BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.

Objective To investigate the therapeutic effects and mechanisms of Hibiseu Manihot L.fructus on type 2 diabetes mellitus(T2DM)mice.Methods T2DM mice were randomly divided into normal group,model group,positive drug group,Hibiseu Manihot L.fructus total extract group,water-solube part group,and Hibiseu Manihot L.fructus ethyl acetate fraction group,with 10 mice in each group.After 4 weeks of treatment,anti-diabetic effects were evaluated by monitoring body mass,fasting blood glucose(FBG),oral glucose tolerance test(OGTT),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),and area under the blood glucose curve(AUC).Liver tissue status was assessed through liver index and hematoxylin-eosin(HE)staining.Results Compared with the model group,the water-solube part and total extract group showed significant improvements in mental status,food intake,body mass,excretion,and the FBG elevation was effectively suppressed,OGTT,FINS,AUC,HOMA-IR and liver index were significantly decreased(P＜0.05 or P＜0.01),the histopathological analysis revealed improved liver tissue morphology.Regarding channel protein expression,compared with the model group,the water-solube part group exhibited significantly upregulated phosphorylation levels of protein kinase B(AKT)and phosphatidylinositol 3-kinase(PI3K)in mouse liver tissue(P＜0.05),furthermore,the positive drug group,total extract group,and water-solube part group all demonstrated markedly increased phosphorylation of adenosine monophosphate-activated protein kinase(AMPK)in hepatic tissues(P＜0.05).Conclusion The water-solube part of fructus of Hibiseu Manihot L fructus.effectively alleviates T2DM symptoms(polyphagia,polydipsia,polyuria,weight loss)and glucose metabolism disorders,with hepatoprotective effects potentially mediated through PI3K/AKT pathway activation and enhanced p-AMPK expression.

Objective To explore the relationship between education level and the risk of all-cause mortality in the middle-aged and elderly (≥45 years old) population in China. Methods Using data from five surveys from 2011-2020, years of education, age, gender, marital status, type of household, alcohol consumption status, smoking status, physical activity, limited ability to perform activities of daily living (ADLs), chronic disease status, and body mass index were collected. According to the survival status，the study participants were divided into a survival group (n=8625) and an all-cause mortality group (n=1735). Cox proportional risk regression model was used to analyze the relationship between years of education and the risk of all-cause mortality in middle-aged and elderly people with stratified analysis. Results The survey was conducted on 10360 research subjects, including 4 983 males and 5 377 females, with an age M(Q_R) of 59(8) years old. A total of 88 187 person years (average 8.512 person years) were followed up, and a total of 1735 deaths were reported over 9 years. The all-cause mortality rate was 19.674 ‰, with an education period M(Q_R) of 5(8) years and a survival time M(Q_R) of 9 (0) years. After adjusting for confounding factors, for every 1 year increase in education, the risk of all-cause mortality decreased by 2.60% [HR=0.974, 95% CI (0.960-0.988)]. The stratified analysis results showed that in the population aged 45-59, for every 1 year increase in education, the risk of all-cause mortality decreased by 1.00% [HR=0.990, 95% CI (0.959,1.021)]; In the population aged 60-74 and over 75, for every 1 year increase in education, the risk of all-cause mortality decreased by 2.70% [HR=0.973, 95% CI (0.948, 0.999)] and 3.50% [HR=0.965, 95% CI (0.929, 1.003)], respectively. Conclusion Improving the education level of middle-aged and elderly people (≥ 45 years old) in China can reduce the risk of all-cause mortality, and elderly education should be vigorously promoted.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

This study was aimed at exploring the epidemic characteristics and spatio-temporal evolution patterns of severe fever with thrombocytopenia syndrome(SFTS)in Henan Province from 2011 to 2022,to provide a reference for prevention and control ef-forts.Data on SFTS in Henan Province from 2011 to 2022 were collected from the Information Management System for Infectious Dis-ease Reporting,and epidemiological characteristics and spatio-temporal evolution patterns were investigated through spatial autocorre-lation analysis,standard deviation ellipse analysis,and spatial-centered transfer curves,on a district-county basis.From 2011 to 2022,a total of 5 471 SFTS cases associated with 81 deaths were reported in Henan Province.The incidence rate showed an increasing trend(χ2trend=23.24,P<0.001),and the average annual incidence was 0.4 677/100 000.The case-fatality rate showed a decreasing trend from 2011 to 2019(χ2trend=8.86,P=0.003),but an increasing trend from 2020 to 2022(χ2trend=12.93,P<0.001).The average an-nual case-fatality rate was 1.48%.The peak incidence period was from May to July;this period accounted for 58.75%of the total cases.Females(59.39%),individuals 60-80 years old(55.40%),and farmers(96.64%)were the high prevalence groups.The disease was distributed primarily in Xinyang City,and Shangcheng County had the highest incidence rate(27.411 8/100 000).Spatial aggregation was observed in the southeastern region(Moran's I>0,P<0.001),and the disease centers were all located in Guangshan County,Xin-yang City,and showed southeast-northwest-southeast-northwest-southeast-northeast-southwest movement during the 12-year pe-riod.In conclusion,from 2011 to 2022,SFTS in Henan Province had a high incidence in May to July,and females,older people,and farmers were the high-risk groups.Spatial aggregation was observed in the southeastern region,along with spread to surrounding areas.Xinyang City is therefore a key area for the prevention and control of SFTS.

Objective To explore the therapeutic effect and potential mechanism of CA330 and OXIRIS adsorbent columns in septic shock.Methods Patients who met the diagnostic criteria for septic shock and admitted to the De-partment of Critical Care Medicine of Shenzhen Third People's Hospital from February 2022 to June 2024 were se-lected.They were randomly divided into an OXIRIS group and a CA330 group according to the random number table method.The CA330 group received hemoperfusion combined with hemodiafiltration using CA330 adsorbent co-lumn,while the OXIRIS group was treated with OXIRIS adsorbent column.Relevant markers of the two groups of patients before and after treatment were collected and compared,including inflammatory markers,bilirubin(total bilirubin[TBil],direct bilirubin[DBil]),coagulation functions(prothrombin time[PT],activated partial throm-boplastin time[APTT],etc),endotoxin(ETX),organ function scores(acute physiology and chronic health score Ⅱ[APACHE Ⅱ],sequential organ failure assessment[SOFA],etc).Molecular biology techniques were adopted to detect changes in inflammation-related gene expression(nuclear factor kappa B[NF-κB],toll-like receptor 4[TLR4],myeloid differentiation factor 88[MyD88]),and oxidative stress factors(glutathione peroxidase[GSH-Px],superoxide dismutase[SOD])in the blood of patients before and after treatment.The safety and effectiveness of two types of adsorbent columns during the treatment process was evaluated.Results A total of 92 patients were included and randomly divided into the OXIRIS group and the CA330 group,with 46 cases in each group.After treatment,the levels of TBil,DBil,and ETX in two groups of patients all showed significant decreases compared with before treatment(all P＜0.01),the levels of TBil,DBil,and ETX in patients in the OXIRIS group after treat-ment were all lower than those in the CA330 group during the same period(all P＜0.05);PT and APTT in both groups shortened significantly compared with before treatment(both P＜0.01),PT and APTT in the OXIRIS group after treatment were both shorter than those in the CA330 group during the same period(both P＜0.05);The APACHE Ⅱ score and SOFA score in patients in the OXIRIS group after treatment were both lower than those in the CA330 group during the same period(both P＜0.05);The levels of serum high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-5,and IL-8 in patients in both groups showed significant decreases compared with before treatment(all P＜0.05),and the levels of these serum markers in the CA330 group after treatment were all lower than those in the OXIRIS group during the same period(all P＜0.05).The gene expression levels of NF-κB,TLR4,and MyD88 in patients in the CA330 group after treatment were all lower than those in the OXIRIS group during the same period(all P＜0.05);The levels of GSH-Px and SOD in pa-tients in the OXIRIS group after treatment were both higher than those in the CA330 group(both P＜0.01).No serious adverse event occurred in patients in the CA330 group and the OXIRIS group during the treatment process.Conclusion OXIRIS may be better in clearing bilirubin and endotoxin,improving coagulation function,protecting organ function,and regulating oxidative stress response in patients,while CA330 may be more prominent in clearing inflammatory markers and regulating inflammation-related gene expression in patients.

Diabetic retinopathy(DR)is a kind of microvascular disease caused by the long-term influence of diabetes mellitus(DM),and it is one of the main cause of global visual impairment and blindness.Its typical characteristics include microaneurysms,hard exudates,macular edema(DME)and neovascularization.Its pathogenesis is diverse,and the root cause is oxidative stress and advanced glycosylation end products.The nuclear red blood cell related factor 2(Nrf2)signa-ling pathway plays an important role in preventing various diseases.As one of the characteristics of DM,hyperglycemia will activate the generation of reactive oxygen species(ROS)in mitochondria.These oxidative stress factors activate the nucle-ar transcription factor κB pathway,becoming the main inducement of various complications of DM.This pathway will in-duce increased transcription of proinflammatory cytokines,including tumor necrosis factor-alpha,transforming growth fac-tor-beta and interleukin-1.The active ingredients of traditional Chinese medicine have significant antioxidant,anti-inflam-matory,anti-apoptotic and angiogenesis-promoting effects,and can block the progression of DR through various mecha-nisms.In this article,the research status of traditional Chinese medicine targeting the Nrf2 signaling pathway in the preven-tion and treatment of DR is reviewed to guide clinical and scientific research.