The Pyroptosis-Related Risk Genes APOBEC3D, TNFRSF14, and RAC2 Were Used to Evaluate Prognosis and as Tumor Suppressor Genes in Breast Cancer.

Background: Pyroptosis is a type of cell death that plays an important role in predicting prognosis and immunoregulation in cancers. However, the pyroptosis-related gene signature for prognosis and immune infiltration prediction has not been studied in breast cancer (BC). Methods: The Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) databases were used to obtain the expression and clinical data of genes. 52 pyroptosis-related genes were obtained from TCGA-BC and estimated differentially expressed genes by the limma program. To categorize the molecular subtypes of pyroptosis-related genes, the ConsensusClusterPlus tool was utilized. Cox and Lasso regression analyses were used to create a signature. TCGA-BC dataset as the training set and the GSE37751 test set for risk research. Gene set enrichment analysis (GSEA) was used to conduct KEGG and GO studies of subtype groups. We also used the ssGSEA approach in the GSVA package to calculate the risk score of immune cells. Finally, pyroptosis-related genes in BC were validated using qPCR and immunohistochemical assays. Clone formation and EDU assays were used to explore the ability of signature genes to regulate the proliferation of BC cells. Results: Based on pyroptosis-related genes, the C1 and C2 subtypes were obtained. Survival analysis results showed that the C2 group had a better prognosis. Then, a three-gene signature (APOBEC3D, TNFRSF14, and RAC2) were created by Lasso regression analysis, which had a good prediction effect in the TCGA-BC and GSE37751 datasets. Our nomogram has a fair degree of accuracy in predicting the survival rates of BC patients. The pyroptosis-related signature has a good predictive effect in evaluating the tumour microenvironment score, 28 types of immune cells and response to immune checkpoint therapy. Finally, qPCR and immunohistochemistry staining results indicated that APOBEC3D, TNFRSF14, and RAC2 expression in BC tissues was low. The results of clone formation and EdU assays showed that high expression of signature genes inhibited the proliferation ability of BC cells. Conclusions: Based on pyroptosis-related genes (APOBEC3D, TNFRSF14, and RAC2), we built a novel prognostic molecular model for BC that might be used to assess prognostic risk and immune infiltration in BC patients. These signature genes are also tumor suppressor genes and may serve as potential targets for BC.

Mechanism-Based Pharmacokinetic Model for the Deglycosylation Kinetics of 20(S)-Ginsenosides Rh2.

Aim: The 20(S)-ginsenoside Rh2 (Rh2) is being developed as a new antitumor drug. However, to date, little is known about the kinetics of its deglycosylation metabolite (protopanoxadiol) (PPD) following Rh2 administration. The aim of this work was to 1) simultaneously characterise the pharmacokinetics of Rh2 and PPD following intravenous and oral Rh2 administration, 2) develop and validate a mechanism-based pharmacokinetic model to describe the deglycosylation kinetics and 3) predict the percentage of Rh2 entering the systemic circulation in PPD form. Methods: Plasma samples were collected from rats after the I.V. or P.O. administration of Rh2. The plasma Rh2 and PPD concentrations were determined using HPLC-MS. The transformation from Rh2 to PPD, its absorption, and elimination were integrated into the mechanism based pharmacokinetic model to describe the pharmacokinetics of Rh2 and PPD simultaneously at 10 mg/kg. The concentration data collected following a 20 mg/kg dose of Rh2 was used for model validation. Results: Following Rh2 administration, PPD exhibited high exposure and atypical double peaks. The model described the abnormal kinetics well and was further validated using external data. A total of 11% of the administered Rh2 was predicted to be transformed into PPD and enter the systemic circulation after I.V. administration, and a total of 20% of Rh2 was predicted to be absorbed into the systemic circulation in PPD form after P.O. administration of Rh2. Conclusion: The developed model provides a useful tool to quantitatively study the deglycosylation kinetics of Rh2 and thus, provides a valuable resource for future pharmacokinetic studies of glycosides with similar deglycosylation metabolism.

Molecular phenotypes and clinical characterization of familial hereditary breast cancer among half and full sisters.

BACKGROUND: Preliminary clinical observations show that contemporaneous hereditary breast cancer (CHBC) patients suffered breast cancer at an early age, which requires further analysis. METHODS: 38 familial hereditary breast cancer patients (18 CHBC patients and 20 non-CHBC patients) were screened out and 152 non-hereditary breast cancer patients were used as control subjects. Clinical pathologic subtypes, age, tumor location, histological grade, lymph node metastasis, and molecular phenotype expression (ER, PR, HER-2, Ki-67, CK5/6, E-cad, P63, and P120) were compared across all subgroups. RESULTS: The incidence of CHBC was 9.47% (18/190) in breast cancer patients. The average ages of onset of CHBC patients, non-CHBC patients, and non-hereditary breast cancer patients were 49.06 ± 6.42, 60.75 ± 9.95 and 61.69 ± 14.34 respectively; whereas there were no significant differences with respect to pathological type or tumor location. There were significant differences in some histological grading (grade II/III), lymph node metastasis and PR expression between hereditary and non-hereditary breast cancers (P < 0.05; P < 0.05 and P < 0.005, respectively). Significantly different HER-2 expression was observed when comparing all hereditary or CHBC patients with non-hereditary breast cancers (P < 0.05 and P < 0.005, respectively). There were significant differences in E-cad and P63 between contemporaneous hereditary and non-hereditary breast cancers (P < 0.005 and P < 0.05, respectively). CONCLUSIONS: CHBC patients accounted for 9.47% (18/190) of breast cancer patients, had earlier disease onset, and showed differences compared to non-hereditary breast cancer patients with respect to molecular phenotype and clinical characteristics.

The effect of the particle size on Fischer-Tropsch synthesis for ZSM-5 zeolite supported cobalt-based catalysts.

A series of mesoporous ZSM-5 zeolite supported cobalt-based catalysts with the cobalt crystal sizes in the range of 4.5-18.1 nm were prepared for syngas conversion. The highly selective synthesis of various liquid fuels including gasoline, jet fuel and diesel range hydrocarbons is achieved with different cobalt nanoparticle sizes.

Predicting the Drug-Drug Interaction Mediated by CYP3A4 Inhibition: Method Development and Performance Evaluation.

The prediction of drug-drug interactions (DDIs) plays critical roles for the estimation of DDI risk caused by inhibition of CYP3A4. The aim of this paper is to develop a physiologically based pharmacokinetic (PBPK)-DDI model for prediction of the DDI co-administrated with ketoconazole in humans and evaluate the predictive performance of the model. The pharmacokinetic and biopharmaceutical properties of 35 approved drugs, as victims, were collected for the development of a PBPK model, which were linked to the PBPK model of ketoconazole for the DDI prediction. The PBPK model of victims and ketoconazole were validated by matching actual in vivo pharmacokinetic data. The predicted results of DDI were compared with actual data to evaluate the predictive performance. The percentage of predicted ratio of AUC (AUCR), Cmax (CmaxR), and Tmax (TmaxR) was 75%, 69%, and 91%, respectively, which were within the twofold threshold (range, 0.5-2.0×) of the observed values. Only 3% of the predicted AUCRs are obviously underestimated. After integration of the reported fraction of metabolism (fm) into the PBPK-DDI model for limited four cases, the model-predicted AUCRs were improved from the twofold range of the observed AUCRs to the 90% confidence interval. The developed method could reasonably predict drug-drug interaction with a low risk of underestimation. The present accuracy of the prediction was improved compared with that of static mechanistic models. The evaluation of predictive performance increases the confidence using the model to evaluate the risk of DDIs co-administrated with ketoconazole before the in vivo DDI study.

The incidence and analysis of ipsilateral occult hernia in patients undergoing hernia repair: a single institution retrospective study of 1066 patients.

BACKGROUND: Misdiagnosis or failure to intraoperatively detect occult hernia in the inguinal region can lead to the recurrence of postoperative hernia and the appearance of local pain symptoms, which affect the patient's quality of life and make it difficult to reperform hernia repair. METHODS: This study included 1066 inguinal hernia patients who underwent surgical treatment at Shanghai Tongren Hospital between January 2016 and October 2018 to investigate ipsilateral occult hernia epidemiology, to analyze the characteristics of ipsilateral occult hernias with regards to patient age, gender, classification and anatomical site, and to explore the superiority and inferiority of the expert hernia surgeons/ non-expert hernia surgeons group and of operation methods in finding occult inguinal hernias. RESULTS: The incidence of ipsilateral occult hernia in the surgical population was 8.26%. Ipsilateral occult hernia included indirect inguinal hernia, direct inguinal hernia, femoral hernia, obturator hernia, and spigelian hernia, among which the highest incidence was direct inguinal hernia (4.11%), followed by indirect inguinal hernia (2.45%). There was no difference in the incidence of ipsilateral occult hernia between males and females, but there were significant differences in the incidence of ipsilateral occult hernia, which decreased gradually with increasing age in patients younger than 70 years-old; there was no difference in incidence in patients over 70 years-old. There were significant differences in the incidence of ipsilateral occult hernia in the bilateral inguinal region between direct and femoral hernia, with the higher incidence found on the right side; in contrast, there was no difference in the incidence of indirect inguinal hernia in the bilateral inguinal region. There was no difference in the ability of experienced physicians to detect ipsilateral occult inguinal hernias, either professionally or by surgery. CONCLUSIONS: Ipsilateral occult inguinal hernia has a higher incidence in patients with inguinal hernia, especially older patients; therefore, it is necessary for experienced surgeons to carefully detect for possible occult hernia during the operation and in elderly patients.

Decoupling nucleation from crystal-growth for the synthesis of nanocrystalline zeolites.

The increasing demands for catalysts with improved accessibility to reactants call for a rational synthesis of nanosized zeolites. Herein we developed a facile approach for highly crystalline MFI-type (Silicalite-1 and ZSM-5) and beta zeolites with variable Si/Al ratios and high yield. This was achieved by kinetically decoupling the nucleation from the growth process of the zeolites in a highly concentrated gel system via a temperature-staged treatment. The carefully controlled low-water environment ensures only nucleation in stage I (aging), and hence the generation of abundant nuclei for the subsequent rapid crystallization within a self-confined space at stage II (growth). The method, without using expensive templates or additives, allows the syntheses of nanosized, well-isolated ZSM-5 (Si/Al = 100-∞, 36-88 nm, yield >85%) and Beta (Si/Al = 25-100, 21-66 nm, yield >95%). The ultra-small crystal size endows ZSM-5 zeolites with good catalytic activity, product selectivity and remarkably longer lifetime in methanol conversion reactions.

Gamma-Ray Irradiation to Accelerate Crystallization of Mesoporous Zeolites.

Gamma-ray (γ-ray) irradiation was introduced into zeolite synthesis. The crystallization process of zeolite NaA, NaY, Silicalite-1, and ZSM-5 were greatly accelerated. The crystallization time of NaA zeolite was significantly decreased to 18 h under γ-ray irradiation at 20 °C, while more than 102 h was needed for the conventional process. Unexpectedly, more mesopores were created during this process, and thus the adsorption capacity of CO2 increased by 6-fold compared to the NaA prepared without γ-ray irradiation. Solid experimental evidence and density function theory (DFT) calculations demonstrated that hydroxyl free radicals (OH*) generated by γ-rays accelerated the crystallization of zeolite NaA. Besides NaA, mesoporous ZSM-5 with MFI topology was also successfully synthesized under γ-ray irradiation, which possessed excellent catalytic performance for methanol conversion, suggesting the universality of this new synthetic strategy for various zeolites.

Morphology-Controlled Synthesis of H-type MFI Zeolites with Unique Stacked Structures through a One-Pot Solvent-Free Strategy.

H-type aluminosilicate zeolites are extensively used as solid-acid catalysts and support materials in industrial catalysis. However, the conventional synthesis methods involving hydrothermal syntheses and ion-exchange processes suffer from severe water pollution and toxic gas emissions. Herein, H-type MFI zeolite catalysts with a unique stacked structure were directly synthesized in the presence of NH4 F and with the help of zeolite confinement through a solvent-free route without further ion-exchange procedures. A range of ex situ and in situ characterization procedures were used to provide evidence of the simultaneous use of pre-made ZSM-5 and NH4 F as a confined Al source and mineralizer, respectively. The confined zeolite framework of ZSM-5 prevented the formation of AlFx species between NH4 F and Al atoms, ensuring that the prepared samples had desirable acidic properties. Moreover, the resulting morphology could be controlled by using different silica substrates. The obtained H-type MFI zeolites showed excellent catalytic performance in methanol-to-gasoline reactions owing to their unique structure and directly exposed acidic sites. The developed one-pot strategy provides an alternative method for the facile synthesis of H-type zeolites with defined morphology.

Selective Transformation of CO2 and H2 into Lower Olefins over In2 O3 -ZnZrOx /SAPO-34 Bifunctional Catalysts.

Because lower olefins (C2 = -C4 = ) are important bulk petrochemicals, their direct production from CO2 hydrogenation is highly attractive. However, the selectivity towards C2 = -C4 = by the modified Fischer-Tropsch synthesis is restricted to 56.7 % with high undesired methane selectivity. Here, a series of bifunctional catalysts containing In2 O3 -ZnZrOx oxides and various SAPO-34 zeolites with different crystal sizes (0.4-1.5 µm) and pore structures was developed for the production of lower olefins by CO2 hydrogenation. The C2 = -C4 = selectivity reached as high as 85 % among all hydrocarbons with very low CH4 selectivity of only 1 % at a CO2 conversion of 17 %. This demonstrated that the small crystal size, hierarchical pore structure, and appropriate amount of Brønsted acid sites of SAPO-34 endowed the bifunctional catalysts with high C2 = -C4 = selectivity. This work shows an efficient way for developing bifunctional catalysts for direct CO2 hydrogenation to lower olefins.

Coagulation and deep vein flow changes following laparoscopic total extraperitoneal inguinal hernia repair: a single-center, prospective cohort study.

BACKGROUND AND PURPOSE: Venous thromboembolism (VTE) is a serious complication encountered in surgical practice. The purpose of this study was to identify changes in coagulation status and deep vein flow parameters, within 24 h postoperatively, for patients undergoing laparoscopic total extraperitoneal inguinal hernia repair (TEP). METHODS: For 144 patients undergoing TEP, coagulation markers including prothrombin time (PT), partial thromboplastin time, thrombin time, D-dimer, fibrinogen, fibrin degradation products (FDP), and international normalized ratio (INR) were monitored preoperatively and in the first morning postoperatively. Echo-Doppler recordings preoperatively and again within 24 h postoperatively were completed for 23 patients to monitor lower extremity deep vein flow parameters including speed of flow (cm/s), diameter (cm), and cross-sectional area (cm2). Clinically significant VTE and other complications were recorded. RESULTS: No significant VTE were diagnosed. Significant increases were seen in the first morning postoperatively for PT, D-dimer, FDP, and INR (P < 0.05). Stratified by age, except for those < 50 years, the ratio of value-outside-the-normal-range (VONR) for D-dimer and FDP increased significantly postoperatively for all age groups. Stratified by operation duration, a significant difference in the ratio of VONR in D-dimer was identified postoperatively between those with an operation duration < 60 min and ≥ 60 min. There were significant decreases in the iliac and common femoral vein flow velocity of the ipsilateral extremity postoperatively (P < 0.05). CONCLUSIONS: Activated hypercoagulability and hampered lower extremity deep vein flow were observed immediately after TEP. DVT formation was more pronounced in older patients and for those with operation duration ≥ 60 min. Proper VTE risk stratification for laparoscopic inguinal hernia repair (LIHR) and prophylaxis early after LIHR should be important clinical considerations.

Clinical significance of peripheral circulating tumor cell counts in colorectal polyps and non-metastatic colorectal cancer.

BACKGROUND: The presence of peripheral circulating tumor cells indicates the possible existence of a tumor in vivo; however, low numbers of circulating tumor cells (CTCs) can be detected in peripheral blood of healthy individuals as well as patients with benign tumors. It is not known whether peripheral CTC counts differ between patients with benign colorectal disease and those with colorectal cancer. METHODS: Comparative analysis of preoperative peripheral circulating tumor cells counts was completed in patients with benign colorectal disease (colorectal polyps) and non-metastatic cancer of the colon and rectum. RESULTS: The results of this analysis showed that patients with colorectal cancer had higher CTC counts than patients with colorectal polyps (3.47 ± 0.32/3.2 ml vs 1.49 ± 0.2/3.2 ml, P < 0.001). Colorectal cancer patients with tumors of the sigmoid colon displayed the highest CTC counts (4.87 ± 0.95/3.2 ml), followed by those with tumors of the rectum (3.73 ± 0.54/3.2 ml), ascending colon (3.5 ± 0.63/3.2 ml), transverse colon (2.4 ± 0.68/3.2 ml), and descending colon (2.08 ± 0.46/3.2 ml). Colorectal polyp patients with polyps in the rectum showed the highest CTC counts (2.2 ± 0.77/3.2 ml), followed by those with polyps in the ascending colon (1.82 ± 0.54/3.2 ml), sigmoid colon (1.38 ± 0.25/3.2 ml), transverse colon (0.75 ± 0.25/3.2 ml), and descending colon (0.33 ± 0.21/3.2 ml). The differences in CTC counts suggest that anatomical location of colorectal tumors may affect blood vessel metastasis. Meanwhile, patients with moderately differentiated and poorly differentiated tumors displayed higher peripheral blood CTC counts compared to those with well-differentiated tumors (P < 0.001). This result suggests that the type of tissue differentiation of colorectal tumors may act as another factor that affects blood vessel metastasis. CONCLUSIONS: Circulating tumor cells can be detected in the peripheral blood of colorectal cancer patients as well as patients with colorectal polyps. The differences in CTC counts suggest that anatomical location and the type of tissue differentiation of colorectal tumors may affect blood vessel metastasis.

Direct conversion of CO2 into liquid fuels with high selectivity over a bifunctional catalyst.

Although considerable progress has been made in carbon dioxide (CO2) hydrogenation to various C1 chemicals, it is still a great challenge to synthesize value-added products with two or more carbons, such as gasoline, directly from CO2 because of the extreme inertness of CO2 and a high C-C coupling barrier. Here we present a bifunctional catalyst composed of reducible indium oxides (In2O3) and zeolites that yields a high selectivity to gasoline-range hydrocarbons (78.6%) with a very low methane selectivity (1%). The oxygen vacancies on the In2O3 surfaces activate CO2 and hydrogen to form methanol, and C-C coupling subsequently occurs inside zeolite pores to produce gasoline-range hydrocarbons with a high octane number. The proximity of these two components plays a crucial role in suppressing the undesired reverse water gas shift reaction and giving a high selectivity for gasoline-range hydrocarbons. Moreover, the pellet catalyst exhibits a much better performance during an industry-relevant test, which suggests promising prospects for industrial applications.

High quality reference genome of drumstick tree (Moringa oleifera Lam.), a potential perennial crop.

The drumstick tree (Moringa oleifera Lam.) is a perennial crop that has gained popularity in certain developing countries for its high-nutrition content and adaptability to arid and semi-arid environments. Here we report a high-quality draft genome sequence of M. oleifera. This assembly represents 91.78% of the estimated genome size and contains 19,465 protein-coding genes. Comparative genomic analysis between M. oleifera and related woody plant genomes helps clarify the general evolution of this species, while the identification of several species-specific gene families and positively selected genes in M. oleifera may help identify genes related to M. oleifera's high protein content, fast-growth, heat and stress tolerance. This reference genome greatly extends the basic research on M. oleifera, and may further promote applying genomics to enhanced breeding and improvement of M. oleifera.

Function of ghrelin and ghrelin receptors in the network regulation of gastric motility.

Numerous previous studies have demonstrated that ghrelin promotes gastric motility when administered peripherally. This effect appears to be regulatory but not directly stimulatory, and therefore may involve a number of complex mechanisms. In the periphery, ghrelin may affect gastric motility through intercellular networks among interstitial cells of Cajal, myenteric nerve cells and smooth muscle cells. The aim of the present study was to investigate the effects and possible mechanisms underlying this hypothesis. The effects of ghrelin on the contraction force of gastric antrum smooth muscle strips of rats were studied in the presence or absence of carbachol (CCh), [D­Lys3]­GHRP­6, atropine, tetrodotoxin (TTX) and nimodipine in vitro. The expression of ghrelin receptors (GHS­Rs) on different cell types in gastric muscle layers was observed by means of immunofluorescence. Ghrelin enhanced smooth muscle strip contraction induced by CCh, but when CCh was absent, this effect was eliminated. Atropine and nimodipine eradicated the muscle strip contraction enhanced by ghrelin, while [D­Lys3]­GHRP­6 was only able to partly block this effect and TTX had no effect on muscle strip contraction. It was identified that ghrelin had no effect on the contractive rhythm of the strips. GHS­R1s were located differentially depending on the cell type, including myenteric nerve cells, interstitial cells of Cajal and smooth muscle cells. In conclusion the present study demonstrated that ghrelin may act as an adjuvant to regulate gastric smooth muscle contraction induced by CCh through GHS­R1s, which are expressed on myenteric nerve cells, Cajal cells and smooth muscle cells. Ghrelin may exert its effects by influencing the functional status of different cell types in the gastric muscle layer to subsequently enhance the contractive effect of cholinergic neurotransmitters and enhance gastric motility.

Highly mesoporous single-crystalline zeolite beta synthesized using a nonsurfactant cationic polymer as a dual-function template.

Mesoporous zeolites are useful solid catalysts for conversion of bulky molecules because they offer fast mass transfer along with size and shape selectivity. We report here the successful synthesis of mesoporous aluminosilicate zeolite Beta from a commercial cationic polymer that acts as a dual-function template to generate zeolitic micropores and mesopores simultaneously. This is the first demonstration of a single nonsurfactant polymer acting as such a template. Using high-resolution electron microscopy and tomography, we discovered that the resulting material (Beta-MS) has abundant and highly interconnected mesopores. More importantly, we demonstrated using a three-dimensional electron diffraction technique that each Beta-MS particle is a single crystal, whereas most previously reported mesoporous zeolites are comprised of nanosized zeolitic grains with random orientations. The use of nonsurfactant templates is essential to gaining single-crystalline mesoporous zeolites. The single-crystalline nature endows Beta-MS with better hydrothermal stability compared with surfactant-derived mesoporous zeolite Beta. Beta-MS also exhibited remarkably higher catalytic activity than did conventional zeolite Beta in acid-catalyzed reactions involving large molecules.

High temperature synthesis of high silica zeolite Y with good crystallinity in the presence of N-methylpyridinium iodide.

A novel synthetic route is designed, employing both high temperature and a nontoxic organic structure-directing agent (SDA), for the synthesis of high silica zeolite Y. The N-methylpyridinium used as an organic SDA is stable during the synthesis, and the high silica zeolite Y shows high hydrothermal stability and good catalytic performance, as well as excellent adsorptive properties.

Comparison of the effects of Mg-6Zn and titanium on intestinal tract in vivo.

To evaluate the ability of Mg-6Zn to replace titanium nails in the reconstruction of the intestinal tract in general surgery, we compared the Mg-6Zn and titanium implants with respect to their effects on rat's intestinal tract by biochemical, radiological, pathological and immunohistochemical methods. The results indicated that Mg-6Zn implants started to degrade at the third week and disintegrate at the fourth week. No bubbles appeared, which may be associated with intestinal absorption of the Mg-6Zn implants. Pathological analyses (containing liver, kidney and cecum tissues) and biochemical measurements, including serum magnesium, creatinine, blood urea nitrogen, glutamic-pyruvic-transaminase and glutamic-oxaloacetic-transaminase proved that degradation of Mg-6Zn did not harm the important organs, which is an improvement over titanium implants. Immunohistochemical results showed that Mg-6Zn could enhance the expression of transforming growth factor-ß1. Mg-6Zn reduced the expression of tumor necrosis factor at different stages. In general, our study demonstrates that the Mg-6Zn alloy had good biocompatibility in vivo and performed better than titanium at promoting healing and reducing inflammation. It may be a promising candidate for stapler pins in intestinal reconstruction.

A meta-analysis of the relationship between lymphatic microvessel density and clinicopathological parameters in breast cancer.

BACKGROUND: Breast cancer is a common malignant neoplasm that is a leading cause of cancer death in women despite recent advances in treatment and research. The role of lymphangiogenesis in breast cancer development remains a source of controversy in current research. OBJECTIVE: The relationship between lymphatic microvessel density (LMVD) and the clinicopathological parameters of breast cancer can be effectively examined by meta-analysis of recent studies. METHODS: A total of 10 relevant studies consisting of 1,044 total patients were examined by electronic searches of PubMed and Embase databases. Weighted mean difference (WMD) and 95% confidence intervals (CI) were estimated and pooled according to standard methods. LMVD data was pooled by tumor size, lymphatic node metastases, and tumor hormone receptor status of estrogen receptors (ER) and progesterone receptors (PR). RESULTS: A remarkable correlation between LMVD and lymph node metastases was observed in pooled analyses using a random-effects model (WMD: 2.72; 95%CI: 2.27, 3.16; P = 0.000). LMVD and tumor size showed a pooled WMD value of 0.00 (95%CI: -0.49, 0.50; P = 0.009), indicating no significant correlation between LMVD and tumor size. LMVD and either ER or PR status showed pooled WMD values of 0.24 (95%CI: -0.30, 0.79; P = 0.004) and -0.12 (95%CI: -0.81, 0.56, P = 0.301), respectively, also indicating no significant correlation between LMVD and ER or PR status. CONCLUSION: A close relationship was observed between LMVD and lymph node metastases, though no correlation between LMVD and other important clinicopathological parameters was apparent. The current meta-analysis suggests that LMVD may be associated with increased metastatic activity in breast cancer, though the full role of lymphangiogenesis in breast cancer remains uncertain.