Farrerol Alleviates Diabetic Cardiomyopathy by Regulating AMPK-Mediated Cardiac Lipid Metabolic Pathways in Type 2 Diabetic Rats.

Diabetic cardiomyopathy (DCM) is a prevalent complication of diabetes mellitus characterized by cardiac dysfunction and myocardial remodeling. Farrerol (FA), an active ingredient in Rhododendron with various pharmacological activities, has an unclear specific role in DCM. Therefore, this study aims to investigate the effects of FA on DCM rats and elucidate its mechanism. The type 2 diabetes mellitus (T2DM) model was induced in adult male Sprague-Dawley rats by administering a high-fat diet for 8 weeks along with STZ injection. Subsequent to successful modeling, FA and the positive drug Dapagliflozin (Dapa) were orally administered via gavage for an additional 8-week period. After administration, the rats' body weight, fasting blood glucose, fasting insulin, and blood lipid profiles were quantified. Cardiac function was assessed through evaluation of cardiac function parameters, histopathological examination and measurement of myocardial enzyme markers were conducted to assess myocardial injury and fibrosis, Oil red O staining was utilized to evaluate myocardial lipid accumulation, wheat germ agglutinin (WGA) staining was used for assessing cardiomyocyte hypertrophy, and Western blot analysis was used to detect the proteins expression level of AMP-activated protein kinase (AMPK) pathway. The rat cardiomyocyte H9c2 were induced with palmitic acid to establish an in vitro cell model of myocardial lipid toxicity. Subsequently, the cells were subjected to treatment with FA and AMPK inhibitor Compound C, followed by assessment of lipid formation and expression levels of proteins related to the AMPK signaling pathway. The findings demonstrated that both FA and Dapa exhibited efficacy in ameliorating diabetic symptoms, cardiac dysfunction, myocardial fibrosis, cardiomyocyte hypertrophy, and lipid accumulation in T2DM rats. Additionally, they were found to enhance AMPK phosphorylation and PPARα expression while down-regulating CD36. Similarly, FA was observed to inhibit lipid formation in H9c2 and activate the AMPK signaling pathway. However, the improved effect of FA on lipotoxic cardiomyocytes induced by palmitic acid was partially reversed by Compound C. Therefore, the activation of the AMPK signaling pathway by FA may enhance cardiac lipid metabolism, thereby improving cardiac dysfunction and myocardial fibrosis in DCM rats.

Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans.

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.

Comprehensive evaluation of the mechanism of Banxia Baizhu Tianma Decoction in ameliorating posterior circulation ischemia vertigo based on integrating fecal short-chain fatty acids and 16S rRNA sequencing.

Posterior circulation ischemia vertigo (PCIV) is vertebrobasilar insufficiency resulting in vertigo. Banxia Baizhu Tianma Decoction (BBTD) is broadly applied to treat PCIV in China, but its efficacy and detailed mechanism remains unclear. Therefore, this study aims to investigate the effects of BBTD on PCIV, and identify important gut microbiota and its derived short-chain fatty acid (SCFA) changes and the detailed mechanism through 16 S rRNA sequencing with SCFAs profiling. In this study, the model of PCIV was established by surgical ligation of the right subclavian artery (RSCA) and right common carotid artery (RCCA). We found that BBTD administration effectively reduced the volume of cerebral infarction and improved neurologic functions, reduced neuronal apoptosis and neuroinflammatory. Moreover, BBTD significantly modulated the diversity and composition of the gut microbiota, including increasing the relative abundance of Lactobacillus, Prevotella and Akkermansia and decreasing relative abundances of Lachnospiraceae, Bacteroidetes (S24-7) and Ruminococcaceae. BBTD treatment also increased propionate content. Propionate mediates the the recovery of neurological functions and anti-apoptotic effects of BBTD in PCIV rat. Our findings wish to discover the potential mechanism of BBTD treatment on PCIV and promote its clinical application.

Preferential HDAC6 inhibitors derived from HPOB exhibit synergistic antileukemia activity in combination with decitabine.

Histone deacetylase 6 (HDAC6) is an emerging drug target to treat oncological and non-oncological conditions. Since highly selective HDAC6 inhibitors display limited anticancer activity when used as single agent, they usually require combination therapies with other chemotherapeutics. In this work, we synthesized a mini library of analogues of the preferential HDAC6 inhibitor HPOB in only two steps via an Ugi four-component reaction as the key step. Biochemical HDAC inhibition and cell viability assays led to the identification of 1g (highest antileukemic activity) and 2b (highest HDAC6 inhibition) as hit compounds. In subsequent combination screens, both 1g and especially 2b showed synergy with DNA methyltransferase inhibitor decitabine in acute myeloid leukemia (AML). Our findings highlight the potential of combining HDAC6 inhibitors with DNA methyltransferase inhibitors as a strategy to improve AML treatment outcomes.

Photoinduced decatungstate-catalyzed C(sp3)-H thioetherification by sulfinate salts.

Thiols and thioesters play crucial roles in pharmaceuticals, biology, and material science as essential organosulfur compounds. Leveraging readily available and cost-effective inert alkanes through direct thioetherification holds promise for yielding high-value-added products. Herein, we present a photoinduced strategy for sulfur-containing modification of inert alkanes utilizing decatungstate as hydrogen atom transfer reagent, offering a straightforward and practical approach for synthesizing thioethers and thioesters.

Dynamic Analysis of the Impact of Micropapillary Component on Different Recurrence Patterns of Pathological Stage IA3 Lung Adenocarcinoma: A Multicenter, Retrospective Study.

BACKGROUND: This study aimed to evaluate the dynamic impact of the micropapillary (MIP) component on local recurrence (LR), distant metastasis (DM), and multiple recurrence (MR) of pathological stage IA3 lung adenocarcinoma. METHODS: Between July 2012 and July 2020, a total of 351 patients at two medical institutions were enrolled in this study. Cumulative incidence of curves, dynamic risk curves, and time-dependent multivariate analysis was performed to evaluate the effect of the MIP component on patients. RESULTS: The 5-year cumulative incidence of total recurrence with or without an MIP component was 34.2% and 12.3%, respectively (p = 0.001). In three recurrence patterns, our findings revealed that the 5-year cumulative incidence of LR (p = 0.048) and DM (p = 0.005) was higher in the 'MIP-present' group than in the 'MIP-absent' group. In the dynamic recurrence curve, the risk of the three recurrence patterns was different and varied over time between the two groups, especially in DM. Moreover, the dynamic cumulative event curve showed that after 1, 2, and 3 years of survival, the cumulative incidence of DM in the group with MIP continued to be higher than that in the group without MIP (all p < 0.05). Time-dependent Cox regression analysis indicated that the MIP component continued to be an independent risk factor for the cumulative incidence of DM in patients with 3-year survival. CONCLUSIONS: Of the three recurrence patterns, the MIP component mainly aggravated the risk of DM in patients with pathological stage IA3 lung adenocarcinoma, which persisted for 3 years.

Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells.

HSP90 has emerged as an appealing anti-cancer target. However, HSP90 inhibitors (HSP90i) are characterized by limited clinical utility, primarily due to the resistance acquisition via heat shock response (HSR) induction. Understanding the roles of abundantly expressed cytosolic HSP90 isoforms (α and ß) in sustaining malignant cells' growth and the mechanisms of resistance to HSP90i is crucial for exploiting their clinical potential. Utilizing multi-omics approaches, we identified that ablation of the HSP90ß isoform induces the overexpression of HSP90α and extracellular-secreted HSP90α (eHSP90α). Notably, we found that the absence of HSP90α causes downregulation of PTPRC (or CD45) expression and restricts in vivo growth of BCR-ABL1+ leukemia cells. Subsequently, chronic long-term exposure to the clinically advanced HSP90i PU-H71 (Zelavespib) led to copy number gain and mutation (p.S164F) of the HSP90AA1 gene, and HSP90α overexpression. In contrast, acquired resistance toward other tested HSP90i (Tanespimycin and Coumermycin A1) was attained by MDR1 efflux pump overexpression. Remarkably, combined CDK7 and HSP90 inhibition display synergistic activity against therapy-resistant BCR-ABL1+ patient leukemia cells via blocking pro-survival HSR and HSP90α overexpression, providing a novel strategy to avoid the emergence of resistance against treatment with HSP90i alone.

Deep learning predicts cervical lymph node metastasis in clinically node-negative papillary thyroid carcinoma.

OBJECTIVES: Precise determination of cervical lymph node metastasis (CLNM) involvement in patients with early-stage thyroid cancer is fairly significant for identifying appropriate cervical treatment options. However, it is almost impossible to directly judge lymph node metastasis based on the imaging information of early-stage thyroid cancer patients with clinically negative lymph nodes. METHODS: Preoperative US images (BMUS and CDFI) of 1031 clinically node negative PTC patients definitively diagnosed on pathology from two independent hospitals were divided into training set, validation set, internal test set, and external test set. An ensemble deep learning model based on ResNet-50 was built integrating clinical variables, BMUS, and CDFI images using a bagging classifier to predict metastasis of CLN. The final ensemble model performance was compared with expert interpretation. RESULTS: The ensemble deep convolutional neural network (DCNN) achieved high performance in predicting CLNM in the test sets examined, with area under the curve values of 0.86 (95% CI 0.78-0.94) for the internal test set and 0.77 (95% CI 0.68-0.87) for the external test set. Compared to all radiologists averaged, the ensemble DCNN model also exhibited improved performance in making predictions. For the external validation set, accuracy was 0.72 versus 0.59 (p = 0.074), sensitivity was 0.75 versus 0.58 (p = 0.039), and specificity was 0.69 versus 0.60 (p = 0.078). CONCLUSIONS: Deep learning can non-invasive predict CLNM for clinically node-negative PTC using conventional US imaging of thyroid cancer nodules and clinical variables in a multi-institutional dataset with superior accuracy, sensitivity, and specificity comparable to experts. CRITICAL RELEVANCE STATEMENT: Deep learning efficiently predicts CLNM for clinically node-negative PTC based on US images and clinical variables in an advantageous manner. KEY POINTS: • A deep learning-based ensemble algorithm for predicting CLNM in PTC was developed. • Ultrasound AI analysis combined with clinical data has advantages in predicting CLNM. • Compared to all experts averaged, the DCNN model achieved higher test performance.

Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering.

α-synuclein (α-Syn) is a presynaptic protein that is involved in Parkinson's and other neurodegenerative diseases and binds to negatively charged phospholipids. Previously, we reported that α-Syn clusters synthetic proteoliposomes that mimic synaptic vesicles. This vesicle-clustering activity depends on a specific interaction of α-Syn with anionic phospholipids. Here, we report that α-Syn surprisingly also interacts with the neutral phospholipid lysophosphatidylcholine (lysoPC). Even in the absence of anionic lipids, lysoPC facilitates α-Syn-induced vesicle clustering but has no effect on Ca2+-triggered fusion in a single vesicle-vesicle fusion assay. The A30P mutant of α-Syn that causes familial Parkinson disease has a reduced affinity to lysoPC and does not induce vesicle clustering. Taken together, the α-Syn-lysoPC interaction may play a role in α-Syn function.

Colonization of multidrug-resistant Gram-negative bacteria increases risk of surgical site infection after hemorrhoidectomy: a cross-sectional study of two centers in southern China.

PURPOSE: The present study aims to determine the rectoanal colonization rate and risk factors for the colonization of present multidrug-resistant bacteria (MDRBs). In addition, the relationship between MDRB colonization and surgical site infection (SSI) following hemorrhoidectomy was explored. METHODS: A cross-sectional study was conducted in the Department of Colorectal Surgery of two hospitals. Patients with hemorrhoid disease, who underwent hemorrhoidectomy, were included. The pre-surgical screening of multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization was performed using rectal swabs on the day of admission. Then, the MDRB colonization rate was determined through the rectal swab. Logistic regression models were established to determine the risk factors for MDRB colonization and SSI after hemorrhoidectomy. A p-value of < 0.05 was considered statistically significant. RESULTS: A total of 432 patients met the inclusion criteria, and the MDRB colonization prevalence was 21.06% (91/432). The independent risk factors for MDRB colonization were as follows: patients who received ≥ 2 categories of antibiotic treatment within 3 months (odds ratio (OR): 3.714, 95% confidence interval (CI): 1.436-9.605, p = 0.007), patients with inflammatory bowel disease (IBD; OR: 6.746, 95% CI: 2.361-19.608, p < 0.001), and patients with high serum uric acid (OR: 1.006, 95% CI: 1.001-1.010, p = 0.017). Furthermore, 41.57% (37/89) of MDRB carriers and 1.81% (6/332) of non-carriers developed SSIs, with a total incidence of 10.21% (43/421). Based on the multivariable model, the rectoanal colonization of MDRBs (OR: 32.087, 95% CI: 12.052-85.424, p < 0.001) and hemoglobin < 100 g/L (OR: 4.130, 95% CI: 1.556-10.960, p = 0.004) were independently associated with SSI after hemorrhoidectomy. CONCLUSION: The rectoanal colonization rate of MDRBs in hemorrhoid patients is high, and this was identified as an independent risk factor for SSI after hemorrhoidectomy.

Iron-loading N and S heteroatom doped porous carbon derived from chitosan and CdS-Tetrahymena thermophila for peroxymonosulfate activation.

Transforming waste into resources is an important strategy to enhance the economic efficiency and reduce the waste entering the environment. In this work, iron-loading N and S co-doped porous carbon materials, as peroxymonosulfate (PMS) activator for pollutants degradation, were prepared by pyrolysis of the mixture of iron loading chitosan and CdS-Tetrahymena thermophila under N2 flow. Chitosan is mainly derived from the shell waste of shrimp and crab, and CdS-Tetrahymena thermophila is produced in the removing process of Cd2+ pollution bioremediation using Tetrahymena thermophila. The synergistic effects of iron related species and heteroatoms (S/N) co-doped porous carbon in the obtained carbon materials improved the performance for activating PMS. The prepared Fe-S-CS-1-900 exhibited high performance for the degradation of Rhodamine B (RhB) by activating PMS. Radical quenching tests and electron paramagnetic resonance measurements suggested that superoxide radical (O2-) and singlet oxygen (1O2) were the primary reactive oxygen species in RhB degradation. These results propose new insights of using biomass waste to derive Fe-loading N and S heteroatom co-doping carbon as PMS activator applied in the removal of organic pollutants.

Photoelectrochemical oxidative C(sp3)-H borylation of unactivated hydrocarbons.

Organoboron compounds are of high significance in organic synthesis due to the unique versatility of boryl substituents to access further modifications. The high demand for the incorporation of boryl moieties into molecular structures has witnessed significant progress, particularly in the C(sp3)-H borylation of hydrocarbons. Taking advantage of special characteristics of photo/electrochemistry, we herein describe the development of an oxidative C(sp3)-H borylation reaction under metal- and oxidant-free conditions, enabled by photoelectrochemical strategy. The reaction exhibits broad substrate scope (>57 examples), and includes the use of simple alkanes, halides, silanes, ketones, esters and nitriles as viable substrates. Notably, unconventional regioselectivity of C(sp3)-H borylation is achieved, with the coupling site of C(sp3)-H borylation selectively located in the distal methyl group. Our method is operationally simple and easily scalable, and offers a feasible approach for the one-step synthesis of high-value organoboron building blocks from simple hydrocarbons, which would provide ample opportunities for drug discovery.

Research Progress on the Preparation and Function of Antioxidant Peptides from Walnuts.

Food-derived peptides have good antioxidant activity and are highly safe for humans; consequently, there has been continuous growth in research on antioxidants, with potential applications in food, medicine, cosmetics, and other fields. Among food-derived peptides, walnut-derived peptides have attracted increasing attention as food-derived peptides rich in eight essential amino acids. This review summarizes the progress made in the development and identification of antioxidant peptides in walnut proteins. This article mainly describes the interaction between reactive oxygen species and cellular antioxidant products, modulation of enzyme content and activity, and regulation of the redox signaling pathways and analyzes the mechanisms of reduction in oxidative stress. Finally, the complex structure-activity relationships of walnut-derived peptides are analyzed based on their amino acid composition and secondary structure of the polypeptides. This review provides a theoretical basis for the production of walnut-derived antioxidant peptides and could help promote the development of the walnut industry.

High-throughput screening as a drug repurposing strategy for poor outcome subgroups of pediatric B-cell precursor Acute Lymphoblastic Leukemia.

Although a great cure rate has been achieved for pediatric BCP-ALL, approximately 15% of patients do not respond to conventional chemotherapy and experience disease relapse. A major effort to improve the cure rates by treatment intensification would result in an undesirable increase in treatment-related toxicity and mortality, raising the need to identify novel therapeutic approaches. High-throughput (HTP) drug screening enables the profiling of patients' responses in vitro and allows the repurposing of compounds currently used for other diseases, which can be immediately available for clinical application. The aim of this study was to apply HTP drug screening to identify potentially effective compounds for the treatment of pediatric BCP-ALL patients with poor prognosis, such as patients with Down Syndrome (DS) or carrying rearrangements involving PAX5 or KMT2A/MLL genes. Patient-derived Xenografts (PDX) samples from 34 BCP-ALL patients (9 DS CRLF2r, 15 PAX5r, 10 MLLr), 7 human BCP-ALL cell lines and 14 hematopoietic healthy donor samples were screened on a semi-automated HTP drug screening platform using a 174 compound library (FDA/EMA-approved or in preclinical studies). We identified 9 compounds active against BCP-ALL (ABT-199/venetoclax, AUY922/luminespib, dexamethasone, EC144, JQ1, NVP-HSP990, paclitaxel, PF-04929113 and vincristine), but sparing normal cells. Ex vivo validations confirmed that the BCL2 inhibitor venetoclax exerts an anti-leukemic effect against all three ALL subgroups at nanomolar concentrations. Overall, this study points out the benefit of HTP screening application for drug repurposing to allow the identification of effective and clinically translatable therapeutic agents for difficult-to-treat childhood BCP-ALL subgroups.

Effects of a ground-glass opacity component on the recurrence and survival of pathological stage IA3 lung adenocarcinoma: a multi-institutional retrospective study.

Background: This study aimed to evaluate the effect of the presence of a radiographically manifested ground-glass opacity (GGO) component on the prognosis of patients with pathological stage IA3 lung adenocarcinoma. Methods: Patients diagnosed with pathological stage IA3 lung adenocarcinoma who underwent radical surgery at two medical institutions in China between July 2012 and July 2020 were enrolled. The cumulative incidence of recurrence (CIR) and cumulative incidence of death (CID) in patients with and without a GGO component were compared. Risk curves for the recurrence and tumor-related death overtime were analyzed between the two groups according to life table. In order to validate the prognostic value of GGO components, the recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated. Decision curve analysis (DCA) was performed to evaluate the clinical benefit rate of different models. Results: Among the 352 included patients, the presence of a GGO component was radiographically shown in 166 (47.2%) patients, while 186 (52.8%) displayed solid nodules. Patients exhibiting the absence of a GGO component had higher incidences of total recurrence (17.2% vs. 3.0%, P<0.001), local-regional recurrence (LRR) (5.4% vs. 0.6%, P=0.010), distant metastasis (DM) (8.1% vs. 1.8%, P=0.008), and multiple recurrences (4.3% vs. 0.6%, P=0.028) than the presence-GGO component group. The 5-year CIR and CID were 7.5% and 7.4% in the presence-GGO component group, and 24.5% and 17.0% in the absence-GGO component group, respectively, with statistically significant differences between the two groups (P<0.05). The risk of recurrence in patients with the presence of GGO components showed a single peak at 3 years postoperatively, while patients with the absence of GGO components showed a double peak at 1 and 5 years after surgery, respectively. However, the risk of tumor-related death peaked in both groups at 3 and 6 years postoperatively. Multivariate Cox analysis showed that the presence of a GGO component was a favorable independent risk factor for pathological stage IA3 lung adenocarcinoma patients (P<0.05). Conclusions: Pathological stage IA3 lung adenocarcinoma with or without GGO components are two types of tumors with different invasive abilities. In clinical practice, we should develop different treatment and follow-up strategies.

A Multi-institutional Analysis of the Combined Effect of Micropapillary Component and Consolidation-to-Tumor Ratio >0.5 on the Prognosis of Pathological, Stage IA3, Lung Adenocarcinoma.

INTRODUCTION: The study investigated the synergistic effect of the micropapillary (MIP) component and consolidation-to-tumor ratio (CTR) on the recurrence and survival of patients with pathologic stage IA3 lung adenocarcinoma. METHODS: We enrolled 419 patients confirmed pathological stage IA3 adenocarcinoma from four institutions. Kaplan-Meier analysis was performed to examine the value of the MIP component and CTR on relapse-free survival (RFS) and overall survival (OS). The cumulative recurrence between different stages was analyzed by using cumulative event curves. RESULTS: RFS (P < 0.0001) and OS (P = 0.008) in the presence of the MIP group were significantly lower than those in the absence of the MIP group, and CTR > 5 only reduced RFS (P = 0.0004), but not OS (P = 0.063), in the patients. In addition, the prognosis of patients with both the MIP component and CTR > 5 was worse than that of those without the MIP component or CTR ≤ 5. Therefore, we established new subtypes of the stage IA3: IA3a, IA3b, and IA3c. RFS and OS for IA3c staging were significantly lower than those for IA3a and IA3b. For IA3c, the cumulative incidence of local recurrence (P < 0.001) and that of distant metastasis (P = 0.004) were significantly higher than those for IA3a and IA3b. CONCLUSIONS: The MIP component combined with CTR > 0.5 can effectively predict the prognosis of patients with pathological stage IA3 lung adenocarcinoma and may offer more detailed recurrence and survival information according to the established subtype stage of IA3.

In vitro studies of factors affecting debridement of dental implants by tricalcium phosphate powder abrasive treatment.

Peri-implantitis is a common complication characterized by inflammation in tissues surrounding dental implants due to plaque accumulation, which can lead to implant failure. While air flow abrasive treatment has been found to be effective for debriding implant surfaces, little is known about the factors that affect its cleaning capacity. This study systematically examined the cleaning capacity of air powder abrasive (APA) treatment with ß-tricalcium phosphate (ß-TCP) powder, using various powder jetting strengths and different particle sizes. Three sizes of ß-TCP powder (S, M, and L) were prepared, and different powder settings (low, medium, and high) were tested. The cleaning capacity was determined by quantifying ink removal, which simulated biofilm removal from the implant surfaces at different time points. The results of the systematic comparisons showed that the most efficient cleaning of implant surfaces was achieved using size M particles with medium setting. Additionally, the amount of powder consumed was found to be critical to cleaning efficiency, and the implant surfaces were altered in all tested groups. These systematically analyzed outcomes may provide insights into the development of potential non-surgical strategies for treating peri-implant diseases.

Big data on the prevalence of injury deaths among 187 488 elderly Chinese in the past 20 years (2000-2020): a systematic review and meta-analysis.

BACKGROUND: This study systematically reviewed injury death and causes in the elderly population in China from 2000 to 2020, to prevent or reduce the occurrence of injuries and death. METHODS: The CNKI, VIP, Wan Fang, MEDLINE, Embase, SinoMed, and Web of Science databases were searched to collect epidemiological characteristics of injury death among elderly over 60 years old in China from January 2000 to December 2020. Random effects meta-analysis was performed to pool injury mortality rate and identify publication bias, with study quality assessed using the AHRQ risk of bias tool. RESULTS: (1) A total of 41 studies with 187 488 subjects were included, covering 125 million elderly. The pooled injury mortality rate was 135.58/105 [95%CI: (113.36 to 162.14)/105], ranking second in the total death cause of the elderly. (2)Subgroup analysis showed that male injury death (146.00/105) was significantly higher than that of females (127.90/105), and overall injury mortality increased exponentially with age (R2 = 0.957), especially in those over 80 years old; the spatial distribution shows that the injury death rate in the central region is higher than that in the east and west and that in the countryside is higher than that in the city; the distribution of death time shows that after entering an aging society (2000-2020) is significantly higher than before (1990-2000). (3) There are more than 12 types of injury death, and the top three are falling, traffic accidents, and suicide. CONCLUSIONS: China's elderly injury death rate is at a high level in the world, with more males than females, especially after the age of 80. There are regional differences. The main types of injury death are falling, traffic, and suicide. During the 14th Five-Year Plan period, for accidental injuries and death, a rectification list for aging and barrier-free environments was issued. PROSPERO REGISTRATION: The systematic review was registered in PROSPERO under protocol number CRD42022359992.