery ligation. Forty-eight successfully modeled rats were randomly divided into the model group （normal saline）， donepezil hydrochloride group （positive control group， 0.2 g/kg）， and YFXF low- and high-dose groups （12.18 and 24.36 g/kg， calculated based on the total amount of crude drug）， respectively. In addition， a sham operation group （normal saline） was set up. There were 12 rats in each group. Daily intragastric administration of drug or normal saline was performed for 30 consecutive days. After the last administration， the spatial cognitive ability of the rats was evaluated， the pathological morphology of the hippocampus was observed， the contents of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） in serum were detected， the expression levels of GRB2/ERK/CRLS1 pathway-related proteins and the mRNA levels of GRB2， CRLS1， NADH dehydrogenase subunit 1（ND1）， Tafazzin （TAZ）， phospholipid scramblase 3（PLSCR3） and the ATP content in hippocampal tissue were measured. RESULTS Compared with the sham operation group， the escape latency of rats in the model group was significantly prolonged （ P ＜0.05）， and the number of crossing platform was significantly reduced （ P ＜0.05）， while the number of pyramidal cells and Nissl bodies in the hippocampus decreased sharply； the content of TNF-α in serum was significantly increased （ P ＜0.05）， and the content of IL-4 was significantly decreased （ P ＜0.05）； the expression levels of GRB2 and CRLS1 proteins， the phosphorylation level of ERK protein， the relative expression levels of GRB2， CRLS1，ND1， TAZ， and PLSCR3 mRNA， and the content of ATP in hippocampal tissue were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological changes in the hippocampal tissue of each administration group were alleviated， and the quantitative indicators were significantly restored （ P ＜0.05）. CONCLUSIONS YFXF may improve hippocampal neuron injury in VAD rats by activating the GRB2/ERK/CRLS1 pathway, maintaining cardiolipin homeostasis， and improving mitochondrial energy metabolism.

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

Objective To explore the mechanisms of Qingre Lidan Jiedu Recipe(QLJR)for improving cognitive dysfunction in rats with high copper load.Methods Seventy-five male SD rats were randomized into normal control group,model group,QLJR group,penicillamine(PCA)group,and QLJR+PCA group.Except for those in the control group,all the rats were fed a high-copper diet for 12 weeks.The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests.Hippocampal expressions of NIX,FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining,and changes in mitochondrial morphology were observed with transmission electron microscopy.Results Behavioral tests showed prolonged target hole latency,shortened latency to enter the dark chamber,and increased error counts of the rats in the model group,which were significantly improved in QLJR+PCA group;the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group.Among all the groups,the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group;NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group.Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups,but their expressions did not differ significantly between QLJR and PCA groups.The rats in the model group showed obvious structural disarray of the mitochondria,which were improved in all the treatment groups.Conclusion QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.

Objective To investigate the impact of overwork on vascular endothelial barrier function in mice.Methods Thirty KM mice were randomized equally into control,overwork for 2 weeks(W2)group and 4 weeks(W4)group.In the latter two groups,the mice were subjected to continuous standing in water for 8 h followed by restraint for 3 h to simulate overwork on a daily basis for 2 and 4 weeks.After modeling,4 mice from each group were intraperitoneally injected with Evans blue dye to assess vascular permeability.In the other 6 mice,serum IL-1β levels were measured using ELISA,and arterial tissues were collected for histological examination and detection of mRNA expressions of occludin,claudin-5,ZO-1,JAM-A and VE-cadherin;immunofluorescence assay was used to detect the protein expressions of claudin-5,ZO-1,VE-cadherin,and Syndecan-1.Results The mice in W2 and W4 groups exhibited slower weight gain,hair loss,reduced activity,and significantly increased serum IL-1β levels.Vascular permeability was significantly increased in W4 group.In W2 group,the endothelial cells were swollen and dissociated,and the intima was rough and irregular;arterial intimal rupture was observed in W4 group.The mRNA expressions of occludin,claudin-5,ZO-1 and JAM-A in the arterial tissues were significantly increased in W2 group but decreased in W4 group,while VE-cadherin mRNA expression were reduced in both groups(P<0.05).The protein expressions of claudin-5,ZO-1,VE-cadherin,and Syndecan-1 were all significantly reduced in W4 group.Conclusion Prolonged overwork can cause damage of the intercellular junction complexes in arterial endothelial cells and the endothelial glycocalyx to result in impaired barrier function and increased vascular permeability in mice.

Objective:To explore the relationship between the hypertensive snowbirds′ length of migratory stay and their blood pressure control and blood pressure levels.Methods:This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds′ length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines.Results:A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants′ self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds′ length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure ( β=-1.19, P=0.003). Conclusions:Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.

AIM: To evaluate the refractive status through computer refractometer and OPD-Scan III auto refractometer in cataract patients after extended depth of focus(EDOF)intraocular lens implantation.METHODS: Retrospective observational study. A total of 61 cases(76 eyes)that received phacomulsification and implanted with TECNIS® Symfony ZXR00 intraocular lens in Shanghai Eye Diseases Prevention & Treatment Center from May 2022 to May 2023 were collected. Measurements from the computer refractometer, OPD-Scan III auto refractometer, and subjective refraction, were taken from all patients on the same day postoperatively.RESULTS: There were statistical significant difference in sphere(S)and spherical equivalent(SE)readings from the computer refractometer and subjective refraction(all P<0.01), with mean differences of -0.67±0.37 D and -0.75±0.35 D, respectively, and the S and SE obtained from computer refractometer more incline to myopia than those from subjective refraction; there were statistical significant difference in computer refractometer and subjective refraction(P<0.01), with a relative small absolute difference(0.21±0.24 D). The S, cylinder(C)and SE of computer refractometer(S, C, SE)were positively correlated with subjective refraction(r=0.7994, 0.7929, and 0.8118, respectively, all P<0.01). Additionally, there were statistical significant differences in S, C and SE of OPD-Scan Ⅲ and subjective refraction(P<0.01), and the absolute differences of S(0.63±0.36 D), C(0.35±0.26 D)and SE(0.53±0.36 D)were small. Furthermore, the S, C and SE of OPD-Scan Ⅲ were positively correlated with subjective refraction(r=0.4410, 0.4982, 0.5224, all P<0.01).CONCLUSION: In patients who received implantation of EDOF lenses, the consistency of computer refractometer, OPD-Scan III auto refractometer and subjective refraction was good. The average difference of the S and SE obtained via computer refractometer was large, but both exhibited a myopic shift relative to those derived from subjective refraction, and the C values demonstrated minimal discrepancy. Furthermore, the differences between OPD-Scan III auto refractometer and subjective refraction were small, but the direction of the difference is unstable, sometimes it is myopic deviation, while sometimes it is hyperopic deviation.

Objective: To explore the associations of physical activity and sleep quality with anxiety and depressive symptoms in college students, in order to provide empirical support and theoretical guidance for mental health intervention among college students. Methods: From March to April 2023, 2 099 college students from universities in 6 different provinces were selected by a convenient sampling method. Physical activity, sleep quality, anxiety and depressive symptoms were evaluated by the International Physical Activity Questionnaire Short Form (IPAQSF), the Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiologic Studies Depression Scale (CESD) and the Anxiety SelfRating Scale (SAS), respectively. Descriptive statistics and Logistic regression models were used to analyze the data. Results: The reporting rates of lowintensity, moderateintensity, and highintensity physical activity among college students were 30.3%, 45.3%, and 24.4%, respectively. Moreover, among the participants, anxiety was detected in 21.6% and depressive symptoms in 39.9%, while 62.3% experienced poor sleep quality. Compared with males, females exhibited a lower proportion of highintensity physical activity (22.3% vs 42.8%), while reported higher proportions of moderateintensity (48.1% vs 40.8%) and lowintensity physical activity (29.5% vs 16.4%). Additionally, the proportion of females reporting poor sleep quality (65.0%) was higher than that of males (58.0%) (χ2=110.15, 10.70, P<0.05). The proportion of girls (43.8%) with depressive sypmtoms was higher than that of boys (33.9%) (χ2=20.48, P<0.05). Logistic regression analysis showed that high physical activity was negatively correlated with anxiety and depression (OR=0.45, 0.33), poor sleep quality was positively correlated with anxiety and depressive symptoms (OR=3.89, 3.94) (P<0.01).The interaction effect between high physical activity and good sleep quality was associated with the reduction of anxiety and depression among college students (OR=0.14, 0.08, P<0.01). Conclusions Physical activity and sleep quality are associated with anxiety and depressive symptoms among college students. The interventions for mental health problems such as depression and anxiety among college students should aim to improve physical activity and sleep quality.