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 explore the mediating role of activities of daily living (ADL) in pain and depressive symptoms in the elderly in China. Methods Utilizing the data from 2020 China Health and Retirement Longitudinal Study, 4403 Chinese elderly individuals aged ≥ 60 years old were selected as the research subjects. Depression Scale (CES-D 10) of the Center for Epidemiological Survey and ADL scale were used in the study. The PROCESS4.1 macro was used to test the mediating effect of daily living activities between pain and depressive symptoms, and the Bootstrap method was applied for verification of the mediating variables. Results A total of 2368 cases of depressive symptoms were detected in the elderly in China, with a detection rate of 53.78%. Pain was positively correlated with depressive symptoms (r=0.27, P<0.01), and activities of daily living were negatively correlated with pain and depressive symptoms (r=-0.27, -0.337, P<0.01). The results showed that the total effect value of pain on depressive symptoms was 0.33, the direct effect value was 0.24, and the mediating effect value of daily living activities was 0.09, accounting for 27.27%. Conclusion Pain and activities of daily living are important factors influencing depressive symptoms in the elderly, and activities of daily living play a partial mediating role in the relationship between pain and depressive symptoms in the elderly.

Objective To explore the applications and effects of professional training-based peer support on self-management of women with gestational diabetes mellitus.Methods A total of 96 patients diagnosed with gestational diabetes mellitus in a tertiary A-level women's hospital in Nanjing from March to June 2023 were conveniently selected as the research subjects,among which 48 patients with gestational diabetes mellitus diagnosed from May to June 2023 were divided into an experimental group,and 48 patients with gestational diabetes mellitus diagnosed from March to April 2023 were included into a control group.The experimental group received professional training-based peer support based on routine nursing,and the control group received routine nursing.The status of self-management,health literacy,quality of life and blood glucose in 2 groups were compared and analyzed.Results 45 patients in the experimental group and 48 patients in the control group completed the study.After intervention,the Self-Management Scale score of the experimental group was(115.11±9.48),which was higher than(78.46±6.27)of the control group;the score of Health Literacy Scale was(145.38±5.22),higher than(92.19±5.75)of the control group;the Quality of Life Scale score was(79.47±4.11),higher than(60.85±2.80)of the control group;the fasting blood glucose concentration and two-hour postprandial glucose concentration in the experimental group were lower than those in the control group,and the difference between 2 groups was statistically significant(P＜0.001).Conclusion Nursing intervention of the professional training-based peer support can effectively improve the levels of self-management,health literacy and quality of life,as well as reduce concentration of blood glucose.

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 of HSP90,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.

OBJECTIVE:The quality of systematic reviews/meta-analyses directly affects the reliability of clinical decision-making basis.Currently,there is no literature quality research on the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis both domestically and internationally.This article will comprehensively evaluate the methodological quality,reporting quality,and evidence quality of the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis.METHODS:Computer searches were conducted on CNKI,WanFang Data,VIP,CBM,PubMed,Embase,and The Cochrane Library.From the establishment of the database until January 24,2024,all systematic reviews/meta-analyses treated with platelet rich plasma versus hyaluronic acid for knee osteoarthritis were collected.Two evaluators independently conducted literature screening and data extraction,and used the AMSTAR 2,PRISMA 2020,and GRADE systems to evaluate and summarize the methodological,reporting,and evidence quality of the included systematic reviews/meta-analyses.RESULTS:A total of 18 qualified systematic reviews/meta-analyses were included,and the results showed that the efficacy and safety of platelet rich plasma might be better than that of hyaluronic acid.The methodological quality of all 18 studies was extremely low;4 reports had poor quality and relatively serious information defects,while 14 reports had moderate quality and some information defects.Among the 275 outcome measures of 16 systematic reviews/meta-analyses,there were 9 medium quality evidence,90 low-quality evidence,and 176 extremely low-quality evidence,with no high-quality evidence.CONCLUSION:At present,the quality of systematic reviews/meta-analyses literature on the treatment of knee osteoarthritis with platelet rich plasma versus hyaluronic acid is relatively low.In the future,the authors of the systematic reviews need to strictly follow the entries of quality evaluation tools such as AMSTAR 2 and PRISMA 2020 in terms of plan registration,research type explanation,retrieval strategy,exclusion list,research site and funding source,bias risk analysis,publication bias evaluation,and public information acquisition,and conduct evidence quality evaluation on the combined results of the systematic reviews/meta-analyses to provide more reliable and rigorous evidence-based basis for clinical practice.

OBJECTIVE:The quality of systematic reviews/meta-analyses directly affects the reliability of clinical decision-making basis.Currently,there is no literature quality research on the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis both domestically and internationally.This article will comprehensively evaluate the methodological quality,reporting quality,and evidence quality of the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis.METHODS:Computer searches were conducted on CNKI,WanFang Data,VIP,CBM,PubMed,Embase,and The Cochrane Library.From the establishment of the database until January 24,2024,all systematic reviews/meta-analyses treated with platelet rich plasma versus hyaluronic acid for knee osteoarthritis were collected.Two evaluators independently conducted literature screening and data extraction,and used the AMSTAR 2,PRISMA 2020,and GRADE systems to evaluate and summarize the methodological,reporting,and evidence quality of the included systematic reviews/meta-analyses.RESULTS:A total of 18 qualified systematic reviews/meta-analyses were included,and the results showed that the efficacy and safety of platelet rich plasma might be better than that of hyaluronic acid.The methodological quality of all 18 studies was extremely low;4 reports had poor quality and relatively serious information defects,while 14 reports had moderate quality and some information defects.Among the 275 outcome measures of 16 systematic reviews/meta-analyses,there were 9 medium quality evidence,90 low-quality evidence,and 176 extremely low-quality evidence,with no high-quality evidence.CONCLUSION:At present,the quality of systematic reviews/meta-analyses literature on the treatment of knee osteoarthritis with platelet rich plasma versus hyaluronic acid is relatively low.In the future,the authors of the systematic reviews need to strictly follow the entries of quality evaluation tools such as AMSTAR 2 and PRISMA 2020 in terms of plan registration,research type explanation,retrieval strategy,exclusion list,research site and funding source,bias risk analysis,publication bias evaluation,and public information acquisition,and conduct evidence quality evaluation on the combined results of the systematic reviews/meta-analyses to provide more reliable and rigorous evidence-based basis for clinical practice.

AIM:To investigate the mechanism by which the Z-DNA-binding protein 1(ZBP1)/receptor-in-teracting protein kinase 1(RIPK1)/mixed lineage kinase domain-like protein(MLKL)pathway modulates the necroptosis of neurons in a mouse model of Alzheimer disease(AD).METHODS:Thirty mice were randomly divided into three groups:normal control(NC)group,APP/PS1 model(MOD)group,and necroptosis inhibitor necrostatin-1(Nec-1)group,each with 10 mice.The learning and memory capacities of mice were assessed using the Morris water maze assays.The pathological morphology of hippocampal tissue was examined based on the HE staining assay.The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in serum samples were measured by ELISA.The phosphory-lation of amyloid precursor protein(APP),Tau protein and the expression levels of proteins related to the ZBP1/RIPK1/MLKL pathway in hippocampal tissue were measured by Western blot.Immunofluorescence analysis was performed to de-tect the positive expression of p-RIPK1,while the mRNA level of ZBP1 was measured by RT-qPCR.RESULTS:Com-pared with NC group,the escape latency of mice in the MOD group was significantly longer(P<0.05),the number of crossing platforms was reduced(P<0.05),and the arrangement of hippocampal neurons was disordered accompanied with nuclear condensation.The concentration of TNF-α in serum was increased,whereas the concentration level of IL-10 was decreased(P<0.05).The expression levels of APP,p-Ttau and ZBP1 proteins in the hippocampal tissue and the ratios of p-RIPK1/RIPK1,p-RIPK3/RIPK3 and p-MLKL/MLKL were significantly upregulated(P<0.05).Similarly,the positive expression level of p-RIPK1 and the mRNA level of ZBP1 in hippocampal tissue were significantly upregulated(P<0.05).Compared with the MOD group,the cognitive function of AD mice,pathological damage of hippocampal tissue,and the levels of TNF-α and IL-10 in serum were reversed in the Nec-1 group(P<0.05).Moreover,the Nec-1 treatment signifi-cantly downregulated the expression levels of the above proteins(P<0.05),and the positive expression of p-RIPK1 and the mRNA level of ZBP1 were significantly decreased(P<0.05).CONCLUSION:The ZBP1/RIPK1/MLKL pathway is involved in the occurrence of neuronal necroptosis and the pathological process of AD mice.Inhibition of this pathway sig-nificantly ameliorates cognitive dysfunction and neuroinflammatory responses in AD mice.

Objective:To investigate relationship between expression of ADGRG5 and clinical prognosis and immune response in pancreatic adenocarcinoma(PAAD).Methods:ADGRG5 expression in PAAD and normal tissues were compared by Wilcoxon rank sum test.Diagnostic value of ADGRG5 was evaluated by ROC curve in PAAD.Kaplan-Meier method and Cox regres-sion analysis were used to evaluate prognostic factors.Gene set enrichment analysis(GSEA)and immune infiltration analysis were applied to annotate biological function of ADGRG5.Results:ADGRG5 expression in PAAD was significantly higher than normal tissue(P=2.8e-32).ADGRG5 had significant diagnostic and prognostic ability for PAAD(AUC=0.866).High ADGRG5 expression predicted a good progress free interval(PFI)(P=0.01),and expression of ADGRG5 was independently associated with PFI(HR:0.656,95%CI:0.433～0.972,P=0.035).ADGRG5 expression was related to regulation of immunomodulatory pathway and function of some types of immune infiltrating cells.Conclusion:Increased ADGRG5 may be a potential biomarker for PAAD diagnosis and prognosis,which affects prognosis of PAAD patients and significantly correlated with immune infiltration.

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 explore the applications and effects of professional training-based peer support on self-management of women with gestational diabetes mellitus.Methods A total of 96 patients diagnosed with gestational diabetes mellitus in a tertiary A-level women's hospital in Nanjing from March to June 2023 were conveniently selected as the research subjects,among which 48 patients with gestational diabetes mellitus diagnosed from May to June 2023 were divided into an experimental group,and 48 patients with gestational diabetes mellitus diagnosed from March to April 2023 were included into a control group.The experimental group received professional training-based peer support based on routine nursing,and the control group received routine nursing.The status of self-management,health literacy,quality of life and blood glucose in 2 groups were compared and analyzed.Results 45 patients in the experimental group and 48 patients in the control group completed the study.After intervention,the Self-Management Scale score of the experimental group was(115.11±9.48),which was higher than(78.46±6.27)of the control group;the score of Health Literacy Scale was(145.38±5.22),higher than(92.19±5.75)of the control group;the Quality of Life Scale score was(79.47±4.11),higher than(60.85±2.80)of the control group;the fasting blood glucose concentration and two-hour postprandial glucose concentration in the experimental group were lower than those in the control group,and the difference between 2 groups was statistically significant(P＜0.001).Conclusion Nursing intervention of the professional training-based peer support can effectively improve the levels of self-management,health literacy and quality of life,as well as reduce concentration of blood glucose.