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Background: Scarce research has reported the efficacy and safety of laparoscopic distal gastrectomy in elderly patients. This retrospective study aimed to compare the outcomes of laparoscopic and open distal gastrectomy for advanced gastric cancer in elderly patients. Methods: A total of 303 elderly patients who underwent distal gastrectomy for advanced gastric cancer from June 2017 to June 2021 were enrolled. Variables used to calculate propensity score matching included sex, age, body mass index, American Society of Anesthesiologists, history of diabetes, and history of hypertension. The statistical significance of continuous variables was tested using an independent sample t test. chi-square or Fisher's exact tests were used for categorical variables. Kaplan–Meier curve and log-rank test were used for the evaluation of 3-year overall survival and recurrence-free survival. Results: After performing 1:1 propensity score matching, 248 patients were included for analysis (laparoscopic = 124, open = 124). Compared with the open group, the laparoscopic group showed significant advantages in estimated blood loss (P < 0.001), pain scale on the first postoperative day (P = 0.002), time to first flatus (P = 0.004), time to first liquid diet (P = 0.005), hospital stays (P < 0.001), and total complications (P = 0.011), but devoted much more operation time (P < 0.001). No statistical difference was observed between the two groups in 3-year recurrence-free survival (P = 0.315) or overall survival (P = 0.159). Conclusions: Our analysis demonstrated that laparoscopic surgery had the advantages of less intraoperative blood loss, fewer postoperative complications, and faster postoperative recovery in distal gastrectomy for advanced gastric, indicating that laparoscopic distal gastrectomy is safe and effective for treating elderly patients with distal gastric cancer. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most frequent malignant brain tumor, the relapse of which is unavoidable following standard treatment. However, the effective treatment for recurrent GBM is lacking, necessitating the understanding of key mechanisms driving tumor recurrence and the identification of new targets for intervention. Here, we integrated single-cell RNA-sequencing data spanning 36 patient-matched primary and recurrent GBM (pGBM and rGBM) specimens, with 6 longitudinal GBM spatial transcriptomics to explore molecular alterations at recurrence, with each cell type characterized in parallel. Genes involved in extracellular matrix (ECM) organization are preferentially enriched in rGBM cells, and MAFK is highlighted as a potential regulator. Notably, we uncover a unique subpopulation of GBM cells that is much less detected in pGBM and highly expresses ECM and mesenchyme related genes, suggesting it may contribute to the molecular transition of rGBM. Further regulatory network analysis reveals that transcription factors, such as NFATC4 and activator protein 1 members, may function as hub regulators. All non-tumor cells alter their specific sets of genes as well and certain subgroups of myeloid cells appear to be physically associated with the mesenchyme-like GBM subpopulation. Altogether, our study provides new insights into the molecular understanding of GBM relapse and candidate targets for rGBM treatment. [ABSTRACT FROM AUTHOR]

Background: During pregnancy, both ovarian hyperstimulation syndrome (OHSS) and pregnancy luteoma could manifest as massive ascites, enlarged ovaries, or elevated serum levels of cancer antigen 125 (CA125), and atypical cells may be found in the ascitic fluid of OHSS patients. Whether this should be treated aggressively as peritoneal carcinomatosis is controversial. Case presentation: A 35-year-old G2P1A1 woman with secondary infertility had a successful pregnancy after one cycle of assisted reproductive technology. The patient complained of lower abdominal distension, oliguria, and poor appetite 19 days after embryo transplantation. She was diagnosed with late-onset OHSS. Although the size of the ovaries decreased bilaterally to the normal range at 12 weeks of gestation after prompt medical care, the ascites increased again after an initial decreasing trend. Elevated serum levels of CA125 (191.1 IU/mL), and suspected adenocarcinoma cells were observed in the ascitic fluid. Although further magnetic resonance imaging examination or diagnostic laparoscopy was recommended, the patient was provided with supportive treatment and closely monitored upon her request. Surprisingly, her ascites diminished, and serum level of CA125 started to decline at 19 weeks of gestation. During cesarean section, pathological examination of the solid mass in the right ovary revealed pregnancy luteoma, which was presumably the other cause of the intractable ascites. Conclusions: Caution should be exercised in cases of suspicious malignant ascites during pregnancy. This may due to OHSS or pregnancy luteoma, in which abnormalities usually regress spontaneously. [ABSTRACT FROM AUTHOR]

The advent of immunotherapy has made an indelible mark on the field of cancer therapy, especially the application of immune checkpoint inhibitors in clinical practice. Although immunotherapy has proven its efficacy and safety in some tumors, many patients still have innate or acquired resistance to immunotherapy. The emergence of this phenomenon is closely related to the highly heterogeneous immune microenvironment formed by tumor cells after undergoing cancer immunoediting. The process of cancer immunoediting refers to the cooperative interaction between tumor cells and the immune system that involves three phases: elimination, equilibrium, and escape. During these phases, conflicting interactions between the immune system and tumor cells result in the formation of a complex immune microenvironment, which contributes to the acquisition of different levels of immunotherapy resistance in tumor cells. In this review, we summarize the characteristics of different phases of cancer immunoediting and the corresponding therapeutic tools, and we propose normalized therapeutic strategies based on immunophenotyping. The process of cancer immunoediting is retrograded through targeted interventions in different phases of cancer immunoediting, making immunotherapy in the context of precision therapy the most promising therapy to cure cancer. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis plays a key role in human cancer, but its function and mechanism in glioma is not clear. P62/SQSTM1 was reported to inhibit ferroptosis via the activation of NRF2 signaling pathway. In this study we reveal a dual role of p62 in ferroptosis of glioblastoma (GBM) according to p53 status. Method: Lipid peroxidation analysis, transmission electron microscopy (TEM), GSH assay were performed to determine the level of ferroptosis. Western blot and qPCR were obtained to detect the expression of ferroptosis markers. Construction of mutant plasmids, immunoprecipitation, luciferase assay and rescue-experiments were performed to explore the regulatory mechanism. Results: P62 overexpression facilitates ferroptosis and inhibits SLC7A11 expression in p53 mutant GBM, while attenuates ferroptosis and promotes SLC7A11 expression in p53 wild-type GBM. P62 associates with p53 and inhibits its ubiquitination. The p53-NRF2 association and p53-mediated suppression of NRF2 antioxidant activity are diversely regulated by p62 according to p53 status. P53 mutation status is required for the dual regulation of p62 on ferroptosis. In wild-type p53 GBM, the classical p62-mediated NRF2 activation pathway plays a major regulatory role of ferroptosis, leading to increased SLC7A11 expression, resulting in a anti-ferroptosis role. In mutant p53 GBM, stronger interaction of mutant-p53/NRF2 by p62 enhance the inhibitory effect of mutant p53 on NRF2 signaling, which reversing the classical p62-mediated NRF2 activation pathway, together with increased p53's transcriptional suppression on SLC7A11 by p62, leading to a decrease of SLC7A11, resulting in a pro-ferroptosis role. Conclusion: Together, this study shows novel molecular mechanisms of ferroptosis regulated by p62; the mutation status of p53 is an important factor that determines the therapeutic response to p62-mediated ferroptosis-targeted therapies in GBM. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is an iron dependent cell death closely associated with p53 signaling pathway and is aberrantly regulated in glioblastoma (GBM), yet the underlying mechanism needs more exploration. Identifying new factors which regulate p53 and ferroptosis in GBM is essential for treatment. Methods: Glioma cell growth was evaluated by cell viability assays and colony formation assays. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays, and transmission electron microscopy were used to assess the degree of cellular lipid peroxidation of GBM. The mechanisms of RND1 in regulation of p53 signaling were analyzed by RT-PCR, western blot, immunostaining, co-immunoprecipitation, ubiquitination assays and luciferase reporter assays. The GBM‐xenografted animal model was constructed and the tumor was captured by an In Vivo Imaging System (IVIS). Results: From the The Cancer Genome Atlas (TCGA) database, we summarized that Rho family GTPase 1 (RND1) expression was downregulated in GBM and predicted a better prognosis of patients with GBM. We observed that RND1 influenced the glioma cell growth in a ferroptosis-dependent manner when GBM cell lines U87 and A172 were treated with Ferrostatin-1 or Erastin. Mechanistically, we found that RND1 interacted with p53 and led to the de-ubiquitination of p53 protein. Furthermore, the overexpression of RND1 promoted the activity of p53-SLC7A11 signaling pathway, therefore inducing the lipid peroxidation and ferroptosis of GBM. Conclusions: We found that RND1, a novel controller of p53 protein and a positive regulator of p53 signaling pathway, enhanced the ferroptosis in GBM. This study may shed light on the understanding of ferroptosis in GBM cells and provide new therapeutic ideas for GBM. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis plays a key role in human cancer, but its function and mechanism in glioma is not clear. P62/SQSTM1 was reported to inhibit ferroptosis via the activation of NRF2 signaling pathway. In this study we reveal a dual role of p62 in ferroptosis of glioblastoma (GBM) according to p53 status. Method: Lipid peroxidation analysis, transmission electron microscopy (TEM), GSH assay were performed to determine the level of ferroptosis. Western blot and qPCR were obtained to detect the expression of ferroptosis markers. Construction of mutant plasmids, immunoprecipitation, luciferase assay and rescue-experiments were performed to explore the regulatory mechanism. Results: P62 overexpression facilitates ferroptosis and inhibits SLC7A11 expression in p53 mutant GBM, while attenuates ferroptosis and promotes SLC7A11 expression in p53 wild-type GBM. P62 associates with p53 and inhibits its ubiquitination. The p53-NRF2 association and p53-mediated suppression of NRF2 antioxidant activity are diversely regulated by p62 according to p53 status. P53 mutation status is required for the dual regulation of p62 on ferroptosis. In wild-type p53 GBM, the classical p62-mediated NRF2 activation pathway plays a major regulatory role of ferroptosis, leading to increased SLC7A11 expression, resulting in a anti-ferroptosis role. In mutant p53 GBM, stronger interaction of mutant-p53/NRF2 by p62 enhance the inhibitory effect of mutant p53 on NRF2 signaling, which reversing the classical p62-mediated NRF2 activation pathway, together with increased p53's transcriptional suppression on SLC7A11 by p62, leading to a decrease of SLC7A11, resulting in a pro-ferroptosis role. Conclusion: Together, this study shows novel molecular mechanisms of ferroptosis regulated by p62; the mutation status of p53 is an important factor that determines the therapeutic response to p62-mediated ferroptosis-targeted therapies in GBM. [ABSTRACT FROM AUTHOR]

Background: Serum lipid abnormalities are generally considered as a major risk factor for type 2 diabetes mellitus (T2DM). However, evidence for the effect of long-term serum lipid fluctuations on future T2DM probability remains limited. Methods: A total of 4475 nondiabetic participants who underwent annual health examinations between 2010 and 2013 were followed for the subsequent 5-year risk of T2DM. The Cox proportional hazards model was performed to evaluate the associations of visit-to-visit variabilities and trajectories of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) with T2DM probability. Results: During the five-year follow-up, 223 newly developed T2DM cases were identified. Compared with the "Low" TG trajectory, "Moderate" and "Moderate-High" TG trajectories were significantly associated with T2DM incidence, with adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) of 1.51 (1.12-2.03) and 2.55 (1.62-4.03), respectively. Additionally, participants in the third and fourth quartiles of TG/standard deviation (SD) were associated with increased T2DM probability when compared with those in the lowest quartile. After excluding individuals with prediabetes, participants with "Moderate-High" TG trajectory still had a 2.43-fold greater risk of T2DM compared with those with "Low" TG trajectory (95 % CI: 1.28-4.63). In addition, compared with participants in "Low" HDL-c trajectory, the future T2DM probability was significantly reduced in those with "Moderate" and "High" HDL-c trajectories, with HR (95 % CI) of 0.52 (0.37-0.72) and 0.38 (0.18-0.80), respectively. After excluding individuals with prediabetes, the "Moderate" HDL-c trajectory remained associated with decreased T2DM probability when compared with "Low" HDL-c trajectory (HR: 0.55, 95 % CI: 0.35-0.88). However, the incidence of T2DM was not associated with the long-term fluctuations of TC and LDL-c. Conclusions: Long-term visit-to-visit variability of TG, and the change trajectories of TG and HDL-c were significantly associated with future T2DM probability. Moreover, these associations were not affected after excluding individuals with prediabetes. [ABSTRACT FROM AUTHOR]

Background: Chinese population has a high prevalence of chronic hepatitis B virus (HBV) infection, the impact of which on pregnancy outcome remains controversial. A single-center retrospective cohort study was performed in Kunming, a multi-ethnic city in south-western China to examine this issue.Methods: The singleton pregnancies delivering at ≥28 weeks gestation under our care in 2005-2017 constituted the study cohort. Maternal characteristics and pregnancy outcome were compared between mothers with and without seropositivity for hepatitis B surface antigen (HBsAg) determined at routine antenatal screening.Results: Among the 49,479 gravidae in the cohort, the 1624 (3.3%) HBsAg seropositive gravidae had a lower incidence of nulliparity (RR 0.963, 95% CI 0.935-0.992) and having received tertiary education (RR 0.829, 95% CI 0.784-0.827). There was no significant difference in the medical history, pregnancy complications, or labor or perinatal outcome, except that HBV carriers had significantly lower incidence of labor induction (RR 0.827, 95% CI 0.714-0.958) and of small-for-gestational age (SGA) infants (RR 0.854, 95% CI 0.734-0.994). On regression analysis, maternal HBV carriage was independently associated with spontaneous labor (aRR 1.231, 95% CI 1.044-1.451) and reduced SGA infants (aRR 0.842, 95% CI 0.712-0.997).Conclusions: Our 3.3% prevalence of maternal HBV infection was around the lower range determined in the Chinese population. The association with spontaneous labor and reduced SGA infants could have helped to promote the perpetuation of the infection through enhanced survival of the offspring infected at birth, thus explaining the high prevalence in the Chinese population. [ABSTRACT FROM AUTHOR]

Objective: Circ-centro-some/spindle pole-associated protein (CSPP1) has been confirmed to be characterized in diverse human malignancies and its ectopic expression may regulate tumor progression and development. However, in hepatocellular carcinoma (HCC), its biological role, clinical significance and molecular mechanism are still unclear. Methods: Circ-CSPP1 expression and its prognostic values in HCC tissues were detected by qRT-PCR or in situ hybridization (ISH), and enriched by using Rnase R. The functional experiments (Circ-CSPP1 was overexpressed or knocked down) were performed in HCC cells. The HCC cell growth was analyzed by CCK-8 assay, transwell, wound healing and colony formation assays. The interation between circ-CSPP1 and miR-577/miR-577 and cyclin E2 (CCNE2) were determined by dual luciferase assay or RNA binding protein immunoprecipitation (RIP) assay. The RNA fluorescence in situ hybridization (FISH) assay was used to detect the subcellular distribution. Finally, an in vivo nude mouse tumor model was constructed. Results: In HCC patients and cells, circ-CSPP1 was aberrantly expressed, and its upregulation predicted poor prognosis, and closely correlated with tumor size and TNM stage. Circ-CSPP1 resisted RnaseR digestion, indicating it is a circular RNA structure. Moreover, overexpression of circ-CSPP1 promoted HCC cell viability, colony formation, migration, and invasion in vitro. Knockdown of circ-CSPP1 showed contrary results. Circ-CSPP1 acts as a miR-577 sponge and positively regulated the target of miR-577, CCNE2. Besides, miR-577 inhibitor rescued the suppressive effects of circ-CSPP1 knockdown on HCC cell growth, whereas was completely reversed by silencing of CCNE2. Finally, the in vivo experiments confirmed that circ-CSPP1 knockdown regulated xenograft tumor volume and downregulated CCNE2, p-Rb, E2F1 and c-myc expression. Conclusion: These findings revealed that circ-CSPP1 contributed to HCC progression by positively regulating CCNE2 via miR-577, thus established its potential as new a prognostic and therapeutic marker for HCC patients. [ABSTRACT FROM AUTHOR]

The incidence and mortality of strokes have increased over the past three decades in China. Ischemic strokes can cause a sequence of detrimental events in patients, including increased permeability and dysfunction of the blood-brain barrier, brain edema, metabolic disturbance, endoplasmic reticulum stress, autophagy, oxidative stress, inflammation, neuron death and apoptosis, and cognitive impairment. Thrombolysis using recombinant tissue plasminogen activator (rtPA) and mechanical embolectomy with a retrievable stent are two recognized strategies to achieve reperfusion after a stroke. Nevertheless, rtPA has a narrow therapeutic timeframe, and mechanical embolectomy has limited rates of good neurological outcomes. EGb761 is a standardized and extensively studied extract of Ginkgo biloba leaves. The ginkgolides and bilobalide that constitute a critical part of EGb761 have demonstrated protective properties towards cerebral injury. Ginkgolides include Ginkgolide A (GA), Ginkgolide B (GB), Ginkgolide C (GC), Ginkgolide J (GJ), Ginkgolide K (GK), Ginkgolide L (GL), and Ginkgolide M (GM). This review seeks to elucidate the neuroprotective effects and mechanisms of ginkgolides, especially GA and GB, and bilobalide in cerebral injury following ischemic strokes. [ABSTRACT FROM AUTHOR]

Background: Diet-related cardiovascular diseases have produced a large health burden in China. Coal miners are a high-risk population for cardiovascular disease, but there is little evidence concerning associations between coal miners' dietary patterns and their 10-year cardiovascular disease risk score levels.Methods: The study included 2632 participants and focused on dietary patterns associated with higher 10-year cardiovascular disease risk score levels. A valid semi-quantitative food frequency questionnaire was used to collect data regarding dietary intake, and dietary patterns were identified using factor analysis combined with cluster analysis. Logistic regression was used to assess associations between dietary patterns and 10-year cardiovascular disease risk score levels.Results: For ground workers, compared with the 'Healthy' pattern, the 'High-salt' and 'Refined grains' patterns were significantly associated with higher 10-year atherosclerotic cardiovascular disease risk score level (OR: 1.50, 95% CI: 1.02-2.21; OR: 1.92, 95% CI: 1.26-2.93) and 10-year ischemic cardiovascular disease risk score level (OR: 2.18, 95% CI: 1.25-3.80; OR: 2.64, 95% CI: 1.48-4.72) adjusted for gender, and behavioural and socioeconomic factors. The 'High-fat and salt' pattern was significantly associated with higher 10-year ischemic cardiovascular disease risk score level (OR: 1.97, 95% CI: 1.13-3.42). For underground workers, the 'High-salt' pattern was significantly associated with higher 10-year atherosclerotic cardiovascular disease risk score level (OR: 1.65, 95% CI: 1.16-2.36) and 10-year ischemic cardiovascular disease risk score level (OR: 1.76, 95% CI: 1.09-2.84).Conclusions: This study provides evidence for dietary patterns associated with higher 10-year cardiovascular disease risk score levels in Chinese miners, and facilitates relevant departments in designing effective dietary guidelines to ameliorate dietary structures. [ABSTRACT FROM AUTHOR]

The online version of the original article can be found at https://doi.org/10.1186/s12935-020-01287-8. References 1 Zhang J, Duan H, Feng Z. Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress. [Extracted from the article]

References 1 Zhang J, Duan H, Feng Z. Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress. The online version of the original article can be found at https://doi.org/10.1186/s12935-020-01287-8. [Extracted from the article]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that circulating microRNAs (miRNAs) can be used as diagnostic biomarkers for melanoma. This study aimed to evaluate the diagnostic value of circulating miRNAs for melanoma. Methods: A comprehensive literature search was conducted and the quality of the included literature was evaluated using QUADAS-2 (Quality Assessment for diagnostic accuracy studies), and the diagnostic accuracy was assessed by pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). We used Deeks' funnel plot to evaluate publication bias. Results: The meta-analysis included 10 articles covering 16 studies, and the results showed that circulating miRNAs provide high diagnostic accuracy for melanoma. The overall pooled sensitivity was 0.87 (95% CI: 0.82–0.91), specificity was 0.81 (95% CI: 0.77–0.85), PLR was 4.6 (95% CI: 3.7–5.8), NLR was 0.16 (95% CI: 0.11–0.23), DOR was 29 (95% CI: 18–49), and AUC was 0.90 (95% CI: 0.87–0.92), respectively. Subgroup analysis showed better diagnostic value in miRNA clusters, European population, plasma miRNAs, and upregulated miRNAs compared to other subgroups. Conclusions: The results indicated that circulating microRNAs can be used as a non-invasive biomarker for the diagnosis of melanoma. [ABSTRACT FROM AUTHOR]

Melanoma is the deadliest form of skin cancer showing rising incidence over the past years. New insights into the mechanisms of melanoma progression contributed to the development of novel treatment options, such as immunotherapies. However, acquiring resistance to treatment poses a big problem to therapy success. Therefore, understanding the mechanisms underlying resistance could improve therapy efficacy. Correlating expression levels in tissue samples of primary melanoma and metastases revealed that secretogranin 2 (SCG2) is highly expressed in advanced melanoma patients with poor overall survival (OS) rates. By conducting transcriptional analysis between SCG2-overexpressing (OE) and control melanoma cells, we detected a downregulation of components of the antigen presenting machinery (APM), which is important for the assembly of the MHC class I complex. Flow cytometry analysis revealed a downregulation of surface MHC class I expression on melanoma cells that showed resistance towards the cytotoxic activity of melanoma-specific T cells. IFNγ treatment partially reversed these effects. Based on our findings, we suggest that SCG2 might stimulate mechanisms of immune evasion and therefore be associated with resistance to checkpoint blockade and adoptive immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. Materials and methods: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. Results: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2–3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. Conclusion: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP. [ABSTRACT FROM AUTHOR]

Background: Human health is seriously threatened by antibiotic-induced intestinal disorders. Herein, we aimed to determine the effects of Autoinducer-2 (AI-2) combined with Lactobacillus rhamnosus GG (LGG) on the intestinal barrier function of antibiotic-induced intestinal dysbiosis neonatal mice. Methods: An antibiotic-induced intestinal dysbiosis neonatal mouse model was created using antibiotic cocktails, and the model mice were randomized into the control, AI-2, LGG, and LGG + AI-2 groups. Intestinal short-chain fatty acids and AI-2 concentrations were detected by mass spectrometry and chemiluminescence, respectively. The community composition of the gut microbiota was analyzed using 16S rDNA sequencing, and biofilm thickness and bacterial adhesion in the colon were assessed using scanning electron microscopy. Transcriptome RNA sequencing of intestinal tissues was performed, and the mRNA and protein levels of HCAR2 (hydroxycarboxylic acid receptor 2), claudin3, and claudin4 in intestinal tissues were determined using quantitative real-time reverse transcription PCR and western blotting. The levels of inflammatory factors in intestinal tissues were evaluated using enzyme-linked immunosorbent assays (ELISAs). D-ribose, an inhibitor of AI-2, was used to treat Caco-2 cells in vitro. Results: Compared with the control, AI-2, and LGG groups, the LGG + AI-2 group showed increased levels of intestinal AI-2 and proportions of Firmicutes and Lacticaseibacillus, but a reduced fraction of Proteobacteria. Specifically, the LGG + AI-2 group had considerably more biofilms and LGG on the colon surface than those of other three groups. Meanwhile, the combination of AI-2 and LGG markedly increased the concentration of butyric acid and promoted Hcar2, claudin3 and claudin4 expression levels compared with supplementation with LGG or AI-2 alone. The ELISAs revealed a significantly higher tumor necrosis factor alpha (TNF-α) level in the control group than in the LGG and LGG + AI-2 groups, whereas the interleukin 10 (IL-10) level was significantly higher in the LGG + AI-2 group than in the other three groups. In vitro, D-ribose treatment dramatically suppressed the increased levels of Hcar2, claudin3, and claudin4 in Caco-2 cells induced by AI-2 + LGG. Conclusions: AI-2 promotes the colonization of LGG and biofilm formation to improve intestinal barrier function in an antibiotic-induced intestinal dysbiosis neonatal mouse model. [ABSTRACT FROM AUTHOR]

Background: Inhibition of p38 MAPK signalling leads to glioblastoma multiform (GBM) tumourigenesis. Nevertheless, the molecular mechanism that induces p38 MAPK signalling pathway silencing during GBM genesis has yet to be determined. Identifying new factors that can regulate p38 MAPK signalling is important for tumour treatment. Methods: Flow cytometry, TUNEL assays, immunofluorescence, JC-1 assays, and western blot analyses were used to detect the apoptosis of GBM cells. The specific methods used to detect autophagy levels in GBM cells were western blot analysis, LC3B protein immunofluorescence, LC3B puncta assays and transmission electron microscopy. The functions of these critical molecules were further confirmed in vivo by intracranial xenografts in nude mice. Tumour tissue samples and clinical information were used to identify the correlation between RND2 and p62 and LC3B expression, survival time of patients, and tumour volumes in clinical patients. Results: By summarizing data from the TCGA database, we found that expression of the small GTPase RND2 was significantly increased in human glioblastomas. Our study demonstrated that RND2 functions as an endogenous repressor of the p38 MAPK phosphorylation complex. RND2 physically interacted with p38 and decreased p38 phosphorylation, thereby inhibiting p38 MAPK signalling activities. The forced expression of RND2 repressed p38 MAPK signalling, which inhibited glioblastoma cell autophagy and apoptosis in vitro and induced tumour growth in the xenografted mice in vivo. By contrast, the downregulation of RND2 enhanced p38 MAPK signalling activities and promoted glioma cell autophagy and apoptosis. The inhibition of p38 phosphorylation abolished RND2 deficiency-mediated GBM cell autophagy and apoptosis. Most importantly, our study found that RND2 expression was inversely correlated with patient survival time and was positively correlated with tumour size. Conclusions: Our findings revealed a new function for RND2 in GBM cell death and offered mechanistic insights into the inhibitory effects of RND2 with regard to the regulation of p38 MAPK activation. [ABSTRACT FROM AUTHOR]

Background: Screening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT. Methods: The prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov − Smirnov test and other statistical methods were used for statistical analysis, x 2 was obtained using the formula x 2 = nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China. Results: Among 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P < 0.001) between these two types of educational institutions. Meanwhile, as for the age-wise distribution of latent infection among 17–20 years old freshmen, the LTBI rate exhibited 10.5%, 11.6%, 12.1% and 13.5%, respectively. Correlation between LTBI rate, the strong positive rate was statistically significant among different ages (χ2 = 34.559, P < 0.001). Over a follow-up period of 2 years, three students were diagnosed with active tuberculosis, one of which was resistant to rifampicin. All three students manifested a strong positive for PPD and declined preventive treatment during TB screening. Conclusions: The data indicates a high rate of LTBI amongst students in areas with a heavy TB burden, potentially leading to cross-regional TB transmission due to the migration of students. Education level might contribute to the limited uptake of TPT. Therefore, improving the implementation of TB preventive treatments is crucial in controlling and preventing TB across schools. [ABSTRACT FROM AUTHOR]

Background: Screening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT. Methods: The prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov − Smirnov test and other statistical methods were used for statistical analysis, x 2 was obtained using the formula x 2 = nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China. Results: Among 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P < 0.001) between these two types of educational institutions. Meanwhile, as for the age-wise distribution of latent infection among 17–20 years old freshmen, the LTBI rate exhibited 10.5%, 11.6%, 12.1% and 13.5%, respectively. Correlation between LTBI rate, the strong positive rate was statistically significant among different ages (χ2 = 34.559, P < 0.001). Over a follow-up period of 2 years, three students were diagnosed with active tuberculosis, one of which was resistant to rifampicin. All three students manifested a strong positive for PPD and declined preventive treatment during TB screening. Conclusions: The data indicates a high rate of LTBI amongst students in areas with a heavy TB burden, potentially leading to cross-regional TB transmission due to the migration of students. Education level might contribute to the limited uptake of TPT. Therefore, improving the implementation of TB preventive treatments is crucial in controlling and preventing TB across schools. [ABSTRACT FROM AUTHOR]

Introduction: Low serum selenium and altered tumour RNA expression of certain selenoproteins are associated with a poor breast cancer prognosis. Selenoprotein expression stringently depends on selenium availability, hence circulating selenium may interact with tumour selenoprotein expression. However, there is no matched analysis to date. Methods: This study included 1453 patients with newly diagnosed breast cancer from the multicentric prospective Sweden Cancerome Analysis Network – Breast study. Total serum selenium, selenoprotein P and glutathione peroxidase 3 were analysed at time of diagnosis. Bulk RNA-sequencing was conducted in matched tumour tissues. Fully adjusted Cox regression models with an interaction term were employed to detect dose-dependent interactions of circulating selenium with the associations of tumour selenoprotein mRNA expression and mortality. Results: 237 deaths were recorded within ~ 9 years follow-up. All three serum selenium biomarkers correlated positively (p < 0.001). All selenoproteins except for GPX6 were expressed in tumour tissues. Single cell RNA-sequencing revealed a heterogeneous expression pattern in the tumour microenvironment. Circulating selenium correlated positively with tumour SELENOW and SELENON expression (p < 0.001). In fully adjusted models, the associations of DIO1, DIO3 and SELENOM with mortality were dose-dependently modified by serum selenium (p < 0.001, p = 0.020, p = 0.038, respectively). With increasing selenium, DIO1 and SELENOM associated with lower, whereas DIO3 expression associated with higher mortality. Association of DIO1 with lower mortality was only apparent in patients with high selenium [above median (70.36 µg/L)], and the HR (95%CI) for one-unit increase in log(FPKM + 1) was 0.70 (0.50–0.98). Conclusions: This first unbiased analysis of serum selenium with the breast cancer selenotranscriptome identified an effect-modification of selenium on the associations of DIO1, SELENOM, and DIO3 with prognosis. Selenium substitution in patients with DIO1-expressing tumours merits consideration to improve survival. [ABSTRACT FROM AUTHOR]

Background: Mitochondria represent a major source of reactive oxygen species (ROS) in cells, and the direct increase in ROS content is the primary cause of oxidative stress, which plays an important role in tumor proliferation, invasion, angiogenesis, and treatment. However, the relationship between mitochondrial oxidative stress-related genes and glioblastoma (GBM) remains unclear. This study aimed to investigate the value of mitochondria and oxidative stress-related genes in the prognosis and therapeutic targets of GBM. Methods: We retrieved mitochondria and oxidative stress-related genes from several public databases. The LASSO regression and Cox analyses were utilized to build a risk model and the ROC curve was used to assess its performance. Then, we analyzed the correlation between the model and immunity and mutation. Furthermore, CCK8 and EdU assays were utilized to verify the proliferative capacity of GBM cells and flow cytometry was used to analyze apoptosis rates. Finally, the JC-1 assay and ATP levels were utilized to detect mitochondrial function, and the intracellular ROS levels were determined using MitoSOX and BODIPY 581/591 C11. Results: 5 mitochondrial oxidative stress-related genes (CTSL, TXNRD2, NUDT1, STOX1, CYP2E1) were screened by differential expression analysis and Cox analysis and incorporated in a risk model which yielded a strong prediction accuracy (AUC value = 0.967). Furthermore, this model was strongly related to immune cell infiltration and mutation status and could identify potential targeted therapeutic drugs for GBM. Finally, we selected NUDT1 for further validation in vitro. The results showed that NUDT1 was elevated in GBM, and knockdown of NUDT1 inhibited the proliferation and induced apoptosis of GBM cells, while knockdown of NUDT1 damaged mitochondrial homeostasis and induced oxidative stress in GBM cells. Conclusion: Our study was the first to propose a prognostic model of mitochondria and oxidative stress-related genes, which provided potential therapeutic strategies for GBM patients. [ABSTRACT FROM AUTHOR]

Background: Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors. In this study, we constructed gene co-expression networks to identify key modules and hub genes involved in the pathogenesis of EC. Results: The MEturquoise module was found to be significantly related to hypertension and the MEbrown module was significantly related to the history of other malignancies. Functional enrichment analysis showed that the MEturquoise module was associated with the GO biological process terms of transcription from RNA polymerase II promoter, positive regulation of male gonad development, endocardial cushion development, and endothelial cell differentiation. The MEbrown module was associated with GO terms DNA binding, epithelial-to-mesenchymal transition, and transcription from RNA polymerase II promoter. A total of 10 hub genes were identified and compared with the available datasets at transcriptional and translational levels. Conclusions: The identified ceRNAs may play a critical role in the progression and metastasis of EC and are thus candidate therapeutic targets and potential prognostic biomarkers. The two modules constructed further provide a useful reference that will advance understanding of the mechanisms of tumorigenesis in EC. [ABSTRACT FROM AUTHOR]

Background: The anti-coagulation protocol of patients with hemorrhage risk primary disease who need extracorporeal membrane oxygenation (ECMO) supported is controversial. This study evaluated the feasibility of a new anti-coagulation strategy, that is heparin-free after 3000 IU heparin loaded in veno-venous ECMO (VV ECMO) supported acute respiratory failure patients with hemorrhage risk. Methods: A retrospective study was performed in a series of hemorrhage risk patients supported with VV ECMO at the First Affiliated Hospital of Zhengzhou University, between June 2012 to Sept 2020. A total of 70 patients received a low heparin bolus of 3000 units for cannulation but without subsequent, ongoing heparin administration. Patients were divided into survival (n = 25) and non-survival group (n = 45). Data of coagulation, hemolysis and membrane lung function were calculated and analyzed. The complications of patients were recorded. Finally, the binary Logistic regression was conducted. Results: The longest heparin-free time was 216 h, and the mean heparin-free time was 102 h. Compared with survivors, the non-survivors were showed higher baseline SOFA score and lower platelet counts in 0.5 h, 24 h, 48 h and 96 h after ECMO applied. However, there was no significant differences between survivors and non-survivors in ACT, APTT, INR, D-dimer, fibrinogen, LDH, blood flow rate, Δp and Ppost-MLO2 (all p < 0.05) of all different time point. Moreover, only the baseline SOFA score was significantly associated with mortality (p < 0.001, OR(95%CI): 2.754 (1.486–5.103)) while the baseline levels of ACT, APTT, INR, platelet, D-dimer, fibrinogen and LDH have no association with mortality. The percentage of thrombosis complications was 54.3% (38/70) including 3 oxygenator changed but there was no significant difference of complications in survival and non-survival groups (p > 0.05). Conclusions: The anticoagulation protocol that no heparin after a 3000 units heparin bolus in VV ECMO supported acute respiratory failure patients with hemorrhage risk is feasible. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the correlation between functional disability and quality of life (QoL). And exploring the interaction of functional disability, basic demographic characteristics and health-related information on QoL among the rural elderly in Anhui Province.Methods: This study used multi-stage stratified cluster sampling in rural Anhui Province from January to July 2018 to conduct a cross-sectional survey of older adults who met the inclusion criteria. The Five-Dimensional European Quality Of Health Scale (EQ-5D) and the WHO Disability Assessment Schedule (WHODAS2.0) scale were used to evaluate the QoL and functional disability, and the basic demographic characteristics of the survey subjects were also collected. Using binary logistic and Classification and regression tree model (CART) models to analyze the data, explore the relationship between functional disability and QoL in the elderly.Results: A total of 3491 older adults were included in the survey, and 3336 completed the entire survey, with an effective response rate of 95.56%. After adjusting for covariables, those who had limited in dimension of mobility (AOR=2.243, 95%CI: 1.743-2.885), getting along (AOR=1.615, 95%CI: 1.173-2.226), life activities (AOR=2.494, 95%CI:1.928-3.226), and social participation (AOR=2.218, 95%CI: 1.656-2.971) had a lower QoL. However, the dimension of cognition (AOR=0.477, 95%CI: 0.372-0.613) is a protective factor for QoL. Additionally, we also observe that 96.3% of those who were unemployed and limited in both mobility and life activities dimensions had a lower QoL, but among those who were robust in both mobility and social participation dimensions and not suffer from chronic diseases, 56.3% had a higher QoL.Conclusions: Our findings indicate that special attention should be paid to the elderly who are unemployed, have limited in cognition, getting along, social participation, mobility, life activities and cognition robust to improve their QoL. This research is of great significance for formulating targeted strategies and measures to improve the QoL for rural elderly. [ABSTRACT FROM AUTHOR]

Background: Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors. In this study, we constructed gene co-expression networks to identify key modules and hub genes involved in the pathogenesis of EC. Results: The MEturquoise module was found to be significantly related to hypertension and the MEbrown module was significantly related to the history of other malignancies. Functional enrichment analysis showed that the MEturquoise module was associated with the GO biological process terms of transcription from RNA polymerase II promoter, positive regulation of male gonad development, endocardial cushion development, and endothelial cell differentiation. The MEbrown module was associated with GO terms DNA binding, epithelial-to-mesenchymal transition, and transcription from RNA polymerase II promoter. A total of 10 hub genes were identified and compared with the available datasets at transcriptional and translational levels. Conclusions: The identified ceRNAs may play a critical role in the progression and metastasis of EC and are thus candidate therapeutic targets and potential prognostic biomarkers. The two modules constructed further provide a useful reference that will advance understanding of the mechanisms of tumorigenesis in EC. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most common and fatal primary tumor in the central nervous system (CNS). Due to the existence of blood–brain barrier (BBB), most therapeutics cannot efficiently reach tumors in the brain, and as a result, they are unable to be used for effective GBM treatment. Accumulating evidence shows that delivery of therapeutics in form of nanoparticles (NPs) may allow crossing the BBB for effective GBM treatment. Methods: Betulinic acid NPs (BA NPs) were synthesized by the standard emulsion approach and characterized by electron microscopy and dynamic light scattering analysis. The resulting NPs were characterized for their anti-tumor effects by cell viability assay, EdU-DNA synthesis assay, cell cycle assay, mitochondrial membrane potential, and PI-FITC apoptosis assay. Further mechanistic studies were carried out through Western Blot and immunostaining analyses. Finally, we evaluated BA NPs in vivo for their pharmacokinetics and antitumor effects in intracranial xenograft GBM mouse models. Results: BA NPs were successfully prepared and formed into rod shape. BA NPs could significantly suppress glioma cell proliferation, induce apoptosis, and arrest the cell cycle in the G0/G1 phase in vitro. Furthermore, BA NPs downregulated the Akt/NFκB-p65 signaling pathway in a concentration dependent manner. We found that the observed anti-tumor effect of BA NPs was dependent on the function of CB1/CB2 receptors. Moreover, in the intracranial GBM xenograft mouse models, BA NPs could effectively cross the BBB and greatly prolong the survival time of the mice. Conclusions: We successfully synthesized BA NPs, which could cross the BBB and demonstrated a strong anti-tumor effect. Therefore, BA NPs may potentially be used for effective treatment of GBM. [ABSTRACT FROM AUTHOR]

Background: We aimed to appraise the impact of the changing national childbirth policy since 2002, currently allowing two children per family, on obstetric workload in a regional referral center in China.Methods: In a retrospective cohort study, temporal changes were examined in relation with maternal demographics, incidence of women with high risk pregnancies and resource statistics in our hospital in managing singleton viable pregnancies (birth from 28 weeks gestational age onwards) for the period 2005-2017.Results: During this 13-year period, the number of singleton livebirths from 28 weeks gestational age onwards was 49,479. Annual numbers of births increased from 1,941 to 2005 to 5,777 in 2017. There were concomitant and significant increases in the incidence of multiparous women (10.6-50.8 %), of age ≥35 years (6.5-24.3 %), with prior caesarean Sec. (2.6-23.6 %), with ≥3 previous pregnancy terminations (1.0-4.9 %), with pre-gestational diabetes (0.2-0.9 %), and with chronic hypertension (0.2-1.2 %). There were associated increases in beds and staff complement and reduced average hospital stay. Nevertheless, while the workload of medical staff remained stable with increasing staff complement, that of midwives increased significantly as reflected by the total births: midwife ratio which increased from 194.1:1 to 320.9:1 (p < 0.001).Conclusions: In our hospital, progressively increasing numbers of annual births in combination with an increased incidence of women with high risk pregnancies took place following the revised national childbirth policy. Only the increase in medical and nursing, but not midwifery, staff was commensurate with workload. Remedial measures are urgently required before the anticipated progressive increase in care demand would overwhelm maternity care with potentially disastrous consequences. [ABSTRACT FROM AUTHOR]

Background: The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE.Methods: From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT.Results: Eighty nine TACE procedures (1.35 ± 0.67; 1-4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), "typical tumor enhancement" (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis.Conclusions: The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Rubisco activase (RCA) regulates the activity of Rubisco and is a key enzyme of photosynthesis. RCA expression was widely reported to affect plant photosynthesis and crop yield, but the molecular basis of natural variation in RCA expression in a wide range of maize materials has not been fully elucidated. Results: In this study, correlation analysis in approximately 200 maize inbred lines revealed a significantly positive correlation between the expression of maize RCA gene ZmRCAβ and grain yield. A genome-wide association study revealed both cis-expression quantitative trait loci (cis-eQTLs) and trans-eQTLs underlying the expression of ZmRCAβ, with the latter playing a more important role. Further allele mining and genetic transformation analysis showed that a 2-bp insertion and a 14-bp insertion in the promoter of ZmRCAβ conferred increased gene expression. Because rice is reported to have higher RCA gene expression than does maize, we subsequently compared the genetic factors underlying RCA gene expression between maize and rice. The promoter activity of the rice RCA gene was shown to be stronger than that of the maize RCA gene, suggesting that replacing the maize RCA gene promoter with that of the rice RCA gene would improve the expression of RCA in maize. Conclusion: Our results revealed two DNA polymorphisms regulating maize RCA gene ZmRCAβ expression, and the RCA gene promoter activity of rice was stronger than that of maize. This work increased understanding of the genetic mechanism that underlies RCA gene expression and identify new targets for both genetic engineering and selection for maize yield improvement. [ABSTRACT FROM AUTHOR]

Background: The differential diagnosis of Parkinson's disease (PD) and multiple system atrophy (MSA) remains a challenge, especially in the early stage. Here, we assessed the value of transcranial sonography (TCS) to discriminate non-tremor dominant (non-TD) PD from MSA with predominant parkinsonism (MSA-P). Methods: Eighty-six MSA-P patients and 147 age and gender-matched non-TD PD patients who had appropriate temporal acoustic bone windows were included in this study. All the patients were followed up for at least 2 years to confirm the initial diagnosis. Patients with at least one substantia nigra (SN) echogenic size ≥18 mm2 were classified as hyperechogenic, those with at least one SN echogenic size ≥25 mm2 was defined as markedly hyperechogenic. Results: The frequency of SN hyperechogenicity in non-TD PD patients was significantly higher than that in MSA-P patients (74.1% vs. 38.4%, p < 0.001). SN hyperechogenicity discriminated non-TD PD from MSA-P with sensitivity of 74.1%, specificity of 61.6%, and positive predictive value of 76.8%. If marked SN hyperechogenicity was used as the cutoff value (≥ 25 mm2), the sensitivity decreased to 46.3%, but the specificity and positive predictive value increased to 80.2 and 80.0%. Additionally, in those patients with SN hyperechogenicity, positive correlation between SN hyperechogenicity area and disease duration was found in non-TD PD rather than in MSA-P patients. In this context, among early-stage patients with disease duration ≤3 years, the sensitivity, specificity and positive predictive value of SN hyperechogenicity further declined to 69.8%, 52.2%, and 66.7%, respectively. Conclusions: TCS could help discriminate non-TD PD from MSA-P in a certain extent, but the limitation was also obvious with relatively low specificity, especially in the early stage. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) are important functional regulators of many biological processes of cancers. However, the mechanisms by which lncRNAs modulate androgen-independent prostate cancer (AIPC) development remain largely unknown. Methods: Next-generation sequencing technology and RT-qPCR were used to assess LEF1-AS1 expression level in AIPC tissues and adjacent normal tissues. Functional in vitro experiments, including colony formation, EDU and transwell assays were performed to assess the role of LEF1-AS1 in AIPC. Xenograft assays were conducted to assess the effect of LEF1-AS1 on cell proliferation in vivo. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) assays were performed to elucidate the regulatory network of LEF1-AS1. Results: The next-generation sequencing results showed that LEF1-AS1 is significantly overexpressed in AIPC. Furthermore, our RT-qPCR assay data showed that LEF1-AS1 is overexpressed in AIPC tissues. Functional experiments showed that LEF1-AS1 promotes the proliferation, migration, invasion and angiogenic ability of AIPC cells in vitro and tumour growth in vivo by recruiting the transcription factor C-myb to the promoter of FZD2, inducing its transcription. Furthermore, LEF1-AS1 was shown to function as a competing endogenous RNA (ceRNA) that sponges miR-328 to activate CD44. Conclusion: In summary, the results of our present study revealed that LEF1-AS1 acts as a tumour promoter in the progression of AIPC. Furthermore, the results revealed that LEF1-AS1 functions as a ceRNA and regulates Wnt/β-catenin pathway activity via FZD2 and CD44. Our results provide new insights into the mechanism that links the function of LEF1-AS1 with AIPC and suggests that LEF1-AS1 may serve as a novel potential target for the improvement of AIPC therapy. [ABSTRACT FROM AUTHOR]

Background: Multiple published studies quantitatively analysing the diagnostic value of MRI, MR arthrography (MRA) and CT arthrography (CTA) for labral lesions of the shoulder have had inconsistent results. The aim of this meta-analysis was to systematically compare the diagnostic performance of MRI, MRA, CTA and CT.Methods: Two databases, PubMed and EMBASE, were used to retrieve studies targeting the accuracy of MRI, MRA, CTA and CT in detecting labral lesions of the shoulder. After carefully screening and excluding studies, the studies that met the inclusion criteria were used for a pooled analysis, including calculation of sensitivity and specificity with 95% confidence intervals (CIs) and the area under the hierarchical summary receiver operating characteristic (HSROC) curves.Results: The retrieval process identified 2633 studies, out of which two reviewers screened out all but 14 studies, involving a total of 1216 patients who were deemed eligible for inclusion in the meta-analysis. The results assessing the diagnostic performance of MRI vs. MRA for detecting labral lesions showed a pooled sensitivity of 0.77 (95% CI 0.70-0.84) vs. 0.92 (95% CI 0.84-0.96), a specificity of 0.95 (95% CI 0.85-0.98) vs. 0.98 (95% CI 0.91-0.99), and an area under the HSROC curve of 3.78 (95% CI 2.73-4.83) vs. 6.01 (95% CI 4.30-7.73), respectively.Conclusion: MRA was suggested for use in patients with chronic shoulder symptoms or a pathologic abnormality. MRI is by far the first choice recommendation for the detection of acute labral lesions. CT should be a necessary supplemental imaging technique when there is highly suspected glenoid bone damage. [ABSTRACT FROM AUTHOR]

Background: Although the primary malignant spleen tumor is relatively rare, lymphoma is the most common splenic malignancy. It can have quite different clinical manifestations that usually lead to relatively poor outcomes, and thus early and accurate diagnosis are of utmost importance. Case presentation: The present study reports a case of a 67-year-old female with high fever, abnormal spleen (diagnosed by PET/CT) and no obvious lymph node enlargement. After being subjected to splenectomy, the patient was diagnosed with splenic diffuse large B cell lymphoma coexisting with gastrointestinal stromal tumor in the stomach. Conclusions: To our knowledge, splenic lymphoma accompanied by gastrointestinal stromal tumor in the stomach is rarely reported. This case report discusses the diagnosis and case management of a patient referring to the existing literature. [ABSTRACT FROM AUTHOR]

Background: The methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with treatment response in glioblastoma(GBM). Using pre-operative MRI techniques to predict MGMT promoter methylation status remains inconclusive. In this study, we investigated the value of features from structural and advanced imagings in predicting the methylation of MGMT promoter in primary glioblastoma patients.Methods: Ninety-two pathologically confirmed primary glioblastoma patients underwent preoperative structural MR imagings and the efficacy of structural image features were qualitatively analyzed using Fisher's exact test. In addition, 77 of the 92 patients underwent additional advanced MRI scans including diffusion-weighted (DWI) and 3-diminsional pseudo-continuous arterial spin labeling (3D pCASL) imaging. Apparent diffusion coefficient (ADC) and relative cerebral blood flow (rCBF) values within the manually drawn region-of-interest (ROI) were calculated and compared using independent sample t test for their efficacies in predicting MGMT promoter methylation. Receiver operating characteristic curve (ROC) analysis was used to investigate the predicting efficacy with the area under the curve (AUC) and cross validations. Multiple-variable logistic regression model was employed to evaluate the predicting performance of multiple variables.Results: MGMT promoter methylation was associated with tumor location and necrosis (P <  0.05). Significantly increased ADC value (P <  0.001) and decreased rCBF (P <  0.001) were associated with MGMT promoter methylation in primary glioblastoma. The ADC achieved the better predicting efficacy than rCBF (ADC: AUC, 0.860; sensitivity, 81.1%; specificity, 82.5%; vs rCBF: AUC, 0.835; sensitivity, 75.0%; specificity, 78.4%; P = 0.032). The combination of tumor location, necrosis, ADC and rCBF resulted in the highest AUC of 0.914.Conclusion: ADC and rCBF are promising imaging biomarkers in clinical routine to predict the MGMT promoter methylation in primary glioblastoma patients. [ABSTRACT FROM AUTHOR]