Distribution and prognostic value of high-sensitivity cardiac troponin T and I across glycemic status: a population-based study.

BACKGROUND: Whether distributions and prognostic values of high-sensitivity cardiac troponin (hs-cTn) T and I are different across normoglycemic, prediabetic, and diabetic populations is unknown. METHODS: 10127 adult participants from the National Health and Nutrition Examination Survey 1999-2004 with determined glycemic status and measurement of at least one of hs-cTn assays were included, from whom healthy participants and presumably healthy diabetic and prediabetic participants were selected to investigate pure impacts of glycemic status on distributions of hs-cTn. The nonparametric method and bootstrapping were used to derive the 99th upper reference limits of hs-cTn and 95% CI. Participants with available follow-up and hs-cTn concentrations of all 4 assays were included in prognostic analyses. Associations of hs-cTn with all-cause and cardiac-specific mortality were modeled by Cox proportional hazard regression under the complex survey design. The incremental value of hs-cTn to an established risk score in predicting cardiac-specific mortality was assessed by the 10-year area under time-dependent receiver operating characteristic curve (AUC) using the Fine-Grey competing risk model. RESULTS: Among 9714 participants included in prognostic analyses, 5946 (61.2%) were normoglycemic, 2172 (22.4%) prediabetic, and 1596 (16.4%) diabetic. Hyperglycemic populations were older than the normoglycemic population but sex and race/ethnicity were similar. During the median follow-up of 16.8 years, hs-cTnT and hs-cTnI were independently associated with all-cause and cardiac-specific mortality across glycemic status. In the diabetic population, adjusted hazard ratios per 1-standard deviation increase of log-transformed hs-cTnT and hs-cTnI (Abbott) concentrations were 1.77 (95% CI 1.48-2.12; P < .001) and 1.83 (95% CI 1.33-2.53; P < .001), respectively, regarding cardiac-specific mortality. In the diabetic but not the normoglycemic population, adding either hs-cTnT (difference in AUC: 0.062; 95% CI 0.038-0.086; P < 0.001) or hs-cTnI (Abbott) (difference in AUC: 0.071; 95% CI 0.046-0.097; P < 0.001) would significantly increase the discriminative ability of the risk score; AUC of the score combined with hs-cTnT would be further improved by incorporating hs-cTnI (0.018; 95%CI 0.006-0.029; P = 0.002). The 99th percentile of hs-cTnT of the presumably healthy diabetic population was higher than the healthy population and had no overlap in 95% CIs, however, for hs-cTnI 99th percentiles of the two populations were very close and 95% CIs extensively overlapped. CONCLUSIONS: Hs-cTnT and hs-cTnI demonstrated consistent prognostic associations across glycemic status but incremental predictive values in hyperglycemic populations only. The susceptibility of hs-cTnT 99th percentiles to diabetes plus the additive value of hs-cTnI to hs-cTnT in diabetic cardiovascular risk stratification suggested hs-cTnI and hs-cTnT may be differentially associated with glycemic status, but further research is needed to illustrate the interaction between hyperglycemia and hs-cTn.

Association between phthalates exposure and myocardial damage in the general population: A cross-sectional study.

BACKGROUND: Cardiovascular consequences of phthalates exposure have been given increasing attention, but the association of phthalates with subclinical cardiovascular disease (CVD) was unknown. Accordingly, this study aimed to investigate the association between phthalates exposure and high-sensitivity cardiac troponin I (hs-cTnI), a marker of myocardial injury, which was detectable in the subclinical stage of CVD. METHODS: Participants aged 6 years or older with available urinary phthalates metabolites and serum hs-cTnI concentrations were included in the National Health and Nutrition Examination Survey 2003-2004 cycle. Multivariable linear regression and weighted quantiles sum (WQS) regression were used to assess the association of hs-cTnI with individual phthalates and their co-exposure. Di-2-ethylhexylphthalate (ΣDEHP), high-molecular-weight phthalate (ΣHMWP), and low-molecular-weight phthalate (ΣLMWP) were defined as the molecular sum of phthalates metabolites in urine. RESULTS: 2241 participants were finally included. The percent change of serum hs-cTnI concentrations related to per 1-standard deviation increase of logarithmic urinary phthalates concentrations was 3.4% (0.1-6.7, P = 0.04) for ΣDEHP, 3.6% (0.3-6.9, P = 0.03) for ΣHMWP, and 3.5% (0.2-6.8, P = 0.04) for ΣLMWP. Co-exposure to phthalates metabolites expressed as the WQS index also demonstrated a positive association with hs-cTnI. A similar association pattern was found in the population with no prior CVD. CONCLUSIONS: This study indicated the potential of phthalates to myocardial injury which may occur even before clinically apparent CVD was identified, emphasizing the significance of reducing phthalates in the prevention of CVD.

[Effect of Intensive Insulin Therapy on Prognosis in Patients With Acute Myocardial Infarction].

Objective To evaluate the clinical efficacy and safety of intensive insulin therapy in the patients with acute myocardial infarction and provide guidance for improving the prognosis. Methods The articles involving the randomized controlled trials(RCT)focusing on the effects of intensive versus conventional insulin therapy on the clinical outcomes of the patients with acute myocardial infarction were retrieved from Cochrane,Embase,PubMed,CNKI,Wanfang Data,VIP,and CBM with the time interval from inception to October 2022.The data of each RCT were extracted and used for meta-analysis in RevMan5.4. Results A total of 8 articles were included in this study,involving 726 patients(372 in the intensive insulin group and 354 in the normal insulin group).The meta-analysis results showed that the intensive insulin group had lower incidence of major cardiovascular adverse events (RR=0.53, 95%CI=0.44-0.64, P<0.001), lower all-cause mortality (RR=0.51, 95%CI=0.33-0.78, P=0.002),lower high-sensitivity C-reactive protein level on day 7(WMD=-2.00,95%CI=-2.17- -1.83,P<0.001),higher left ventricular ejection fraction on day 30 (WMD=3.94, 95%CI=2.45-5.43,P<0.001), and higher incidence of hypoglycemia events (RR=2.96, 95%CI=1.12-7.83,P=0.030) than the normal insulin group.There was no significant difference between the two groups in terms of no-reflow event after percutaneous coronary intervention(RR=0.39,95%CI=0.14-1.13,P=0.080). Conclusion Intensive insulin therapy might be associated with more clinical benefits in the patients with acute myocardial infarction,while the conclusion remains to be confirmed by more studies.

Anti-Xa level monitoring of low-molecular-weight heparin during intermittent venovenous hemofiltration.

Low-molecular-weight heparin (LMWH) is an anticoagulant used to prevent clotting during blood purification treatments. This study aimed to evaluate the clinical use of the anti-factor Xa level (anti-Xa) for monitoring LMWH anticoagulant levels during intermittent venovenous hemofiltration (IVVHF). This prospective observational study enrolled patients who required IVVHF for renal failure in Beijing Hospital between May 2019 and February 2021. The LMWH anticoagulation was assessed by the coagulation grade of the filter and line. One hundred and ten participants were included. There were 90 patients with a filter and line coagulation grade of ≤ 1 and 20 patients with grade > 1. The anti-Xa level of 0.2 IU/mL was a critical value. The multivariable logistic regression analysis showed that anti-Xa level > 0.2 IU/mL (odd ratio [OR] = 2.263; 95% CI: 1.290-4.871, P = 0.034) and cardiovascular disease (OR = 10.028; 95% CI: 1.204-83.488; P = 0.033) were independently associated with the coagulation grade of the filter and line. Anti-Xa level could monitor LMWH anticoagulation during IVVHF.

Evaluation of the safety and efficacy of a novel Anatomical classification and dUal anchoRing theory to Optimize the tavR strategy for pure severe Aortic regurgitation (AURORA): a prospective cohort study.

BACKGROUND: Success rate of transcatheter aortic valve replacement (TAVR) in aortic regurgitation (AR) patients is relatively low on account of the absence of calcified anchoring structures. Morphological classification and corresponding TAVR strategies for AR are lacking yet. METHODS: The AURORA study is a prospective, multicenter, single-arm cohort study to evaluate the safety and efficacy of transfemoral TAVR for severe AR in patients with high or prohibitive risk for surgery. Patients who are ≥ 65 years and diagnosed with severe pure AR as defined by the Echocardiographic Core Laboratory will be consecutively enrolled for further multidetector computed tomography (MDCT) scanning and multiplanar analyses. Based on a new anatomical classification and dual anchoring theory, patients will be classified into 4 types according to the level of the anchoring area. Types 1, 2 and 3 (at least 2 anchoring areas) will undergo the TAVR procedure with a domestic Chinese self-expanding valve (VitaFlow Valve, MicroPort, Shanghai, China), whereas type 4 (0 or 1 anchoring area) patients will be considered unsuitable for TAVR and will receive medical treatment. Our goal is to recruit 100 patients to account for 10% missing data or loss of patients to follow-up. Procedural, 30-day, 6-month and 12-month outcomes will be assessed according to Valve Academic Research Consortium-3 criteria. DISCUSSION: The AURORA study will establish a new AR anatomical classification based on dual anchoring theory through MDCT multiplanar measurement and assess the safety and efficacy of TAVR guided by this new classification and strategy in AR patients. TRIAL REGISTRATION: This Study was registered at Chinses Clinical Trial Registry. The registration number: ChiCTR2200055415; The date of registration: 9, January 2022; The URL of the registration: http://www.chictr.org.cn/showproj.aspx?proj=141209 .

Aldehyde dehydrogenase 2 protects cardiomyocytes against lipotoxicity via the AKT/glycogen synthase kinase 3 beta pathways.

Aldehyde dehydrogenase 2, a mitochondrial matrix enzyme, plays a crucial role in protecting the heart against stress, such as ischemia reperfusion and alcohol injury. The present study aimed to investigate the effect of aldehyde dehydrogenase 2 on lipotoxic cardiomyopathy and to explore the possible mechanisms in vitro. Primary cardiomyocytes in the lipotoxic group were treated with oxidatively modified low-density lipoprotein (50 mg/L) for 24 h. Overexpression of aldehyde dehydrogenase 2 was achieved using the aldehyde dehydrogenase 2 activator, Alda-1 (20 µM). We found that cardiomyocyte apoptosis was attenuated by aldehyde dehydrogenase 2 overexpression. In addition, aldehyde dehydrogenase 2 overexpression inhibited the expression of BCL2 associated X, apoptosis regulator (BAX) and caspase 3, while it enhanced protein kinase B (AKT) and glycogen synthase kinase 3 beta (GSK-3ß) phosphorylation. The results suggested that aldehyde dehydrogenase 2 is cardioprotective against lipotoxic cardiomyopathy, probably by reducing apoptosis through the AKT/glycogen synthase kinase 3 beta (GSK-3ß) pathway. Our findings partially revealed the molecular mechanism of aldehyde dehydrogenase 2's cardioprotective effect against lipotoxic injury, and suggest a new therapeutic strategy to treat lipotoxic cardiomyopathy.

LncRNA MIR7-3HG executes a positive role in retinoblastoma progression via modulating miR-27a-3p/PEG10 axis.

Homo sapiens MIR7-3 host gene (MIR7-3HG), a long non-coding RNA, has been reported to be connected with the progression of several tumors and could be served as a prognostic marker. Our study intends to explore the biological function and potential molecular mechanism of MIR7-3HG in Retinoblastoma (Rb) progression. Two Rb cell lines Y79 and WERI-Rb-1 were applied to perform functional assays. Expression of MIR7-3HG in Rb tissues and cells were determined with the support of GEO database and qRT-PCR experiment. The effects of MIR7-3HG on cell activity and apoptosis were assessed through cell counting kit 8 and flow cytometry assays, respectively. Targeted connections between MIR7-3HG and miR-27a-3p, as well as miR-27a-3p and PEG10 were speculated by bioinformatics prediction software and verified by performing dual luciferase assays. Further interrelationships among MIR7-3HG, miR-27a-3p, and PEG10 were explored through rescue assays. MIR7-3HG overexpression was detected in Rb tissues and cell lines. Depletion of MIR7-3HG reduced the activity of Rb cells and increased the apoptosis of Rb cells, and vice versa. In addition, further exploration perceived that MIR7-3HG, miR-27a-3p, and PEG10 generated a competing endogenous RNA (ceRNA) mechanism to regulate Rb cells activity and apoptosis. Our results indicated that MIR7-3HG functioned as a ceRNA to up-regulate PEG10 expression via sponging miR-27a-3p to promote the proliferation of Rb cells and suppress the apoptosis of Rb cells, exhibiting a group of potential target molecules for Rb treatment in the future.

Cost-effective optimization of gellan gum production by Sphingomonas paucimobilis using corn steep liquor.

Gellan gum, produced by Sphingomonas paucimobilis, is increasingly used in food and pharmaceutical industries as stabilizing, emulsifying, texturing and gelling agents. However, its high production costs may limit its full commercial potential. Therefore, in this study, we investigated ways to reduce gellan gum production costs and improve yields. We first revealed corn steep liquor (CSL) as a cost-effective nutrient source that can improve gellan gum yields. We then systematically optimized culture conditions even further, and revealed that the addition of Triton X-100 surfactant and selected inorganic nitrogen sources improved gellan gum production. Under our optimized conditions (glucose 33.75 g/L, CSL 10 g/L, urea 2.5 g/L, MgSO4 1.08 g/L, KH2PO4 3.24 g/L, K2SO4 1 g/L and Triton X-100 0.75 g/L), we yielded a maximum concentration of 14.41 g/L, which was about 1.5-fold higher than non-optimized CSL-based medium. Our findings highlight the use of CSL as a cost effective and promising nutrient source for industrial production of gellan gum.

ALDH2 deficiency inhibits Ox-LDL induced foam cell formation via suppressing CD36 expression.

Foam cell formation plays an important role in the initiation and progression of atherosclerosis. Aldehyde dehydrogenase 2 (ALDH2), a key enzyme for aldehyde metabolism, is associated with coronary artery disease and affects atherosclerotic plaque vulnerability. However, the role of ALDH2 in foam cell formation remains unclear. Using peritoneal macrophages from ALDH2-deficient and control mice, we found that ALDH2 deficiency suppressed foam cell formation induced by oxidized low-density lipoproteins (ox-LDL) but not acetylated low-density lipoproteins (ac-LDL) ex vivo. After incubation with ox-LDL, ALDH2-deficient macrophages expressed lower levels of CD36 but the expression of other lipid metabolism-related proteins including SRA, LOX-1, ABCA-1, ABCG-1 and ACAT-1 was not changed in ALDH2-/- macrophages. Using CD36 inhibitor, we confirmed that CD36 contributes to the effect of ALDH2 on foam cell formation. PPARγ was downregulated in ox-LDL treated ALDH2-/- macrophages. 4-HNE was increased by ALDH2 deficiency and high concentration of 4-HNE suppressed the expression of PPARγ. These data suggest that ALDH2 plays an important role in foam cell formation via 4-HNE/PPARγ/CD36 pathway.

Aldehyde Dehydrogenase-2 Attenuates Myocardial Remodeling and Contractile Dysfunction Induced by a High-Fat Diet.

BACKGROUND/AIMS: Consumption of a high-fat (HF) diet exacerbates metabolic cardiomyopathy through lipotoxic mechanisms. In this study, we explored the role of aldehyde dehydrogenase-2 (ALDH2) in myocardial damage induced by a HF diet. METHODS: Wild-type C57 BL/6J mice were fed a HF diet or control diet for 16 weeks. ALDH2 overexpression was achieved by injecting a lentiviral ALDH2 expression vector into the left ventricle. RESULTS: Consumption of a HF diet induced metabolic syndrome and myocardial remodeling, and these deleterious effects were attenuated by ALDH2 overexpression. In addition, ALDH2 overexpression attenuated the cellular apoptosis and insulin resistance associated with a HF diet. Mechanistically, ALDH2 overexpression inhibited the expression of c-Jun N-terminal kinase (JNK)-1, activated protein 1 (AP-1), insulin receptor substrate 1 (IRS-1), 4- hydroxynonenal, caspase 3, transforming growth factor ß1, and collagen I and III, and enhanced Akt phosphorylation. CONCLUSION: ALDH2 may effectively attenuate myocardial remodeling and contractile defects induced by a HF diet through the regulation of the JNK/AP-1 and IRS-1/Akt signaling pathways. Our study demonstrates that ALDH2 plays an essential role in protecting cardiac function from lipotoxic cardiomyopathy.

MnO2/MWCNTs Nanocomposites as Highly Efficient Catalyst for Indoor Formaldehyde Removal.

Formaldehyde (HCHO) is a main indoor pollutant that is capable of harming the health of residents. Here, we fabricated a novel MnO2/MWCNTs nanocomposite film for non-photocatalytic, room temperature removal of indoor HCHO. MnO2/MWCNTs nanocomposites with various amounts of a-MWCNTs, which were fabricated by a co-precipitation method, were assembled into composite films using vacuum filtration and solvent evaporation. Structural analysis confirms that MnO2 nanoparticles are homogeneously distributed on a-MWCNTs. The acetyl acetone method was used to characterize the catalytic activity of MnO2/MWCNTs nanocomposites. The results show that MnO2/MWCNTs composites with 30 wt% a-MWCNTs present the highest catalytic activity due to a highly active surface. The catalytic activity of MnO2/MWCNTs composite film was characterized in a glovebox at room temperature and showed good removal of HCHO. This study suggests that supporting catalysts on MWCNTs and then assembling them into fibers (1D), films (2D) or aerogels (3D) is a worthwhile approach to promote catalytic activity and prevent dust pollution.

[Establishment and evaluation of a warfarin-dosing algorithm in Chinese Han population].

OBJECTIVE: To develop and evaluate a warfarin-dosing algorithm method which can be used to guide the adjustment of warfarin maintenance dose in Chinese Han population. METHODS: A total of 512 patients with steady warfarin taking were recruited from Beijing Hospital during May 2012 to December 2014. Indications for warfarin prescribing included prosthetic heart valve, atrial fibrillation and pulmonary embolism. Genomic DNAs were extracted from blood samples and used for the genetic polymorphism analysis of VKORC1 and CYP2C9 (include (*)3 and (*)13 alleles). Warfarin dose, demographic variabilities and amiodarone compliance were recorded during regular visit. These patients were randomly divided into groups using the method of random number table, 384 patients were randomly selected as derivation group, the remaining 128 cases as the validation group.Using data from derivation group, a warfarin-dosing algorithm was established based on the genetic information, demographic characteristics and concomitant compliance by a multiple linear regression analysis parameter. Then the accuracy of newly developed algorithm method was further evaluated by comparing the predicting dose with the actual dose in the validation group. RESULTS: The stable dose of warfarin was tightly associated with factors like age, height, weight, VKORC1 -1639G>A, CYP2C9(*)3, CYP2C9(*)13 and amiodarone usage. Newly developed algorithm method exhibited better prediction effect (R(2)=0.682, P<0.01) as compared with that of previously reported algorithm methods. The weights of VKORC1 and CYP2C9 for predicting of warfarin dosage were estimated to more than 50%. Using this method, 62.5% of patients in the validation group could be well recognized, in which the predicting dose of warfarin was within 20% of the actual dose, and only 7.81% patients showed underestimated prediction warfarin dose while 29.69% patients showed overestimated values. CONCLUSION: Newly developed algorithm method can be used for the guidance of warfarin maintenance dose adjustment in Chinese Han population.

Identification and Functional Assessment of a New CYP2C9 Allelic Variant CYP2C9*59.

CYP2C9, one of the most important drug-metabolizing enzymes, is responsible for metabolizing approximately 15% of clinically important drugs, including warfarin, diclofenac, and losartan. Similar to other CYP members, human CYP2C9 exhibits marked genetic polymorphisms among individuals of different ethnicities. In this study, a novel missense mutation (1300A>T) was identified in a warfarin-sensitive patient after a genetic screen of three candidate genes related to high variability in response to warfarin doses. This base transversion leads to an Ile-to-Phe amino acid substitution at codon 434 within the CYP2C9 protein, and this new variant has been named a novel allele, CYP2C9*59, by the Human CYP Allele Nomenclature Committee (http://www.cypalleles.ki.se/cyp2c9.htm). The exogenous expression of CYP2C9.59 in insect cell microsomes revealed that, despite a similar protein expression level as wild-type CYP2C9, variant CYP2C9.59 exhibited significantly reduced maximal velocity, Vmax, and/or increased Michaelis constant, Km, values toward three CYP2C9-specific substrates. Our data suggest that the 1300A>T mutation can greatly decrease the enzymatic activity of the CYP2C9 protein both in vitro and in vivo.

Berberine Attenuates Vascular Remodeling and Inflammation in a Rat Model of Metabolic Syndrome.

Berberine is a natural product that shows benefits for metabolic syndrome (MS). However, the effects of berberine on the improvement of vascular inflammation and remodeling in MS remain unclear. This study aimed to investigate whether berberine could prevent vascular remodeling and inflammation in the MS condition. A rat model of MS was established, and MS rats were divided into two groups: MS group without berberine treatment, and MSB group with berberine treatment (each group n-10). Ten normal Wistar rats were used as controls (NC group). Vascular damage was examined by transmission electron microscopy and pathological staining. Compared to the NC group, the secretion of inflammatory factors was increased and the aortic wall thicker in the MS group. The MSB group exhibited decreased secretion of inflammatory factors and improved vascular remodeling, compared to the MS group. In addition, the levels of p38 mitogen-activated protein kinase (p38 MAPK), activating transcription factor 2 (ATF-2) and matrix metalloproteinase 2 (MMP-2) were significantly decreased in the MSB group compared to the MS group. In conclusion, our data show that berberine improves vascular inflammation and remodeling in the MS condition, and this is correlated with the ability of berberine to inhibit p38 MAPK activation, ATF-2 phosphorylation, and MMP-2 expression.

Characterization of a novel CYP2C9 mutation (1009C>A) detected in a warfarin-sensitive patient.

Warfarin is the most frequently prescribed anticoagulant for the long-term treatment in the clinic. Recent studies have shown that polymorphic alleles within the CYP2C9, VKORC1, and CYP4F2 genes are related to the warfarin dosage requirement. In this study, a novel non-synonymous mutation (1009C>A) in CYP2C9 was detected in a warfarin-hypersensitive patient, while the other two candidate genes were both found to be homozygous for the wild-type alleles. The newly identified point mutation results in an amino acid substitution at position 337 of the CYP2C9 protein (P337T) and has been designated as the novel allele CYP2C9*58. When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. These data suggested that when compared with wild-type CYP2C9.1, the enzymatic activity of the novel allelic variant has been greatly reduced by the 1009C>A mutation. If patients carrying this allele take drugs metabolized by CYP2C9, their metabolic rate might be slower than that of wild-type allele carriers and thus much more attention should be paid to their clinical care.

Multiple correlations of mRNA expression and protein abundance in human cytokine profile.

With the development of genomic study, researchers found that it is insufficient to predict protein expression from quantitative mRNA data in large scale, which is contrary to the traditional opinion that mRNA expression correlates with protein abundance at the single gene level. To try to solve the apparent conflicting views, here we set up a series of research models and chose soluble cytokines as targets. First, human peripheral blood mononuclear cell (PBMC) from one health donor was treated with 16 continuously changing conditions, the protein and mRNA profile were analyzed by multiplex Luminex and genomic microarray, respectively. Among the tested genes, around half mRNA correlated well with their corresponding proteins (ρ > 0.8), however if we put all the genes together, the correlation coefficient for the 16 conditions varied from 0.29 to 0.71. Second, PBMC from 14 healthy donors were stimulated with the same condition and it was found that the correlation coefficient went down (ρ < 0.6). Third, 28 rheumatoid arthritis (RA) patients were tested for their response to the same external stimuli and it turned out different individual displayed different protein expression pattern as expect. Lastly, autoimmune disease cohorts (8 diseases including RA, 103 patients in total) were assayed on the whole view. It was observed that there was still some similarity in the protein profile among patients from the single disease type although completely different patterns were displayed across different disease categories. This study built a good bridge between single gene analysis and the whole genome study and may give a reasonable explanation for the two conflicting views in current biological science.

Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy: a meta-analysis.

BACKGROUND: This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium (GIK) therapy on clinical outcomes in acute coronary syndrome (ACS) patients receiving reperfusion therapy. METHODS: We searched the PubMed, Web of Science, MEDLINE, Embase, and Cochrane Library databases from inception to April 26, 2022, for randomized controlled trials (RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy. The primary endpoint was major adverse cardiovascular events (MACEs). RESULTS: Eleven RCTs with 884 patients were ultimately included. Compared with placebos, high-dose GIK markedly reduced MACEs (risk ratio [RR] 0.57, 95% confidence interval [95% CI]: 0.35 to 0.94, P=0.03) and the risk of heart failure (RR 0.48, 95% CI: 0.25 to 0.95, P=0.04) and improved the left ventricular ejection fraction (LVEF) (mean difference [MD] 2.12, 95% CI: 0.40 to 3.92, P=0.02) at 6 months. However, no difference was observed in all-cause mortality at 30 d or 1 year. Additionally, high-dose GIK was significantly associated with increased incidences of phlebitis (RR 4.78, 95% CI: 1.36 to 16.76, P=0.01), hyperglycemia (RR 9.06, 95% CI: 1.74 to 47.29, P=0.009) and hypoglycemia (RR 6.50, 95% CI: 1.28 to 33.01, P=0.02) but not reinfarction, hyperkalemia or secondary reperfusion. In terms of oxidative stress-lowering function, high-dose GIK markedly reduced superoxide dismutase (SOD) activity but not glutathione peroxidase (GSH-Px) or catalase (CAT) activity. CONCLUSION: Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK. Moreover, with a higher incidence of complications such as phlebitis, hyperglycemia, and hypoglycemia. Furthermore, there were no observed survival benefits associated with high-dose GIK. More trials with long-term follow-up are still needed.

Longitudinal Analysis of Renal Function Changes in Elderly Populations: Health Status Evaluation and Risk Factor Assessment.

Background: This study aims to investigate GFR decline in elderly subjects with varying physical conditions and analyze key risk factors impacting renal function changes. Methods: We obtained data from patients between 2017 and 2019, and matched healthy elderly subjects based on gender and age. Data collected for all subjects included annual measurements of fast blood glucose (GLU), glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-c), blood albumin (ALB), blood uric acid (UA), urine protein (UP), and systolic blood pressure (SBP). Additionally, information on coexisting diseases was gathered. The Full Age Spectrum (FAS) equation was used to calculate eGFR. Results: A total of 162 patients with complete 3-year renal dynamic imaging were included, including 84 patients in the kidney disease group (K group) and 78 patients in the non-kidney disease group (NK group). Ninety individuals were selected as the healthy group (H group). The annual decline rate in the K group was the fastest, which exceeded 5mL/min/1.73m2 (P < 0.05). Group (K group: ß=-40.31, P<0.001; NK group: ß=-26.96, P<0.001), ALB (ß=-0.38, P=0.038) and HbA1c (ß=1.36, P=0.029) had a significant negative impact on the eGFR changes. For participants who had negative proteinuria: K group had the most significant annual eGFR decline. Conclusion: The presence of kidney disease, along with proteinuria nor not, can lead to a marked acceleration in kidney function decline in elderly. We categorize elderly individuals with an annual eGFR decline of more than 5 mL/min/1.73m2 as the "kidney accelerated aging" population.

Age- and sex-specific 99th percentile upper reference limits for high-sensitivity cardiac troponin T in Chinese older people: Real-world data mining.

BACKGROUND: This study aims to investigate the impact of age and sex on high-sensitivity cardiac troponin T (hs-cTnT) and establish 99th percentile upper reference limits (URLs) in older individuals utilizing large-scale real-world data. METHODS: 40,530 outpatient hs-cTnT results were obtained from the laboratory database from January 1, 2018, to December 31, 2023. Our study included 4,199 elderly outpatients (aged ≥ 60) without cardiovascular disease or other heart-related chronic conditions. Nested analysis of variance was used to explore the necessity of partitioning reference intervals (RIs) by sex and age groups. RIs were established by the refineR algorithm and assessed based on ≤ 10% test results of validation data set outside the new RIs. RESULTS: RIs for hs-cTnT in the older population needed to be partitioned by sex and age groups ([standard deviation ratio] SDRage = 0.75; SDRsex = 0.49). URLs in older Chinese adults were 21.8 ng/L for males, 16.5 ng/L for females, and 20.7 ng/L for the overall participant group. URLs for males aged 60-69, 70-79, and ≥ 80 were 13.7, 19.4, and 31.0 ng/L, respectively. Female values were 10.1, 17.2, and 22.0 ng/L. Importantly, manufacturer-reported RIs do not suffice for Chinese individuals aged ≥ 70. Validation data showed that 2.7-5.2% of test results fell outside the new RIs, confirming the validity of the results. CONCLUSION: This study establishes age- and sex-specific 99th percentile URLs for hs-cTnT in Chinese older individuals, thereby enhancing the accuracy of clinical assessments.