[This corrects the article DOI: 10.1016/j.apsb.2024.09.010.].

Objective: To investigate the methylation status of the RUNX family transcription factor 3 ( RUNX3)promoter and its mRNA expression in sepsis patients , and to analyze their relationship with the prognosis of sepsis. Methods: Differentially expressed genes related to sepsis , including RUNX3 , were identified from multiple datasets obtained from the gene expression omnibus (GEO) database. The gene expression and methylation sites were validated. A total of 120 patients with sepsis were included. Clinical data were recorded , and blood samples were collected at enrollment. Relative expression levels of RUNX3 in blood samples and promoter methylation status were detected using qPCR and methylation⁃specific PCR ( MSP) , respectively. Pearson correlation coefficients were used to analyze the correlation between RUNX3 levels in patient blood and clinical indicators. Kaplan⁃Meier analysis was performed to plot survival curves , and Cox proportional hazards regression analysis was conducted to identify factors affecting the prognosis of sepsis patients. Results: Data set analysis revealed that RUNX3 was a differentially methylated gene associated with the prognosis of sepsis. The mRNA expression level of RUNX3 was lower in the non-survivor group compared to the survivor group (P < 0. 05) , and the methylation ratio of RUNX3 was higher in the non-survivor group than in the survivor group (P < 0. 05) . In sepsis patients , RUNX3 mRNA expression levels were negatively correlated with interleukin-6 ( IL-6) , procalcitonin ( PCT) , C-reactive protein ( CRP) , acute physiology and chronic health evaluation ( APACHE Ⅱ ) score , and sequential organ failure assessment ( SOFA) score. Kaplan-Meier analysis showed that the 28-day survival rate in the methylated group was lower than that in the unmethylated group ( P < 0. 05) . Cox regression analysis results indicated that RUNX3 promoter methylation was an independent risk factor for predicting the 28-day prognosis of sepsis patients. Conclusion In sepsis patients , the mRNA levels of RUNX3 were reduced , and the degree of promoter methylation was higher. RUNX3 promoter methylation was an independent risk factor for the 28-day prognosis of sepsis patients and could serve as a prognostic biomarker for sepsis.

To explore the prevalence and related risk factors of osteoporosis (OP) in the elderly ≥60 years old in Jiuting Town, Songjiang District, Shanghai City. A total of 2 175 local residents aged ≥60 years old who participated in the questionnaire survey at the physical examination center of Jiuting Community Health Service Center, Songjiang District, Shanghai City from July 2021 to December 2022 were selected by a cross-sectional study with multi-stage sampling method. Questionnaire survey, blood test and bone mineral density (BMD) test were conducted.The differences in all the parameters among the elderly with different bone mass level were analyzed using t-test, chi-square test, binary logistic regression was used to screen the potential risk factors of OP.The results showed that the prevalence of OP in the elderly aged≥60 years old in Jiuting Town was 45.89%.The prevalence of OP increased gradually with the advanced age. The prevalence rate of male was significantly lower than that of female( χ2=211.94, P<0.01).Single factor analysis showed that Dairy products( χ2=9.01, P<0.05), taking calcium( χ2=42.88, P<0.05), physical exercise( χ2=24.73, P<0.05), exercise time( χ2=76.40, P<0.05) and sun exposure( χ2=55.71, P<0.05) were the protective factors for osteoporosis. Multifactor analysis showed that female( wald χ 2=71.46, P<0.001) were the risk factors for osteoporosis. The age of the osteoporosis group was older than that of the non-osteoporosis group [osteoporosis group (72.47±6.89) years old, non-osteoporosis group (68.73±6.34) years old, and the difference was statistically significant, t=-11.67, P<0.05]. The waist circumference, alanine aminotransferase (ALT), creatinine (CR), blood urea nitrogen (BUN) and uric acid (UA) in the non-osteoporosis group were higher than those in the osteoporosis group, and the difference was statistically significant (all P<0.05). The levels of high-density lipoprotein (HDL)[osteoporosis group (1.34±0.35) mol/L, non-osteoporosis group (1.41±0.35) mol/L, t=-4.51, P<0.05] and alkaline phosphatase (ALP)[osteoporosis group (88.46±25.65) mol/L, osteoporosis group (94.56±32.32) mol/L, t=-4.79, P<0.05] in the osteoporosis group were lower than those in the non-osteoporosis group.Low awareness of the knowledge of osteoporosis risk factors(smoking, drinking coffee, high salt and drinking alcohol are 47.28%, 24.15%, 47.79% and 44.90%, respectively), diagnosis and treatment(The symptoms, prognosis, screening methods, medication time and follow-up screening time of osteoporosis were 26.87%, 17.88%, 21.77%, 6.65% and 15.99%, respectivel) and prevention(exercise mode, high calcium food, optimal age of calcium supplementation, the effect of vitamin D on OP, and the appropriate amount of milk to prevent osteoporosis were 33.16%, 42.01%, 13.27%, 12.07%, 9.01%, respectively) were in Jiuting Town. In conclusion, the prevalent rate of OP in the elderly ≥60 years old in Jiuting Town is 45.89%.The main risk factors are female and advanced age. Drinking tea, dairy products, combination of meat and vegetable, taking calcium, physical exercise and sun exposure were the protective factors for osteoporosis. The awareness rate of osteoporosis related knowledge is low, and health education should be strengthened in order to control and prevent the occurrence and development of osteoporosis.

To explore the prevalence and related risk factors of osteoporosis (OP) in the elderly ≥60 years old in Jiuting Town, Songjiang District, Shanghai City. A total of 2 175 local residents aged ≥60 years old who participated in the questionnaire survey at the physical examination center of Jiuting Community Health Service Center, Songjiang District, Shanghai City from July 2021 to December 2022 were selected by a cross-sectional study with multi-stage sampling method. Questionnaire survey, blood test and bone mineral density (BMD) test were conducted.The differences in all the parameters among the elderly with different bone mass level were analyzed using t-test, chi-square test, binary logistic regression was used to screen the potential risk factors of OP.The results showed that the prevalence of OP in the elderly aged≥60 years old in Jiuting Town was 45.89%.The prevalence of OP increased gradually with the advanced age. The prevalence rate of male was significantly lower than that of female( χ2=211.94, P<0.01).Single factor analysis showed that Dairy products( χ2=9.01, P<0.05), taking calcium( χ2=42.88, P<0.05), physical exercise( χ2=24.73, P<0.05), exercise time( χ2=76.40, P<0.05) and sun exposure( χ2=55.71, P<0.05) were the protective factors for osteoporosis. Multifactor analysis showed that female( wald χ 2=71.46, P<0.001) were the risk factors for osteoporosis. The age of the osteoporosis group was older than that of the non-osteoporosis group [osteoporosis group (72.47±6.89) years old, non-osteoporosis group (68.73±6.34) years old, and the difference was statistically significant, t=-11.67, P<0.05]. The waist circumference, alanine aminotransferase (ALT), creatinine (CR), blood urea nitrogen (BUN) and uric acid (UA) in the non-osteoporosis group were higher than those in the osteoporosis group, and the difference was statistically significant (all P<0.05). The levels of high-density lipoprotein (HDL)[osteoporosis group (1.34±0.35) mol/L, non-osteoporosis group (1.41±0.35) mol/L, t=-4.51, P<0.05] and alkaline phosphatase (ALP)[osteoporosis group (88.46±25.65) mol/L, osteoporosis group (94.56±32.32) mol/L, t=-4.79, P<0.05] in the osteoporosis group were lower than those in the non-osteoporosis group.Low awareness of the knowledge of osteoporosis risk factors(smoking, drinking coffee, high salt and drinking alcohol are 47.28%, 24.15%, 47.79% and 44.90%, respectively), diagnosis and treatment(The symptoms, prognosis, screening methods, medication time and follow-up screening time of osteoporosis were 26.87%, 17.88%, 21.77%, 6.65% and 15.99%, respectivel) and prevention(exercise mode, high calcium food, optimal age of calcium supplementation, the effect of vitamin D on OP, and the appropriate amount of milk to prevent osteoporosis were 33.16%, 42.01%, 13.27%, 12.07%, 9.01%, respectively) were in Jiuting Town. In conclusion, the prevalent rate of OP in the elderly ≥60 years old in Jiuting Town is 45.89%.The main risk factors are female and advanced age. Drinking tea, dairy products, combination of meat and vegetable, taking calcium, physical exercise and sun exposure were the protective factors for osteoporosis. The awareness rate of osteoporosis related knowledge is low, and health education should be strengthened in order to control and prevent the occurrence and development of osteoporosis.

The adipose tissue of mammals represents an important energy-storing and endocrine organ, and its dysfunction is relevant to the onset of several health problems, including non-alcoholic fatty liver disease (NAFLD). However, whether treatments targeting adipose dysfunction could alleviate NAFLD has not been well-studied. Adrenomedullin 2 (ADM2), belonging to the CGRP superfamily, is a protective peptide that has been shown to inhibit adipose dysfunction. To investigate the adipose tissue-specific effects of ADM2 on NAFLD, adipose-specific ADM2-overexpressing transgenic (aADM2-tg) mice were developed. When fed a high-fat diet, aADM2-tg mice displayed decreased hepatic triglyceride accumulation compared to wild-type mice, which was attributable to the inhibition of hepatic de novo lipogenesis. Results from lipidomics studies showed that ADM2 decreased ceramide levels in adipocytes through the upregulation of ACER2, which catalyzes ceramide catabolism. Mechanically, activation of adipocyte HIF2α was required for ADM2 to promote ACER2-dependent adipose ceramide catabolism as well as to decrease hepatic lipid accumulation. This study highlights the role of ADM2 and adipose-derived ceramide in NAFLD and suggests that its therapeutic targeting could alleviate disease symptoms.

Objective:To evaluate the relationship between Sestrin2 and mitochondrial DNA (mtDNA)-NOD-like receptor associated protein 3 (NLRP3) inflammasome pathway during endotoxin-induced myocardial injury in mice.Methods:One hundred and eighty-four clean-grade healthy male ICR mice, aged 8-12 weeks, weighing 20-25 g, were used in this study. One hundred and sixty-eight mice were divided into 7 groups ( n=24 each) using the random number table method: normal control group (N group), lipopolysaccaride(LPS) group (L group), mtDNA group, LPS+ mtDNA group (M group), normal control+ negative control adeno-associated virus (AAV-NC)group (NC group), LPS+ mtDNA+ AAV-NC group (MC group), and LPS+ mtDNA+ Sestrin2 overexpression adeno-associated virus (AAV-Sestrin2) group (MSgroup). Another 10 mice were used to detect the transfection effect of AAV-Sestrin2, and the left 6 mice were used for mtDNA extraction. The model of endotoxemia was developed by intraperitoneal injection of LPS 10 mg/kg. mtDNA 5 mg/kg was intraperitoneally injected in mtDNA group, and mtDNA 5 mg/kg was intraperitoneally injected at 30 min after LPS injection in M group.AAV-Sestrin2 150 μl was injected via the tail vein in MS group, and the equal volume of AAV-NC was injected via the tail vein in MC and NC groups. Four weeks after virus injection, LPS 10 mg/kg was intraperitoneally injected and 30 min later mtDNA 5 mg/kg was intraperitoneally injected in MS and MC groups. Blood samples were collected at 24 h after LPS injection for determination of serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities (by biochemical assay), concentrations of serum cardiac troponin I (cTnI), interleukin-18 (IL-18) and interleukin-1beta (IL-1β)(by enzyme-linked immunesorbent assay), and expression of mtDNA (by quantitative real-time polymerase chain reaction). The animals were sacrificed after the end of blood sampling and myocardial tissues were obtained for determination of the contents of reactive oxygen species (ROS), total antioxidant capacity (T-AOC), and adenosine triphosphate (ATP) and expression of NOD-like receptor associated protein 3 (NLRP3), active subunit p20 of caspase-1 (caspase-1p20) and apoptosis-associated microprotein (ASC) in myocardial tissues (by Western blot) and for microscopic examination of the pathological changes after HE staining (with a light microscope). Results:Compared with N group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly increased, the expression of mtDNA was up-regulated, the ROS content in myocardial tissues was increased, the T-AOC and ATP contents in myocardial tissues were decreased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was up-regulated( P<0.05), and the pathological changes of myocardial tissues were aggravated in L group and mtDNA group.Compared with L group and mtDNA group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly increased, the expression of mtDNA was up-regulated, the ROS content in myocardial tissues was increased, the T-AOC and ATP contents in myocardial tissues were decreased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was up-regulated( P<0.05), and the pathological changes of myocardial tissues were aggravated in M group. Compared with M group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly decreased, the expression of mtDNA was down-regulated, the ROS content in myocardial tissues was decreased, the T-AOC and ATP contents in myocardial tissues were increased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was down-regulated( P<0.05), and the pathological changes of myocardial tissues were significantly attenuated in MS group. Conclusions:Sestrin2 can reduce endotoxin-induced myocardial injury in mice by alleviating mitochondrial damage, inhibiting oxidative stress, protecting mtDNA from oxidative damage, and then inhibiting mtDNA-NLRP3 inflammasome pathway.

Objective To investigate the role and molecular mechanism of Sirt1 in renal injury in diabetic mice under acute inflammatory state.Methods Forty SPF grade C57BL/6J male mice,8 weeks old,weighing 20-25 g were selected.The mice were divided into five groups by random number table meth-od:control group(group C),diabetic group(group D),lipopolysaccharide(LPS)+diabetic group(group L),LPS+diabetic+Sirt1 blocker EX527 group(group E),and LPS+diabetic+Sirt1 agonist ginkgoflavone sapogenins group(group G),8 mice in each group.After successful preparation of the diabet-ic mouse model,group L was injected intraperitoneally with LPS 10 mg/kg.Group E was injected intraper-itoneally with EX527 5 mg/kg(dissolved in DMSO 0.2 ml)1 hour before giving LPS treatment to diabetic mice.Group G was injected intraperitoneally with 200 mg/kg of ginkgoflavone sapogenins(dissolved in DMSO 0.2 ml)1 hour before LPS treatment was given to diabetic mice,groups C and D underwent an in-traperitoneal injection of 2％DMSO 0.15 ml at the same time point.24-hours urine volume was collected and 24-hours urinary protein concentration was determined,and blood was taken from the posterior eyes to detect serum Scr and BUN concentrations.After kidney tissues were removed,IL-1βand IL-18 concentra-tions were measured by ELISA,nitrate reductase assay for nitric oxide(NO)content in kidney,iron ion an-tioxidant capacity assay for total antioxidant capacity(T-AOC),qPCR and Western blot assay for Sirtl,caspase-1,NLRP3,and ASC mRNA expression and protein content.The acetylated FoxO3a protein content was detected by immunoprecipitation,the reactive oxygen species(ROS)content was calculated by di-hydroethidium staining,the pyroptosis rate was calculated by immunofluorescence double staining,HE stai-ning was performed,and the pathological results were observed under light microscope.Results Compared with group C,24-hours urine volume,urine protein concentration,serum Scr and BUN concentration,con-centrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,ROS content and pyroptosis rate were significantly increased,T-AOC activity was signifi-cantly decreased in groups D,L,E,and G(P＜0.05).Compared with group D,24-hours urine volume,urine protein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1 β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,ROS content and pyroptosis rate were significantly increased,T-AOC activity was significantly decreased in groups L,E,and G(P＜0.05).Compared with group L,24-hours urine volume,urine protein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,acetylated FoxO3a protein content,ROS content,and pyroptosis rate were significantly increased,T-AOC activity,Sirt1 mRNA expression and protein content,and FoxO3a mRNA expression were significantly decreased in group E(P＜0.05),24-hours urine volume,urine pro-tein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,acetylated FoxO3a protein con-tent,ROS content and pyroptosis rate were significantly decreased,T-AOC activity,Sirt1 mRNA expression and protein content were significantly increased in group G(P＜0.05).Compared with group E,24-hours urine volume,urinary protein concentration,serum Scr and BUN concentration,concentrations of renal tissue IL-1β,IL-18,and NO,NLRP3,caspase-1,and ASC mRNA expressions and protein contents,acetylated FoxO3a protein content,ROS content,and pyroptosis rate were significantly decreased,T-AOC activity,Sirt1 mRNA expression and protein content were significantly increased in group G(P＜0.05).Conclusion In diabetic mice under acute inflammatory state,elevated Sirt1 reduces kidney injury by de-creasing acetylated FoxO3a protein content,reduced urine volume,urine protein concentration,serum Scr and BUN concentration,inflammatory factor concentrations and apoptosis levels in renal tissue,and attenua-ted oxidative stress and inflammation levels.

Objective:To evaluate the role of silencing regulatory protein (SIRT1) and its associated microRNAs (miRNAs) in dexmedetomidine-induced attenuation of renal damage in diabetic mice.Methods:SPF grade C57 male mice, aged 8 weeks, in which diabetes mellitus model was developed by intraperitoneal injection of 1% streptozotocin, were used.Thirty mice in which the model was successfully developed were divided into 5 groups ( n=6 each) using the random number table method: diabetes mellitus group (D group), diabetes mellitus + dexmedetomidine group (DD group), diabetes mellitus + dexmedetomidine + EX527 group (DDE group), diabetes mellitus + dexmedetomidine + miR-34a-3p-agomir group (DDH group), and diabetes mellitus + dexmedetomidine + miR-34a-3p-agomirNC group (DDC group). Six normal mice were selected as control group (C group). Dexmedetomidine 40 μg/kg was intraperitoneally injected once every 2 h, 3 times in total in DD, DDE, DDH and DDC groups.miR-34a-3p-agomir and miR-34a-3p-agomirNC 2.5 mmol were intraperitoneally injected via the tail vein at 72 h before dexmedetomidine administration once every 3 days, 2 times in total in DDH and DDC groups, respectively.SIRT1 inhibitor EX527 10 mg/kg was intraperitoneally injected at 1 h before dexmedetomidine administration in group DDE.At 24 h after the end of administration, serum concentrations of IL-6, IL-18, Cr and BUN, contents of nitric oxide (NO) and total antioxidant capacity (T-AOC), ROS activity, and expression of SIRT1, FoxO3a and P53 protein and mRNA, and expression of miR-217, miR-138 and miR-34a in renal tissues were determined. Results:Compared with group C, the serum IL-6, IL-18, Cr and BUN concentrations, contents of T-AOC and NO, and ROS activity were significantly increased, the expression of P53 protein and mRNA, miR-34a, miR-217 and miR-138 was up-regulated, and the expression of SIRT1 and FoxO3a protein and mRNA was down-regulated in group D ( P<0.05). Compared with group D, serum IL-6, IL-18, Cr and BUN concentrations, ROS activity and NO content were significantly decreased, T-AOC content was increased, the expression of SIRT1 and FoxO3a protein and mRNA was up-regulated, and the expression of miR-34a was down-regulated in group DD ( P<0.05). Compared with group DD, the serum IL-6, IL-18, Cr and BUN concentrations, NO content and ROS activity were significantly increased, T-AOC content was decreased, and the expression of SIRT1 and FoxO3a protein and mRNA was down-regulated in group DDE and group DDH ( P<0.05), no significant change was found in the expression of P53 protein and mRNA, miR-217, miR-34a and miR-138 in group DDE ( P>0.05), and the expression of P53 protein and mRNA and miR-34a was significantly up-regulated in group DDH ( P<0.05). Conclusions:The mechanism by which dexmedetomidine attenuates renal injury may be related to down-regulation of miR-34a expression, which further up-regulates SIRT1/FoxO3 expression and decreases oxidative stress in diabetic mice.

OBJECTIVE To isolate and ide ntify the chemical constituents of the root of Ardisia virens and preliminarily evaluate the in vitro anti-inflammatory activity of the compounds. METHODS The ethyl acetate extraction part from 70％ ethanol extract of the root of A. virens were separated and purified by silica gel column chromatography ，ODS column chromatography ， etc. The structures of the compounds were identified according to physical and chemical properties and spectral data. The inflammation model of RAW 264.7 cells was induced by lipopolysaccharide ，and anti-inflammatory activity of the compound was investigated by MTT assay. RESULTS A total of 11 compounds were isolated from the ethyl acetate extraction part ，and were identified as cyclamiretin A （1），α-spinasterol （2），（3S，5R，6S，7E）-3，5，6-trihydroxy-7-megastigmen-9-one （3）， （+）-angelicoidenol（4），octadeca-dienoic acid- 2，3-dihydroxypropyl ester （5），α-linolenic acid （6），glycerol monooleate （7），5， 5′-（4，7-hexadecadlene-1，16-diyl）bisresorcinol（8），1-（3，5-dihydroxyphenyl）heptan-1-one（9），5-heptylresorcinol and （10） 5-n-nonylresorcinol（11）. The in vitro anti-inflammatory results showed that 80，40，20，10，5 μg/mL of compounds 2，8，9 and 10 could reduce the cell survival rate in different degrees. CONCLUSIONS Compounds 1-11 are isolated from this plant for the first time，and compound 8 is a new natural product. Compound 2，8，9 and 10 show certain anti-inflammatory activity in vitro .

OBJECTIVE To separate and identif y the chemical constituen ts in 70％ ethanol extract of Sabia parviflora ，and to preliminarily evaluate their in vitro antioxidant activity. METHODS The chemical constituents were separated and purified by silica gel，ODS reversed-phase silica gel ，Sephadex-LH20 column and preparative high performance liquid chromatography. The structures of the isolated compounds were identified by 1H-NMR，13C-NMR and ESI-MS. The in vitro antioxidant activities of the compounds were investigated by 2，2-diphenyl-1-picrylhydrazyl radical （DPPH·），2，2′-azino-bis（3-ethylbenzothiazoline-6- sulfonate）diammonium radical （ABST+）and hydroxyl radical （OH·）. RESULTS A total of 9 compounds were isolated from the 70％ ethanol extracts of S. parviflora . They were identified as rutin （1），diiononyl phthalate （2），dibutyl phthalate （3），vomifoliol （4），rhododendrol（5），quercetin-3-O-gentiobioside（6），narcissoside（7），kaempferol-3-O-rutinoside（8）and bonaroside （9）. The in vitro antioxidant results showed that compound 1-9 showed certain in vitro antioxidant activity ，and the half scavenging concentrations of compound 1，6，7 and 8 to DPPH ·，ABST+，OH·were lower than 70 μg/mL. CONCLUSIONS Vomifoliol， rhododendrol and bonaroside are isolated from S. parviflora for the first time ，and rutin ，quercetin-3-O-gentiobioside，narcissoside and kaempferol- 3-O-rutinoside show good in vitro antioxidant activity.