ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

Cognitive dysfunction has emerged as a significant health challenge in aging societies, among which Alzheimer's disease(AD)and related dementia have become one of the leading causes of death among the elderly.These diseases are characterized by insidious onset and progressive deterioration, often reaching irreversible advanced stages at initial diagnosis, making early detection and prevention imperative.As the frontline of public health management, communities bear the responsibility for screening and managing major chronic diseases.However, community-based cognitive screening in China still remains in its nascent stages, lacking systematic management and prevention guidelines.This guideline, established under a multidisciplinary collaborative framework and adhering to evidence-based medicine principles, systematically reviews and analyzes the latest clinical evidence worldwide.Utilizing the GRADE(Grading of Recommendations Assessment, Development and Evaluation)system to evaluate evidence quality and following the RIGHT(Reporting Items for Practice Guidelines in Healthcare)statement for standardized guideline development, it ultimately presents 17 recommendations through three rounds of Delphi expert consultations.The core recommendations of this guideline is mainly to use digital cognitive scales to conduct large-scale community cognitive screening for the active individuals aged 60 or above.Stratification and staging should be performed based on screening results, and digital cognitive files with quantified risk factor grading should be established, followed by the formulation of personalized artificial intelligence(AI)prevention and control programs.This guide is the first in China and internationally to propose a quantitative grading system for low, medium, and high-risk factors associated with AD and vascular dementia(VD). It aims to provide standardized principles and practical pathways to advance China's ambitious goals: achieving ≥80% public awareness of dementia prevention knowledge, ≥80% cognitive screening rate among the elderly, ≥80% intervention guidance rate for at-risk populations, and ≥50% medical consultation rate for suspected cognitive impairment cases.

Objective To investigate the clinical effect of dapagliflozin combined with sacubitril-valsar-tan in the treatment of non-reduced ejection fraction type heart failure(non-HFrEF).Methods A total of 120 patients with non-HFrEF diagnosed and treated in this hospital from January to December 2022 were selected as the study subjects and divided into the observation group and control group by the random number method,60 cases in each group.The both groups were treated with conventional treatments such as β-receptor blockers and diuretics,the patients in the control group were treated with sacubitril-valsartan(Noxinto),and the pa-tients in the observation group were treated with dapagliflozin on the basis of the control group for 6 months.The clinical efficacy,serum N-terminal B-type natriuretic peptide precursor(NT-proBNP),hypersensitivity-C-reactive protein(hs-CRP),serum creatinine(SCr),serum potassium,cardiac color Doppler ultrasound param-eters,6 min walk test(6MWT)distance before treatment and in 6 months after treatment,and the occurrence of major adverse cardiovascular events(MACE)during treatment were compared between the two groups.Re-sults After 6 months of treatment,the total effective rate in the observation group was 93.3%,which was higher than 80%in the control group,and the difference was statistically significant(P=0.032).After 6 months of treatment,the levels of NT-proBNP and hs-CRP in the two groups were significantly decreased compared with those before treatment,moreover the observation group was lower than the control group,and the difference was statistically significant(P<0.05).After 6 months of treatment,LVEF and 6MWT dis-tance in the two groups were increased compared with those before treatment,LVEDV and LVESV were de-creased compared with those before treatment,moreover the change amplitude of the above indexes in the ob-servation group were greater than those in the control group,and the differences were statistically significant(P<0.05).The incidence rate of MACE in the observation group was lower than that in the control group(16.7%vs.5.0%),and the difference was statistically significant(P<0.05).Conclusion Dapagliflozin combined with sacubitril-valsartan in the treatment of non-HFrEF could significantly reduce the levels of NT-proBNP and hs-CRP,improve the cardiac function,increase the exercise tolerance,decrease the incidence rate of MACE and improve the prognosis.

Cognitive dysfunction has emerged as a significant health challenge in aging societies, among which Alzheimer's disease(AD)and related dementia have become one of the leading causes of death among the elderly.These diseases are characterized by insidious onset and progressive deterioration, often reaching irreversible advanced stages at initial diagnosis, making early detection and prevention imperative.As the frontline of public health management, communities bear the responsibility for screening and managing major chronic diseases.However, community-based cognitive screening in China still remains in its nascent stages, lacking systematic management and prevention guidelines.This guideline, established under a multidisciplinary collaborative framework and adhering to evidence-based medicine principles, systematically reviews and analyzes the latest clinical evidence worldwide.Utilizing the GRADE(Grading of Recommendations Assessment, Development and Evaluation)system to evaluate evidence quality and following the RIGHT(Reporting Items for Practice Guidelines in Healthcare)statement for standardized guideline development, it ultimately presents 17 recommendations through three rounds of Delphi expert consultations.The core recommendations of this guideline is mainly to use digital cognitive scales to conduct large-scale community cognitive screening for the active individuals aged 60 or above.Stratification and staging should be performed based on screening results, and digital cognitive files with quantified risk factor grading should be established, followed by the formulation of personalized artificial intelligence(AI)prevention and control programs.This guide is the first in China and internationally to propose a quantitative grading system for low, medium, and high-risk factors associated with AD and vascular dementia(VD). It aims to provide standardized principles and practical pathways to advance China's ambitious goals: achieving ≥80% public awareness of dementia prevention knowledge, ≥80% cognitive screening rate among the elderly, ≥80% intervention guidance rate for at-risk populations, and ≥50% medical consultation rate for suspected cognitive impairment cases.

Objective:To investigate the efficacy and safety of tenofovir amibufenamide in patients over 65 years old with chronic hepatitis B and liver cirrhosis.Methods:We recruited 45 patients in Linyi People's Hospital with chronic hepatitis B and liver cirrhosis who were treated with TMF antiviral therapy for 48 weeks, compared the virologic response rate and HBV DNA decrease level at 12, 24 and 48 weeks, and the changes in hepatitis B surface antigen, alanine aminotransferase, glomerular filtration rate, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum phosphorus and blood lipids, and the changes in ALT normalization rate at 48 weeks. P<0.05 was statistically significant. Results:The age of the enrolled patients was 69.0 (67.0, 72.5) years. At 12, 24, and 48 weeks of treatment, the complete virological response rates were 32.4% (12/37), 70.0% (28/40), and 84.6% (33/39) respectively, and the level of HBV DNA decreased from baseline ( P＜0.05). After 48 weeks of treatment, the level of HBsAg decreased ( P<0.05), and there was no negative HBsAg conversion and seroconversion. After 48 weeks of treatment, the level of ALT decreased ( P<0.05). At 48 weeks of treatment, the rates of ALT reverted to normality were 88.9% (16/18) and 70.4% (19/27), respectively. There was no significant difference in the levels of glomerular filtration rate, creatinine, phosphorus, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol estimated at baseline before and after treatment ( P＞0.05), and no serious adverse events were observed. Conclusions:For patients over 65 years old with chronic hepatitis B and liver cirrhosis, TMF can significantly inhibit HBV DNA replication, and the ALT normalization rate is high and well tolerated.

Objective:To observe the stimulation of cigarette smoke extract(CSE)at different times influencing the alveolar macrophage efferocytosis and phagocytosis function,and to explore the effect of CSE on inflammatory response in lung diseases and molecular mechanism.Methods:Rat alveolar macrophages NR8383 were intervened with 10%CSE for 6 h,12 h,24 h,48 h,divided into 6 h blank control group,6 h-10%CSE group,12 h blank control group,12 h-10%CSE group,24 h blank control group,24 h-10%CSE group,48 h blank control group,48 h-10%CSE group.10%CSE intervention 12 h in combination with PPAR inhibitor/ago-nist,divided into PPAR inhibitor group and PPAR agonist group.Alamar Blue colorimetry was used to detect the proliferation and toxi-city of PPAR agonist on NR8383 cells.Flow cytometry was used to detect the efferocytosis and phagocytosis of NR8383 cells,and M1 and M2 polarizations.The contents of TNF-α,TGF-β1 and MFG-E8 were detected by enzyme-linked immunosorbent assay.Western blot was used to detect the expressions of PPARγ and CD36 protein.mRNA expressions of PPARγ and CD36 were detected by qPCR.Results:After 6 hours of 10%CSE stimulation,the phagocytosis and efferocytosis of NR8383 cells were increased,the expression of PPARγ was down-regulated,the expression of CD36 mRNA was increased,and the expressions of TNF-α,TGF-β1 and MFG-E8 were increased,but there was no obvious polarization direction.After 12 hours CSE stimulation,the efferocytosis and phagocytosis functione of NR8383 cells were significantly decreased,the expressions of PPARγ and CD36 were significantly down-regulated,the expression of TNF-α was increased,the expressions of TGF-β1 and MFG-E8 were decreased,and the cells were polarized to M1-type macrophages.After 24 hours of intervention,the efferocytosis rate of NR8383 cells were decreased,but the phagocytosis function of E.coli was increased,the expression of PPARγ was down-regulated,the expressions of CD36 protein was decreased,the expression of TNF-α was decreased,while there was no statistical difference,the expressions of TGF-β1 and MFG-E8 were still decreased,and there was obvious tendency of M1 polarization.After 48 h,the efferocytosis rate of NR8383 cells were still decreased,but the phagocy-tosis ability was significantly increased,the expression of PPARγ was significantly decreased,the expression of CD36 was significantly increased,the expression of TNF-α was decreased,the expressions of TGF-β1 and MFG-E8 were increased,and the polarization of macrophages towards M1 and M2 were increased.After 12 h stimulation with 10%CSE combined with PPAR agonist and inhibitor,it was found that PPAR agonist enhanced the efferocytosis and phagocytosis of NR8383 cells,up-regulated the expression of PPARγ and CD36,inhibited the expression of inflammatory factor TNF-α,and promoted the expressions of anti-inflammatory factor TGF-β1 and cytokinesis cofactor MFG-E8.Conclusion:With the stimulation time of CSE,alveolar macrophages gradually change from the activated state of early inflammatory response to chronic inflammatory response,which leads to alveolar macrophage efferocytosis and phagocyto-sis dysfunction,and the mechanism is related to the inhibition of PPARγ pathway.

Objective To explore the clinical characteristics and prognostic outcomes of patients with acute myocardial infarction complicated by Coronavirus Disease 2019 (COVID-19). Methods A retrospective study was conducted in 76 patients with acute myocardial infarction. Based on the presence of COVID-19, they were divided into the COVID-19 group (n=42) and the control group (n=34). General clinical conditions, laboratory examination indicators, interventional treatment characteristics, incidence of complications during hospitalization and prognosis were compared between the two groups. Independent influencing factors for coronary thrombotic lesions in acute myocardial infarction patients were analyzed. Results The diastolic blood pressure, left ventricular ejection fraction and lymphocyte count were significantly lower, while lipoprotein a, C-reactive protein, serum ferritin, fibrinogen, and D-dimer were significantly higher in the COVID-19 group than those in the control group (P < 0.05). The proportions of coronary thrombotic lesions, baseline TIMI flow of grade 0 to 1, thrombus burden of grade 4 to 5, use of GP Ⅱb/Ⅲa inhibitors and thrombus aspiration in the COVID-19 group were significantly higher than those in the control group (P < 0.05). Multivariate Logistic regression analysis revealed that COVID-19 and increased D-dimer were independent risk factors for coronary thrombotic lesions in acute myocardial infarction patients. The average length of hospital stay was significantly longer in the COVID-19 group than that in the control group (P < 0.05). A 6-month follow-up showed that the incidence of major adverse cardiac events (MACEs) was significantly higher in the COVID-19 group than that in the control group (P=0.014). Conclusion Patients with acute myocardial infarction complicated by COVID-19 exhibit a higher coronary thrombus load and have a poor prognosis.

Damp-heat syndrome is one of the common syndromes of various clinical diseases.Current studies have shown that intestinal flora is closely related to damp-heat syndrome,but the specific molecular biological mechanism related to intestinal flora and damp-heat syndrome is not yet clear.In this paper,the molecular biological mechanism of damp-heat syndrome is discussed from the perspective of intestinal flora related signaling pathways,so as to provide ideas for the essence of damp-heat syndrome and clinical diagnosis and treatment.

Objective To explore the molecular mechanism of CAFs promoting energy metabolism of EC9706 cells by collecting conditioned media of cancer-associated fibroblasts(CAFs).Methods Cell viability was detected by MTT,and the CAFs conditioned medium(CAFM)most suitable for indirect co-culture was selected with EC9706 cultured in DMEM high glucose medium as control.The contents of lactic acid and glucose in the supernatant of EC9706 cells were determined by colorimetry.The energy metabolism of EC9706 cells in DMEM and CAFM was detected by seahorse system energy metabolism analysis system.Real time quantitative polymerase chain reaction(RT-qPCR)and western blotting were used to detect the mRNA and protein expression of energy metabolism related molecules.Results Compared with normal esophageal fibroblast conditioned medium(NFM),CAFs conditioned medium of 50%-60%and 70%-80%cell fusion degree promoted the proliferation of EC9706 cells(P<0.01),and CAFM groups with 70%-80%cell fusion degree promoted the proliferation of EC9706 cells compared with the control group.When the CAFM content was 60%,the proliferation of EC9706 cells was significantly increased(P<0.01).Compared with DMEM,CAFM could increase glucose uptake,superlactate content,basal respiratory value,basal glycolysis,compensatory glycolysis(P<0.05),non-mitochondrial oxygen consumption,maximum respiratory value,oxygen consumption for ATP synthesis,and reserve respiratory capacity(P<0.01)of EC9706 cells.RT-qPCR results showed that CAFM could also up-regulate the Hypoxic-inducible factor-1α(HIF-1α),Hexokinase-2(HK2)and Monocarboxylic acid transporter 1(MCT1)of EC9706 cells(P<0.05).Expression of Glucose transporter 1(GLUT1),Pyruvate kinase 2(PKM2)mRNA(P<0.01).Western blot showed that compared with DMEM,the protein expression of HK2,PKM2,MCT1 and GLUT1 was significantly increased(P<0.01).Conclusion CAFM can promote energy metabolism of EC9706 cells by promoting mRNA and protein expressions of HK2,PKM2,HK2,GLUT1,MCT1 and MCT4 under in vitro culture conditions.