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Background: The Nightmare Distress Questionnaire (NDQ), known and commonly used for its adequate psychometric properties, is the most widely used instrument for the measurement of nightmare distress. This study aimed to assess the psychometric properties of a newly translated Arabic version of the Nightmare Distress Questionnaire (NDQ-AV). Methods: A total of 546 Lebanese adolescents was recruited for this study and completed the NDQ-AV, the Insomnia Severity Index (ISI), and the eight-item Depression, Anxiety and Stress Scale (DASS-8). Results: The results of the exploratory factor analysis (EFA) and the confirmatory factor analysis (CFA) supported both a one-factor model and a two-factor model of the NDQ-AV, with the latter consisting of seven items within both factors. The first factor was referred to as the "general nightmare distress and coping" while the second was named "nightmare impact and perception". The reliability of the scale was excellent (α = 0.930 and ω = 0.915). Moreover, measurement invariance was shown across gender, demonstrating that this measure performs consistently for both men and women. Additionally, the NDQ-AV scores exhibited excellent reliability alongside factorial and concurrent validity. Conclusion: In conclusion, these results support the psychometric validity of the Arabic version of the NDQ. The availability of the NDQ-AV is expected to facilitate the understanding of nightmare distress within the Lebanese context. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety symptoms among medical students are often a concern. The Patient Health Questionnaire-Four (PHQ-4), an important tool for depression and anxiety screening, is commonly used and easy to administer. This study aimed to assess and update the longitudinal measurement invariance and psychometric properties of the simplified Chinese version. Methods: A three-wave longitudinal survey was conducted among healthcare students using the PHQ-4. Structural validity was based on one-factor, two-factor, and second-order factor models, construct validity was based on the Self-Rated Health Questionnaire (SRHQ), Sleep Quality Questionnaire (SQQ), and Rosenberg Self-Esteem Scale (RSES), and longitudinal measurement invariance (LMI), internal consistency, and test–retest reliability were based on structural consistency across three time points. Results: The results of the confirmatory factor analysis indicated that two-factor model was the best fit, and LMI was supported at three time points. Inter-factor, factor-total, and construct validity correlations of the PHQ-4 were acceptable. Additionally, Cronbach's alpha, McDonald's omega, and the intraclass correlation coefficient demonstrated acceptable/moderate to excellent reliability of the PHQ-4. Conclusions: This study adds new longitudinal evidence that the Chinese version of the PHQ-4 has promising LMI and psychometric properties. Such data lends confidence to the routine and the expanded use of the PHQ-4 for routine screening of depression and anxiety in Chinese healthcare students. [ABSTRACT FROM AUTHOR]

Background: Pulmonary embolism (PE) is a life-threatening thromboembolic disease for which there is limited evidence for effective prevention and treatment. Our goal was to determine whether genetically predicted circulating blood cell traits could influence the incidence of PE. Methods: Using single variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) analyses, we identified genetic associations between circulating blood cell counts and lymphocyte subsets and PE. GWAS blood cell characterization summary statistics were compiled from the Blood Cell Consortium. The lymphocyte subpopulation counts were extracted from summary GWAS statistics for samples from 3757 individuals that had been analyzed by flow cytometry. GWAS data related to PE were obtained from the FinnGen study. Results: According to the SVMR and reverse MR, increased levels of circulating white blood cells (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.81-0.95, p = 0.0079), lymphocytes (OR: 0.90, 95% CI: 0.84-0.97, p = 0.0115), and neutrophils (OR: 0.88, 95% CI: 0.81–0.96, p = 0.0108) were causally associated with PE susceptibility. MVMR analysis revealed that lower circulating lymphocyte counts (OR: 0.84, 95% CI: 0.75-0.94, p = 0.0139) were an independent predictor of PE. According to further MR results, this association may be primarily related to HLA-DR+ natural killer (NK) cells. Conclusions: Among European populations, there is a causal association between genetically predicted low circulating lymphocyte counts, particularly low HLA-DR+ NK cells, and an increased risk of PE. This finding supports observational studies that link peripheral blood cells to PE and provides recommendations for predicting and preventing this condition. [ABSTRACT FROM AUTHOR]

Background: There is a growing attention on intuitive eating (IE) styles in the Western world that has not yet reached Arab countries, which is likely due to the lack of psychometrically sound measures of the IE construct for Arabic-speaking people. The current study aims to examine the psychometric properties of an Arabic translation of the most widely used measure of IE—the Intuitive Eating Scale-2 (IES-2), in an Arabic-speaking community population from Lebanon. Methods: Two samples of Arabic-speaking community adults from Lebanon (sample 1: n = 359, 59.9% females, age 22.75 ± 7.04 years; sample 2: n = 444, 72.7% females, age 27.25 ± 9.53 years) were recruited through online convenience sampling. The translation and back-translation method was applied to the IES-2 for linguistic validation. Factorial validity was investigated using an Exploratory Factor Analysis & Confirmatory Factor Analysis strategy. Composite reliability and sex invariance were examined. We also tested convergent and criterion-related validity through correlations with other theoretically plausible constructs. Results: Nine out of the original 23 items were removed because they either loaded below 0.40 and/or cross-loaded too highly on multiple factors. This resulted in four domains (Unconditional Permission to Eat, Eating for Physical Rather than Emotional Reasons, Reliance on Hunger and Satiety Cues, and Body-Food Choice Congruence) and 14 items retained. Internal reliability estimates were excellent, with McDonald's ω values ranging from 0.828 to 0.923 for the four factors. Multigroup analysis established configural, thresholds, metric, scalar, strict invariance across gender. Finally, higher IES-2 total scores were significantly correlated with lower body dissatisfaction scores and more positive eating attitudes, thus attesting to convergent and criterion-related validity of the scale. Conclusions: The current findings provide preliminary evidence for the appropriate psychometric qualities of the Arabic 14-item, four-factor structure IES-2; thereby supporting its use at least among Arabic-speaking community adults. Plain English Summary: Diet restriction has proven costly and ineffective in promoting long-term weight loss. As an alternative, innovative behavioral approaches have been proposed, such as intuitive eating (IE) practices. IE focuses on enhancing intrinsic motivation for eating healthily, thus creating effective, sustainable lifestyle changes. The Intuitive Eating Scale-2 (IES-2) is the most widely used measure to assess IE in patients and the general population. This scale explores four components of IE: Unconditional Permission to Eat (i.e., not trying to stave off hunger and refusing to label certain foods as forbidden), Eating for Physical Rather than Emotional Reasons (i.e., eating when physically hungry rather than for emotional reasons), Reliance on Hunger and Satiety Cues (i.e., trusting one's own internal satiety and hunger cues and relying on them to guide eating behaviors), and Body-Food Choice Congruence (i.e., the extent to which individuals make food choices that promote their body functioning and performance). Since its development, the IES-2 has been translated into different languages and validated in different countries and populations. However, no Arabic version of the IES-2 is yet available. We proposed in the current study to examine the psychometric properties of an Arabic translation of the IES-2 in an Arabic-speaking community population from Lebanon. Findings provided preliminary evidence for the appropriate psychometric qualities of the Arabic IES-2; thereby supporting its use at least among Arabic-speaking community adults. [ABSTRACT FROM AUTHOR]

Background: Previous reports have described hypogonadism associated with virus infection such as hantavirus, human immunodeficiency virus (HIV) or severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). However, to our best knowledge there has been no case report of secondary hypogonadism following hand, foot, and mouth disease (HFMD).Case Presentation: A previously healthy 28-year-old man with no history of major physical and psychological trauma, presented with bilateral gynecomastia and erectile dysfunction 2 weeks after HFMD. Laboratory testament showed the level of gonadotropin hormones declined. Imaging examination demonstrated no major abnormal change in pituitary or reproductive system. The diagnosis of hypogonadism was established. Then the patient was ordered to maintain mental health outward of hospital without drug intervention. One month after presentation, his gonadotropin hormone level and sexual desire had recovered, while bilateral gynecomastia and erectile dysfunction symptoms disappeared.Conclusions: Physicians should notice the possibility for hypogonadism in adult patients with a recent history of HFMD. [ABSTRACT FROM AUTHOR]

Background: Diabetes can cause extensive enteric nervous system (ENS) injuries and gastrointestinal motility disorder. In developing possible treatments, researchers have engaged in tissue regeneration engineering with the very promising bone marrow-derived mesenchymal stem cells (BMSCs). However, BMSCs have poor homing ability to the targeted tissues after intravenous injection. Thus, we aimed to investigate whether enhancing the expression of E-selectin ligand on BMSCs could improve their homing ability and subsequently influence their role in ENS remodeling in diabetic mice. Methods: First, we constructed the fucosylation modification of CD44 on BMSCs through a fucosyltransferase VII (FTVII) system to generate a Hematopoietic Cell E-/L-selectin Ligand (HCELL) property, a fucosylated sialyllactosaminyl glycovariant of CD44 that potently binds E-selectin. Next, FTVII-modified and unmodified BMSCs labeled with green fluorescent protein (GFP) were injected into diabetic mice through the tail vein to compare their homing ability to the gastrointestinal tract and their effect on ENS remodeling, respectively. A bioluminescent imaging system was used to evaluate the homing ability of GFP-labeled BMSCs with and without FTVII modification, to the gastrointestinal tract. Gastrointestinal motility was assessed by gastrointestinal transient time, defecation frequency, stool water content and colon strips contractility. Immunofluorescence staining and western blotting were used to assess the expression levels of protein gene product 9.5 (PGP9.5), glial fibrillary acidic protein (GFAP) and glial cell line-derived neurotrophic factor (GDNF). Results: The FTVII-mediated α(1,3)-fucosylation modification of CD44 on BMSCs generated a HCELL property. Bioluminescent imaging assays showed that FTVII-modified BMSCs had enhanced homing ability to gastrointestinal tract, mainly to the colon, 24 h after injection through the tail vein. Compared with diabetic mice, FTVII-modified BMSCs significantly promoted the gastrointestinal motility and the ENS remodeling, including intestinal peristalsis (P < 0.05), increased feces excretion (P < 0.05) and the water content of the feces (P < 0.05), restored the spontaneous contraction of the colon (P < 0.05), and upregulated the protein expression levels of PGP9.5 (P < 0.01), GFAP (P < 0.001), and GDNF (P < 0.05), while unmodified BMSCs did not (P > 0.05). Conclusions: CD44 fucosylation modification on murine BMSCs promotes homing ability to the gastrointestinal tract and ENS remodeling in diabetic mice. [ABSTRACT FROM AUTHOR]

Background: Cryptogenic multifocal ulcer stenosing enteritis (CMUSE) is a rare disease characterized by multiple superficial ulcers, stenosis, and obstruction of the small intestine of unknown origin, and the course can recur.Case Presentation: We encountered a 62-year-old male patient with intestinal obstruction. The patient was admitted to the hospital for surgical treatment due to intestinal obstruction, and was diagnosed with cryptogenic multifocal ulcer stenosis enteritis due to comprehensive surgery and postoperative pathological considerations.Conclusion: In the future, we will continue to follow up the patient. The present study aims to remind clinicians of this disease, and reduce the incidence of misdiagnosis. [ABSTRACT FROM AUTHOR]

Background: Sirtuin-7 (SIRT7) is associated with the maintenance of tumorigenesis. However, its functional roles and oncogenic mechanisms in prostate cancer (PCa) are poorly understood. Here, we investigated the roles and underlying molecular mechanisms of SIRT7 in PCa cell growth and androgen-induced autophagy. Methods: The LNCap and 22Rv1 PCa cell lines were subjected to quantitative reverse transcription (RT)-PCR to characterize their genes encoding SIRT7, AR, and SMAD4. The proteins produced from these genes were quantified by western blotting and immunoprecipitation analysis. SIRT7-depleted cells were produced by transfection with plasmid vectors bearing short hairpin RNAs against SIRT7. The proliferation of each cell line was assessed by CCK8 and EdU assays. Autophagic flux was tracked by mRFP–GFP–LC3 adenovirus under an immunofluorescence microscope. Apoptosis was evaluated by flow cytometry. Tumors were induced in mouse axillae by injection of the cell lines into mice. Tumor morphology was examined by immunohistochemistry and relative tumor growth and metastases were compared by a bioluminescence-based in vivo imaging system. Results: SIRT7 depletion significantly inhibited cell proliferation, androgen-induced autophagy, and invasion in LNCap and 22Rv1 cells (in vitro) and mouse xenograft tumors induced by injection of these cells (in vivo). SIRT7 knockdown also increased the sensitivity of PCa cells to radiation. Immunohistochemical analysis of 93 specimens and bioinformatic analysis revealed that SIRT7 expression was positively associated with androgen receptor (AR). Moreover, the AR signal pathway participated in SIRT7-mediated regulation of PCa cell proliferation, autophagy, and invasion. SIRT7 depletion downregulated the AR signal pathway by upregulating the level of SMAD4 protein in PCa cells. Conclusion: SIRT7 plays an important role in the development and progression of human PCa and may be a promising prognostic marker for prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms.Methods: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis.Results: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes.Conclusion: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC. [ABSTRACT FROM AUTHOR]

Background: Diabetes can lead to extensive damage to the enteric nervous system (ENS), causing gastrointestinal motility disorders. However, there is currently a lack of effective treatments for diabetes-induced ENS damage. Enteric neural precursor cells (ENPCs) closely regulate the structural and functional integrity of the ENS. L-Fucose, is a dietary sugar that has been showed to effectively ameliorate central nervous system injuries, but its potential for ameliorating ENS damage and the involvement of ENPCs in this process remains uncertain. Methods: Genetically engineered mice were generated for lineage tracing of ENPCs in vivo. Using diabetic mice in vivo and high glucose-treated primary ENPCs in vitro, the effects of L-Fucose on the injured ENS and ENPCs was evaluated by assessing gastrointestinal motility, ENS structure, and the differentiation of ENPCs. The key signaling pathways in regulating neurogenesis and neural precursor cells properties, transforming growth factor-β (TGF-β) and its downstream signaling pathways were further examined to clarify the potential mechanism of L-Fucose on the injured ENS and ENPCs. Results: L-Fucose improved gastrointestinal motility in diabetic mice, including increased defecation frequency (p < 0.05), reduced total gastrointestinal transmission time (p < 0.001) and bead expulsion time (p < 0.05), as well as enhanced spontaneous contractility and electric field stimulation-induced contraction response in isolated colonic muscle strips (p < 0.001). The decrease in the number of neurons and glial cells in the ENS of diabetic mice were reversed by L-Fucose treatment. More importantly, L-Fucose treatment significantly promoted the proportion of ENPCs differentiated into neurons and glial cells both in vitro and in vivo, accompanied by inhibiting SMAD2 phosphorylation. Conclusions: L-Fucose could promote neurogenesis and gliogenesis derived from ENPCs by inhibiting the SMAD2 signaling, thus facilitating ENS regeneration and gastrointestinal motility recovery in type 1 diabetic mice. 7Zzihak_jncvcnfCNwCPXs Video Abstract [ABSTRACT FROM AUTHOR]

Background: TDP-43 (43-kD transactive response DNA-binding protein) is a DNA-/RNA-binding protein that plays an important role in several nervous system diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Whether it plays an important role in glioma patients is unknown. Methods: Datasets were downloaded from the Chinese Glioma Genome Atlas (CGGA) website (http://www.cgga.org.cn/). Cox survival analysis was performed to determine the relationship between TARDBP gene expression and the overall survival of glioma patients. GO analyses were performed to determine the biological functions of the TARDBP gene. Finally, we used PRS type, age, grade, IDH mutation status, 1p/19q codeletion status, and expression value of the TARDBP gene to construct a prediction model. With this model, we can predict patients' 1-, 2-, 3-, 5-, and 10-year survival rates. Results: The TARDBP gene plays an important role in glioma patients. The expression of the TARDBP gene has a significant correlation with glioma patient survival. We also constructed an ideal prediction model. Conclusion: Our findings suggest that the TARDBP gene and the protein it encodes play important roles in glioma patients. The expression of the TARDBP gene has a significant correlation with the overall survival of glioma patients. [ABSTRACT FROM AUTHOR]

Background: The renin-angiotensin system (RAS) has been implicated in atherosclerotic lesions and progression to chronic kidney diseases. We examined regulatory roles of angiotensin-converting enzyme 2 (ACE2) in the apolipoprotein E (ApoE) knockout (KO) kidneys. Methods: The 3-month-old wild-type, ApoEKO, ACE2KO and ApoE/ACE2 double-KO (DKO) mice in a C57BL/6 background were used. The ApoEKO mice were randomized to daily deliver either Ang II (1.5 mg/kg) and/or human recombinant ACE2 (rhACE2; 2 mg/kg) for 2 weeks. We examined changes in pro-inflammatory cytokines, renal ultrastructure, and pathological signaling in mouse kidneys. Results: Downregulation of ACE2 and nephrin levels was observed in ApoEKO kidneys. Genetic ACE2 deletion resulted in modest elevations in systolic blood pressure levels and Ang II type 1 receptor expression and reduced nephrin expression in kidneys of the ApoE/ACE2 DKO mice with a decrease in renal Ang-(1-7) levels. These changes were linked with marked increases in renal superoxide generation, NADPH oxidase (NOX) 4 and proinflammatory factors levels, including interleukin (IL)-1beta, IL-6, IL-17A, RANTES, ICAM-1, Tumor necrosis factor-alpha (TNF-alpha) and TNFRSF1A. Renal dysfunction and ultrastructure injury were aggravated in the ApoE/ACE2 DKO mice and Ang IIinfused ApoEKO mice with increased plasma levels of creatinine, blood urea nitrogen and enhanced levels of Ang II in plasma and kidneys. The Ang II-mediated reductions of renal ACE2 and nephrin levels in ApoEKO mice were remarkably rescued by rhACE2 supplementation, along with augmentation of renal Ang-(1-7) levels. More importantly, rhACE2 treatment significantly reversed Ang II-induced renal inflammation, superoxide generation, kidney dysfunction and adverse renal injury in ApoEKO mice with suppression of the NOX4 and TNF-alpha-TNFRSF1A signaling. However, rhACE2 had no effect on renal NOX2 and TNFRSF1B expression and circulating lipid levels. Conclusions: ACE2 deficiency exacerbates kidney inflammation, oxidative stress and adverse renal injury in the ApoE-mutant mice through modulation of the nephrin, NOX4 and TNF-alpha-TNFRSF1A signaling. While rhACE2 supplementation alleviates inflammation, renal dysfunction and glomerulus injury in the ApoE-mutant mice associated with upregulations of Ang-(1-7) levels and nephrin expression and suppression of the TNF-alpha-TNFRSF1A signaling. Strategies aimed at enhancing the ACE2/Ang-(1-7) actions may have important therapeutic potential for atherosclerotic renal injury and kidney diseases. [ABSTRACT FROM AUTHOR]

Background: Although anterolateral decompression and instrumentation has several advantages in treating thoracolumbar burst fractures, the risk factors for supplementary posterior instrumentation are still unclear. Methods: We retrospectively reviewed 238 patients who underwent anterolateral decompression and instrumentation for single-level thoracolumbar burst fractures from January 2010 and March 2012. The influences of several potential risk factors that might affect supplementary posterior instrumentation were assessed using univariate and multivariate analyses. Results: Twenty seven patients who developed worsening back pain without neurological deterioration after the anterolateral approach treatment need further posterior instrumentation fixation. The univariate analysis showed that age, disruption of the posterior longitudinal ligament complex (PLC), and fracture level were the risk factors for supplementary posterior instrumentation. However, age and integrity of the PLC were the independent risk factors for supplementary posterior instrumentation by multivariate analyses. Conclusions: Supplemental posterior instrumentation was necessary in 11.3% of cases following anterolateral decompression and instrumentation in the present study. Older age and disruption of the PLC were the independent risk factors in prediction of supplementary posterior instrumentation in treating thoracolumbar burst fractures. [ABSTRACT FROM AUTHOR]

Background Although anterolateral decompression and instrumentation has several advantages in treating thoracolumbar burst fractures, the risk factors for supplementary posterior instrumentation are still unclear. Methods We retrospectively reviewed 238 patients who underwent anterolateral decompression and instrumentation for single-level thoracolumbar burst fractures from January 2010 and March 2012. The influences of several potential risk factors that might affect supplementary posterior instrumentation were assessed using univariate and multivariate analyses. Results Twenty seven patients who developed worsening back pain without neurological deterioration after the anterolateral approach treatment need further posterior instrumentation fixation. The univariate analysis showed that age, disruption of the posterior longitudinal ligament complex (PLC), and fracture level were the risk factors for supplementary posterior instrumentation. However, age and integrity of the PLC were the independent risk factors for supplementary posterior instrumentation by multivariate analyses. Conclusions Supplemental posterior instrumentation was necessary in 11.3% of cases following anterolateral decompression and instrumentation in the present study. Older age and disruption of the PLC were the independent risk factors in prediction of supplementary posterior instrumentation in treating thoracolumbar burst fractures. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression. Methods and results: The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4's protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions. Conclusion: P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved. [ABSTRACT FROM AUTHOR]

Background: Gastric lymphangioma is one of the highly rare benign tumors characterized by multilocular or unilocular lymphatic spaces. Herein, we report a case of lymphangioma in the gastric antrum.Case Presentation: A 77-year-old male patient who had been experiencing epigastric discomfort for a year was presented to our hospital. A gastric subepithelial lesion was diagnosed by upper endoscopy and was entirely excised via diatal subtotal gastrectomy. Endoscopic ultrasonography revealed an echoless homogenous echo pattern in the third wall layer. A lymphangioma was diagnosed by pathologic investigation of the resected specimen. The PubMed, Embase and Web of Science databases were reviewed for literature in English while using the keywords of "gastric lymphangioma" or "lymphangioma of stomach" or "gastric lymphatic cyst" or "lymphatic cyst of stomach" and the results were discussed.Conclusion: Gastric lymphangioma is a rarely occurring submucosal tumor that should be considered when diagnosing subepithelial lesions in the stomach. [ABSTRACT FROM AUTHOR]

Background: Anxiety and depression are psychiatric disorders that often coexist and share some features. Developing a simple and cost-effective tool to assess anxiety and depression in the Arabic-speaking population, predominantly residing in low- and middle-income nations where research can be arduous, would be immensely beneficial. The study aimed to translate the four-item composite Patient Health Questionnaire – 4 (PHQ-4) into Arabic and evaluate its psychometric properties, including internal reliability, sex invariance, composite reliability, and correlation with measures of psychological distress. Methods: 587 Arabic-speaking adults were recruited between February and March 2023. An anonymous self-administered Google Forms link was distributed via social media networks. We utilized the FACTOR software to explore the factor structure of the Arabic PHQ-4. Results: Confirmatory factor analysis (CFA) indicated that fit of the two-factor model of the PHQ-4 scores was modest (χ2/df =.13/1 =.13, RMSEA =.001, SRMR =.002, CFI = 1.005, TLI = 1.000). Internal reliability was excellent (McDonald's omega =.86; Cronbach's alpha =.86). Indices suggested that configural, metric, and scalar invariance were supported across sex. No significant difference was found between males and females in terms of the PHQ-4 total scores, PHQ-4 anxiety scores, and PHQ-4 depression scores. The total score of the PHQ-4 and its depression and anxiety scores were significantly and moderately-to-strongly associated with lower wellbeing and higher Depression Anxiety and Stress Scale (DASS) total and subscales scores. Conclusion: The PHQ-4 proves to be a reliable, valid, and cost-effective tool for assessing symptoms related to depression and anxiety. To evaluate the practical effectiveness of the Arabic PHQ-4 and to further enhance the data on its construct validity, future studies should assess the measure in diverse contexts and among specific populations. [ABSTRACT FROM AUTHOR]

Background: The Sleep Condition Indicator (SCI), an insomnia measurement tool based on the updated Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria with sound psychometric properties when applied in various populations, was evaluated here among healthcare students longitudinally, to demonstrate its measurement properties and invariance in this particularly high-risk population. Methods: Healthcare students of a Chinese university were recruited into this two-wave longitudinal study, completing the simplified Chinese version of the SCI (SCI-SC), Chinese Regularity, Satisfaction, Alertness, Timing, Efficiency, Duration (RU_SATED-C) scale, Chinese Patient Health Questionnaire-4 (PHQ-4-C), and sociodemographic variables questionnaire (Q-SV) between September and November 2022. Structural validity, measurement invariance (MI), convergent and discriminant validity, internal consistency, and test–retest reliability of the SCI-SC were examined. Subgroups of gender, age, home location, part-time job, physical exercise, and stress-coping strategy were surveyed twice to test cross-sectional and longitudinal MI. Results: We identified 343 valid responses (62.9% female, mean age = 19.650 ± 1.414 years) with a time interval of seven days. The two-factor structure was considered satisfactory (comparative fit index = 0.953–0.989, Tucker–Lewis index = 0.931–0.984, root means square error of approximation = 0.040–0.092, standardized root mean square residual = 0.039–0.054), which mostly endorsed strict invariance except for part-time job subgroups, hence establishing longitudinal invariance. The SCI-SC presented acceptable convergent validity with the RU_SATED-C scale (r ≥ 0.500), discriminant validity with the PHQ-4-C (0.300 ≤ r < 0.500), internal consistency (Cronbach's alpha = 0.811–0.835, McDonald's omega = 0.805–0.832), and test–retest reliability (intraclass correlation coefficient = 0.829). Conclusion: The SCI-SC is an appropriate screening instrument available for assessing insomnia symptoms among healthcare students, and the promising measurement properties provide additional evidence about validity and reliability for detecting insomnia in healthcare students. [ABSTRACT FROM AUTHOR]

Background: A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15–20+6 weeks) of free beta human chorionic gonadotropin (free β-hCG). And the study was conducted to explore the relationship between maternal serum free β-hCG and adverse pregnancy outcomes (APO). Methods: We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free β-hCG group (free β-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free β-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups. Results: The gravidity and parity in the elevated free β-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free β-hCG levels (RRs: 1.996, 95% CI: 1.322–3.014; 1.469, 95% CI: 1.130–1.911 and 1.257, 95% CI: 1.029–1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103–2.443 and 1.101, 95% CI: 1.011–1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free β-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121–1.307, P < 0.001). Conclusions: APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free β-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free β-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free β-hCG level and the occurrence of APO. [ABSTRACT FROM AUTHOR]

Background: Cases with intussusception caused by either intestinal hemangiomas or appendiceal mucinous neoplasms are extremely rare. Case presentation: In this study, we reported a 47-year-old male presented with paroxysmal abdominal pain and postprandial bloating for 3 days. CT results indicated a high possibility of secondary intussusception in ascending colon. Histopathology indicated a mixed type of cavernous and capillary hemangioma, combined with low-grade appendiceal mucinous neoplasms (LAMNs) and intestinal obstruction. The patient underwent laparotomy and right hemicolectomy. Finally, the patient was followed up for 4 months with no disease progression. Conclusions: Rare studies reported the intestine hemangiomas coincided with appendix low-grade mucinous tumor. Its manifestations are not specific, which is a challenge in the preoperative diagnosis. For cases with intussusception that was not observed in time, it may lead to intestinal necrosis and diffuse peritonitis. Additionally, the ruptured mucinous tumor in the appendix may lead to pathogenesis of pseudomyxoma peritonei. Therefore, accurate diagnosis and appropriate surgery-based treatment contribute to the improvement of prognosis and severe outcomes among these patients. [ABSTRACT FROM AUTHOR]

Background: Chromogranin A (CgA), synaptophysin (Syn) and the Ki-67 index play significant roles in diagnosis or the evaluation of the proliferative activity of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, little is known about whether these biological markers change during tumor metastasis and whether such changes have effect on prognosis. Methods: We analyzed 35 specimens of both primary and metastatic tumor from 779 patients who had been diagnosed as GEP-NENs at Wuhan Union Hospital from August 2011 to October 2019. The heterogeneity of CgA, Syn and Ki-67 index was evaluated by immunohistochemical analysis. Results: Among these 779 patients, the three most common sites of NENs in the digestive tract were the pancreas, rectum and stomach. Metastases were found in 311 (39.9%) patients. Among the 35 patients with both primary and metastatic pathological specimens, differences in the Ki-67 level were detected in 54.3% of the patients, while 37.1% showed a difference in CgA and only 11.4% showed a difference in Syn. Importantly, due to the difference in the Ki-67 index between primary and metastatic lesions, the WHO grade was changed in 8.6% of the patients. In addition, a Kaplan–Meier survival analysis showed that patients with Ki-67 index variation had a shorter overall survival (p = 0.0346), while neither Syn variation nor CgA variation was related to patient survival (p = 0.7194, p = 0.4829). Conclusions: Our data indicate that primary and metastatic sites of GEP-NENs may exhibit pathological heterogeneity. Ki-67 index variation is closely related to the poor prognosis of patients with tumor metastasis, but neither Syn variation nor CgA variation is related to patient prognosis. Therefore, clinicopathologic evaluation of the primary tumor and metastatic sites could be helpful for predicting the prognosis. [ABSTRACT FROM AUTHOR]

Background: Our previous study found that bone marrow-derived mesenchymal stem cells (BMSCs) promote Helicobacter pylori (H pylori)-associated gastric cancer (GC) progression by secreting thrombospondin-2 (THBS2). Extracellular vesicles (EVs) are important carriers for intercellular communication, and EVs secreted by BMSCs have been shown to be closely related to tumor development. The aim of this study was to investigate whether BMSC-derived microvesicles (MVs, a main type of EV) play a role in H. pylori-associated GC by transferring THBS2. Methods: BMSCs and THBS2-deficient BMSCs were treated with or without the supernatant of H. pylori for 12 h at a multiplicity of infection of 50, and their EVs were collected. Then, the effects of BMSC-derived MVs and THBS2-deficient BMSC-derived MVs on the GC cell line MGC-803 were assessed by in vitro proliferation, migration, and invasion assays. In addition, a subcutaneous xenograft tumor model, a nude mouse intraperitoneal metastasis model, and a tail vein injection metastasis model were constructed to evaluate the effects of BMSC-derived MVs and THBS2-deficient BMSC-derived MVs on GC development and metastasis in vivo. Results: BMSC-derived MVs could be readily internalized by MGC-803 cells. BMSC-derived MVs after H. pylori treatment significantly promoted their proliferation, migration and invasion in vitro (all P < 0.05) and promoted tumor development and metastasis in a subcutaneous xenograft tumor model, a nude mouse intraperitoneal metastasis model, and a tail vein injection metastasis model in vivo (all P < 0.05). The protein expression of THBS2 was significantly upregulated after H. pylori treatment in BMSC-derived MVs (P < 0.05). Depletion of the THBS2 gene reduces the tumor-promoting ability of BMSC-MVs in an H. pylori infection microenvironment both in vitro and in vivo. Conclusion: Overall, these findings indicate that MVs derived from BMSCs can promote H. pylori-associated GC development and metastasis by delivering the THBS2 protein. 16ZaMehzoqZcatB8td6PJe Video Abstract [ABSTRACT FROM AUTHOR]

Background and Aims: We sought to identify novel molecular subtypes of ulcerative colitis (UC) based on large-scale cohorts and establish a clinically applicable subtyping system for the precision treatment of the disease. Methods: Eight microarray profiles containing colon samples from 357 patients were utilized. Expression heterogeneity was screened out and stable subtypes were identified among UC patients. Immune infiltration pattern and biological agent response were compared among subtypes to assess the value in guiding treatment. The relationship between PRLR and TNFSF13B genes with the highest predictive value was further validated by functional experiments. Results: Three stable molecular subtypes were successfully identified. Immune cell infiltration analysis defined three subtypes as innate immune activated UC (IIA), whole immune activated UC (WIA), and immune homeostasis like UC (IHL). Notably, the response rate towards biological agents (infliximab/vedolizumab) in WIA patients was the lowest (less than 10%), while the response rate in IHL patients was the highest, ranging from 42 to 60%. Among the featured genes of subtypes, the ratio of PRLR to TNFSF13B could effectively screen for IHL UC subtype suitable for biological agent therapies (Area under curve: 0.961–0.986). Furthermore, we demonstrated that PRLR expressed in epithelial cells could inhibit the expression of TNFSF13B in monocyte-derived macrophages through the CXCL1-NF-κB pathway. Conclusions: We identified three stable UC subtypes with a heterogeneous immune pattern and different response rates towards biological agents for the first time. We also established a precise molecular subtyping system and classifier to predict clinical drug response and provide individualized treatment strategies for UC patients. [ABSTRACT FROM AUTHOR]

Background: The current study sought to perform a meta-analysis to compare the preoperative staging of endoscopic ultrasonography (EUS) and multidetector computed tomography (MDCT) in gastric carcinoma. Methods: Articles published between January 1, 2000, and April 1, 2016, that compared EUS with MDCT were included, and data were presented as 2 × 2 tables. The sensitivities, specificities and summary receiver operating characteristic (ROC) curves for T and N staging were calculated using a bivariate mixed effects model. Data were weighted by generic variance and then pooled by random-effects modeling. Results: Eight studies comprising 1736 patients were included in this meta-analysis. For T1 staging, the sensitivity value for EUS (82%) was significantly higher than that for MDCT (41%) (relative risk (RR): 2.06, 95% confidence interval (CI) 1.07-3.94; P = 0.030). For lymph node involvement, the sensitivity value for EUS (91%) was also significantly higher than that for MDCT (77%) (RR 1.14, 95% CI 1.05-1.23; P = 0.001). However, the specificity values of both EUS and MDCT were quite low, at 49 and 63%, respectively. No significant differences in T2-4 staging between EUS and MDCT were noted. Conclusion: This meta-analysis indicates that EUS may be superior to MDCT in preoperative T1 and N staging. Additionally, the low specificity values of EUS and MDCT for N staging merits attention. [ABSTRACT FROM AUTHOR]

Background: There is a lack of effective therapies for enteric nervous system (ENS) injury. Our previous study showed that transplanted bone marrow-derived mesenchymal stem cells (BMSCs) play a "glia-like cells" role in initiating ENS regeneration in denervated mice. Cellular energy metabolism is an important factor in maintaining the biological characteristics of stem cells. However, how cellular energy metabolism regulates the fate of BMSCs in the ENS-injured microenvironment is unclear. Methods: The biological characteristics, energy metabolism, and histone methylation levels of BMSCs following ENS injury were determined. Then, glutamate dehydrogenase 1 (Glud1) which catalyzes the oxidative deamination of glutamate to α-KG was overexpressed (OE) in BMSCs. Further, OE-Glud1 BMSCs were targeted–transplanted into the ENS injury site of denervated mice to determine their effects on ENS regeneration. Results: In vitro, in the ENS-injured high-glutamate microenvironment, the ratio of α-ketoglutarate (α-KG) to succinate (P < 0.05), the histone demethylation level (P < 0.05), the protein expression of glial cell markers (P < 0.05), and the gene expression of Glud1 (P < 0.05) were significantly increased. And the binding of H3K9me3 to the GFAP, S100B, and GDNF promoter was enhanced (P < 0.05). Moreover, α-KG treatment increased the monomethylation and decreased the trimethylation on H3K9 (P < 0.01) and H3K27 (P < 0.05) in BMSCs and significantly upregulated the protein expression of glial cell markers (P < 0.01), which was reversed by the α-KG competitive inhibitor D-2-hydroxyglutarate (P < 0.05). Besides, overexpression of Glud1 in BMSCs exhibited increases in monomethylation and decreases in trimethylation on H3K9 (P < 0.05) and H3K27 (P < 0.05), and upregulated protein expression of glial cell markers (P < 0.01). In vivo, BMSCs overexpressing Glud1 had a strong promotion effect on ENS regeneration in denervated mice through H3K9/H3K27 demethylation (P < 0.05), and upregulating the expression of glial cell protein (P < 0.05). Conclusions: BMSCs overexpressing Glud1 promote the expression of glial cell markers and ENS remodeling in denervated mice through regulating intracellular α-KG and H3K9/H3K27 demethylation. [ABSTRACT FROM AUTHOR]

Background: Drug-resistant tuberculosis (TB) continues to be a public health threat. There are few studies on transmission and genotyping of MDR-TB family households in China. This study aimed to investigate transmission of multidrug-resistant tuberculosis (MDR-TB) within family households by deletion-targeted multiplex polymerase chain reaction (DTM-PCR), mycobacterial interspersed repetitive unit variable number tandem repeats (MIRU-VNTR) genotyping.Methods: Among 993 MDR-TB patients registered from Wuhan Institute for Tuberculosis Control, drug resistance and the time interval between the index patients and secondary patients were analyzed in 49 MDR-TB patients from 23 families, in which 22 MDR-TB strains from 11 families who had matched strains were genotyped by DTM-PCR and standard 24-loci MIRU-VNTR genotyping method.Results: The time interval between the index patients and the secondary patients ranged from half a month to 110 months. Thirteen secondary patients developed active MDR-TB within two years and accounted for 50% (13/26) of all secondary patients. Among eleven pairs of MDR-TB families, six pairs had identical genotypes, the cluster rate was 54.5% (12/22); three pairs had a single MIRU-VNTR locus variation. If a single MIRU-VNTR locus variation was tolerated in the cluster definition, the cluster rate raised to 81.8% (18/22).Conclusions: The family households of MDR-TB patients are at risk for infection of MDR-TB. To reduce transmission, MDR-TB patients should be diagnosed earlier and promptly treated in an effective manner, meanwhile, the close family contacts should be screened for TB infection. [ABSTRACT FROM AUTHOR]

Objectives: Internal fixation with multiple cannulated compression screws is an optional treatment for femoral neck fracture. Recently, fully threaded cannulated compression screws (FTCCS) have been introduced to fix fresh femoral neck fractures (FNF). The purpose of this study was to investigate the effectiveness of FTCCS. Patients and methods: Patients with FNF fixed by multiple FTCCS from February 1st, 2014 to August 31st, 2017 were included in this study. They were followed for at least 12 months postoperatively. Nonunion, osteonecrosis of the femoral head (ONFH), fixation failure, reoperation, and femoral neck shortening (FNS) were used to evaluate the outcomes. Risk factors including age, sex, fracture side, fracture displacement, fracture stability, fixation configuration, and screw numbers were analyzed. Results: A total of 113 patients including 67 males and 46 females with an average age of 48.4 ± 13.4 years were included. The mean duration of follow-up was 27.1 months (range: 12–51 months). The incidence of nonunion, ONFH, fixation failure, and reoperation was 15.9%, 22.1%, 8.8%, and 24.8%, respectively. The rates of nonunion and reoperation were significantly higher in displaced fractures and unstable fractures. And patients with an unstable fracture had a higher risk of internal fixation failure. The median length of FNS was 2.9 mm (interquartile range: 0.9–6.5 mm, range: 0–17.5 mm). Age was a significant risk factor for FNS. Conclusions: The screw fixation method with FTCCS provided encouraging clinical results which may be a rational choice for the treatment of fresh FNF. Displaced fractures and unstable fractures were attributed to the higher incidence of complications. Trial registration: ChiCTR, ChiCTR1800017200. Registered 17 July 2018-Retrospectively registered, http: www.chictr.org.cn/showprojen.aspx?proj=29182. [ABSTRACT FROM AUTHOR]

Background: T cells generated from thymopoiesis are essential for the immune system, and recent single-cell studies have contributed to our understanding of the development of thymocytes at the genetic and epigenetic levels. However, the development of double-positive (DP) T cells, which comprise the majority of thymocytes, has not been well investigated. Methods: We applied single-cell sequencing to mouse thymocytes and analyzed the transcriptome data using Seurat. By applying unsupervised clustering, we defined thymocyte subtypes and validated DP cell subtypes by flow cytometry. We classified the cell cycle phases of each cell according to expression of cell cycle phase-specific genes. For immune synapse detection, we used immunofluorescent staining and ImageStream-based flow cytometry. We studied and integrated human thymocyte data to verify the conservation of our findings and also performed cross-species comparisons to examine species-specific gene regulation. Results: We classified blast, rearrangement, and selection subtypes of DP thymocytes and used the surface markers CD2 and Ly6d to identify these subtypes by flow cytometry. Based on this new classification, we found that the proliferation of blast DP cells is quite different from that of double-positive cells and other cell types, which tend to exit the cell cycle after a single round. At the DP cell selection stage, we observed that CD8-associated immune synapses formed between thymocytes, indicating that CD8sp selection occurred among thymocytes themselves. Moreover, cross-species comparison revealed species-specific transcription factors (TFs) that contribute to the transcriptional differences of thymocytes from humans and mice. Conclusions: Our study classified DP thymocyte subtypes of different developmental stages and provided new insight into the development of DP thymocytes at single-cell resolution, furthering our knowledge of the fundamental immunological process of thymopoiesis. [ABSTRACT FROM AUTHOR]

Background: In this study scales and items for the Oral Cancer Quality-of-life Questionnaire (QOL-OC) were designed and the instrument was evaluated.Methods: The QOL-OC was developed and modified using the international definition of quality of life (QOL) promulgated by the European Organization for Research and Treatment of Cancer (EORTC) and analysis of the precedent measuring instruments. The contents of each item were determined in the context of the specific characteristics of oral cancer. Two hundred thirteen oral cancer patients were asked to complete both the EORTC core quality of life questionnaire (EORTC QLC-C30) and the QOL-OC. Data collected was used to conduct factor analysis, test-retest reliability, internal consistency, and construct validity.Results: Questionnaire compliance was relatively high. Fourteen of the 213 subjects accepted the same tests after 24 to 48 h demonstrating a high test-retest reliability for all five scales. Overall internal consistency surpasses 0.8. The outcome of the factor analysis coincides substantially with our theoretical conception. Each item shows a higher correlation coefficient within its own scale than the others which indicates high construct validity.Conclusions: QOL-OC demonstrates fairly good statistical reliability, validity, and feasibility. However, further tests and modification are needed to ensure its applicability to the quality-of-life assessment of Chinese oral cancer patients. [ABSTRACT FROM AUTHOR]

Background: Multiple pregnancies are one of the major safety concerns of in vitro fertilization (IVF) due to the increased risk of maternal and neonatal complications. Single embryo transfer is the most effective way to reduce the risk of multiple pregnancies. Selection of the embryo and optimization of the implantation environment are crucial to retain the success rate when the number of transferred embryos is diminished. Fresh embryo transfer with supra-physiological levels of hormones has been suggested to have an adverse effect on implantation. Elective frozen embryo transfer has been suggested to result in a higher rate of live birth than fresh embryo transfer. However, there is still a lack of evidence from randomized clinical trials comparing the efficacy and safety between frozen and fresh single blastocyst transfers.Methods/design: We are conducting a randomized controlled trial in women aged 20-35 undergoing their first cycle of IVF with or without intracytoplasmic sperm injection. After ovarian stimulation with a gonadotropin-releasing hormone antagonist protocol, women who obtain four or more embryos on day 3 of the embryo culture are randomized into two parallel groups: a single fresh blastocyst transfer group and a single frozen blastocyst transfer group (all blastocysts vitrified and a deferred frozen blastocyst transfer). The primary outcome is singleton live birth.Discussion: The results of this study will provide evidence for the efficacy and safety of the strategy of elective frozen single blastocyst transfer in women with a good prognosis.Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IOR-14005405 . Registered on 30 Oct 2014. [ABSTRACT FROM AUTHOR]

Background: Several studies on the association of tumor necrosis factor alpha (TNF-α) polymorphisms with recurrent pregnancy loss (RPL) risk have reported conflicting results. The present meta-analysis was conducted to provide a more precise estimation of these relationships and to investigate the real association between TNF-α polymorphisms and RPL. Methods: An extensive eligible literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library from their inceptions to May 12, 2015. Specific inclusion criteria were used to evaluate articles. The odds ratio (OR) with 95% confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA12.0 software. Results: 10 case-control studies including 1430 RPL patients and 1727 healthy controls were identified. Metaanalysis indicated that TNF-α-308G/A (rs1800629) polymorphism in the TNF-α gene correlated with elevated RPL risk whereas no significant association was observed between TNF-α-238G/A (rs361625) and RPL. Conclusions: The current meta-analysis demonstrates that TNF-α-308G/A polymorphism in the TNF-α gene is associated with susceptibility to RPL. [ABSTRACT FROM AUTHOR]

Liver metastasis is a frequent occurrence in patients with breast cancer; however, the available treatments are limited and ineffective. While liver-specific homing of breast cancer cells is an important feature of metastasis, the formation of liver metastases is not random. Indeed, breast cancer cell factors contribute to the liver microenvironment. Major breakthroughs have been achieved recently in understanding breast cancer liver metastasis (BCLM). The process of liver metastasis consists of multiple steps and involves various factors from breast cancer cells and the liver microenvironment. A further understanding of the roles of breast cancer cells and the liver microenvironment is crucial to guide future work in clinical treatments. In this review we discuss the contribution of breast cancer cells and the liver microenvironment to liver metastasis, with the aim to improve therapeutic efficacy for patients with BCLM. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a complex multifactor disorder and genetic factors have been implicated in its pathogenesis. Our previous genome-wide association study (GWAS) had identified allele frequencies in several single nucleotide polymorphisms (SNPs) in gene USP34 (Ubiquitin-Specific Protease 34) were significantly different between PCOS cases and controls. This study was aimed to replicate the previous results in another independent cohort. Methods: One thousand two hundred eighteen PCOS cases and 1057 controls were recruited. Genotyping of two SNPs (rs17008097 and rs17008940) in USP34 gene were performed by TaqMan-MGB probe assay and genotype-phenotype analysis was conducted subsequently. Results: The differences of allele or genotype frequencies were not significant statistically between PCOS and controls, even after age and BMI adjustment. For clinical and metabolic features (LH, T and HOMA-IR) analysis in PCOS cases, no statistical differences among three genotypes of rs17008097 and rs17008940 were found. However, rs17008940 was shown to be slightly associated with BMI in PCOS cases rather than in controls, even after age adjustment (TC vs CC P = 0.006, OR = 1.042, 95% CI 1.012-1.073; TT vs CC P = 0.037, OR = 1.050, 95% CI 1.003-1.100). Conclusions: USP34 gene polymorphisms (rs17008097 and rs17008940) may not be associated with PCOS in the Han Chinese women. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional imaging techniques as magnetic resonance enterography (MRE) may offer additional information on transmural inflammation, stricturing and fistulising complications in Crohn's disease (CD). The purpose of our study was to evaluate the diagnostic accuracy of Magnetic Resonance Imaging (MRI) combined with Diffusion-weighted Imaging (DWI) and MRE for determination of inflammation in small bowel CD. Methods: MR imaging examination was performed with a GE Signa EXCITE 3.0 T MRI scanner. The optimal b value in DWI with a learning cohort of patients was determined. The diagnostic accuracy for active lesions and disease activity were accessed by MRE combined with DWI. Results: The b value 800 s/mm² group showed the highest diagnostic sensitivity (74.19%) for diagnostic assessment of active Crohn's lesions on DWI. MRE combined with DWI showed the highest sensitivity (93.55%), specificity (89.47%) and diagnostic accuracy (92%) compared with MRE or DWI alone. The segmental MR score (MR-score-S) showed a significantly positive correlation with the Capsule Endoscopy Crohn's Disease Activity Index Score (CECDAI-S) (r = 0.717, p < 0.01). The total MR score (MR-score-T) showed significant association with C-reactive protein (CRP) (r = 0.445, p = 0.019) and erythrocyte sedimentation rate (ESR) (r = 0.688, p < 0.01). Conclusions: MRE combined with DWI improves the diagnostic accuracy for active lesions and correlates the endoscopic disease activity. MRE with DWI could represent a non-invasive tool in assessing active inflammation in CD. [ABSTRACT FROM AUTHOR]

Background Recent evidence suggests that aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas including gastric cancer. Speckle-type POZ protein, SPOP, is an E3 ubiquitin ligase adaptor, and it is found to inhibit oncogenic signaling. However, the molecular mechanisms are largely unknown. Methods In this study, we characterized the expression of SPOP in 88 pairs of gastric cancer tissues and adjacent tissues by immunohistochemical staining and Western blotting. The relationship between SPOP expression and clinical pathologic factors was analyzed. Transfected gastric cancer cell lines were used in cell viability, wound healing and colony formation assays. The interaction of SPOP with Gli2 and other related apoptotic proteins was assessed by immunoprecipitation, Western blotting, real-time PCR and dual luciferase reporter assays. Intracellular interaction of SPOP and Gli2 was visualized by immunofluorescent staining in gastric cancer cells. Results Immunohistochemical staining of SPOP can be detected in gastric cancer tissues but much less than adjacent gastric tissues (P < 0.01). High SPOP expression is negatively correlated with lymph node metastasis, poor histological differentiation, and tumor malignancy according to TNM staging. In vitro experiments revealed that over-expression of SPOP prevented tumor cells from proliferation, migration and colony formation in gastric cancer cell lines. Likewise, repression of SPOP promoted cell viability, migration, proliferation, and attenuated apoptosis. Mechanistic studies revealed that increasing SPOP accelerated Gli2 degradation but regardless of Gli2 synthesis. Furthermore, cytoplasmic Gli2 decreased markedly along with the abundant expression of SPOP in MKN45 cells. Conclusions Our findings indicate that SPOP plays critical roles in suppressing gastric tumorigenesis through inhibiting Hh/Gli2 signaling pathway. It may provide an alternative strategy for developing therapeutic agents of gastric cancer in future. [ABSTRACT FROM AUTHOR]

Background: The majority of beta-defensin family members are exclusively expressed in the epididymis, and some members have been shown to play essential roles in sperm maturation and fertility in rats, mice and humans. Therefore, beta-defensins are hypothesized to be potential targets for contraception and infertility diagnosis and treatment. Clarifying the regulatory mechanisms for the expression of these genes is necessary. Androgen/androgen receptor (AR) signaling plays an important regulatory role in epididymal structure and function. However, very little is known about the androgenic regulation on the production and secretion of the epididymal beta-defensins. Methods: The expression of beta-defensins was detected by quantitative RT-PCR. The androgen dependence of beta-defensins was determined by bilateral orchiectomy and androgen supplementation. The androgen response elements (AREs) in the promoters of beta-defensins were identified using the MatInspector software. The binding of AR to AREs was assayed by ChIP-PCR/qPCR. Results: We demonstrated that 23 mouse caput epididymal beta-defensins were differentially regulated by androgen/androgen receptor. Six genes, Defb18, 19, 20, 39, 41, and 42, showed full regulation by androgens. Ten genes, Defb15, 30, 34, 37, 40, 45, 51, 52, 22 and Spag11a, were partially regulated by androgens. Defb15, 18, 19, 20, 30, 34, 37, 39, 41, 42, 22 and Spag11a were associated with androgen receptor binding sites in their promoter or intronic regions, indicating direct regulation of AR. Six genes, Defb1, 12, 13, 29, 35, and spag11b/c, exhibited an androgen-independent expression pattern. One gene, Defb25, was highly dependent on testicular factors rather on androgens. Conclusions: The present study provides novel insights into the mechanisms of androgen regulation on epididymal beta-defensins, enabling a better understanding of the function of beta-defensins in sperm maturation and fertility. [ABSTRACT FROM AUTHOR]

Background Polycystic ovary syndrome (PCOS) patients are at increased risk of pregnancy complications, which may impair pregnancy outcome. Transfer of fresh embryos after superovulation may lead to abnormal implantation and placentation and further increase risk for pregnancy loss and complications. Some preliminary data suggest that elective embryo cryopreservation followed by frozen-thawed embryo transfer into a hormonally primed endometrium could result in a higher clinical pregnancy rate than that achieved by fresh embryo transfer. Methods/Design This study is a multicenter, prospective, randomized controlled clinical trial (1:1 treatment ratio of fresh vs. elective frozen embryo transfers).. A total of 1,180 infertile PCOS patients undergoing the first cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection will be enrolled and randomized into two parallel groups. Participants in group A will undergo fresh embryo transfer on day 3 after oocyte retrieval, and participants in group B will undergo elective embryo cryopreservation after oocyte retrieval and frozen-thawed embryo transfer in programmed cycles. The primary outcome is the live birth rate. Our study is powered at 80 to detect an absolute difference of 10 at the significance level of 0.01 based on a two-sided test. Discussion We hypothesize that elective embryo cryopreservation and frozen-thawed embryo transfer will reduce the incidence of pregnancy complications and increase the live birth rate in PCOS patients who need IVF to achieve pregnancy. [ABSTRACT FROM AUTHOR]

Background: Acute gastrointestinal illness (AGI) is an important public-health problem worldwide. Previous national studies of the incidence of AGI in China were performed decades ago, and detailed information was not available. This study therefore sought to determine the magnitude, distribution, and burden of self-reported AGI in China. Methods: Twelve-month, retrospective face-to-face surveys were conducted in 20 sentinel sites from six provinces between July 2010 and July 2011. Results: In total, 39686 interviews were completed. The overall adjusted monthly prevalence of AGI was 4.2% (95% confidence interval, 4.0-4.4), corresponding to 0.56 episodes of AGI per person-year. Rates of AGI were highest in children aged < 5 years. Healthcare was sought by 56.1% of those reporting illness. Of the cases who visited a doctor, 32.7% submitted a stool sample. The use of antibiotics was reported by 49.7% of the cases who sought medical care and 54.0% took antidiarrhoeals. In the multivariable model, gender, age, education, household type, residence, season, province and travel were significant risk factors of being a case of AGI. Conclusions: This first population-based study in China indicated that AGI represents a substantial burden of health. Further research into the specific pathogens is needed to better estimate the burden of AGI and foodborne disease in China. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a complex disease having both genetic and environmental components. Candidate genes with insulin metabolism have been hypothesized to be involved in the etiology of this syndrome. In the present study, we investigated the genetic association between polymorphisms in the insulin receptor (INSR) gene and PCOS. Methods: A total of 260 family trios were recruited and performed a family-based analysis to assess linkage and association between four single nucleotide polymorphisms (SNPs) (rs1799817, rs2059807, rs8108622 and rs10500204) of INSR gene and PCOS. Results: Using the transmission disequilibrium test (TDT), we failed to find that rs1799817 (p = 0.486), rs2059807 (p = 0.195), rs8108622 (p = 0.866) and rs10500204 (p = 1.0) were significantly overtransmitted to PCOS offspring from their parents. Conclusion: No significant evidence of association or linkage was found in the four tested markers, indicating that our family samples did not support susceptibility of the INSR gene to PCOS. [ABSTRACT FROM AUTHOR]

Background: To evaluate basal testosterone (T) levels during follicular phase of the menstrual cycle as a predictor for ovarian response and in vitro fertilization (IVF) outcome. Method: We analyzed data retrospectively from hospital-based IVF center including one thousand two hundred and sixty Chinese Han women under their first IVF cycle reached the ovum pick-up stage, without polycystic ovary syndrome (PCOS) or endometriosis undergoing long IVF protocol. Patients were divided into 2 groups. Group 1: patients with diminished ovarian reserve (basal FSH >10 IU/L) (n = 187); Group 2: patients with normal ovarian reserve (basal FSH < = 10 IU/L) (n = 1073). We studied the association of basal T levels with ovarian response and IVF outcome in the two groups. Long luteal down-regulation protocol was used in all patients, that is, the gonadotropin releasing hormone agonist was administered in the midluteal phase of the previous cycle and use of recombinant FSH was started when satisfactory pituitary desensitization was achieved. Results: Basal T levels were markly different between pregnant and non-pregnant women in Group 1; whereas not in Group 2. A testosterone level of 47.85 ng/dl was shown to predict pregnancy outcome with a sensitivity of 52.8% and specificity of 65.3%; and the basal T was correlated with the numbers of large follicles (> 14 mm) on HCG day in Group 1. Significantly negative correlations were observed between basal T, days of stimulation and total dose of gonadotropins after adjusting for confounding factors in both groups. Conclusion: In women with diminished ovarian reserve, basal T level was a predictor for the number of large follicles on HCG day and pregnancy outcome; but could not in those with normal serum FSH. Basal T levels were associated with both days of stimulation and total dose of gonadotropins, indicating that lower level of T might relate with potential ovarian poor response. [ABSTRACT FROM AUTHOR]

Background: Globally, colorectal cancer (CRC) affects more than 1 million people each year. In addition to non-modifiable and other environmental risk factors, Fusobacterium nucleatum infection has been linked to CRC recently. In this study, we explored mechanisms underlying the role of Fusobacterium nucleatum infection in the progression of CRC in a mouse model. Methods: C57BL/6 J-Adenomatous polyposis coli (APC) Min/J mice [APC (Min/+)] were treated with Fusobacterium nucleatum (109 cfu/mL, 0.2 mL/time/day, i.g., 12 weeks), saline, or FadA knockout (FadA−/−) Fusobacterium nucleatum. The number, size, and weight of CRC tumors were determined in isolated tumor masses. The human CRC cell lines HCT29 and HT116 were treated with lentiviral vectors overexpressing chk2 or silencing β-catenin. DNA damage was determined by Comet assay and γH2AX immunofluorescence assay and flow cytometry. The mRNA expression of chk2 was determined by RT-qPCR. Protein expression of FadA, E-cadherin, β-catenin, and chk2 were determined by Western blot analysis. Results: Fusobacterium nucleatum treatment promoted DNA damage in CRC in APC (Min/+) mice. Fusobacterium nucleatum also increased the number of CRC cells that were in the S phase of the cell cycle. FadA−/− reduced tumor number, size, and burden in vivo. FadA−/− also reduced DNA damage, cell proliferation, expression of E-cadherin and chk2, and cells in the S phase. Chk2 overexpression elevated DNA damage and tumor growth in APC (Min/+) mice. Conclusions: In conclusion, this study provided evidence that Fusobacterium nucleatum induced DNA damage and cell growth in CRC through FadA-dependent activation of the E-cadherin/β-catenin pathway, leading to up-regulation of chk2. [ABSTRACT FROM AUTHOR]