Identification of extracellular polymeric substances layer barrier in chloroquine phosphate-disturbed anammox consortia and mechanism dissection on cytotoxic behavior by computational chemistry.

The over-dosing use of chloroquine phosphate (CQ) poses severe threats to human beings and ecosystem due to the high persistence and biotoxicity. The discharge of CQ into wastewater would affect the biomass activity and process stability during the biological processes, e.g., anammox. However, the response mechanism of anammox consortia to CQ remain unknown. In this study, the accurate role of extracellular polymeric substances barrier in attenuating the negative effects of CQ, and the mechanism on cytotoxic behavior were dissected by molecular spectroscopy and computational chemistry. Low concentrations (≤6.0 mg/L) of CQ hardly affected the nitrogen removal performance due to the adaptive evolution of EPS barrier and anammox bacteria. Compact protein of EPS barrier can bind more CQ (0.24 mg) by hydrogen bond and van der Waals force, among which O-H and amide II region respond CQ binding preferentially. Importantly, EPS contributes to the microbiota reshape with selectively enriching Candidatus_Kuenenia for self-protection. Furthermore, the macroscopical cytotoxic behavior was dissected at a molecular level by CQ fate/distribution and computational chemistry, suggesting that the toxicity was ascribed to attack of CQ on functional proteins of anammox bacteria with atom N17 (f-=0.1209) and C2 (f+=0.1034) as the most active electrophilic and nucleophilic sites. This work would shed the light on the fate and risk of non-antibiotics in anammox process.

Time-series analysis of the association between air pollution exposure and outpatient visits for dry eye disease: a case study in Zhengzhou, China.

Background: Dry eye disease (DED) is a prevalent ocular surface disease that significantly impacts patients' quality of life. The association between air pollution and the risk of dry eye disease remains uncertain. Methods: Data on outdoor air pollutants, meteorological information, and outpatient visits for DED were collected from July 1, 2014, to December 31, 2019. The relationship between ambient air pollutants and DED outpatient visits was analyzed using a generalized additive model with a Poisson distribution. Results: Among the 5,204 DED patients included in the study, 63.76% were female and 36.24% were male. The single-pollutant model revealed a significant association between a 10 µg/m3 increase in concentrations of fine-particulate matter with a median aerometric diameter of less than 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) and outpatient visits for DED. Fine-particulate matter with a median aerometric diameter of less than 2.5 µm (PM2.5) showed a significant association with DED outpatient visits in males and the 19-59 years age group. The strongest associations between air pollutants and outpatient visits were observed in male patients and during the cold season. Conclusion: The noteworthy correlation between air pollutants and DED outpatient visits can offer evidence for policy makers and underscore the significance of reinforcing environmental protection.

Identification of an angiogenesis-related risk score model for survival prediction and immunosubtype screening in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is an incurable B-cell malignancy, but with the emergence of immunotherapy, a potential cure is hopeful. The individualized interaction between the tumor and bone marrow (BM) microenvironment determines the response to immunotherapy. Angiogenesis is a constant hallmark of the BM microenvironment in MM. However, little is known about the potency ability of angiogenesis-associated genes (AAGs) to regulate the immune microenvironment of MM patients. METHODS: We comprehensively dissected the associations between angiogenesis and genomic landscapes, prognosis, and the immune microenvironment by integrating 36 AAGs. Immunohistochemistry was performed to verify the correlation between angiogenic factor expression and patient prognosis. Single-sample gene set enrichment analysis was applied to quantify the relative abundance of 28 infiltrating cells. The AAG score was constructed using the least absolute shrinkage and selection operator Cox regression model. RESULTS: Angiogenesis was closely correlated with MM patient prognosis, and the mutation intensity of the AAGs was low. Immunohistochemistry confirmed that high microvessel density predicted poor prognosis. Three AAG clusters and two gene clusters with distinct clinical outcomes and immune characteristics were identified. The established AAG_score model performed well in predicting patient prognosis and active immunotherapy response. The high-AAG_score subgroup was characterized by reduced immune cell infiltration, poor prognosis, and inactive immunotherapy response. Multivariate analyses indicated that the AAG_score was strongly robust and independent among the prognostic variables. CONCLUSION: This study revealed that angiogenesis is significantly related to MM patient prognosis and immune phenotype. Evaluating the AAG signature was conducive to predicting patient response to immunotherapy and guiding more efficacious immunotherapy strategies.

A Fast-Response AIE-Active Ratiometric Fluorescent Probe for the Detection of Carboxylesterase.

Hepatocellular carcinoma (HCC) is associated with a high mortality rate worldwide. The therapeutic outcomes can be significantly improved if diagnosis and treatment are initiated earlier in the disease process. Recently, the carboxylesterase (CaE) activity/level in human plasma was reported to be a novel serological biomarker candidate for HCC. In this article, we fabricated a new fluorescent probe with AIE characteristics for the rapid detection of CaE with a more reliable ratiometric response mode. The TCFISE probe showed high sensitivity (LOD: 93.0 µU/mL) and selectivity toward CaE. Furthermore, the good pH stability, superior resistance against photobleaching, and low cytotoxicity highlight the high potential of the TCFISE probe for application in the monitoring of CaE activity in complex biological samples and in live cells, tissues, and animals.

Paeoniflorin Ameliorates BiPN by Reducing IL6 Levels and Regulating PARKIN-Mediated Mitochondrial Autophagy.

Background: Bortezomib-induced peripheral neuropathy (BiPN) is a common complication of multiple myeloma (MM) treatment that seriously affects the quality of life of patients. The purpose of the present study was to explore the therapeutic effect of paeoniflorin on BiPN and its possible mechanism. Methods: ELISA was used to measure the level of interleukin-6 (IL6) in the plasma of MM patients, and bioinformatics analysis was used to predict the mechanism underlying the effect of paeoniflorin on peripheral neuropathy. Cell and animal models of BiPN were constructed to evaluate mitochondrial function by measuring cell viability and mitochondrial quality and labeling mitochondria with MitoTracker Green. Nerve injury in mice with BiPN was assessed by behavioral tests, evaluation of motor nerve conduction velocity, hematoxylin-eosin (HE) staining, electron microscopy and analysis of the levels of reactive oxygen species (ROS). Western blotting and immunohistochemistry (IHC) were used to assess the expression of autophagy-related proteins. Results: In MM patients, IL6 levels were positively correlated with the degree of PN. The results of bioinformatics analysis suggested that paeoniflorin ameliorated PN by altering inflammation levels and mitochondrial autophagy. Paeoniflorin increased PC12 cell viability and mitochondrial autophagy levels, alleviated mitochondrial damage, and reduced IL6 levels. In addition, paeoniflorin effectively improved the behavior of mice with BiPN, relieved sciatic nerve injury in mice, increased the expression of LC3II/I, beclin-1, and Parkin in sciatic nerve cells, and increased the expression of LC3B and Parkin in the nerve tissue. Conclusion: The present study confirmed that paeoniflorin significantly ameliorated peripheral neuropathy (PN) caused by bortezomib, possibly by reducing IL6 levels to regulate PARKIN-mediated mitochondrial autophagy and mitochondrial damage.

lnc-AC145676.2.1-6-3 plays an important role in intestinal acute graft-versus-host disease through the regulation of interleukin-1ß.

INTRODUCTION: Acute graft-versus-host disease (aGVHD) is one of the major complications of allogeneic hematopoietic stem cell transplantation, and the liver, skin, and gastrointestinal tract are the main target organs. The most common type is intestinal aGVHD. Long noncoding RNAs (lncRNAs) have coregulatory functions and participate in a variety of intracellular regulatory processes. We investigated the expression of lncRNAs and their mechanisms in the development of aGVHD. METHODS: The participants included 15 patients with aGVHD and 4 healthy controls (HCs). To generate profiles of abnormally expressed lncRNAs, peripheral blood mononuclear cell (PBMC) lncRNAs from four patients and four HCs were validated by high-throughput sequencing and quantitative real-time-PCR (qRT-PCR). A number of databases, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, miRanda, TargetScan, and Metascape, were used for bioinformatics analysis. Bioinformatics analysis indicated that overexpression of lnc-AC145676.2.1-6-3 might induce aGVHD via the interleukin (IL)-1ß axis and a downstream miRNA. After the higher levels of lnc-AC145676.2.1-6-3 in other patients were confirmed by qRT-PCR, serum IL-1ß, IL-6, and tumor necrosis factor-α were measured by enzyme linked immunosorbent assays. RESULTS: In our study, a large number of lncRNAs were found in PBMCs of patients with intestinal aGVHD, and bioinformatics analysis showed that the upregulated lncRNA lnc-AC145676.2.1-6-3 probably affected the progression of intestinal aGVHD by regulating the hsa-miR-3064-5p/IL-1ß axis. In addition, the changes in lncRNA expression levels were positively correlated with the clinical characteristics of intestinal aGVHD. CONCLUSION: Our results suggest that lncRNAs in PBMCs may become new biomarkers and therapeutic targets for intestinal aGVHD.

Efficacy of artificial intelligence-based screening for diabetic retinopathy in type 2 diabetes mellitus patients.

AIM: To explore the efficacy of artificial intelligence (AI)-based screening for diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) patients. METHODS: Data were obtained from 549 T2DM patients who visited the Fundus Disease Center at Henan Provincial People's Hospital from 2018/10-2020/09. DR identification and grading were conducted by two retina specialists, EyeWisdom®DSS and EyeWisdom®MCS, with ophthalmologist grading as reference standard, efficacy of EyeWisdom was evaluated according to sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: Ophthalmologists detected 324 DR cases. Among them, there were 43 of mild non-proliferative DR (NPDR), 79 of moderate NPDR, 61 of severe NPDR, and 141 of proliferative DR (PDR). EyeWisdom®DSS detected 337 DR and EyeWisdom®MCS detected 264 DR. Sensitivity and specificity of EyeWisdom®DSS were 91.0%(95 %CI: 87.3%-93.8%) and 81.3% (95 %CI: 75.5%-86.1%), while EyeWisdom®MCS correctly identified 76.2%(95 %CI: 71.1%-80.7%) of patients with DR and 92.4%(95 %CI: 87.9%-95.4%) of patients without DR. EyeWisdom®DSS showed 76.5%(95 %CI: 69.6%-82.3%) sensitivity and 78.4%(95 %CI: 73.7%-82.5%) specificity for detecting NPDR and 64.5%(95 %CI: 56.0%-72.3%) sensitivity and 93.1%(95 %CI: 90.1%-95.3%) specificity for diagnosing PDR. CONCLUSION: EyeWisdom®DSS is effective in screening for DR, and the accuracy of EyeWisdom®MCS was higher for identifying patients without DR. It is valuable to carry out AI-based DR screening in poorer regions.

A novel circRNA-miRNA-mRNA network revealed exosomal circ-ATP10A as a biomarker for multiple myeloma angiogenesis.

The importance of angiogenesis in multiple myeloma (MM) is unquestionable; however, to date, the success of antiangiogenic therapies has been fairly limited. Exosomal circular RNAs (circRNAs) have been proven to be pivotal players in angiogenesis in various cancers. Nevertheless, their role in MM remains unknown. Therefore, we aimed to identify differentially expressed circRNAs in peripheral blood exosomes from MM patients and explore their diagnostic and prognostic values. We screened 2,052 circRNAs with significant differential expression between MM patients and healthy controls via high-throughput sequencing. qRT-PCR confirmed that the expression of circ-ATP10A was significantly increased in MM patients. The bioinformatics analyses suggested that circ-ATP10A can act as a microRNA (miRNA) sponge and regulate the expression of downstream vascular endothelial growth factor-B (VEGFB), hypoxia-inducible factor-1alpha (HIF1A), platelet-derived growth factor subunit A (PDGFA), and fibroblast growth factor (FGF). The immunohistochemical results indicated that the circ-ATP10A level was positively correlated with the protein levels of VEGFB and marrow microvessel density (MVD) in MM patients, and the receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and Kaplan-Meier survival curve analyses confirmed it as a prognostic biomarker. Collectively, our study indicates that exosomal circ-ATP10A is a valuable prognostic biomarker in MM and may promote MM angiogenesis by targeting hsa-miR-6758-3p/hsa-miR-3977/hsa-miR-6804-3p/hsa-miR-1266-3p/hsa-miR-3620-3p and modulating their downstream mRNAs, such as VEGFB, HIF1A, PDGF, and FGF.

Heavy menstrual bleeding due to primary myelofibrosis in a woman: a case report.

Heavy menstrual bleeding (HMB) due to primary myelofibrosis (PMF) is secondary to progressive pancytopenia, which is a rare and difficult to treat condition. We report this case with the aim of sharing our experiences and exploring a safe and effective way to treat patients with HMB due to PMF. A 40-year-old woman who had been taking combined oral contraceptives (COCs) for eight years was admitted to our hospital with HMB. A bone marrow biopsy report and genetic testing confirmed the diagnosis of PMF. Norethisterone tablets had an unsatisfactory hemostatic effect. The patient underwent a hysteroscopy and the insertion of a levonorgestrel intrauterine system (LNG-IUS). At the 5-month follow-up, the patient had a lower menstruation bleeding volume. COCs are unsuitable for managing the menstruation of patients with PMF in the long run. Endometrial ablation is the long-term method. However, the patient's fertility requirements should be taken into account. The insertion of an LNG-IUS after hysteroscopic curettage to exclude endometrial malignant lesions is recommended.

West Lake staging: A new staging system orchestrated by X-ray and MRI on knee osteoarthritis.

Purpose: To investigate the differences on X-ray and MRI among each stage of knee osteoarthritis (KOA) and further propose a new staging system called West Lake (WL) staging. Methods: A cross-sectional study was conducted on patients with KOA. Stage I, II, III, and IV were divided based on stepwise treatment strategy of Knee osteoarthritis (KOA). Joint space widths (JSW) were measured on X-rays, whereas cartilage injuries (CI) and bone marrow lesions (BML) were evaluated on MRI. The differences of them across the groups were calculated by T-test. Receiver operating characteristic (ROC) curves were rendered to obtain the areas under the curves (AUC), Youden index and corresponding cut-off points. Results: Eventually, there were significant differences on JSW, CI, and BML between stage II/III and III/IV, while no significant differences between stage I/II. In stage II/III, the AUC of JSW, CI, BML was 0.99, 0.76, 0.71 and the Youden index was 0.94, 0.38, 0.45, meanwhile the cut-off points were ≤5.1 mm, >1, >2. In stage III/IV, the AUC of JSW, CI, BML was 0.96, 0.79, 0.74 and the Youden index was 0.84, 0.58, 0.38, meanwhile the cut-off points were ≤3.2 mm, >3, >4. Conclusion: The WL staging was described as follows: Stage I, X-ray shows no joint space narrow, normal MRI or MRI shows cartilage degeneration and only 1 or 2 sections are involved in BML. Stage II, X-ray shows joint space narrow, MRI shows cartilage defect but no full-thickness cartilage defect, meanwhile 3 or 4 sections are involved in BML. Stage III, X-ray shows serious joint space narrow even JSW disappeared, MRI shows full-thickness cartilage defect, more than 4 sections are involved in BML.

Distribution of diabetic retinopathy in diabetes mellitus patients and its association rules with other eye diseases.

The study aims to explore the distribution characteristics and influencing factors of diabetic retinopathy (DR) in diabetes mellitus (DM) patients and association rules of eye diseases in these patients. Data were obtained from 1284 DM patients at Henan Provincial People's Hospital. Association rules were employed to calculate the probability of the common occurrence of eye-related diseases in DM patients. A web visualization network diagram was used to display the association rules of the eye-related diseases in DM patients. DR prevalence in people aged < 40 years (≥ 58.5%) was higher than that in those aged 50-60 years (≤ 43.7%). Patients with DM in rural areas were more likely to have DR than those in urban areas (56.2% vs. 35.6%, P < 0.001). DR prevalence in Pingdingshan City (68.4%) was significantly higher than in other cities. The prevalence of DR in patients who had DM for ≥ 5 years was higher than in other groups (P < 0.001). About 33.07% of DM patients had both diabetic maculopathy and DR, and 36.02% had both diabetic maculopathy and cataracts. The number of strong rules in patients ≥ 60 years old was more than those in people under 60 in age, and those in rural areas had more strong rules than those in urban areas. DM patients with one or more eye diseases are at higher risks of other eye diseases than general DM patients. These association rules are affected by factors such as age, region, disease duration, and DR severity.

Armoring Black Phosphorus Anode with Stable Metal-Organic-Framework Layer for Hybrid K-Ion Capacitors.

Potassium-ion capacitors (KICs) are promising for sustainable and eco-friendly energy storage technologies, yet their slow reaction kinetics and poor cyclability induced by large K-ion size are a major obstacle toward practical applications. Herein, by employing black phosphorus nanosheets (BPNSs) as a typical high-capacity anode material, we report that BPNS anodes armored with an ultrathin oriented-grown metal-organic-framework (MOF) interphase layer (BPNS@MOF) exhibit regulated potassium storage behavior for high-performance KICs. The MOF interphase layers as protective layer with ordered pores and high chemical/mechanical stability facilitate K ion diffusion and accommodate the volume change of electrode, beneficial for improved reaction kinetics and enhanced cyclability, as evidenced by substantial characterizations, kinetics analysis and DFT calculations. Consequently, the BPNS@MOF electrode as KIC anodes exhibits outstanding cycle performance outperforming most of the reported state-of-art KICs so far.

Ethanol Extracts of Solanum lyratum Thunb Regulate Ovarian Cancer Cell Proliferation, Apoptosis, and Epithelial-to-Mesenchymal Transition (EMT) via the ROS-Mediated p53 Pathway.

Ovarian cancer is a type of common gynecological tumors with high incidence and poor survival. The anticancer effects of the traditional Chinese medicine Solanum lyratum Thunb (SLT) have been intensively investigated in various cancers but in ovarian cancer is rare. The current study is aimed at investigating the effect of SLT on ovarian cancer cells. Lactate dehydrogenase (LDH) and MTT assays indicated that SLT concentrations of 0.25 and 0.5 µg/mL were not cytotoxic and had significant inhibitory effects on the cell viabilities of A2780 and SKOV3 cells, hence were used for subsequent experiments. Flow cytometric and western blot analysis revealed that SLT effectively suppressed ovarian cancer cell proliferation via inducing cell cycle arrest and increasing apoptosis. Cell cycle and apoptosis-related protein expressions were also regulated in SLT-treated cells. Moreover, DCFH-DA and western blot assays demonstrated that SLT enhanced ROS accumulation and subsequently activated the p53 signaling pathway. However, SLT-regulated ovarian cancer cell proliferation, apoptosis, migration, invasion, and EMT were significantly reversed by an ROS inhibitor (NAC, N-acetyl-L-cysteine). Furthermore, A2780 and SKOV3 cells cocultured with M0 macrophages showed that SLT activated the polarization of M0 macrophages to M1 macrophages and inhibited the polarization to M2 macrophages, with the increased percentage of CD86+ cells and decreased percentage of CD206+ cells were detected. In summary, this study illustrated the anticancer effects of SLT on ovarian cancer cells, suggesting that SLT may have the potential to provide basic evidence for the discovery of antiovarian cancer agents.

Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2.

Objective: The long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has emerged as a novel player in hepatocellular carcinoma (HCC). Hypoxia is a common characteristic of the microenvironment of HCC. This study aimed to investigate whether lncRNA-NEAT1 is induced by hypoxia in HCC, and the mechanism that underlies LncRNA-NEAT1 function. Methods: The expression changes of lncRNA-NEAT1 in HCC cell lines under hypoxic conditions were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The regulatory effect of HIF-1α on lncRNA-NEAT1 was confirmed with chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The function of lncRNA-NEAT1 on HCC cell growth under hypoxic conditions was determined by CCK-8 assay and flow cytometry. lncRNA -NEAT1 was predicted to serve as a competing endogenous RNA (ceRNA) within microRNA (miRNA)/mRNA axes based on microarray data, public HCC-related datasets and integrative bioinformatics analysis, and the miR-199a-3p/UCK2 axis was selected and validated by qRT-PCR, western blotting, RNA immunoprecipitation, and luciferase reporter analyses. The role of miR-199a-3p/UCK2 in HCC and its functional association with lncRNA-NEAT1 were assessed both in vitro and in vivo. Results: LncRNA-NEAT1 expression was significantly induced by hypoxia in SNU-182 and HUH7 cells. HIF-1α was shown to regulate lncRNA-NEAT1 transcription. Under hypoxic conditions, lncRNA-NEAT1 maintained the growth of HCC cells and inhibited apoptosis and cell cycle arrest. LncRNA-NEAT1 was predicted to regulate a panel of HCC-associated miRNA-mRNA pairs consisting of 8 miRNAs and 13 mRNAs. LncRNA-NEAT1 was shown to function as a ceRNA of miR-199a-3p/UCK2 both in HCC cells under hypoxic conditions and in an animal model. Conclusion: LncRNA-NEAT1 is a hypoxia-responsive lncRNA in HCC cell lines Insilico evidence suggested that LncRNA-NEAT1 may sustainthe growth of HCC cells by regulating HCC-associated mRNAs that interact with tumor-suppressive miRNAs. The lncRNA-NEAT1/miR-199a-3p/UCK2 pathway may contribute to the progression of HCC cell lines in a hypoxic microenvironment and therefore may represent a novel therapeutic target for HCC.

Ti3C2Tx MXene Nanosheets as a Robust and Conductive Tight on Si Anodes Significantly Enhance Electrochemical Lithium Storage Performance.

Exploring Si-based anode materials with high electrical conductivity and electrode stability is crucial for high-performance lithium-ion batteries (LIBs). Herein, we propose the fabrication of a Si-based composite where Si porous nanospheres (Si p-NSs) are tightly wrapped by Ti3C2Tx (Tx stands for the surface groups such as -OH, -F) MXene nanosheets (TNSs) through an interfacial assembly strategy. The TNSs as a conductive and robust tight of the Si p-NSs can effectively improve electron transport and electrode stability, as revealed by substantial characterizations and mechanical simulations. Moreover, the TNSs with rich surface groups enable strong interfacial interactions with the Si p-NS component and a pseudocapacitive behavior, beneficial for fast and stable lithium storage. Consequently, the Si p-NS@TNSs electrode with a high Si content of 85.6% exhibits significantly enhanced battery performance compared with the Si p-NSs electrode such as high reversible capacity (1154 mAh g-1 at 0.2 A g-1), long cycling stability (up to 2000 cycles with a 0.026% capacity decay rate per cycle), and excellent rate performances. Notably, the Si p-NS@TNSs electrode-based LIB full cell delivers a high energy uptake of 405 Wh kg-1, many-times higher than that of the Si p-NSs full cell. This work offers a strategy to develop advanced Si-based anode materials with desirable properties for high-performance LIBs.

A panel of collagen genes are associated with prognosis of patients with gastric cancer and regulated by microRNA-29c-3p: an integrated bioinformatics analysis and experimental validation.

Background: The systematic expression characteristics and functions of collagen genes in gastric cancer (GC) have not been reported. Through public data integration, combined with bioinformatics analysis, we identified a panel of collagen genes overexpressed in GC. The functions of these genes were analyzed and validated in a GC-related cohort. microRNAs that may potentially target such genes were investigated in vitro. Methods: Four GC-related datasets retrieved from the Gene Expression Omnibus (GEO) were used to extract differentially expressed genes (DEGs) in GC. Functional annotation was performed to identify the potential roles of the identified DEGs. The association of candidate genes involved in the prognosis of GC patients (n=876) was determined using data provided by the Kaplan-Meier-plotter database, The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) repository, and a GC-related dataset (GSE15459). The expression characteristics of candidate genes and their associations with clinical parameters were validated in our in-house cohort (n=58). MicroRNAs able to target the identified candidate genes were predicted and confirmed using qRT-PCR, Western blotting, and dual-luciferase reporter assays in vitro. Results: After the integration of four GEO datasets, 76 DEGs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these DEGs were significantly enriched in ECM-related functions and pathways. A group of collagen genes was significantly upregulated in the GC tissues and constituted a protein-protein interaction network as important nodes. Some of these collagen genes were closely associated with poor prognosis in GC patients. Overexpression of COL1A1 and COL4A1 was confirmed in our in-house cohort, and this was related to prognosis and certain clinicopathological parameters. We found that microRNA-29c-3p could directly target COL1A1 and COL4A1 in BGC-823 cells. Conclusions: Collagen genes identified in this study were associated with patient prognosis in GC and may represent diagnostic markers or potential therapeutic targets. Aberrant expression of such candidate genes may be induced by microRNA-29c-3p.

Short-term outcomes of traction-assisted versus conventional endoscopic submucosal dissection for superficial gastrointestinal neoplasms: a systematic review and meta-analysis of randomized controlled studies.

BACKGROUND: In recent years, some traction-assisted approaches have been introduced to facilitate endoscopic submucosal dissection (ESD) procedures by reducing the procedure time and risks related to the procedure. However, the relative advantages of traction-assisted endoscopic submucosal dissection (T-ESD) are still being debated. This study aimed to assess the efficacy of T-ESD for the treatment of superficial gastrointestinal neoplasms. METHODS: We searched MEDLINE, Embase, and Cochrane library up to March 31, 2019 for randomized controlled trials (RCTs) comparing T-ESD and conventional endoscopic submucosal dissection (C-ESD) for superficial gastrointestinal neoplasms. The main endpoints are en bloc resection, complete resection, procedure time, perforation, and delayed bleeding. Pooled risk ratio (RR), Peto odds ratio (OR), and mean difference (MD) were calculated to compare T-ESD and C-ESD. This study is registered with PROSPERO, number CRD42018108135. RESULTS: A total of 7 RCTs with 1007 patients were included in this meta-analysis. There were no significant differences between the T-ESD and C-ESD groups in the pooled estimate of en bloc resection, complete resection, and delayed bleeding (RR = 1.00, 95% CI 0.99, 1.01, I2 = 0%, P = 0.66; RR = 1.00, 95% CI 0.98, 1.03, I2 = 0%, P = 0.81; OR = 0.95, 95% CI 0.48, 1.86, I2 = 19%, P = 0.87,respectively). The pooled estimate indicated that the procedure time was significantly shorter in the T-ESD group (MD = - 16.19, 95% CI - 29.24, - 3.13, I2 = 87%, P = 0.02) than in the C-ESD group. Compared to C-ESD, T-ESD was associated with lower incidence of perforation (OR = 0.32, 95% CI 0.11, 0.91, I2 = 0%, P = 0.03). CONCLUSIONS: T-ESD is a safe and effective treatment option with a low perforation rate and shorter procedure time than C-ESD for superficial gastrointestinal neoplasms. Future multi-center (including European populations), randomized controlled trials of larger sample size and long-term outcomes of T-ESD are required.

Natural killer cells inhibit metastasis of ovarian carcinoma cells and show therapeutic effects in a murine model of ovarian cancer.

Ovarian cancer has the highest mortality rate and is the most common of all gynecologic malignancies. Novel treatments for ovarian cancer are urgently required to improve outcomes and the overall survival of patients. The present study investigated whether immunotherapy with natural killer (NK) cells affected the survival of mice with ovarian cancer. Results analysis identified adjunctive NK cells as a potential therapeutic method in ovarian cancer. Patient-derived ovarian cells were isolated, cultured and subsequently injected subcutaneously into immune deficient BALB/c-nude mice. Human NK cells were isolated from peripheral blood mononuclear cells and cultured for expansion in vitro. The present results demonstrated that ovarian cells in BALB/c-nude mice did not induce spontaneous ovarian cancer cell metastasis in the NK-treated group. In addition, NK cells activated immune cells in the immune system, which resulted in inhibition of ovarian tumor growth in vitro and in a murine xenograft model of ovarian cancer. The data also indicated that cytotoxic activity of NK cells prevented migration and invasion of ovarian cancer cells, which contributed to prevention of systemic metastasis and suggested that NK cells could be effective cells for therapy against ovarian cancer. Furthermore, NK cells induced apoptosis and increased the number of cluster of differentiation (CD)4+, CD8+ as well as cytotoxic T lymphocyte responses by intravenous injection in a murine xenograft model of ovarian cancer. These results suggested that NK cells inhibited the systemic metastasis for ovarian cancer cells. In conclusion, the present study suggested that NK cell immunotherapy inhibited systemic metastasis of ovarian cancer cells and improved the survival rate of mice. Sufficient supplementation of NK cells may serve as a promising immunotherapeutic strategy for ovarian cancer.

Recurrent ovarian hemorrhage in a patient with aplastic anemia: A case report.

RATIONALE: Recurrent ovarian hemorrhage resulting in ovarian infarction may lead to a life-threatening intraperitoneal hemorrhage in women with bleeding disorders such as aplastic anemia (AA). Moreover, it is seen as ovarian tumors in the diagnosis. The authors report a clinical case with the aim of sharing our experiences and exploring the ways to diagnose, treat, and avoid ovarian hemorrhage. PATIENTS CONCERNS: A 48-year-old woman with AA had suffered from a serious abdominal distension for the past 24 hours, which had occurred intermittently for the past 15 years. DIAGNOSES: Pelvic ultrasonography had revealed a large anechoic area of fluid in the abdomen without any sign of primary hemorrhage each time she had experienced an episode over the past 15 years. The volume of pelvic fluid had decreased after anti-inflammatory and hemostatic treatment. At presentation, the abdominal computed tomography suggested an ovarian tumor with a massive hemoperitoneum (a right ovarian mass, 5.7 × 5.0 × 5.0 cm in size, with a large amount of abdominal and pelvic fluid). INTERVENTIONS: Surgery was performed with respect to the bilateral uterine adnexa. On laparotomy, there were blood clots of approximately 6.0 × 6.0 × 5.0 cm surrounding the right ovary and approximately 400 mL bloody fluid in the abdomen. OUTCOMES: The patient recovered without incident and was transferred to a hematology ward 1 week later. Postoperative pathology confirmed hemorrhagic infarction of the right ovary. LESSONS: In conclusion, continuous ovarian bleeding can cause ovarian infarction to women with bleeding disorders and it may be confused with an ovarian tumor. Moreover, an earlier ovariectomy procedure under stable conditions or treatment with gonadotropin-releasing hormone that prevent bleeding via ovulation suppression may be effective for such cases.