Outcomes of Patients Presenting With Non-ST Elevation Myocardial Infarction Who Underwent Surgical Revascularization.

Non-ST-segment elevation myocardial infarction (NSTEMI) is a leading cause of emergency hospitalization across Europe. This study evaluates the in-hospital and mid-term outcomes of patients who underwent coronary artery bypass graft (CABG) after NSTEMI. A retrospective analysis of all cases who underwent isolated CABG after NSTEMI from September 2017 to September 2022 at our center. Patients were stratified according to in-hospital survival. Patient characteristics, operative details, and procedural complications were compared between those who survived and those who did not. Predictors of in-hospital and mid-term mortality were evaluated using logistic and Cox regression modeling. Kaplan-Meier analysis was used to generate a survival curve for all alive patients at the time of discharge. Among 1,011 patients (median age 64 [56 to 72] years, 852 [84.3%] male), 735 (72.7%) underwent urgent, 239 (23.6%) elective, and 37 (3.7%) emergency CABG. The in-hospital mortality was 1.5% (15/1,011 patients). Those who died were more likely to be New York Heart Association class III/IV, have left ventricular ejection fraction <21%, severe renal impairment, peripheral vascular disease (PVD), or poor mobility. Emergency procedures, preoperative ventilation, inotropic support, and intra-aortic balloon pump (IABP) use were also more prevalent among those who died. Logistic regression modeling revealed new postoperative stroke (odds ratio 22.0, 95% confidence interval 3.6 to 135.5, p = 0.001), preoperative IABP use (11.4; 2.4 to 53.7, p = 0.002), new hemodialysis (9.6; 2.7 to 34.7, p <0.001), PVD (5.6; 1.6 to 20.0, p = 0.008), and poor mobility (odds ratio 4.8, 95% confidence interval 1.3 to 18.2, p = 0.022) as independent predictors of in-hospital mortality. In conclusion, new postoperative stroke, preoperative IABP use, new hemodialysis, PVD, and poor mobility are independent predictors of mortality in patients with NSTEMI who underwent isolated CABG.

A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators.

Obesity and type 2 diabetes have reached pandemic proportion. ALDH2 (acetaldehyde dehydrogenase 2, mitochondrial) is the key metabolizing enzyme of acetaldehyde and other toxic aldehydes, such as 4-hydroxynonenal. A missense Glu504Lys mutation of the ALDH2 gene is prevalent in 560 million East Asians, resulting in reduced ALDH2 enzymatic activity. We find that male Aldh2 knock-in mice mimicking human Glu504Lys mutation were prone to develop diet-induced obesity, glucose intolerance, insulin resistance, and fatty liver due to reduced adaptive thermogenesis and energy expenditure. We find reduced activity of ALDH2 of the brown adipose tissue from the male Aldh2 homozygous knock-in mice. Proteomic analyses of the brown adipose tissue from the male Aldh2 knock-in mice identifies increased 4-hydroxynonenal-adducted proteins involved in mitochondrial fatty acid oxidation and electron transport chain, leading to markedly decreased fatty acid oxidation rate and mitochondrial respiration of brown adipose tissue, which is essential for adaptive thermogenesis and energy expenditure. AD-9308 is a water-soluble, potent, and highly selective ALDH2 activator. AD-9308 treatment ameliorates diet-induced obesity and fatty liver, and improves glucose homeostasis in both male Aldh2 wild-type and knock-in mice. Our data highlight the therapeutic potential of reducing toxic aldehyde levels by activating ALDH2 for metabolic diseases.

Characterizing Conformational Change of a Thermoresponsive Polymeric Nanoparticle with Raman Spectroscopy.

Molecular conformational changes in the collapsing and reswelling processes occurring during the phase transition at the lower critical solution temperature (LCST) of the polymer are not well understood. In this study, we characterized the conformational change of Poly(oligo(Ethylene Glycol) Methyl Ether Methacrylate)-144 (POEGMA-144) synthesized on silica nanoparticles using Raman spectroscopy and zeta potential measurements. Changes in distinct Raman peaks associated with the oligo(Ethylene Glycol) (OEG) side chains (1023, 1320, and 1499 cm-1) with respect to the methyl methacrylate (MMA) backbone (1608 cm-1) were observed and investigated under increasing and decreasing temperature profiles (34 °C to 50 °C) to evaluate the polymer collapse and reswelling around its LCST (42 °C). In contrast to the zeta potential measurements that monitor the change in surface charges as a whole during the phase transition, Raman spectroscopy provided more detailed information on vibrational modes of individual molecular moieties of the polymer in responding to the conformational change.

Eyes and the heart: what a clinician should know.

The eye is prone to various forms of afflictions, either as a manifestation of primary ocular disease or part of systemic disease, including the cardiovascular system. A thorough cardiovascular examination should include a brief ocular assessment. Hypertension and diabetes, for example, would present with retinopathy and dyslipidaemia would present with corneal arcus. Multisystem autoimmune diseases, such as Graves' disease, rheumatoid arthritis and sarcoidosis, would present with proptosis, episcleritis and scleritis, respectively. Myasthenia gravis, while primarily a neuromuscular disease, presents with fatigable ptosis and is associated with Takotsubo cardiomyopathy and giant cell myocarditis. Connective tissue diseases such as Marfan syndrome, which commonly presents with aortic root dilatation, would be associated with ectopia lentis and myopia. Wilson's disease, which is associated with arrhythmias and cardiomyopathies, would present usually with the characteristic Kayser-Fleischer rings. Rarer diseases, such as Fabry disease, would be accompanied by ocular signs such as cornea verticillata and such cardiac manifestations include cardiac hypertrophy as well as arrhythmias. This review examines the interplay between the eye and the cardiovascular system and emphasises the use of conventional and emerging tools to improve diagnosis, management and prognostication of patients.

Role of spleen density in predicting postoperative complications in patients with acute mesenteric ischemia.

BACKGROUND: Acute mesenteric ischemia (AMI) is a life-threatening surgical emergency with a poor prognosis. This study assessed the association of diffuse reduction of spleen density (DROSD) with postoperative complications and identified risk factors for adverse outcomes in AMI patients after surgery. METHODS: Patients who were diagnosed with AMI and underwent surgical operations between April 2006 and July 2021 were enrolled. Spleen density was assessed using preoperative non-enhanced computed tomography. The lowest quartile of spleen density in all patients was regarded as the cutoff value for DROSD. Univariate and multivariate analyses were performed to determine the risk factors related to postoperative outcomes after surgery. RESULTS: According to the diagnostic cutoff, patients with a spleen density ≤49.07 HU were defined as DROSD. In a cohort of 97 patients, 34.0% developed complications within 30 days of surgery. The multivariate analysis illustrated that DROSD was an independent risk factor for prognostic outcomes in AMI patients after surgery. CONCLUSION: Patients with low spleen density were prone to postoperative complications. As an imaging method, preoperative assessment of spleen density is a novel predictor that can be used clinically to identify high-risk AMI patients with poor prognosis.

Stilbenes with potent cytotoxicity from the seedcases of Paeonia suffruticosa Andrews.

Stilbenes (based on the 1,2-diphenylethylene skeleton) are a class of plant polyphenols with rich structural and bioactive diversity. Twenty-six stilbenes, including five undescribed compounds (7,8-dioxy-4,3',5'-trihydroxystilbene, trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B), were isolated from the seedcases of Paeonia suffruticosa Andrews. Their structures were elucidated by spectroscopic analyses and comparison with previously reported data. The absolute configurations of trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B were assigned from their respective electronic circular dichroism (ECD) spectra. Additionally, the structures of known compounds suffruticosols A, B and rockiol B were revised and the absolute configurations of them, and along with (+)-davidiol A, were also further determined by ECD. The isolated compounds, trans-gnetin H, cis-gnetin H and suffruticosol E, were found to have potent cytotoxicity against the DU-145 and MDA-MB-231 cell lines with IC50 values of 4.89-8.61 µM. The preliminary antitumor structure-activity relationship of these stilbenes is discussed as well.

(±)-Pheharmines A-B, two pairs of racemic alkaloids with a morpholino[4,3,2-hi]ß-carboline core, from the roots of Peganum harmala.

Two pairs of unprecedented ß-carboline-phenylpropanoid heterogeneous alkaloids, (±)-pheharmines A-B (1-4), characterized by a morpholino[4,3,2-hi]ß-carboline core with two chiral centers, were isolated from the roots of Peganum harmala. The structures, including their absolute configurations, were identified using spectroscopic analyses and electronic circular dichroism (ECD) calculations. The biosynthetic hypothesis for the formation of pheharmines A-B was proposed. Compounds 1-4 exhibited moderate cytotoxic activities against HL-60 cell lines.

Cephalotaxine-type and homoerythrina-type alkaloids with antiproliferative effects from Cephalotaxus fortunei.

Twenty-two cephalotaxine-type and ten homoerythrina-type alkaloids, including seven previously undescribed ones, were isolated from the twigs and leaves and the seed kernels of Cephalotaxus fortunei. Their structures were established by spectroscopic analysis, single crystal X-ray diffraction, and ECD calculation methods. Cephalofortunine A ß-N-oxide (1) is the first nitrogen-oxidized homoerythrina-type alkaloid. The isolated compounds were evaluated for their in vitro antiproliferative effects against two human leukemia cell lines (THP-1 and K562). All compounds showed different levels of antiproliferation in THP-1 and K562 cells with GI50 values of 0.24-29.55 µM. Hainanensine (31) was the most active against two cancer cell lines with GI50 values of 0.24 ± 0.07, and 0.29 ± 0.01 µM, respectively.

Preoperative Anemia Is a Predictor of Worse Postoperative Outcomes Following Open Pancreatoduodenectomy: A Propensity Score-Based Analysis.

Background: Preoperative anemia is a common clinical situation proved to be associated with severe outcomes in major surgeries, but not in pancreatic surgery. We aim to study the impact of preoperative anemia on morbidity and mortality in patients undergoing open pancreatoduodenectomy and use propensity score matching (PSM) to balance the basal data and reduce bias. Methods: We analyzed the data of consecutive patients undergoing open pancreatoduodenectomy with a complete record of preoperative hemoglobin, at two pancreatic centers in China between 2015 and 2019. Anemia is defined as hemoglobin less than 12 g/dl for male and 11 g/dl for female, following Chinese criteria. We compared clinical and economic outcomes before and after PSM and used logistic regression analysis to assess the correlation between variables and anemia. Results: The unmatched initial cohort consisted of 517 patients. A total of 148 cases (28.6%) were diagnosed with anemia at admission, and no case received a preoperative blood transfusion or anti-anemia therapy. After PSM, there were 126 cases in each group. The rate of severe postoperative complications was significantly higher in the anemia group than in the normal group (43.7% vs. 27.0%, p = 0.006), among which the differences in prevalence of clinically relevant postoperative pancreatic fistula (CR-POPF) (31.0% vs. 15.9%, p = 0.005) and cardiac and cerebrovascular events (4.0% vs. 0.0%, p = 0.024) were the most significant. The costs involved were more in the anemia group (26958.2 ± 21671.9 vs. 20987.7 ± 10237.9 USD, p = 0.013). Among anemic patients, receiver operating characteristic (ROC) curve analysis shows the cut-off value of hemoglobin, below which, patients are prone to suffer from major complications (104.5 g/l in male and 90.5 g/l in female). Among all patients, multivariate analysis showed that preoperative obstructive jaundice [odds ratio (OR) = 1.813, 95% confidence interval (CI) (1.206-2.725), p = 0.004] and pancreatic ductal adenocarcinoma [OR = 1.861, 95% CI (1.178-2.939), p = 0.008] were predictors of anemia. Among paired patients, preoperative anemia [OR = 2.593, 95% CI (1.481-5.541), p = 0.001] and malignant pathology [OR = 4.266, 95% CI (1.597-11.395), p = 0.004] were predictors of postoperative severe complications. Conclusion: Preoperative anemia is a predictor of worse postoperative outcomes following open pancreatoduodenectomy and needs to be identified and treated.

An Insight into Antihyperlipidemic Effects of Polysaccharides from Natural Resources.

Hyperlipidemia is a chronic metabolic disease caused by the abnormal metabolism of lipoproteins in the human body. Its main hazard is to accelerate systemic atherosclerosis, which causes cerebrovascular diseases such as coronary heart disease and thrombosis. At the same time, although the current hypolipidemic drugs have a certain therapeutic effect, they have side effects such as liver damage and digestive tract discomfort. Many kinds of polysaccharides from natural resources possess therapeutic effects on hyperlipidemia but still lack a comprehensive understanding. In this paper, the research progress of natural polysaccharides on reducing blood lipids in recent years is reviewed. The pharmacological mechanisms and targets of natural polysaccharides are mainly introduced. The relationship between structure and hypolipidemic activity is also discussed in detail. This review will help to understand the value of polysaccharides in lowering blood lipids and provide guidance for the development and clinical application of new hypolipidemic drugs.

The psoas muscle density as a predictor of postoperative complications and 30-day mortality for acute mesenteric ischemia patients.

OBJECTIVE: Low muscle mass and quality is associated with poor surgical outcomes. Psoas muscle density (PMD)is a validated surrogate for muscle quality that can be easily measured from a clinical computed tomography (CT) scan. The objective of this study was to investigate the association between PMD and short-term postoperative outcomes in patients with acute mesenteric ischemia (AMI). METHODS: From April 2006 and September 2019, the clinical data of all patients who underwent surgical intervention with a preoperative diagnosis of AMI and had preoperative non-contrast CT images available were retrospectively reviewed. PMD was measured by CT at the third lumbar vertebra. The lowest quartile of PMD for men and women in all patients was used as sex-specific cut-off values for low PMD. Univariate and multivariate analyses evaluating risk factors of postoperative complications and 30-day mortality were performed. RESULTS: The cohort consisted of 88 patients with a mean age of 58.8 ± 16.2 years, of whom 21 (23.9%) patients had low PMD based on the diagnostic cut-off values (40.5 HU for men and 28.4 HU for women), 35 (39.8%) patients developed complications within 30 days of the operation, and 10 (11.3%) patients died within 30 days of surgery. Low PMD patients had a higher risk of postoperative complications and 30-day mortality than patients without low PMD patients. In a multivariate analysis, low PMD and low psoas muscle area (PMA) were independent predictors of postoperative complications. However, only low PMD remained an independent risk factor for 30-day mortality. CONCLUSIONS: Preoperative assessment of the PMD on CT can be a practical method for identifying AMI patients at risk for postoperative complications and 30-day mortality.

Routine postoperative noninvasive respiratory support and pneumonia after elective surgery: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Postoperative pulmonary complications, including pneumonia, are a substantial cause of morbidity. We hypothesised that routine noninvasive respiratory support was associated with a lower incidence of pneumonia after surgery. METHODS: Systematic review and meta-analysis of RCTs comparing the routine use of continuous positive airway pressure (CPAP), noninvasive ventilation (NIV), or high-flow nasal oxygen (HFNO) against standard postoperative care in the adult population. We searched MEDLINE (PubMed), EMBASE, and CENTRAL from the start of indexing to July 27, 2021. Articles were reviewed and data extracted in duplicate, with discrepancies resolved by a senior investigator. The primary outcome was pneumonia, and the secondary outcome was postoperative pulmonary complications. We calculated risk difference (RD) with 95% confidence intervals using DerSimonian and Laird random effects models. We assessed risk of bias using the Cochrane risk of bias tool. RESULTS: From 18 513 records, we included 38 trials consisting of 9782 patients. Pneumonia occurred in 214/4403 (4.9%) patients receiving noninvasive respiratory support compared with 216/3937 (5.5%) receiving standard care (RD -0.01 [95% confidence interval: -0.02 to 0.00]; I2=8%; P=0.23). Postoperative pulmonary complications occurred in 393/1379 (28%) patients receiving noninvasive respiratory support compared with 280/902 (31%) receiving standard care (RD -0.11 [-0.23 to 0.01]; I2=79%; P=0.07). Subgroup analyses did not identify a benefit of CPAP, NIV, or HFNO in preventing pneumonia. Tests for publication bias suggest six unreported trials. CONCLUSION: The results of this evidence synthesis do not support the routine use of postoperative CPAP, NIV, or HFNO to prevent pneumonia after surgery in adults. CLINICAL TRIAL REGISTRATION: PROSPERO: CRD42019156741.

Clinical anatomy of cast specimens of the pancreatic duct / 解剖学报

Objective To explore the distribution and structure of pancreatic ducts and lobules in human pancreas and explore their clinical application value. Methods Three human pancreatic specimens were dissected, 2 of which were fresh whole pancreas samples which were collected from the donated human bod)' after dead,UW organ preservation solution was immediately perfused, and the pancreatic duct was rinsed at low pressure. The surface and internal structure of 1 case was observed as a fixed specimen. Paraffin sections were taken for HE staining to observe the structure of lobules and the distribution of catheters in the leaves. Results The gross specimen showed that the pancreas was composed of lobules of different sizes, with thin layers of connective tissue between the lobules. The pancreatic duct had a complete cast structure and could be clearly displayed to the main duct and the branches of the interlobular duct. The diameters of the interlobular ducts varied widely, and finally a main trunk flowed into the main duct. Each trunk was distributed independently, and the distal pancreatic duct formed a lobule-like structure with different sizes of lobules and no interlobular communication. HE staining showed that the pancreatic lobules were surrounded by connective tissue, in which vascular and ductal structures were visible. Intralobular duct could also be observed in the pancreatic lobules. Conclusion The cast specimen of the human pancreatic duct can clearly show the branch distribution of the pancreatic duct, and the study of the morphological of the pancreatic duct and lobular structure is of great reference value for understanding the clinical problems.

Noradrenergic terminal short-term potentiation enables modality-selective integration of sensory input and vigilance state.

Recent years have seen compelling demonstrations of the importance of behavioral state on sensory processing and attention. Arousal plays a dominant role in controlling brain-wide neural activity patterns, particularly through modulation by norepinephrine. Noradrenergic brainstem nuclei, including locus coeruleus, can be activated by stimuli of multiple sensory modalities and broadcast modulatory signals via axonal projections throughout the brain. This organization might suggest proportional brain-wide norepinephrine release during states of heightened vigilance. Here, however, we have found that low-intensity, nonarousing visual stimuli enhanced vigilance-dependent noradrenergic signaling locally in visual cortex, revealed using dual-site fiber photometry to monitor noradrenergic Ca2+ responses of astroglia simultaneously in cerebellum and visual cortex and two-photon microscopy to monitor noradrenergic axonal terminal Ca2+ dynamics. Nitric oxide, following N-methyl-d-aspartate receptor activation in neuronal nitric oxide synthase-positive interneurons, mediated transient acceleration of norepinephrine-dependent astroglia Ca2+ activation. These findings reveal a candidate cortical microcircuit for sensory modality-selective modulation of attention.

Cephalotaxine-type alkaloids with antiproliferation effects from the branches and leaves of Cephalotaxus fortunei var. alpina.

Eight cephalotaxine-type alkaloids (1-8), including two new compounds cephafortunines A and B (1-2), were isolated from the branches and leaves of Cephalotaxus fortunei var. alpina. Their structures were identified by a series of spectroscopic methods (MS, UV, IR, 1D, and 2D NMR) and comparison with the reported data of known analogs. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations. 1-8 were evaluated for their in vitro antiproliferation effects against two human leukemia cell lines (U937 and HL-60). All compounds showed different levels of antiproliferation effects against U937 cells with GI50 values of 4.21-23.70 µM. 4 and 5 were the most active against U937 cells with GI50 values of 4.21 and 6.58 µM and against HL-60 cells with GI50 values of 6.66 and 6.70 µM, respectively. 4 and 5 arrested HL-60 cell cycle in G0/G1 phase.

Refinement of an open-microcavity optical biosensor for bacterial endotoxin test.

The Limulus Amebocyte Lysate (LAL) test is an in vitro assay widely used in the pharmaceutical and biotechnology industries to detect bacterial endotoxins. Endotoxin is a structural component of the cell wall of Gram-negative bacteria, which has serious pathogenic effects in the body and may cause dysfunction of multiple organ systems and increased risk of mortality. To address the growing need for LAL assays due to the increased demand from drug and vaccine manufacturers, we have developed a new LAL assay approach. Our detection mechanism is different and improved from those currently used in the industry, leading to increased test sensitivity and reduced assay time. Our study utilizes an open-microcavity photonic-crystal biosensor to quantify endotoxin concentrations. It has demonstrated an improved LAL assay sensitivity by 10 fold compared to the commercial standard methods and reduced the time needed for the assay by more than half. In addition, this approach requires as little as 5 µL of LAL reagent per test, thereby decreasing costs and conserving horseshoe crabs. The results reported in this paper indicate the possibility of using the photonic-crystal biosensor based approach for significant enhancements of endotoxin testing.

Preoperative Nutrition Support May Reduce the Prevalence of Postoperative Pancreatic Fistula after Open Pancreaticoduodenectomy in Patients with High Nutritional Risk Determined by NRS2002.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.

Conversion of rice husk into fermentable sugar and silica using acid-catalyzed ionic liquid pretreatment.

Rice husk is a bulky byproduct with a high silica content from rice milling. In this study, the application of an acid-catalyzed ionic liquid (IL) pretreatment was studied for processing rice husks with a rugged structure. The pretreatment conditions were 130°C for 30 min with 1.2 wt% HCl. The results of enzymatic hydrolysis demonstrated that cellulose conversion of HCl-BMIMCl-treated at 48 h was increased by 660.05%, 538.81%, and 376.55% compared with the untreated, HCl-treated, and BMIMCl-treated rice husks, respectively. Composition analysis demonstrated that most of the hemicellulose was removed in the acid-IL combined treatment. Moreover, scanning electron microscopy, X-ray diffraction (XRD), and Fourier transform infrared analyses indicated that the crystalline structure and outer silica layer of the rice husks were efficiently broken up. The results revealed that the HCl-catalyzed dissolution is highly favorable for the industrial application of rick husks in the production of fermentable sugar and high-purity silica.

Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review.

Perivascular epithelioid cell tumor (PEComa) is a mesenchymal tumor rarely described in the liver. Sonazoid is a new ultrasound contrast with both vascular and post-vascular phases due to the uptake of Kupffer cell. CD68 is a defined immunohistorical staining marker for macrophage including Kupffer cell. No previous cases have been reported to reveal Kupffer images in the post-vascular phase by using Sonazoid and pathologic characters of CD68 positive cell in PEComa. Herein, we describe the first case to present Sonazoid contrast-enhanced ultrasonography (CEUS) findings in Kupffer images and CD68 positive cell in hepatic PEComa which may lead to rethink of the phagocytic properties of macrophages.

A Novel ALDH2 Activator AD-9308 Improves Diastolic and Systolic Myocardial Functions in Streptozotocin-Induced Diabetic Mice.

Diabetes mellitus has reached epidemic proportion worldwide. One of the diabetic complications is cardiomyopathy, characterized by early left ventricular (LV) diastolic dysfunction, followed by development of systolic dysfunction and ventricular dilation at a late stage. The pathogenesis is multifactorial, and there is no effective treatment yet. In recent years, 4-hydroxy-2-nonenal (4-HNE), a toxic aldehyde generated from lipid peroxidation, is implicated in the pathogenesis of cardiovascular diseases. Its high bioreactivity toward proteins results in cellular damage. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that detoxifies 4-HNE. The development of small-molecule ALDH2 activator provides an opportunity for treating diabetic cardiomyopathy. This study found that AD-9308, a water-soluble andhighly selective ALDH2 activator, can improve LV diastolic and systolic functions, and wall remodeling in streptozotocin-induced diabetic mice. AD-9308 treatment dose-dependently lowered serum 4-HNE levels and 4-HNE protein adducts in cardiac tissue from diabetic mice, accompanied with ameliorated myocardial fibrosis, inflammation, and apoptosis. Improvements of mitochondrial functions, sarco/endoplasmic reticulumcalcium handling and autophagy regulation were also observed in diabetic mice with AD-9308 treatment. In conclusion, ADLH2 activation effectively ameliorated diabetic cardiomyopathy, which may be mediated through detoxification of 4-HNE. Our findings highlighted the therapeutic potential of ALDH2 activation for treating diabetic cardiomyopathy.