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 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 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 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.

ObjectiveThis study aimed to investigate the HIV genotypic subtypes and molecular transmission clusters among men who have sex with men （MSM） with newly reported HIV infections in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunnan Province， China， between 2010 and 2019. The study aimed to identify potential high-risk transmitters and provide reference data for screening， management， and intervention of infection sources. MethodsPlasma samples from newly reported HIV-positive MSM individuals in Dehong Prefecture between 2010 and 2019 were collected. The viral pol gene fragments were amplified， sequenced， and genotyped. Genetic distances （GD） between pairwise sequences were analyzed and calculated. MEGA 7.0 and Gephi were used for phylogenetic and molecular transmission network analysis. ResultsA total of 159 newly reported HIV infections among MSM were included in the study， with successful genotyping of 100 cases. Nine HIV-1 subtypes were identified， with the most prevalent being CRF01_AE subtype （52%）， followed by CRF07_BC subtype （31%）， CRF55_01B subtype （10%）， and others （7%）. Cluster analysis revealed a total network access rate of 67%， forming three transmission clusters. CRF01_AE subtype formed two transmission clusters with 38 and 3 infected individuals， while CRF07_BC subtypes formed one transmission cluster with 26 infected individuals. The transmission network within the CRF01_AE clusters exhibited a more complex relationship. Significant differences in educational level were observed between the two main transmission clusters. ConclusionThe predominant HIV subtypes among newly reported MSM cases in Dehong Prefecture between 2010 and 2019 were CRF01_AE and CRF07_BC. Significant cultural differences are observed between the main transmission clusters. Continued monitoring of genotypic subtypes and targeted interventions within transmission clusters are warranted.

ObjectiveTo explore the mechanism of Qigesan （QGS） in intervening in the migration and invasion of esophageal carcinoma TE-1 cells. MethodMicroarray technology was used to screen differentially expressed genes （DEGs） in the normal group and the QGS group， and the ontological functions and signaling pathways of DEGs were analyzed. The thiazolyl tetrazolium （MTT） assay was used to detect the effect of QGS on the viability of TE-1 cells. In the subsequent experiments for verification， a blank group， a transforming growth factor-β₁ （TGF-β₁） group， a TGF-β₁ + QGS group， and a TGF-β₁ + SB431542 group were set up. The cell morphology in each experimental group was observed by microscopy. The migration and invasion abilities of cells were detected by wound healing assay， and the mRNA expression levels of E-Cadherin， vimentin， Smad2， and Smad7 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of E-Cadherin， vimentin， p-Smad2/3， Smad2/3， and Smad7 was detected by Western blot. ResultThere were 1 487 DEGs between the QGS group and the blank group， including 1 080 down-regulated ones （accounting for 72.63%） and 407 up-regulated ones. The down-regulated genes were mainly involved in biological processes such as cytoskeletal protein binding， ATP binding， adenylate nucleotide binding， and adenylate ribonucleotide binding， and the involved Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways included TGF-β signaling pathway， cell cycle， extracellular matrix-receptor interaction protein， tumor pathways， and oocyte meiosis. The up-regulated genes were mainly involved in RNA binding， DNA binding， transcriptional regulator activity， transcriptional activator activity， and nucleotide binding， and the KEGG pathways involved mainly included mitogen-activated protein kinase （MAPK） signaling pathway， bladder cancer， renal cell carcinoma， cancer pathways， and p53 signaling pathway. Compared with the blank group， the inhibition rate of cell viability of TE-1 cells increased after QGS （20， 30， 40， 60， 80 mg·L^-1） intervention for 12， 24， 36， 48， 60 h （P<0.05）， and the inhibition rate was time- and dose-dependent. Compared with the blank group， the TGF-β₁ group showed lengthened cells with fibroblast phenotype. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group showed shortened cells with normal morphology and epithelial phenotype. The cell morphology in the TGF-β₁ + SB431542 group was similar to that of the TGF-β₁ + QGS group. Compared with the blank group， the TGF-β₁ group showed potentiated ability of cell migration and invasion （P<0.05）. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group and the TGF-β₁ + SB431542 group showed inhibited and weakened migration and invasion abilities of cells （P<0.05）. However， there was no significant difference in migration and invasion abilities between the TGF-β₁ + QGS group and the TGF-β₁ + SB431542 group. The mRNA expression levels of vimentin and Smad2 in the TGF-β₁ group were higher （P<0.05）， and the mRNA expression levels of E-Cadherin and Smad7 were lower （P<0.05） than those in the blank group. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group and the TGF-β₁+ SB431542 group exhibited decreased expression levels of vimentin and Smad2 mRNA （P<0.05）， and elevated expression levels of E-Cadherin and Smad7 mRNA （P<0.05）. Compared with the blank group， the TGF-β₁ group showed up-regulated protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and reduced protein expression levels of E-Cadherin and Smad7 （P<0.05）. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group and the TGF-β₁ + SB431542 group displayed decreased protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and increased protein expression levels of E-Cadherin and Smad7 （P<0.05）. ConclusionThe ethyl acetate extract of QGS inhibits the epithelial-mesenchymal transition （EMT） of TE-1 cells through the TGF-β₁ pathway to reduce the migration and invasion of TE-1 cells.