Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Plasma metabolomics combined experimental verification was employed for investigating of the hypoglycemic effect of Panax notoginseng saponins (PNS) on type 2 diabetes mellitus (T2DM) mice. Forty C57BL/6J mice were randomly divided into control and experimental groups after one week of adaptive feeding. The mice in control group were fed conventionally, and the T2DM model was established in mice of the experimental group by intraperitoneal injection of streptozotocin following twelve weeks of feeding on a high-fat diet (HFD). All experiments were approved by the Ethical Committee Experimental Animal Center of North Sichuan Medical College (NSMC2022023). After the failure cases during modeling were eliminated, the remaining mice were randomly divided into model group (T2DM), low dose [200 mg·kg^-1·d^-1] and high dose [300 mg·kg^-1·d^-1] PNS groups. Mice in normal and model groups were given equal amounts of normal saline by gavage. The mice were administered intragastrically with PNS for 6 weeks, and their body weight, food intake, water intake and fasting blood glucose (FBG) were measured weekly. Oral glucose tolerance test (OGTT) was performed at the 5th week of administration. The changes of liver functions and blood lipids were detected by collecting blood from eyeballs. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were detected in the blood and the activity of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were analyzed in the liver by kit, respectively. Subsequently, the changes in plasma endogenous metabolites from each group were determined based on metabolomics, and the pathway enrichment analysis of differential metabolites was performed using KEGG database. NF-κB signaling pathway, TNF-α and IL-6 in liver were detected by western blot, respectively. The results showed that T2DM mice were successfully constructed. High dose of panax notoginseng saponins (HPNS) can reduce the FBG in T2DM mice while low dose of PNS (LPNS) has no significant effect on FBG. HPNS improves the liver function, reduces the levels of blood lipids, TNF-α and IL-6, and increases the activity of GSH-Px, CAT and SOD in liver of T2DM mice. Metabolomics results showed that 45 metabolites were significantly changed in the plasma of model group compared with control, and 20 metabolites were significantly changed after HPNS treatment. Pathway enrichment indicated that arachidonic acid metabolism, linoleic acid metabolism, glutathione metabolism and carnitine synthesis were changed in the blood of T2DM mice, and HPNS improved the abnormal metabolism of arachidonic acid and linoleic acid in T2DM mice. Western blot showed that HPNS could inhibit the NF-κB pathway and reduce the expression of TNF-α and IL-6 in the liver of T2DM mice, suggesting that PNS may exert the antidiabetic effect by inhibiting NF-κB pathway, regulating arachidonic acid and linoleic acid metabolism to reduce inflammatory factors and oxidative stress, improve liver function in T2DM mice.

Here,5 important pathogens carried by ticks in Maanshan City,Anhui Province,China were identified.In to-tal,642 ticks were collected from 13 villages around Maanshan City and identified by morphological and mitochondrial COI genes.The 16S rRNA gene of Francisella tularensis,ssrA gene of Bartonella,16S rRNA,ompA and ompB genes of Rickett-sia,16S rRNA and gltA genes of Anaplasma,and groEL and rpoB genes of Coxiella were sequenced.Reference sequences were retrieved from a public database.Phylogenetic trees were constructed with MEG A1 1.0 software.In total,36 Rickettsiae isolates were detected in 640 Haemaphysalis longicornis ticks,which included 20 isolates of Rickettsia heilongjian-gensis,16 of Candidatus Rickettsia jingxinensis,2 of Ana-plasma bovis,and 186 of Coxiella-like endosymbiont.R.hei-longjiangensis HY2 detected in this study and Anhui B8 strain,Ca.R.jingxinensis QL3 and those from Shanxi Prov-ince and Jiangsu Province,A.bovis JX4 and those from Shanxi Province were clustered on the same branch.Overall,17 ticks had combined infections and none of the 5 bacteria were detected in two Amblyomma testudinarium ticks.This is the first report of Ca.R.jingxinensis detected in H.longicornis ticks from Anhui Province.It is recommended that the two types of Rickettsia that cause spotted fever and A.bovis should be reported to local health authorities to initiate appropriate prevention and control measures.

To investigate the recent prevalence and molecular epidemiological characteristics of por-cine diarrhea viruses in Sichuan Province,this study used fluorescence quantitative PCR to detect porcine diarrhea samples from multiple regions in Sichuan Province from 2021 to 2023.RT-PCR was used to identify the genotypes of PEDV,PoRVA,PDCoV,and PTV,and their genetic variabil-ity,evolutionary characteristics,and recombination events were analyzed.The results showed that PEDV,PoRVA,PDCoV,and PTV were still prevalent in Sichuan region,with overall positive rates of 14.2％(40/281),13.2％(37/281),15.6％(44/281),and 12.5％(35/281),respectively.PEDV mixed infection with other pathogens was the most common.This study obtained a total of six strains of G2b PEDV,three strains of G3 PDCoV,three strains of G9P[13]PoRVA,one strain of G3P[13]PoRVA,three strains of Type 5 PTV,and one strain of Type 9 PTV.Compared to the seven vaccine strains including CV777,DR13,KPEDV-9,Chinju99,KNU-0801,AJ1102,and LW/L,the 6 PEDV strains showed multiple amino acid mutation sites in the COE region and S1D epitope region.Among them,the strains PSCLZ01 and PSCMY04 formed a separate branch in the phylogenetic tree.The three PDCoV strains have a closer genetic evolution distance to the previ-ously prevalent strains in Sichuan,but they also have 6-48 amino acid mutations compared to them.The four PoRVA strains have 104-108 amino acid variations in the VP4 gene compared to the early vaccine strain LLR,and they have 25 common amino acid variations in the VP7 gene.From the phylogenetic tree,the VP7 gene of RSCMY01/G3P[13]belongs to the same branch as the Heilongjiang strain LNCY,but its VP4 gene clusters with the Sichuan strain SCYA-C7,indica-ting that this PoRVA strain may have undergone genetic reassortment during inter-provincial transmission between different genotypes.It is worth noting that in the detected samples of PTV-5 and PTV-9,other diarrheal viruses tested negative,indicating that these two genotypes of PTV may be important pathogens causing porcine diarrhea.Additionally,the S gene of PEDV PSCLZ01 strain and PDCoV PCSCMY02 strain have undergone recombination events,and their parental strains come from different regions,both domestic and international.These findings reveal the main types of porcine diarrheal viruses,as well as their genetic diversity and variations in Sichuan Province in recent years.This study enriches the molecular epidemiological data of porcine diarrhe-al pathogens in the region and provides an important theoretical basis for the prevention,control,and purification of porcine diarrhea in the local area.

Objective:To analyze the effect of peripheral blood hematopoietic stem cells(PBSC)collection from unrelated donors and its influencing factors.Methods:A retrospective analysis was conducted on the mobilization and collection of PBSC from 113 unrelated donors at Yueyang Central Hospital from January 2021 to December 2023.Results:113 donors were successfully mobilized.The average count of PBSC mononuclear cells(MNC)and CD34+cells were(12.40±7.41)x 108/kg and(10.64±8.07)x 106/kg,respectively.Univariate analysis showed that the PBSC CD34+cells ratio of male donors was significantly higher than that in female donors(P=0.015).The peripheral blood(PB)white blood cell(WBC)count before collection was positively correlated with the PBSC nucleated cells count(r=0.388),and the donor's body weight,the PB CD34+cell ratio before collection were positively correlated with the PBSC CD34+cell ratio(r=0.259,r=0.780).The daily dose of rhG-CSF was negatively correlated with the PBSC CD34+cell ratio(r=-0.285).Both rhG-CSF agents achieved successful mobilization.Multivariate analysis showed that PB WBC count before collection was a factor affecting the count of PBSC nucleated cells(P＜0.001),while the PB CD34+cell ratio before collection was a factor affecting the PBSC CD34+cell ratio(P＜0.001).Conclusion:The mobilization and collection of PBSC from unrelated donors are good,and the PB WBC count and CD34+cell ratio before collection are reliable indicators for predicting the collection effect.

Objective To investigate the effect of hedysarum polysacchcaide(HPS)on nuclear transcription factor-κB(NF-κB)/IκB kinase β(IKKβ)signaling pathway in cardiac tissue of db/db mice with diabetic cardiomyopathy(DCM).Methods Altogether 60 7-week-old male db/db mice were randomly divided into model group,control group and experimental-H,-M,-L groups,with 12 mice in each group.In addition,12 db/m mice of the same week age were selected as the normal group.Normal group and model group were given 0.9％NaCl by intragastric administration.Experimental-L,-M,-H groups were given 50,100 and 200 mg·kg-1 HPS suspension by intragastriction,respectively.Control group was given 4 mg·kg-1 rosiglitazone suspension by intragastric administration.Six groups of rats were given the drug once a day for 8 weeks.The contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in myocardial tissue were detected by enzyme-linked immunosorbent assay.The mRNA expression levels of NF-κB and IKKβ in myocardial tissue were detected by real-time fluorescence quantitative polymerase chain reaction.The correlation between the expression of NF-κB protein and the content of TNF-α and IL-6 was analyzed.Results The contents of IL-6 in myocardial tissue of normal,model,control and experimental-H groups were(1.24±0.54),(7.72±0.24),(2.90±0.50)and(2.78±0.56)ng·L-1;the contents of TNF-α were(1.96±0.52),(5.25±0.72),(2.84±0.86)and(2.82±0.58)ng·L-1;the mRNA expression levels of NF-κB were I.00±0.00,3.35±0.81,2.05±0.44 and 1.67±0.22;the mRNA expression levels of IKKβ were 1.00±0.00,2.92±0.07,1.51±0.07 and 1.41±0.08,respectively.Compared with the model group,the above indexes of the control and experimental-H groups were statistically significant(P＜0.01,P＜0.05).The expression of NF-κB protein was positively correlated with the content of IL-6 and TNF-α,and the correlation coefficients were 0.866 and 0.740(all P＜0.01).Conclusion HPS can alleviate the damage of myocardial pathology in mice,reduce myocardial collagen deposition and fibrosis,its mechanism may be through regulating the expression of NF-κB/IKKβ signaling pathway to play a role in inhibiting the inflammatory reaction.

AIM: To analyze the current status, hotspots and trends of studies on the treatments of diabetic retinopathy.METHODS: Relevant literatures on diabetic retinopathy in Chinese National Knowledge Infrastructure(CNKI)and Web of Science core collection database were retrieved from creation to June 15, 2023, and CiteSpace 6.2.R2 and VOSviewer were used to conduct visualized analysis with the country/issuing institution, research author and keywords.RESULTS: A total of 5 919 Chinese literatures and 11 475 English literatures were included. The top three countries with global publications are the United States, China and the United Kingdom, respectively. The top three institutions for issuing articles at abroad are Harvard Medical School, Harvard University and Johns Hopkins University, while the top three institutions for issuing articles in China are the Eye Hospital of China Academy of Chinese Medical Science, Hunan University of Chinese Medicine, and Zhongshan Ophthalmic Center of Sun Yat-sen University. The research results of high-frequency keywords in both Chinese and English show that the laser photocoagulation, vitrectomy, traditional Chinese medicine therapy, vascular endothelial growth factor and ranibizumab are research hotspots.CONCLUSIONS: In recent years, the research hotspots of diabetic retinopathy mainly focus on surgery, vascular protective agents, traditional Chinese medicine therapy, anti-vascular endothelial growth factor, etc., and the research trend mainly focuses on anti-vascular endothelial growth factor drugs.

OBJECTIVE: The study explores the effects of electroacupuncture (EA) at the governing vessel (GV) on proteomic changes in the hippocampus of rats with cognitive impairment. METHODS: Healthy male rats were randomly divided into 3 groups: sham, model and EA. Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups. Rats in the EA group were treated with EA at Shenting (GV24) and Baihui (GV20) for 7 d. Neurological deficit was scored using the Longa scale, the learning and memory ability was detected using the Morris water maze (MWM) test, and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation (iTRAQ). The Western blot (WB) analysis was used to detect the proteins and validate the results of iTRAQ. RESULTS: Compared with the model group, the neurological deficit score was significantly reduced, and the escape latency in the MWM test was significantly shortened, while the number of platform crossings increased in the EA group. A total of 2872 proteins were identified by iTRAQ. Differentially expressed proteins (DEPs) were identified between different groups: 92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group, while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group. Most of the DEPs were involved in oxidative phosphorylation, glycolipid metabolism and synaptic transmission. Furthermore, we also verified 4 DEPs using WB technology. Although the WB results were not exactly the same as the iTRAQ results, the expression trends of the DEPs were consistent. The upregulation of heat-shock protein β1 (Hspb1) was the highest in the EA group compared to the model group. CONCLUSION EA can effect proteomic changes in the hippocampus of rats with cognitive impairment. Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Proteomics ; Cognitive Dysfunction/therapy* ; Hippocampus