Metabolic syndrome score as an indicator in a predictive nomogram for lymph node metastasis in endometrial cancer.

BACKGROUND: Lymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer. METHODS: This study is based on patients diagnosed with EC in Peking University People's Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors. RESULTS: The prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size > = 2 cm, myometrial invasion > = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81-0.90) and 0.77 (95% CI: 0.77-0.83), respectively (P < 0.01). In the validation group (N = 359), the AUC was 0.87 (95% CI: 0.82-0.93) and 0.80 (95% CI: 0.74-0.87) for the nomogram and the Mayo criteria, respectively (P = 0.01). Calibration plots revealed the satisfactory performance of the nomogram. Decision curve analysis showed a positive net benefit of this nomogram, which indicated clinical value. CONCLUSION: This model may promote risk stratification and individualized treatment, thus improving the prognosis.

Discovery and identification of a novel small molecule BCL-2 inhibitor that binds to the BH4 domain.

The B-cell lymphoma 2 (BCL-2) protein family plays a pivotal role in regulating the apoptosis process. BCL-2, as an antiapoptotic protein in this family, mediates apoptosis resistance and is an ideal target for cell death strategies in cancer therapy. Traditional treatment modalities target BCL-2 by occupying the hydrophobic pocket formed by BCL-2 homology (BH) domains 1-3, while in recent years, the BH4 domain of BCL-2 has also been considered an attractive novel target. Herein, we describe the discovery and identification of DC-B01, a novel BCL-2 inhibitor targeting the BH4 domain, through virtual screening combined with biophysical and biochemical methods. Our results from surface plasmon resonance and cellular thermal shift assay confirmed that the BH4 domain is responsible for the interaction between BCL-2 and DC-B01. As evidenced by further cell-based experiments, DC-B01 induced cell killing in a BCL-2-dependent manner and triggered apoptosis via the mitochondria-mediated pathway. DC-B01 disrupted the BCL-2/c-Myc interaction and consequently suppressed the transcriptional activity of c-Myc. Moreover, DC-B01 inhibited tumor growth in vivo in a BCL­2­dependent manner. Collectively, these results indicate that DC-B01 is a promising BCL-2 BH4 domain inhibitor with the potential for further development.

Discovery and characterization of a novel cGAS covalent inhibitor for the treatment of inflammatory bowel disease.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, acts as a nucleotidyl transferase that catalyzes ATP and GTP to form cyclic GMP-AMP (cGAMP) and plays a critical role in innate immunity. Hyperactivation of cGAS-STING signaling contributes to hyperinflammatory responses. Therefore, cGAS is considered a promising target for the treatment of inflammatory diseases. Herein, we report the discovery and identification of several novel types of cGAS inhibitors by pyrophosphatase (PPiase)-coupled activity assays. Among these inhibitors, 1-(1-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)prop-2-yn-1-one (compound 3) displayed the highest potency and selectivity at the cellular level. Compound 3 exhibited better inhibitory activity and pathway selectivity than RU.521, which is a selective cGAS inhibitor with anti-inflammatory effects in vitro and in vivo. Thermostability analysis, nuclear magnetic resonance and isothermal titration calorimetry assays confirmed that compound 3 directly binds to the cGAS protein. Mass spectrometry and mutation analysis revealed that compound 3 covalently binds to Cys419 of cGAS. Notably, compound 3 demonstrated promising therapeutic efficacy in a dextran sulfate sodium (DSS)-induced mouse colitis model. These results collectively suggest that compound 3 will be useful for understanding the biological function of cGAS and has the potential to be further developed for inflammatory disease therapies.

Exploring novel systemic therapies for pancreatic cancer: a review of emerging anti-PD-1/PD-L1 combination therapy.

Despite attempts to apply single therapy such as surgical treatment, chemotherapy, or radiotherapy, pancreatic cancer (PC) is still one of the most lethal solid tumors. Moreover, immune checkpoint inhibitors against PD-1/PD-L1, which have shown good efficacies against many other solid tumors, have not shown encouraging results in PC treatment. Therefore, some studies are evaluating the efficacies of combination therapies based on anti-PD-1/PD-L1 for PC. In this review, we summarized the emerging anti-PD-1/PD-L1 combination therapies for PC in these years. We realized that anti-PD-1/PD-L1-based combination therapies have the potential to be efficacious in PC treatment, and further relevant studies are needed. Moreover, we elucidated the reasons for the ineffectiveness of anti-PD-1/PD-L1 alone in PC treatment. We concluded that this was mainly because PC has an immunosuppressive tumor microenvironment and develops drug resistance during treatment. Anti-PD-1/PD-L1-based combination therapeutic regimens that alter the immunosuppressive tumor microenvironment and reduce the development of drug resistance in PC are summarized in this review, and we expect that these regimens will achieve good clinical application prospects.

Establishing a reference range for thromboelastography maximum amplitude in patients administrating with antiplatelet drugs.

OBJECTIVE: We aimed to establish the reference range of thromboelastograph (TEG) maximum amplitude (MA) in patients taking antiplatelet drugs. METHODS: Between August 2015 and July 2018, a total of 4614 patients administrating with antiplatelet drugs (clopidogrel and aspirin) were retrospectively analyzed in this study. For MAA parameter, we used the 10th and 90th percentiles to establish a reference range. The Spearman correlation was used for the correlation analysis among the inhibition rate of adenosine diphosphate (ADP%) and MAADP , inhibition rate of arachidonic acid (AA%) and MAAA . Then, through receiver operating characteristic (ROC) curve analysis of the best cutoff point, the reference ranges of MAADP and MAAA could be deduced. Consistency evaluation was performed by statistical analysis of ADP% and MAADP , AA% and MAAA pairing for 4459 patients. RESULTS: The reference range of MAA was 8.1-25.8 mm. The reference range of MAADP was 19.8-43.2 mm, and the corresponding sensitivity of two endpoints was 0.796, 0.856 and specificity were 0.897, 0.904, respectively. The reference range of MAAA was 18.9-37.7 mm, and the corresponding sensitivity of two endpoints was 0.819, 0.829 and specificity were 0.922, 0.896, respectively. The inconsistency rate of ADP% and MAADP , and AA% and MAAA was 20.1% (898 cases) and 16.6% (738 cases), respectively. CONCLUSIONS: The reference range of MAADP and MAAA established by us were better in sensitivity and specificity. MAADP and MAAA were more accurate than conventional inhibition rate analysis in guidance of antiplatelet therapy, especially in patients with excessive low MA or high MAA .

Intradialytic blood pressure pattern recognition based on density peak clustering.

End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD) and requires hemodialysis (HD) for survival. Intradialytic blood pressure (IBP) measurements are necessary to ensure patient safety during HD treatments and have critical clinical and prognostic significance. Studies on IBP measurements, especially IBP patterns, are limited. All related studies have been based on a priori knowledge and artificially classified IBP patterns. Therefore, the results were influenced by subjective concepts. In this study, we proposed a new approach to identify IBP patterns to classify ESRD patients. We used the dynamic time warping (DTW) algorithm to measure the similarity between two series of IBP data. Five blood pressure (BP) patterns were identified by applying the density peak clustering algorithm (DPCA) to the IBP data. To illustrate the association between BP patterns and prognosis, we constructed three random survival forest (RSF) models with different covariates. Model accuracy was improved 3.7-6.3% by the inclusion of BP patterns. The results suggest that BP patterns have critical clinical and prognostic significance regarding the risk of cerebrovascular events. We can also apply this clustering approach to other time series data from electronic health records (EHRs). This work is generalizable to analyses of dense EHR data.

The effect of donor-recipient gender mismatch on short- and long-term graft survival in kidney transplantation: a systematic review and meta-analysis.

BACKGROUND: There is no limitation of gender matching in renal transplantation. This study was intended to evaluate its effect on short- and long-term graft survival. METHODS: PubMed, the Web of Knowledge, Medline, the Cochrane Library, and two additional Chinese databases were searched. The data were then abstracted and meta-analyzed. RESULTS: 14 studies involving 445 279 patients were included. Each study reported data on the four gender matches (male donor-male recipient, MDMR; male donor-female recipient, MDFR; female donor-male recipient, FDMR; female donor-female recipient, FDFR). The pooled risk ratios (RRs) for 0.5-, 1-, 2-, 3-, 5-, and 10-yr graft survival rates showed that the FDMR group had the worst outcomes, and when recipients were female, short-term graft survival was worse, but long-term graft survival was better. The differences between groups changed with time. CONCLUSIONS: FDMR patients showed poor graft survival. The female recipients had worse short-term graft survival but the best long-term graft survival. This study introduces an important consideration into donor-recipient matching in renal transplantation.

Sling Versus Abduction Brace Shoulder Immobilization After Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis.

Background: The optimal immobilization position of the shoulder after rotator cuff repair is controversial. Purpose: To compare the clinical outcomes and incidence of retears after arthroscopic rotator cuff repair between patients who used an abduction brace versus a sling for postoperative shoulder immobilization. Study Design: Systematic review; Level of evidence, 1. Methods: This systematic review and meta-analysis was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched the PubMed, MEDLINE, and Embase electronic databases for randomized controlled trials (RCTs) that compared abduction brace and sling immobilization after arthroscopic rotator cuff repair using single-row, double-row, or suture-bridge fixation. Clinical scores, pain severity, and retear rates were compared between patients with abduction brace versus sling immobilization. Results: Of 1572 retrieved studies, 4 RCTs with a total of 224 patients (112 patients with abduction brace and 112 patients with sling) were included in the qualitative analysis, and 3 of the RCTs were included in the quantitative analysis (meta-analysis). There were no significant differences between the abduction brace and sling immobilization groups in the Constant-Murley score at 3 months (weighted mean difference [WMD], 0.26 [95% CI, -1.30 to 1.83]; P = .74; I 2 = 84%), 6 months (WMD, 1.91 [95% CI, -0.17 to 4.00]; P = .07; I 2 = 85%), and 12 months (WMD, 0.55 [95% CI, -1.37 to 2.47]; P = .57; I 2 = 0%); the visual analog scale score for pain at 1 week (WMD, 0.10 [95% CI, -0.20 to 0.41]; P = .51; I 2 = 0%), 3 weeks (WMD, -0.12 [95% CI, -0.34 to 1.00]; P = .29; I 2 = 0%), 6 weeks (WMD, -0.12 [95% CI, -0.30 to 0.06]; P = .20; I 2 = 0%), and 12 weeks (WMD, -0.13 [95% CI, -0.27 to 0.02]; P = .09; I 2 = 18%); or the retear rate at 3 months (risk ratio, 0.63 [95% CI, 0.09 to 4.23]; P = .64; Z = 0.47%) postoperatively. Conclusion: Our systematic review demonstrated a lack of significant differences between the abduction brace and sling immobilization groups regarding postoperative clinical scores, pain severity, and tendon healing.

Development of a native-locus dual reporter system for the efficient screening of the hyper-production of natural products in Streptomyces.

Streptomyces is renowned for its abundant production of bioactive secondary metabolites, but most of these natural products are produced in low yields. Traditional rational network refactoring is highly dependent on the comprehensive understanding of regulatory mechanisms and multiple manipulations of genome editing. Though random mutagenesis is fairly straightforward, it lacks a general and effective strategy for high throughput screening of the desired strains. Here in an antibiotic daptomycin producer S. roseosporus, we developed a dual-reporter system at the native locus of the daptomycin gene cluster. After elimination of three enzymes that potentially produce pigments by genome editing, a gene idgS encoding the indigoidine synthetase and a kanamycin resistant gene neo were integrated before and after the non-ribosomal peptidyl synthetase genes for daptomycin biosynthesis, respectively. After condition optimization of UV-induced mutagenesis, strains with hyper-resistance to kanamycin along with over-production of indigoidine were efficiently obtained after one round of mutagenesis and target screening based on the dual selection of the reporter system. Four mutant strains showed increased production of daptomycin from 1.4 to 6.4 folds, and significantly improved expression of the gene cluster. Our native-locus dual reporter system is efficient for targeting screening after random mutagenesis and would be widely applicable for the effective engineering of Streptomyces species and hyper-production of these invaluable natural products for pharmaceutical development.

[Characteristics of Benthic Diatom Community Structure and Water Ecological Health Evaluation in the Lalin River Basin].

With the improvement of public requirements for the health status of aquatic ecosystems, there have been innovative assessment methods developed for aquatic ecosystems. In this study, benthic algae assemblages and water quality variables were analyzed to develop a benthic diatom-based index of biotic integrity (D-IBI) for the assessment of the aquatic environment in the Lalin River. In addition, using redundancy analysis (RDA) based on dominant species and physicochemical indexes, the ecological distribution characteristics of the benthic diatom community were revealed, and the key influencing factors were identified. The results showed that the benthic diatom community structure in the Lalin River basin had obvious spatial differences. The application of the index revealed that the water quality could be described as excellent condition in the upper reaches of the Lalin River, good to common condition in the middle of the sites, and moderate to poor condition in the downstream. The assessment further revealed that the main reason for the degradation of the Lalin River ecosystem was nutrient enrichment through agricultural land use.

Post-crotonylation oxidation by a monooxygenase promotes acetyl-CoA synthetase degradation in Streptomyces roseosporus.

Protein post-translational modifications (PTMs) with various acyl groups play central roles in Streptomyces. But whether these acyl groups can be further modified, and the influences of these potential modifications on bacterial physiology have not been addressed. Here in Streptomyces roseosporus with rich crotonylation, a luciferase monooxygenase LimB is identified to elaborately regulate the crotonylation level, morphological development and antibiotic production by oxidation on the crotonyl groups of an acetyl-CoA synthetase Acs. This chemical modification on crotonylation leads to Acs degradation via the protease ClpP1/2 pathway and lowered intracellular crotonyl-CoA pool. Thus, we show that acyl groups after PTMs can be further modified, herein named post-PTM modification (PPM), and LimB is a PTM modifier to control the substrate protein turnover for cell development of Streptomyces. These findings expand our understanding of the complexity of chemical modifications on proteins for physiological regulation, and also suggest that PPM would be widespread.

Environmental and health impacts of functional graphenic materials and their ultrasonically altered products.

Graphenic materials have excited the scientific community due to their exciting mechanical, thermal, and optoelectronic properties for a potential range of applications. Graphene and graphene derivatives have demonstrated application in areas stretching from composites to medicine; however, the environmental and health impacts of these materials have not been sufficiently characterized. Graphene oxide (GO) is one of the most widely used graphenic derivatives due to a relatively easy and scalable synthesis, and the ability to tailor the oxygen containing functional groups through further chemical modification. In this paper, ecological and health impacts of fresh and ultrasonically altered functional graphenic materials (FGMs) were investigated. Model organisms, specifically Escherichia coli, Bacillus subtilis, and Caenorhabditis elegans, were used to assess the consequences of environmental exposure to fresh and ultrasonically altered FGMs. FGMs were selected to evaluate the environmental effects of aggregation state, degree of oxidation, charge, and ultrasonication. The major findings indicate that bacterial cell viability, nematode fertility, and nematode movement were largely unaffected, suggesting that a wide variety of FGMs may not pose significant health and environmental risks.

Mirror-image arachnoid cysts in a pair of monozygotic twins: a case report and review of the literature.

Mirror-imaging of arachnoid cysts (ACs) in monozygotic twins (MZ) is extremely rare. We describe a pair of MZ who developed mirror-imaging of ACs in the temporal fossas, and we also review the literature. Brain computer tomography (CT) and Magnetic Resonance Imaging (MRI) of the MZ revealed mirror-imaging of vast lesions of cerebrospinal fluid intensity in their temporal fossas. This is the second ever report of such a case according to the available literature. Unlike the prior case, our patients were 14 months, which is a much younger age than the patients of the previous report. Consequently, our case is better in supporting a genetic origin in the pathogenesis of AC. The findings in our case indicate that early neuroimaging is mandatory in the counterpart of the symptomatic patient with AC, irrespective of the absence of symptoms.

Gibberellic acid application on biomass, oxidative stress response, and photosynthesis in spinach (Spinacia oleracea L.) seedlings under copper stress.

The mechanism of Cu tolerance in plants and its control measures are of considerable significance for the remediation of Cu-contaminated soils. Gibberellic acid (GA3) is involved in plant growth and development and in the response to heavy metal stress. In the present study, changes in the biomass, oxidative stress response responses, and photosynthesis of spinach seedlings were examined under Cu stress with exogenous GA3 applied at concentrations of 0, 3, 5, 10, 20, 40, 60, or 80 mg L-1. Under Cu stress, the plant Cu concentration and oxidative damage were greater, photosynthetic parameters and biomass declined, and antioxidant enzyme activities and the proline concentration increased. However, spinach growth did not terminate, indicating that spinach seedlings had strong Cu tolerance. When low concentrations of GA3 (3-5 mg L-1) were added to Cu-stressed spinach seedlings, the damage caused by Cu stress to spinach seedlings was reduced, and the Cu tolerance of spinach seedlings was enhanced, which mainly manifested as reduced oxidation damage, an increased proline concentration, elevated antioxidant enzyme activities, decreased Cu concentration in leaves, and increased Cu concentration in roots, increased photosynthetic parameters, and an increased in the total biomass. In contrast, additions of GA3 at concentrations higher than 40 mg L-1 intensified oxidative damage and decreased the activities of antioxidant enzymes, photosynthetic parameters, and biomass. Additionally, the Cu concentration increased in leaves and decreased Cu concentration in roots, indicating that high concentrations of GA3 aggravated stress damage and severely influenced physiological functions in spinach seedlings. In summary, the application of 3-5 mg L-1 GA3 to spinach seedlings in Cu-contaminated soil can be used to reduce Cu toxicity to plants and increase Cu tolerance.

Fine-Tuning Cas9 Activity with a Cognate Inhibitor AcrIIA4 to Improve Genome Editing in Streptomyces.

Efficient enabling technology is required for synthetic biology in Streptomyces due to its natural product reservoir. Though the CRISPR-Cas9 system is powerful for genome editing in this genus, the proposed Cas9 toxicity has limited its application. Here on the basis of previous inducible Cas9 expression at the transcriptional and translational levels coupled with atpD overexpression, a Cas9 cognate inhibitor AcrIIA4 was further introduced to fine-tune the Cas9 activity. In both laboratory and industrial Streptomyces species, we showed that, compared to the constitutively expressed Cas9, incorporating AcrIIA4 increased the conjugation efficiency from 700- to 7000-fold before induction, while a comparable 65%-90% editing efficiency was obtained even on multiple loci for simultaneous deletion after Cas9 expression was induced, along with no significant off-targets. Thus, AcrIIA4 could be a modulator to control Cas9 activity to significantly improve genome editing, and this new toolkit would be widely adaptable and fasten genetic engineering in Streptomyces.

[Management of patients with iatrogenic pseudoaneurysm of carotid and vertebral artery].

OBJECTIVE: To evaluate the formation mechanism and management of iatrogenic pseudoaneurysms of carotid and vertebral artery. METHODS: Four patients with iatrogenic pseudoaneurysms were identified at our department from April 2004 to February 2009. One was caused by radiotherapy and the others due to surgical trauma. Two parents were treated with balloon occlusion of parent artery. Stent grafts were deployed in the other two patients to ensure the patency of parent arteries and occlusion of pseudoaneurysm. RESULTS: One patient with pseudoaneurysm of internal carotid artery developed decompensation after balloon occlusion. Unfortunately, long-term paralysis occurred after decompressive craniectomy. The other patients with vertebral artery pseudoaneurysm achieved an excellent outcome after balloon occlusion. The therapeutic effect of stent grafts in two internal carotid artery pseudoaneurysms was achieved. No recurrence was found during a post-operative follow-up of 15 months to 6 years. CONCLUSION: Iatrogenic pseudoaneurysms of carotid and vertebral artery deserve a priority attention. Cerebrovascular angiography should be performed if needed. The neurosurgical intervention for iatrogenic pseudoaneurysms may yield an excellent outcome.

The emerging role of circulating tumor cells in cancer management.

Circulating tumor cells (CTCs) are cells that are shed from the primary tumor and circulate in the blood, and their metastasis and formation of a secondary tumor are closely associated with cancer-related death. Therefore, regulating tumor metastasis through CTCs can be a novel strategy to fight cancer. It has been demonstrated that CTCs can reflect the profile of the primary tumor and provide valuable information about intratumoral heterogeneity and their evolution over time. Moreover, the revelation of the relationship between metastasis and CTCs suggests that CTC regulation represents a promising novel anticancer strategy. Above all, at the molecular level, genetic analysis might be vital in the new era of gene-targeted cancer therapies and contribute to personalized anti-metastasis tumor treatments. In this review, we will focus on the biological significance of CTCs in the peripheral blood and discuss their potential clinical implications in cancer management.

Decreased expression of TRPM4 is associated with unfavorable prognosis and aggressive progression of endometrial carcinoma.

Transient Receptor Potential Melastatin 4 (TRPM4) is a nonselective channel conducting monovalent ions and indirectly regulates intracellular Ca2+. Aberrant expression has been reported in a number of cancers. However, the biological function of TRPM4 in endometrial carcinoma (EC) is still unknown. We find that decreased TRPM4 expression is significantly correlated with a poor prognosis, overall survival (OS, P<0.001) and recurrence-free survival (P=0.002) through The Cancer Genome Atlas (TCGA) datasets in mRNA level. Multivariate Cox regression analysis suggests that TRPM4 is an independent prognostic factor for OS in EC patients. In vitro assays show that TRPM4-deletion results in significant promotion of proliferation and migration in EC cells. We then conducted a gene set enrichment analysis (GSEA) and according to the results, the expression of TRPM4 is modulated by estrogen, which is inhibited by ER antagonist. Furthermore, the silencing of TRPM4 causes a decreased p53 and hyper-activation of EMT, PI3K/AKT/mTOR signaling pathway in EC, as demonstrated in vitro. Overall, these results indicate that TRPM4 is clinically useful in predicting EC prognosis and represent a potential candidate as a new therapeutic target.

Increased Serum Calcium Level Promotes the Risk of Lymph Node Metastasis in Endometrial Cancer.

PURPOSE: The early predictive values of diagnostic markers for lymph node metastasis (LNM) in endometrial cancer (EC) are still unclear at present. The purpose of this study is to explore the relationship between serum calcium and LNM in EC. METHODS: We identified all patients with EC who underwent surgery between January 2012 and December 2016. Patient characteristics and various preoperative clinicopathologic data were obtained from medical records and were reviewed retrospectively. These patients were divided into two groups according to the pathology of their lymph node. Logistic regression models analyzed the relationship between the ionized calcium and LNM of EC patients, while adjusting for the potential confounders. RESULTS: A total of 448 patients were assessed. Univariate analysis showed that ionized calcium, CA125 level, tumor grade, peritoneal cytology, FIGO stage, histological type, LVSI, and myometrial invasion were positively correlated with LNM (all P<0.05). The risk of LNM increased with the promotion of serum ionized calcium (P for trend <0.01). Ionized calcium level was significant before and after the adjustment of cofounders (unadjusted: OR=11.9, 95% CI: 4.8-29.6, P< 0.01; model I: OR=11.3, 95% CI: 4.5-28.8, P< 0.01; model II: OR=5.2, 95% CI: 1.6-17.2, P< 0.05). Additionally, the risk of ionized calcium was especially evident in patients whose age was older than 60, BMI<28 kg/m2, grade 3, negative peritoneal cytology and endometrioid endometrial adenocarcinoma. CONCLUSION: Ionized calcium level was highly associated with LNM in EC and acted as a potential biomarker in predicting the risk of LNM in EC.

Effects of copper treatment on mineral nutrient absorption and cell ultrastructure of spinach seedlings.

The accumulation of heavy metals in soil has serious influence on plant growth and ecosystem balance. It is of great importance to explore the mechanism of plant tolerance to heavy me-tals. Although spinach is supposed to have strong Cu tolerance, the effects of Cu on mineral element absorption and cell ultrastructure are still unclear. In this study, the growth of spinach seedlings, the absorption of mineral elements and the ultrastructure of leaf cells were examined in a pot experiment. The results showed that Cu2+ accumulation in the root of spinach seedling was less than that in the shoot when CuSO4 concentration was 100 mg·L-1, with root growth being increased and shoot growth being slightly decreased. When copper concentration continued to increase, the growth parameters continuously declined. When the CuSO4 concentrations were less than 400 mg·L-1, the foliar N, K, Ca, Mg and Fe concentrations of spinach seedling increased, and that of P decreased. The concentrations of N, P and K in roots went down and that of Ca, Mg and Fe went up. All organelles in leaf cells were clearly visible. The basal granule layer was arranged orderly, and the inner and outer membranes of chloroplasts were intact. When the CuSO4 concentrations exceeded 600 mg·L-1, foliar N concentration increased while that of P, K, Ca, Mg and Fe decreased. The concentrations of N, P, K, Ca, Mg and Fe in roots declined. The cell ultrastructure of spinach seedlings substantially changed with the increases of CuSO4 treated concentrations. The chloroplast in leaf cells became rounder, the chloroplast membrane became thinner, the stroma and basal granule layer became less, and the layer accumulation height decreased. The nucleus was broken up and small black spots were found in vacuoles and cell walls, which might be attributed to the enhancement of intracellular swelling pressure caused by high accumulation of Cu2+. In conclusion, low concentration of CuSO4 had little negative effect on the life activities of spinach seedlings, and the high concentrations of CuSO4 did not terminate their growth, indicating that spinach seedlings had strong copper resistance.