External quality assessment scheme for sperm DNA fragmentation: a pilot study in China.

BACKGROUND: The aim of this article is to establish an external quality assessment (EQA) scheme for sperm Deoxyribonucleic acid (DNA) fragmentation (SDF) detection, and to assess the feasibility of the scheme. In addition, this article provides some case analysis of abnormal results in order to really help improve the performance of the laboratory. RESULTS: In 2021 and 2022, 10 and 28 laboratories in China volunteered to participate in the EQA program respectively. Two samples were selected for EQA each year, a large spread of results was obtained for the four samples, and the highest values were 13.7, 4.2, 8.0 and 4.0 times the lowest respectively. The coefficients of variation (CVs) were very high for the four samples, at 46.6%, 30.1%, 26.7% and 30.3%, respectively. The CVs of the samples with high SDF values were lower than those of the samples with low SDF values. There was no significant difference between the results of sperm chromatin structure assay (SCSA) and sperm chromatin dispersion (SCD). For the 10 laboratories that participated in EQA in 2021 and 2022, the CVs of low SDF value samples and high SDF value samples decreased from 46.6% and 30.1% in 2021 to 32.5% and 22.7% in 2022, respectively. CONCLUSION: This is the first study to evaluate the EQA program on SDF, which involved a number of laboratories and was demonstrated to be feasible. It is recommended that all laboratories participate in the EQA of SDF to ensure the accuracy of the results.

RéSUMé: CONTEXTES: L'objectif de cet article est d'établir un système externe d'évaluation de la qualité (EEQ) pour la détection de la fragmentation de l'ADN des spermatozoïdes (SDF) et d'évaluer la faisabilité de ce système. En outre, cet article fournit une analyse de cas de résultats anormaux afin d'aider réellement à améliorer les performances du laboratoire. RéSULTATS: En 2021 et 2022, respectivement 10 et 28 laboratoires en Chine se sont portés volontaires pour participer au programme EEQ. Deux échantillons ont été sélectionnés chaque année pour l'EEQ ; un large éventail de résultats a été obtenu pour les quatre échantillons, et les valeurs les plus élevées étaient respectivement de 13,7, 4,2, 8,0 et 4,0 fois les plus faibles. Les coefficients de variation (CV) étaient très élevés pour les quatre échantillons, soit respectivement 46,6 %, 30,1 %, 26,7 % et 30,3 %. Les CV des échantillons avec des valeurs de SDF élevées étaient inférieurs à ceux des échantillons avec de faibles valeurs de SDF. Il n'y avait pas de différence significative entre les résultats du test de structure de la chromatine des spermatozoïdes (SCSA) et ceux de la dispersion de la chromatine des spermatozoïdes (SCD). Pour les 10 laboratoires qui ont participé à l'EEQ en 2021 et 2022, les CV des échantillons à faible valeur de SDF et ceux des échantillons à valeur élevée de SDF ont diminué, passant respectivement de 46,6 % et 30,1 % en 2021 à 32,5 % et 22,7 % en 2022. CONCLUSIONS: Il s'agit de la première étude à évaluer le programme externe d'évaluation de la qualité (EEQ) de l'analyse de la SDF, qui a impliqué un certain nombre de laboratoires, et qui s'est avéré réalisable. Il est recommandé que tous les laboratoires participent à l'EEQ de la SDF afin d'en assurer l'exactitude des résultats.

GlycoTCFM: Glycoproteomics Based on Two Complementary Fragmentation Methods Reveals Distinctive O-Glycosylation in Human Sperm and Seminal Plasma.

Human semen, consisting of spermatozoa (sperm) and seminal plasma, represents a special clinical sample type in human body fluid. Protein glycosylation in sperm and seminal plasma plays key roles in spermatogenesis, maturation, capacitation, sperm-egg recognition, motility of sperm, and fertilization. In this study, we profiled the most comprehensive O-glycoproteome map of human sperm and seminal plasma using our recently presented Glycoproteomics based on Two Complementary Fragmentation Methods (GlycoTCFM). We showed that sperm and seminal plasma contain many novel and distinctive O-glycoproteins, which are mostly located in the extracellular region (seminal plasma) and sperm membrane, enriched in the biological processes of cell adhesion and angiogenesis, and mainly involved in multiple biological functions including extracellular matrix structural constituents and binding. Based on GlycoTCFM, we created a comprehensive human sperm and seminal plasma O-glycoprotein database that contains 371 intact O-glycopeptides and 202 O-glycosites from 68 O-glycoproteins. Interestingly, 105 manually confirmed O-glycosites from 25 O-glycoproteins were reported for the first time, and they were mainly modified by core 1 O-glycans. We also found that three highly abundant, highly complex, and highly O-glycosylated proteins (semenogelin-1, semenogelin-2, and equatorin) may play important roles in sperm or seminal plasma composition and function. These data deepen our knowledge about O-glycosylation in sperm and seminal plasma and lay the foundation for the functional study of O-glycoproteins in male infertility.

Cellular uptake, intracellular behavior, and acute/sub-acute cytotoxicity of a PEG-modified quantum dot with promising in-vivo biomedical applications.

Quantum Dots (QDs) modified with branched Polyethylene Glycol-amine (6- or 8-arm PEG-amine) coupled with methoxy PEG (mPEG) hold great promise for in vivo biomedical applications due to a long half-life in blood and negligible toxicity. However, the potential risks regarding their concomitant prolonged co-incubation with cardiovascular and blood cells remains inconclusive. In the present study, the feasible, effective and convenient proliferating-restricted cell line models representing the circulatory system were established to investigate the cellular internalization followed by intracellular outcomes and resulting acute/sub-acute cytotoxicity of the 6-arm PEG-amine/mPEG QDs. We found a dose-, time- and cell type-dependent cellular uptake of the 6-arm PEG-amine/mPEG QDs, which was ten-fold lower compared to the traditional linear PEG-modified counterpart. The QDs entered cells via multiple endocytic pathways and were mostly preserved in Golgi apparatus for at least one week instead of degradation in lysosomes, resulting in a minimal acute cytotoxicity, which is much lower than other types of PEG-modified QDs previously reported. However, a sub-acute cytotoxicity of QDs were observed several days post exposure using the concentrations eliciting no-significant acute cytotoxic effects, which was associated with elevated ROS generation caused by QDs remained inside cells. Finally, a non-cytotoxic concentration of the QDs was identified at the sub-acute cytotoxic level. Our study provided important information for clinical translation of branched PEG-amine/mPEG QDs by elucidating the QDs-cell interactions and toxicity mechanism using the proliferation-restricted cell models representing circulatory system. What's more, we emphasized the indispensability of sub-acute cytotoxic effects in the whole biosafety evaluation process of nanomaterials like QDs.

Proteomic Landscape of Human Spermatozoa: Optimized Extraction Method and Application.

Human spermatozoa proteomics exposed to some physical, biological or chemical stressors is being explored. However, there is a lack of optimized sample preparation methods to achieve in-depth protein coverage for sperm cells. Meanwhile, it is not clear whether antibiotics can regulate proteins to affect sperm quality. Here, we systematically compared a total of six different protein extraction methods based the combination of three commonly used lysis buffers and physical lysis strategies. The urea buffer combined with ultrasonication (UA-ultrasonication) produced the highest protein extraction rate, leading to the deepest coverage of human sperm proteome (5685 protein groups) from healthy human sperm samples. Since the antibiotics, amoxicillin and clarithromycin, have been widely used against H. pylori infection, we conduct a longitudinal study of sperm proteome via data-independent acquisition tandem mass spectrometry (DIA-MS/MS) on an infected patient during on and off therapy with these two drugs. The semen examination and morphological analysis were performed combined with proteomics analysis. Our results indicated that antibiotics may cause an increase in the sperm concentration and the rate of malformed sperm and disrupt proteome expression in sperm. This work provides an optimized extraction method to characterize the in-depth human sperm proteome and to extend its clinical applications.

Extend the Survival of Human Sperm In Vitro in Non-Freezing Conditions: Damage Mechanisms, Preservation Technologies, and Clinical Applications.

Preservation of human spermatozoa in vitro at normothermia or hypothermia maintaining their functions and fertility for several days plays a significant role in reproductive biology and medicine. However, it is well known that human spermatozoa left in vitro deteriorate over time irreversibly as the consequence of various stresses such as the change of osmolarity, energy deficiency, and oxidative damage, leading to substantial limitations including the need for semen examinations, fertility preservation, and assisted reproductive technology. These problems may be addressed with the aid of non-freezing storage techniques. The main and most effective preservation strategies are the partial or total replacement of seminal plasma with culture medium, named as extenders, and temperature-induced metabolic restriction. Semen extenders consist of buffers, osmolytes, and antioxidants, etc. to protect spermatozoa against the above-mentioned adverse factors. Extended preservation of human spermatozoa in vitro has a negative effect on sperm parameters, whereas its effect on ART outcomes remains inconsistent. The storage duration, temperature, and pre-treatment of semen should be determined according to the aims of preservation. Advanced techniques such as nanotechnology and omics have been introduced and show great potential in the lifespan extension of human sperm. It is certain that more patients will benefit from it in the near future. This review provided an overview of the current knowledge and prospects of prolonged non-freezing storage of human sperm in vitro.

Effective suppression of triple negative breast cancer by paclitaxel nanoparticles conjugated with transmembrane TNF-α monoclonal antibody.

Transmembrane TNF-α (tmTNF), a transmembrane form of TNF-α, was reported overexpressed in approximately 84% of triple-negative breast cancer (TNBC) patients and has emerged as a valid candidate biomarker for targeting TNBC. Paclitaxel is a first-line chemotherapeutic agent for the treatment of triple-negative breast cancer, but suffers from low water solubility, resulting in its low bioavailability. To achieve site-specific delivery of the anticancer chemotherapeutic drug (paclitaxel) on TNBC, we developed tmTNF-α monoclonal antibody (mAb)-conjugated paclitaxel (PTX) nanoparticles (NPs) (tmTNF-α mAb-PTX NPs) as potential nanocarriers. This targeted delivery-therapy nanocarriers was conducted by using an emulsification-evaporation method. tmTNF-α mAb-PTX NPs displayed favorable physicochemical properties. Compared with the control groups, tumor growth in human MDA-MB-231 xenograft mice was suppressed significantly by tmTNF-α mAb-PTX NPs. TmTNF-α mAb-PTX NPs exerts anti-tumor effects via promoting apoptosis and regulating mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) / protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) cascade, as well as AMP-activated protein kinase (AMPK) and nuclear factor Kappa-B (NF-κB) pathways. Moreover, tmTNF-α mAb-PTX NPs can inhibit the process of epithelial-mesenchymal transition (EMT) in TNBC to suppress tumor progression and metastasis. Together, the novel tmTNF-α mAb-PTX NPs based targeted drug delivery system is a potentially highly effective approach for treating TNBC.

Construction and validation of a transcription factors-based prognostic signature for ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is one of the most common and lethal malignant tumors worldwide and the prognosis of OC remains unsatisfactory. Transcription factors (TFs) are demonstrated to be associated with the clinical outcome of many types of cancers, yet their roles in the prognostic prediction and gene regulatory network in patients with OC need to be further investigated. METHODS: TFs from GEO datasets were collected and analyzed. Differential expression analysis, WGCNA and Cox-LASSO regression model were used to identify the hub-TFs and a prognostic signature based on these TFs was constructed and validated. Moreover, tumor-infiltrating immune cells were analyzed, and a nomogram containing age, histology, FIGO_stage and TFs-based signature were established. Potential biological functions, pathways and the gene regulatory network of TFs in signature was also explored. RESULTS: In this study, 6 TFs significantly associated with the prognosis of OC were identified. These TFs were used to build up a TFs-based signature for predicting the survival of patients with OC. Patients with OC in training and testing datasets were divided into high-risk and low-risk groups, according to the median value of risk scores determined by the signature. The two groups were further used to validate the performance of the signature, and the results showed the TFs-based signature had effective prediction ability. Immune infiltrating analysis was conducted and abundance of B cells naïve, T cells CD4 memory resting, Macrophages M2 and Mast cells activated were significantly higher in high-risk group. A nomogram based on the signature was established and illustrated good predictive efficiencies for 1, 2, and 3-year overall survival. Furthermore, the construction of the TFs-target gene regulatory network revealed the potential mechanisms of TFs in OC. CONCLUSIONS: To our best knowledge, it is for the first time to develop a prognostic signature based on TFs in OC. The TFs-based signature is proven to be effective in predicting the survival of patients with OC. Our study may facilitate the clinical decision-making for patients with OC and help to elucidate the underlying mechanism of TFs in OC.

Rapid cryopreservation of small quantities of human spermatozoa by a self-prepared cryoprotectant without animal component.

Cryopreservation of small quantities of human spermatozoa whilst maintaining adequate post-thawing motility has been found an essential challenge for male fertility preservation. Therefore, the study used an effective, and convenient rapid-freezing method to freeze small amounts of human spermatozoa by adding self-prepared cryoprotectant (SPC) without animal component. In the feasibility experiment, no significant differences in progressive motility, normal sperm morphology, vitality or DNA fragmentation index between the conventional slow freezing and rapid freezing were realised. The present study prospectively analysed the effects of sperm freezing and resuscitation in 175 patients with severe oligozoospermia (sperm concentration <1 × 106 /ml). We observed the 120 severe oligozoospermia specimens had a mean recovery rate of 60.19% ± 10.43% and a mean cryosurvival rate of 68.0% ± 9.17%. In addition, 55 cryptozoospermia specimens were analysed. The small-volume cryopreservation showed advantages. The total sperm recovery, motility recovery and sperm loss rates were 98.48%, 50.17% and 1.52% respectively. In short, the SPC is safe and effective, and can be used to rapidly freeze severe oligozoospermia specimens. That is useful for successful sperm freezing whilst avoiding the risk of azoospermia in the later stages and promoting comprehensive fertility preservation.

Breaking through the Size Control Dilemma of Silver Chalcogenide Quantum Dots via Trialkylphosphine-Induced Ripening: Leading to Ag2Te Emitting from 950 to 2100 nm.

Ag2Te is one of the most promising semiconductors with a narrow band gap and low toxicity; however, it remains a challenge to tune the emission of Ag2Te quantum dots (QDs) precisely and continuously in a wide range. Herein, Ag2Te QDs emitting from 950 to 2100 nm have been synthesized via trialkylphosphine-controlled growth. Trialkylphosphine has been found to induce the dissolution of small-sized Ag2Te QDs due to its stronger ability to coordinate to the Ag ion than that of 1-octanethiol, predicated by the density functional theory. By controlling this dissolution effect, the monomer supply kinetics can be regulated, achieving precise size control of Ag2Te QDs. This synthetic strategy results in state-of-the-art silver-based QDs with emission tunability. Only by taking advantage of such an ultrawide emission has the sizing curve of Ag2Te been obtained. Moreover, the absolute photoluminescence quantum yield of Ag2Te QDs can reach 12.0% due to their well-passivated Ag-enriched surface with a density of 5.0 ligands/nm2, facilitating noninvasive in vivo fluorescence imaging. The high brightness in the long-wavelength near-infrared (NIR) region makes the cerebral vasculature and the tiny vessel with a width of only 60 µm clearly discriminable. This work reveals a nonclassical growth mechanism of Ag2Te QDs, providing new insight into precisely controlling the size and corresponding photoluminescence properties of semiconductor nanocrystals. The ultrasmall, low-toxicity, emission-tunable, and bright NIR-II Ag2Te QDs synthesized in this work offer a tremendous promise for multicolor and deep-tissue in vivo fluorescence imaging.

Prognostic Role of S100A8 in Human Solid Cancers: A Systematic Review and Validation.

BACKGROUND: S100A8 plays a key role in many cellular processes and is highly expressed in various solid cancers. However, the prognostic role of S100A8 has not been well defined. Therefore, we conducted a quantitative meta-analysis to investigate whether or not S100A8 could be used as a prognostic biomarker in solid tumors. METHODS: PubMed, Web of Science, Embase, and Cochrane library were searched to acquire relevant studies that evaluated the association between expression of S100A8 and prognosis of cancer patients. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were extracted to evaluate the association between S100A8 overexpression and Overall Survival (OS), Disease-Free Survival (DFS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS). The expression of S100A8 was also validated by Flow cytometry, immunohistochemistry (IHC), and western blot. RESULTS: A total of 2,817 patients from 13 independent studies, ranging from 43 to 1,117 patients in size, were statistically analyzed. Our results indicated that a high level of S100A8 expression was significantly associated with poor OS, poor DFS, and poor PFS/RFS. In term of clinical pathological characteristics, a high expression level of S100A8 was significantly associated with differentiation grades, lymphatic metastasis, ER statue, and PR statue. The validation studies showed that the expression of S100A8 was at high levels in MDA-MB-231 (79.7%), MDA-MB-453 (89.2%), HTB-9 (70.2%), and T24 (53.3%) cells and it was higher in breast cancer tissue and bladder cancer tissue than their corresponding para-carcinoma tissue. CONCLUSIONS: S100A8 overexpression was significantly associated with poor clinical prognosis in cancer patients. S100A8 is potential a prognostic biomarker in breast cancer and bladder cancer. More well-designed studies with adequate prognostic data are needed to confirm the prognostic role of S100A8 revealed in this study.

LncRNA PART1 Exerts Tumor-Suppressive Functions in Tongue Squamous Cell Carcinoma via miR-503-5p.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) accounts for one-third of oral cancers. Previous studies had reported that lncRNA/miRNA regulated the biological behaviors of different cancer cells. However, the mechanisms of PART1 in regulating tumorigenesis and TSCC development via targeting miR-503-5p had not been studied. METHODS: The expressions of PART1 and miR-503-5p in tissues and cultured cell lines were detected by qRT-PCR. StarBase 3.0 was used to predict the binding sites of PART1, then dual-luciferase assay and RNA pull-down assay were executed to confirm whether miR-503-5p was a target of PART1. TSCC cells were co-transfected with PART1-overexpressed plasmid or miR-503-5p mimics in vitro, and the transfection efficiency was evaluated through qRT-PCR. Western blot was performed to assess the expressions of EMT-related proteins. CCK-8 and clone formation assays were conducted to detect cell proliferation, TUNEL assay was used to detect apoptosis, and transwell assay was executed to test migration and invasion. RESULTS: The low PART1 expression and high miR-503-5p expression were found in TSCC tissues and cell lines (CAL-27 and SCC9). PART1 expression was positively correlated with patients' prognosis. The targeting and binding relationship between PART1 and miR-503-5p was confirmed, and overexpressed PART1 diminished the expression of miR-503-5p as well. Moreover, PART1 facilitated apoptosis, inhibited proliferation, invasion and migration of TSCC cells, and these influences were impeded by miR-503-5p overexpression. CONCLUSION: LncRNA PART1 played a cancer-suppressing role in TSCC by targeting miR-503-5p, which provided a potential target for TSCC treatment.

Monitoring Neuroinflammation with an HOCl-Activatable and Blood-Brain Barrier Permeable Upconversion Nanoprobe.

A reliable tool for real-time tracking the neuroinflammatory progress is highly desired for interpretation and treatment of neurological disorders. Herein, a blood-brain barrier (BBB) permeable and HOCl-activatable upconversion (UC) nanoprobe with NIR emission was designed for visual study on neuroinflammation (NI) in vivo. This UC probe consists of three parts: upconversion nanoparticles (UCNPs) as signal reporter, the Cy-HOCl dye acting as energy acceptor of UCNPs as well as the recognition unit of HOCl, and amphiphilic polymers endowing the probe with biocompatibility and BBB permeability. Upon intravenous injection into mice, the probe crossed the BBB via low-density lipoprotein receptor related protein (LRP) mediated transcytosis and was then lightened up by overproduced HOCl in an NI process. This probe was able to differentiate inflammation and the normal state of the brain in LPS-induced NI and monitor the progress of NI occurring in mice with cerebral stroke, providing a practical tool for noninvasive and visual assessment of NI.

The effect of an alternative chromosome 17 probe on fluorescence in situ hybridization for the assessment of HER2 amplification in invasive breast cancer.

Fluorescent in situ hybridization (FISH) is commonly used to determine the ratio of human epidermal growth factor receptor 2 (HER2) to centromere enumeration probe for chromosome 17 (CEP17), which further determines HER2 gene status in breast cancer. However, due to copy number alteration in CEP17, inaccurate diagnoses can occur. The current study was performed to investigate the diagnostic value of an alternative CEP17 reference probe for HER2 status in invasive breast cancer. A higher-order repeat in the centromeric region of chromosome 17 was identified and an alternative probe (SCEP17) was subsequently prepared. Karyotype analysis of peripheral blood was used to detect SCEP17 probe specificity. Using a HER2/CEP17 probe, karyotype analysis revealed two strong green signals at the centromere of chromosome 17 and one weaker signal at the other centromere. However, two strong hybridization signals at the centromere of chromosome 17 were observed when the HER2/SCEP17 probe was used. In the 425 patients with invasive breast cancer, no statistical difference was observed between HER2/SCEP17 and HER2/CEP17 when detecting HER2 gene amplification (P=0.157). However, in terms of copy number, the SCEP17 probe exhibited a reduced number compared with the conventional CEP17 probe (P<0.001). In conclusion, the HER2/SCEP17 probe may lead to increased accuracy HER2 status assessment in invasive breast cancer. However, a further large-scale and prospective clinical trial is required for confirmation of the potential benefits of using the HER2/SCEP17 probe.

Quantitative evaluation of computed and voxelwise computed diffusion-weighted imaging in breast cancer.

OBJECTIVES: To assess the value of computed diffusion-weighted imaging (cDWI) and voxelwise computed diffusion-weighted imaging (vcDWI) in breast cancer. METHODS: This retrospective study involved 130 patients (age range, 25-70 years; mean age ± standard deviation, 48.6 ± 10.5 years) with 130 malignant lesions, who underwent MRI examinations, including a DWI sequence, prior to needle biopsy or surgery. cDWIs with higher b-values of 1500, 2000, 2500, 3000, 3500, and 4000 s/mm2, and vcDWI were generated from measured (m) DWI with two lower b-values of 0/600, 0/800, or 0/1000 s/mm2. The signal-to-noise ratio (SNR) and contrast ratio (CR) of all image sets were computed and compared among different DWIs by two experienced radiologists independently. To better compare the CR with the SNR, the CR value was multiplied by 100 (CR100). RESULTS: The CR of vcDWI, and cDWIs, except for cDWI1000, differed significantly from that of measured diffusion-weighted imaging (mDWI) (cDWI1000: CR = 0.4904, p = 0.394; cDWI1500: CR = 0.5503, p = 0.006; cDWI2000: CR = 0.5889, p < 0.001; cDWI2500: CR = 0.6109, p < 0.001; cDWI3000: mean = 0.6214, p < 0.001; cDWI3500: CR = 0.6245, p < 0.001; cDWI4000: CR = 0.6228, p < 0.001). The vcDWI provided the highest CR, while the CRs of all cDWI image sets improved with increased b-values. The SNR of neither cDWI1000 nor vcDWI differed significantly from that of mDWI, but the mean SNRs of the remaining cDWIs were significantly lower than that of mDWI. The SNRs of cDWIs declined with increasing b-values, and the initial decrease at low b-values was steeper than the gradual attenuation at higher b-values; the CR100 rose gradually, and the two converged on the b-value interval of 1500-2000 s/mm2 . CONCLUSIONS: The highest CR was achieved with vcDWI; this could be a promising approach easier detection of breast cancer. ADVANCES IN KNOWLEDGE: This study comprehensively compared and evaluated the value of the emerging post-processing DWI techniques (including a set of cDWIs and vcDWI) in breast cancer.

Exosome plays an important role in the development of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers around the world. However, the early biomarkers for its detection and treatment are limited currently. Exosomes, classified as intercellular messenger shuttling their cargoes between cells, regulate cell differentiation and tissue development. They contain messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), proteins, lipids and transcription factors. Therefore, exosomes play a crucial role in the development of HCC. In this review, we highlight the exosomal cargoes which could serve as biomarkers for the prediction and diagnosis of HCC. Exosomes are involved in metastases of HCC and they show great potential in immunotherapy and drug resistance mechanism. In summary, exosome suggests new clues in clinical application of HCC.

Prognostic Value of HMGA2 in Human Cancers: A Meta-Analysis Based on Literatures and TCGA Datasets.

Background: Emerging evidences have shown that the high-mobility group protein A2 (HMGA2) can aberrantly express in human cancers, and it could be an unfavorable prognostic factor in cancer patients. However, the prognostic value of HMGA2 was still unclear. Therefore, in this study, we explored the potential prognostic value of HMGA2 in human cancers by using meta-analysis based on published literatures and The Cancer Genome Atlas (TCGA) datasets. Methods: Through searching PubMed, Embase, Web of Science and Cochrane Library databases, we were able to identify the studies evaluating the prognostic value of HMGA2 in cancers. Then, UALCAN and TCGA datasets were used to validate the results of our meta-analysis. Results: In all, 15 types of cancers were included in this meta-analysis. Pooled results showed that high level of HMGA2 was significantly correlated with poor OS (HR = 1.88, 95% confidence interval (CI) = 1.68-2.11, P < 0.001) and poor DFS (HR = 2.49, 95% CI = 1.44-4.28, P = 0.001) in cancer patients. However, subgroup analyses revealed that the high expressed HMGA2 was associated with poor OS in head and neck cancer, gastric cancer and colorectal cancer, but not esophageal cancer and ovarian cancer. Based on TCGA datasets, we analyzed 9944 patients with 33 types of cancers. Significant association between HMGA2 overexpression and poor OS was found in 14 types of cancers. Taken together, consistent results were observed in clear cell renal cell carcinoma, esophageal adenocarcinoma, head and neck cancer, hepatocellular carcinoma, ovarian carcinoma, and pancreatic ductal adenocarcinoma. Conclusion: Our meta-analysis showed the significance of HMGA2 and its prognostic value in various cancers. High level of HMGA2 could be associated with poor OS in patients with clear cell renal cell carcinoma, head and neck cancer, hepatocellular carcinoma and pancreatic ductal adenocarcinoma, but not esophageal adenocarcinoma and ovarian carcinoma.

Gd-DTPA-coupled Ag2Se quantum dots for dual-modality magnetic resonance imaging and fluorescence imaging in the second near-infrared window.

Near-infrared (NIR) fluorescent quantum dots (QDs) are ideal platforms to fabricate multifunctional contrast agents for multimodal imaging. Herein, second near-infrared window fluorescent (NIR-II) Ag2Se QDs were coupled with gadopentetate dimeglumine injection (Gd-DTPA) for dual-modality T1-weighted magnetic resonance (MR) imaging and fluorescence imaging. In vitro experiments suggested that the prepared Ag2Se-Gd QDs exhibit low cytotoxicity, remarkable T1-weighted MR imaging, and fluorescence imaging contrast properties. In vivo experiment results showed that Ag2Se-Gd QDs were the preferred contrast agents for dual-modality T1-weighted MR imaging and fluorescence imaging with high spatial resolution. Moreover, excellent temporal resolution and high tissue penetration depth were also achieved by fluorescence imaging. These results indicate the potential of Ag2Se-Gd QDs as multifunctional contrast agents for multimodal imaging in clinical diagnosis and research.

Risk of infection in patients with spondyloarthritis and ankylosing spondylitis receiving antitumor necrosis factor therapy: A meta-analysis of randomized controlled trials.

Antitumor necrosis factor (TNF) agents have been widely used for the treatment of spondyloarthritis (SpA) and ankylosing spondylitis (AS). However, these agents may increase the risk of infection due to suppressing the immune response. The present meta-analysis was performed to systematically investigate the risk of overall infection, serious infection and tuberculosis in patients with SpA and AS treated with anti-TNF agents. Medline, Embase and the Cochrane library were searched for randomized controlled trials (RCTs) published between January 1998 and December 2015 about infection in patients with SpA receiving anti-TNF therapy. Data were pooled to obtain relative risks (RRs) along with their 95% confidence intervals (CIs). A total of 25 RCTs investigating SpA, including 12 investigating AS specifically, were eligible for the meta-analysis. Similar risks of overall infection were reported in patients with SpA (RR, 1.03; 95% CI, 0.92-1.15) and AS (RR, 1.06; 95% CI, 0.91-1.24) treated with anti-TNF agents. The RR of serious infection for patients with SpA or AS receiving anti-TNF therapy compared with a placebo was 1.27 (95% CI, 0.67-2.38) and 1.57 (95% CI, 0.63-3.91), respectively. In addition, 4 RCTs with outcomes of tuberculosis in patients with SpA receiving anti-TNF agents were identified, all in infliximab-treated patients (RR, 2.52; 95% CI, 0.53-12.09). However, due to the limited number of RCTs, this finding should be interpreted with caution. The present meta-analysis did not find any significantly increased risk of infection associated with anti-TNF therapy in patients with SpA or AS. However, due to short duration of follow-up in the RCTs and the rarity of serious infections and tuberculosis, patients treated with anti-TNF agents still should be closely monitored in clinical practice.

Risk of tuberculosis in patients treated with TNF-α antagonists: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: An increased risk of tuberculosis (TB) has been reported in patients treated with TNF-α antagonists, an issue that has been highlighted in a WHO black box warning. This review aimed to assess the risk of TB in patients undergoing TNF-α antagonists treatment. METHODS: A systematic literature search for randomised controlled trials (RCTs) was performed in MEDLINE, Embase and Cochrane library and studies selected for inclusion according to predefined criteria. ORs with 95% CIs were calculated using the random-effect model. Subgroup analyses considered the effects of drug type, disease and TB endemicity. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: 29 RCTs involving 11 879 patients were included (14 for infliximab, 9 for adalimumab, 2 for golimumab, 1 for etanercept and 3 for certolizumab pegol). Of 7912 patients allocated to TNF-α antagonists, 45 (0.57%) developed TB, while only 3 cases occurred in 3967 patients allocated to control groups, resulting in an OR of 1.94 (95% CI 1.10 to 3.44, p=0.02). Subgroup analyses indicated that patients of rheumatoid arthritis (RA) had a higher increased risk of TB when treated with TNF-α antagonists (OR 2.29 (1.09 to 4.78), p=0.03). The level of the evidence was recommended as 'low' by the GRADE system. CONCLUSIONS: Findings from our meta-analysis indicate that the risk of TB may be significantly increased in patients treated with TNF-α antagonists. However, further studies are needed to reveal the biological mechanism of the increased TB risk caused by TNF-α antagonists treatment.

Analysis and assessment of the nutrients, biochemical indexes and heavy metals in the Three Gorges Reservoir, China, from 2008 to 2013.

The Three Gorges Reservoir, the world's largest hydropower project, has operated stably for more than five years. To understand its water quality status, the nutrient and biochemical indexes, the total nitrogen (TN), the total phosphorus (TP), the potassium permanganate index (CODMn), the five-day biochemical oxygen demand (BOD5) and fecal coliform (F. coli), as well as the heavy metals (Cu, Hg, As, Cd, Zn and Pb) of samples collected from 10 sites during the time period of 2008-2013 were studied via using multiple analysis approaches. For each parameter, pictures of the spatial and temporal distributions were presented, and the reasons behind their variation trends were elaborated. Principal component analysis (PCA) was applied to identify the types of pollution. The Canadian Council of Ministers of the Environment Water Quality Index (CCME-WQI) was calculated to concisely mark the water quality. In addition, a human health risk assessment of the heavy metals in a representative site was conducted. The results showed that the water quality state in the Three Gorges Reservoir was intricate but stable and acceptable from 2008 to 2013. The TN, TP and Pb were considered to be the key pollution indexes. Enforcements to alleviate industrial and urban pollution, along with ship management, have worked. The decrease in heavy metal concentrations from upstream to downstream was associated with the self-purification of the reservoir. However, rural pollution became worse in those years. Improper agricultural activity was an important reason for this trend. For local residents, drinking water was generally safe, but cancer caused by As and Pb is a potential issue.