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Reaction of a quaternary ammonium salt with GaCl 3 in concentrated HCl aqueous solution led to an organic-inorganic hybrid perovskite material [Me 3 NCMe 3 ][GaCl 4 ] (1), which shows a two-step off-on-off second harmonic generation (SHG) response with a rapid and large temperature interval.

Halogen engineering offers a means of enhancing the physical properties of materials by fine-tuning the rotational energy barrier and dipole moment, which proved to be effective in achieving switchable phase transitions and optical responses in materials. In this work, by substituting the methyl group in ligand N -ethyl-1,5-diazabicyclo[3.3.0]octane (CH 3 CH 2 -3.3.0-Dabco) with halogen atoms X (Cl or Br) and then contining to react it with FeBr 3 in a HBr aqueous solution, we successfully synthesized three kinds of organic-inorganic hybrid switchable phase-change materials, [CH 3 CH 2 -3.3.0-Dabco]FeBr 4 ( 1 ), [ClCH 2 -3.3.0-Dabco]FeBr 4 ( 2 ), and [BrCH 2 -3.3.0-Dabco]FeBr 4 ( 3 ), which were fully characterized by single-crystal X-ray diffraction and variable-temperature powder X-ray diffraction. Compared to compound 1 , compounds 2 and 3 show two pairs of reversible phase transitions, dielectric anomalies, and a second-harmonic-generation effect, which are successfully induced due to the halogen substitution. This study offers an effective molecular design strategy for the exploration and construction of iron halide organic-inorganic hybrid materials with temperature-adjustable physical properties.

Background: The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS), especially in patients with diminished ovarian reserve (DOR). During in vitro fertilization-embryo transfer (IVF-ET) treatment, luteal phase estrogen pretreatment may enhance follicular development synchronization and yield of mature oocytes. However, the effect of estrogen pretreatment in DOR patients with elevated basal follicle-stimulating hormone (FSH) levels has not been well studied., Methods: We retrospectively analyzed the clinical data of patients with elevated basal FSH levels and DOR (401 cycles) who underwent IVF/intracytoplasmic monosperm injection (ICSI)-assisted conception. Both groups were treated with a flexible gonadotropin-releasing hormone (GnRH) antagonist regimen and were further divided into two groups according to whether they received luteal estrogen pretreatment. There were 79 patients in the estrogen pretreatment group and 322 patients in the control group. On the second day of the menstrual cycle, gonadotropin (Gn) stimulation of the ovaries was initiated. The general characteristics, clinical, biological parameters and outcomes of the two groups were compared., Results: The basic profiles of the two groups were similar (P > 0.05). More patients in the pretreatment group showed FSH rebound after gonadotropin (Gn) initiation, resulting in a significantly higher number of Gn days and total Gn than those in the control group (P < 0.05). There was no statistically significant difference in the number of days of antagonist use, follicle output rate (FORT), number of metaphase II(MII)eggs obtained, number of Two pronuclei (2PN) fertilized, number of D 3 quality embryos, blastocyst formation rate, fresh embryo clinical pregnancy rate, cumulative pregnancy rate, and non-transferable embryo rate between the two groups (P > 0.05)., Conclusions: The use of luteal phase estrogen pretreatment in patients with elevated basal FSH combined with DOR resulted in high FSH levels after the release of negative feedback, which was detrimental to early follicular growth, did not increase the follicular output rate, may have increased the use and duration of controlled ovarian stimulation drugs, and did not increase the number of eggs gained or improve clinical outcomes., (© 2024. The Author(s).)

Rationale: Desmoplastic small round cell tumor (DSRCT) is a rare and rapidly metastasizing soft tissue sarcoma, distinguished by its unique cell morphology and pleomorphic differentiation., Patient Concerns: This report describes the case of an 18-year-old male diagnosed with abdominopelvic DSRCT exhibiting metastases to the peritoneum, liver, pleura, bone, and muscle. The patient primarily presented with symptoms of incomplete intestinal obstruction and an abdominal mass., Diagnoses: Colonoscopy revealed lumen stenosis caused by external compression mass. Contrast-enhanced computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed multiple lesions in the abdominopelvic cavity. A needle biopsy of an abdominal wall lesion established it as a malignant tumor, origin unknown. Immunohistochemical staining post-surgery showed positive results for Cytokeratin (CK), CK7, Desmin, Vimentin, Caudal type homeobox 2 (CDX2), and Ki-67. Fluorescence in situ hybridization analysis revealed an Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1 (EWSR1) rearrangement, and next-generation sequencing identified an EWSR1-Wilms tumor protein 1 (WT1) gene fusion., Interventions: The patient underwent laparoscopic exploratory surgery, which encompassed biopsy, ascites drainage, adhesion lysis, reinforcement of weakened sections of the small intestinal walls, and repositioning of twisted intestines. Postoperatively, the treatment protocol included fasting, rehydration, gastrointestinal decompression, and parenteral nutrition. However, the patient did not received chemotherapy., Outcomes: The patient declined further treatment and deceased in early November., Lessons: This case highlights the nonspecific nature of DSRCT symptoms. In clinical practice, it is crucial to meticulously evaluate unexplained intestinal obstruction in young patients, considering DSRCT as a differential diagnosis to avoid delays in diagnosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To evaluate the left ventricular (LV) myocardial tissue characteristics in early adult obesity and its association with regional adipose tissue and ectopic fat deposition., Methods: Forty-nine obese adults (mean body mass index: 29.9 ± 2.0 kg/m 2 ) and 44 healthy controls were prospectively studied. LV native and post-contrast T 1 values, extracellular volume fraction (ECV), regional adipose tissue (epicardial, visceral, and subcutaneous adipose tissue (EAT, VAT, and SAT)), and ectopic fat deposition (hepatic and pancreatic proton density fat fractions (H-PDFF and P-PDFF)) based on magnetic resonance imaging were compared. The association was assessed by multivariable linear regression., Results: The obese participants showed reduced global ECV compared to the healthy controls (p < 0.05), but there was no significant difference in global native or post-contrast T 1 values between the two groups. Additionally, the obese individuals exhibited higher EAT, VAT, SAT, H-PDFF, and P-PDFF than the controls (p < 0.05). ECV was associated with insulin resistance, dyslipidemia, and systolic blood pressure (SBP) (p < 0.05). Multiple linear regression demonstrated that H-PDFF and SAT were independently associated with ECV in entire population (β =  - 0.123 and - 0.012; p < 0.05)., Conclusions: Reduced myocardial ECV in patients with mild-to-moderate obesity and its relationship to SBP may indicate that cardiomyocyte hypertrophy, rather than extracellular matrix expansion, is primarily responsible for myocardial tissue remodeling in early adult obesity. Our findings further imply that H-PDFF and SAT are linked with LV myocardial tissue remodeling in this cohort beyond the growth difference and cardiovascular risk factors., Clinical Trials Registration: Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476)., Clinical Relevance Statement: Myocardial fibrosis in severe obesity predicts poor prognosis. We showed that cardiomyocyte hypertrophy, not myocardial fibrosis, is the main myocardial tissue characteristic of early obesity. This finding raises the possibility that medical interventions, like weight loss, may prevent cardiac fibrosis., Key Points: • Myocardial tissue characteristics in early adult obesity are unclear. • Myocardial extracellular volume fraction (ECV) can be quantitatively evaluated using T 1 mapping based on cardiac magnetic resonance imaging (MRI). • Cardiac MRI-derived ECV may noninvasively evaluate myocardial tissue remodeling in early adult obesity., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objectives: The prevention and treatment of liver transplant rejection remain challenging. We investigated the pathophysiological mechanisms of liver transplant rejection in rats and screened candidate genes to determine their degree of rejection response for possible development of potential therapeutic targets., Materials and Methods: Brown Norway-Brown Norway transplant tolerant models and Lewis-Brown Norway transplant rejection models were established. We collected liver tissue and venous blood at 7 days posttransplant for hematoxylin and eosin staining and RNA sequencing analysis, respectively. We conducted differential expression gene analysis, KEGG and GO enrichment analysis. We performed immunohistochemistry to detect highly expressed immunerelated proteins, including lymphocyte-specific protein tyrosine kinase, linker for activation of T cells, and 70-kDa T-cell receptor zeta-chain-associated protein kinase., Results: Significant differences were found in liver function and Banff scores between rejection and tolerant groups, indicating the successful establishment of liver transplant models. RNA-sequencing screened 7521 differentially expressed genes, with 3355 upregulated and 3058 downregulated. KEGG analysis of upregulated genes showed that 8 of the top 20 enrichment pathways were associated with immune system processes and 5 were related to immune system diseases. Among these immune pathways, 289 genes were upregulated; of these, 147 genes were removed after comparison with the IMMPORT database, of which 97 genes were significantly changed. Our GO analysis showed upregulated genes mainly participating in immune response processes, with downregulated genes mainly participating in metabolic processes. Real-time polymerase chain reaction and immunohistochemistry verified expression of the immune-related proteins, consistent with RNAsequencing results, which were mainly expressed in inflammatory cells in sinus and portal vein., Conclusions: Immune-related genes were found to be associated with liver transplant rejection. The 3 immune-related genes that we analyzed may play a role in liver transplant rejection and can possibly serve as candidate markers for monitoring the degree of liver transplant rejection.

Black phosphorus (BP) exhibits significant potential for clinical applications. However, further research is necessary to uncover the unknown biological functions of BP and broaden its applications across various fields. This study investigates the potential of BP as a targeting PPAR-γ agonist to overcome chemoresistance in the treatment of pancreatic adenocarcinoma (PAAD) using 2D and 3D cell lines, patient-derived organoids (PDOs), and mouse models. RNA-sequencing analysis shows that BP treatment enriches differentially expressed genes in the PPAR pathway, and molecular modeling predicts the potential docking site between BP and PPAR-γ. Transcriptional activity assays are further to verify the activation of PPAR-γ. BP-activated PPAR-γ inhibits cancer stem cell (CSC) properties and expression of biomarkers such as CD44 and c-Myc, which are involved in chemoresistance. Notably, CD44 overexpression in tumor cells renders them susceptible to BP while insensitive to gemcitabine. This indicates that BP preferentially targets stem-like cells, which exhibit heightened resistance to chemotherapeutic drugs. A combination treatment strategy involving BP and gemcitabine is developed, demonstrating enhanced treatment efficacy of PAAD in both in vitro and in vivo models. Thus, BP serves as a PPAR-γ agonist capable of reversing chemoresistance, establishing it as a potent anti-tumor approach for the treatment of PAAD., (© 2023 Wiley-VCH GmbH.)

AIFM2 is a crucial NADH oxidase involved in the regulation of cytosolic NAD + . However, the role of AIFM2 in the progression of human cancers remains largely unexplored. Here, we elucidated the clinical implications, biological functions, and molecular mechanisms of AIFM2 in hepatocellular carcinoma (HCC). We found that AIFM2 is significantly upregulated in HCC, which is most probably caused by DNA hypomethylation and downregulation of miR-150-5p. High expression of AIFM2 is markedly associated with poor survival in patients with HCC. Knockdown of AIFM2 significantly impaired, while forced expression of AIFM2 enhanced the metastasis of HCC both in vitro and in vivo. Mechanistically, increased mitochondrial biogenesis and oxidative phosphorylation by activation of SIRT1/PGC-1α signaling contributed to the promotion of metastasis by AIFM2 in HCC. In conclusion, AIFM2 upregulation plays a crucial role in the promotion of HCC metastasis by activating SIRT1/PGC-1α signaling, which strongly suggests that AIFM2 could be targeted for the treatment of HCC., (© 2023. Springer Nature America, Inc.)

Orthotopic rat liver transplantation (OLT) is a complex microsurgical procedure extensively applied to basic science, myriad complications can occur, but incision-related self-biting has not been reported after OLT. For the project of tolerance induction through stem cells, we performed OLT from Lewis to Brown Norway (BN) rats as an acute rejection model and divided the study was into the transverse incision group (n = 15) and midline incision group (n = 22), while cyclosporine A was subcutaneously injected for 10-day immunosuppression use, lidocaine cream was used for pain-relieving. The recipient survival and wound status were the primary endpoint of this study. For the transverse incision group, 30-day survival rate was 40% (6/15), self-biting occurred in 13 cases in 7-39 days, the degree 1 of biting occurred in 1 cases, the degree 2 in 2 cases. The degree 3 in 10 cases, which caused death or euthanasia, the self-biting rate was 86.7% (13/15), For the midline incision group, 30-day survival rate was 100% (22/22), the degree 1 of self-biting occurred in 3 cases, no severe self-biting occurred. There were significant differences for survival ( p  = 0.0003) and for self-biting rate ( p  < 0.01) between two groups. In conclusion, incision-related self-biting behavior occurs due to incisional injury, the transverse incision is severely pain-causing; the midline one is effective to avert occurrences., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shaotang zhou reports was provided by 10.13039/501100016330Henan Provincial People's Hospital. Shaotang zhou reports a relationship with Henan Provincial People's Hospital that includes: employment and funding grants. Shaotang zhou has patent pending to n/a. none., (© 2023 The Authors.)

Fertilization failure is a significant manifestation of unexplained male infertility. Previous work has suggested a genetic origin. In this study, we report on a man with unexplained infertility from a large consanguineous marriage family. Whole-exome sequencing and Sanger sequencing identified a homozygous frameshift variation of the IQ motif containing N (IQCN; GenBank: NM&#95;001145304.1; c.1061&#95;1062delAT; p.Y354Sfs*13) in the proband and one of his two brothers, who also remained infertile. Analyses of spermatozoa by quantitative RT-PCR indicated that the level of IQCN mRNA was significantly reduced compared to fertile men and the protein could not be detected by western blotting and immunofluorescent staining in the proband. Immunofluorescent staining of spermatozoa from fertile men showed that IQCN was located in the acrosomal region and translocated to the equatorial segment after the acrosome reaction. The proband spermatozoa had abnormal morphology and function. Finally, the proband couple underwent IVF with donor sperm and a healthy baby was born. Furthermore, we developed an Iqcn-KO mouse model using the CRISPR/Cas9 technique. Sperm quality, except for sperm motility, and the fertility of male Iqcn-/- mice were consistent with those of the proband. In conclusion, the findings in humans and mice demonstrate that the homozygous frameshift variant of IQCN causes male infertility owing to autosomal-recessive fertilization failure., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pancreatic cancer (PC) is a malignant tumor of the digestive system that has a bad prognosis. N6-methyladenosine (m6A) is involved in a wide variety of biological activities due to the fact that it is the most common form of mRNA modification in mammals. Numerous research has accumulated evidence suggesting that a malfunction in the regulation of m6A RNA modification is associated with various illnesses, including cancers. However, its implications in PC remain poorly characterized. The methylation data, level 3 RNA sequencing data, and clinical information of PC patients were all retrieved from the TCGA datasets. Genes associated with m6A RNA methylation were compiled from the existing body of research and made available for download from the m6Avar database. The LASSO Cox regression method was used to construct a 4-gene methylation signature, which was then used to classify all PC patients included in the TCGA dataset into either a low- or high-risk group. In this study, based on the set criteria of |cor| > 0.4 and p value < 0.05. A total of 3507 gene methylation were identified to be regulated by m6A regulators. Based on the univariate Cox regression analysis and identified 3507 gene methylation, 858 gene methylation was significantly associated with the patient's prognosis. The multivariate Cox regression analysis identified four gene methylation (PCSK6, HSP90AA1, TPM3, and TTLL6) to construct a prognosis model. Survival assays indicated that the patients in the high-risk group tend to have a worse prognosis. ROC curves showed that our prognosis signature had a good prediction ability on patient survival. Immune assays suggested a different immune infiltration pattern in patients with high- and low-risk scores. Moreover, we found that two immune-related genes, CTLA4 and TIGIT, were downregulated in high-risk patients. We generated a unique methylation signature that is related to m6A regulators and is capable of accurately predicting the prognosis for patients with PC. The findings might prove useful for therapeutic customization and the process of making medical decisions., Competing Interests: The authors declare no conflict of interest regarding the publication of this paper., (Copyright © 2023 Tianle Zou et al.)

Background: Abdominal ectopic fat deposition and excess visceral fat depots in obesity may be related to cardiovascular disease (CVD) as both are involved in the metabolic syndrome (MetS). The awareness of the link between abdominal adiposity and subclinical cardiac remodeling would help improve treatment and outcome. Besides, liver fibrosis has also shown a potential relationship with cardiac dysfunction. Thus, we aimed to investigate the associations of magnetic resonance (MR)-based abdominal adiposity and hepatic shear stiffness with subclinical left ventricular (LV) remodeling while taking account of MetS-related confounders in adults free of overt CVD., Methods: This was an exploratory, prospective study of 88 adults (46 subjects with obesity, 42 healthy controls) who underwent 3 T cardiac and body MR exams. Measures of abdominal MR included hepatic and pancreatic proton density fat fraction (H-PDFF and P-PDFF), hepatic shear stiffness by MR elastography, and subcutaneous and visceral adipose tissue (SAT and VAT). Cardiac measures included epicardial adipose tissue (EAT) and parameters of LV geometry and function. Associations were assessed using Pearson correlation and multivariable linear regression analyses, in which age, sex, and MetS-related confounders were adjusted for., Results: The LV ejection fractions of all participants were within the normal range. Higher H-PDFF, P-PDFF, SAT and VAT were independently associated with lower LV global myocardial strain parameters (radial, circumferential and longitudinal peak strain [PS], longitudinal peak systolic strain rate and diastolic strain rate) (β = - 0.001 to - 0.41, p < 0.05), and P-PDFF, SAT and VAT were independently and positively associated with LV end-diastolic volume and stroke volume (β = 0.09 to 3.08, p ≤ 0.02) in the over-all cohort. In the obesity subgroup, higher P-PDFF and VAT were independently associated with lower circumferential and longitudinal PS, respectively (β = - 0.29 to - 0.05, p ≤ 0.01). No independent correlation between hepatic shear stiffness and EAT or LV remodeling was found (all p ≥ 0.05)., Conclusions: Ectopic fat depositions in the liver and pancreas, and excess abdominal adipose tissue pose a risk of subclinical LV remodeling beyond MetS-related CVD risk factors in adults without overt CVD. VAT may play a more considerable role as a risk factor for subclinical LV dysfunction than does SAT in individuals with obesity. The underlying mechanisms of these associations and their longitudinal clinical implications need further investigation., (© 2023. The Author(s).)

Objective: To explore the genetic basis for 4 patients with globozoospermia., Methods: Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing., Results: All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3' UTR region., Conclusion: DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.

Background: Accumulated evidence highlights the significance of the crosstalk between epigenetic and epitranscriptomic mechanisms, notably 5-methylcytosine (5mC) and N 6 -methyladenosine (m 6 A). Herein, we conducted a widespread analysis regarding the crosstalk between 5mC and m 6 A regulators in hepatocellular carcinoma (HCC)., Methods: Pan-cancer genomic analysis of the crosstalk between 5mC and m 6 A regulators was presented at transcriptomic, genomic, epigenetic, and other multi-omics levels. Hub 5mC and m 6 A regulators were summarized to define an epigenetic and epitranscriptomic module eigengene (EME), which reflected both the pre- and post-transcriptional modifications., Results: 5mC and m 6 A regulators interacted with one another at the multi-omic levels across pan-cancer, including HCC. The EME scoring system enabled to greatly optimize risk stratification and accurately predict HCC patients' clinical outcomes and progression. Additionally, the EME accurately predicted the responses to mainstream therapies (TACE and sorafenib) and immunotherapy as well as hyper-progression. In vitro, 5mC and m 6 A regulators cooperatively weakened apoptosis and facilitated proliferation, DNA damage repair, G2/M arrest, migration, invasion and epithelial-to-mesenchymal transition (EMT) in HCC cells. The EME scoring system was remarkably linked to potential extrinsic and intrinsic immune escape mechanisms, and the high EME might contribute to a reduced copy number gain/loss frequency. Finally, we determined potential therapeutic compounds and druggable targets (TUBB1 and P2RY4) for HCC patients with high EME., Conclusions: Our findings suggest that HCC may result from a unique synergistic combination of 5mC-epigenetic mechanism mixed with m 6 A-epitranscriptomic mechanism, and their crosstalk defines therapeutic response and pharmacogenomic landscape., (© 2023. The Author(s).)

Context: The mechanism of tetrandrine (TET) in hepatocellular carcinoma (HCC) progression and sorafenib (Sora) chemosensitivity deserves investigation., Objective: Using network pharmacology approaches to elucidate the mechanisms of TET in HCC., Materials and Methods: CCK-8, colony formation, and flow cytometry assays were used to measure cell phenotypes. BALB/c nude mice were divided into Control, Sora (10 mg/kg), TET (50 mg/kg), and TET + Sora (10 mg/kg Sora plus 50 mg/kg TET) groups to evaluate the antitumor effects of TET for 21 days. Sora and TET were given by intraperitoneal injection or oral gavage., Results: For SMMC7721 (IC 50 = 22.5 μM) and PLC8024 (IC 50 = 18.4 μM), TET (10, 20 μM) reduced colony number (0.68 ± 0.04- and 0.50 ± 0.04-fold, 0.56 ± 0.04- and 0.42 ± 0.02-fold), induced cell cycle arrest at G0/G1 stage (1.22 ± 0.03- and 1.39 ± 0.07-fold, 1.37 ± 0.06- and 1.55 ± 0.05-fold), promoted apoptosis (2.49 ± 0.26- and 3.63 ± 0.33-fold, 2.74 ± 0.42- and 3.73 ± 0.61-fold), and inactivated PI3K/AKT/mTOR signalling. Sora (10 μM) decreased cell proliferation, enhanced apoptosis, and inhibited PI3K/AKT/mTOR signalling, and these effects were further aggravated in the combination group. Activating PI3K/AKT/mTOR reversed the effects of TET on cell proliferation and Sora sensitivity. In the combination group, tumour volumes and weights were decreased to 202.3 ± 17.4 mm 3 and 151.5 ± 25.8 mg compared with Sora (510.6 ± 48.2 mm 3 and 396.7 ± 33.5 mg)., Discussion and Conclusions: TET enhances Sora sensitivity by inactivating PI3K/AKT/mTOR, suggesting the potential of TET as a chemosensitizer in HCC.

Background: The diagnostic performance for hepatocellular carcinoma (HCC) is hampered using gadoxetic acid-enhanced magnetic resonance (MR) imaging due to the high incidence of transient severe motion in arterial phase (AP). Dynamic contrast enhanced computed tomography (CT) imaging yield high detection rate for hepatic nodules in AP, and the combined use of CT arterial phase (CTAP) imaging with gadoxetic acid-enhanced MR imaging may improve the diagnostic performance for HCC. Thus, this study aimed to determine whether the combined use of CTAP and gadoxetic acid-enhanced MR imaging can improve the diagnostic performance for HCC based on various imaging diagnostic criteria., Methods: A total of 169 surgically histologically confirmed hepatic nodules (137 HCCs and 32 non-HCC-nodules) were retrospectively enrolled. Two different imaging protocol sets were reviewed: (I) full gadoxetic acid-enhanced magnetic resonance imaging (MRI) sequences; and (II) CTAP imaging combined with the gadoxetic acid-enhanced MRI but excluding the MR imaging AP images. Three independent reviewers followed the 2018 Liver Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), and 2018 Korean guidelines to characterize these heaptic nodules by reviewing the two imaging protocol sets and the diagnostic peformance were compared by using McNemar test., Results: The detection rate of AP hyperenhancement (APHE) was higher in CTAP than in the MR arterial phase (MRAP) for hepatic nodules (87.57% vs. 75.15%) and HCCs (97.08% vs. 82.48%) (all P<0.001). For the LI-RADS criteria, the Protocol-II increased the sensitivity to 75.91% from 70.80% of Protocol-I (P=0.016), with a minimal decrease of the specificity to 71.88% from 75.00% (P=1.000). For the EASL criteria, the numerical increases were found of Protocol-II than Protocol-I in both sensitivity (81.02% vs. 78.10%) and specificity (75.00% vs. 71.88%), but with no statistical significance. For the Korean criteria, the Protocol-II increased the sensitivity to 94.89% from 83.21% of Protocol-I (P<0.001). The specificity increased to 65.63% from 62.50%, with no statistical significance (P=1.000)., Conclusions: Using CTAP instead of gadoxetic acid-enhanced MRAP can improve the diagnostic sensitivity for HCC and also yields a comparable specificity. Thus, the combined use of CTAP and gadoxetic acid-enhanced MR imaging may improve the diagnostic performance for HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4968/coif). XW and LN are from GE Healthcare China. The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Inserting diffusion weighted imaging (DWI) into the time interval between post contrast and hepatobiliary phase (HBP) is time saving and health economic friendly. However, whether DWI would be affected before and after Gd-EOB-DTPA is still unknown. This study aims to validate whether the DWI at both low and high b-values is affected before and after Gd-EOB-DTPA enhancement., Methods: From July 2019 to November 2019, seventy-three patients who satisfied the inclusion criteria were enrolled. Those patients were scanned with multiple b-value (b-value of 0, 50, 800, 1,000, and 1,200 s/mm 2 ) DWI using a 3.0 T magnetic resonance (MR) scanner before and after the injection of Gd-EOB-DTPA. The final imaging diagnosis of the malignant liver lesions were made by histopathological analysis. The lesion-liver contrast intensity ratio (CIR) and the apparent diffusion coefficients (ADCs) of hepatic parenchyma and lesions at each b-value was evaluated. The Student's t -test or Mann-Whitney U test was used to compare the CIR and ADC between the MR images before and after contrast agent injection. In addition, the Student's t -test or Mann-Whitney U test was used to compare the ADC values between benign and malignant lesions. Receiver operating characteristics (ROC) curves were used to assess the area under the curve (AUC) of the ADC values in differentiating between benign and malignant lesions., Results: For the CIRs comparison, the CIRs showed no statistical significance before and after Gd-EOB-DTPA on b =0 (1.34±1.15 vs. 1.45±1.48, P=0.664), b=50 (1.23±1.13 vs. 1.35±1.34, P=0.982), b=800 (1.19±0.87 vs. 1.19±0.94, P=0.946), b=1,000 (1.21±0.90 vs. 1.32±1.05, P=0.294) and b=1,200 (1.25±1.03 vs. 1.45±1.48, P=0.165) s/mm 2 . For the ADC value comparison, the ADC also showed no statistical significance before and after Gd-EOB-DTPA on b=50 (4.04±2.82 vs. 3.91±3.00, P=0.151), b=800 (1.68±0.71 vs. 1.67±0.76, P=0.163), b=1,000 (1.53±0.69 vs. 1.50±0.70, P=0.078) and b=1,200 (1.48±0.66 vs. 1.48±0.70, P=0.294) s/mm 2 ., Conclusions: DWI scanned between the interval of dynamic enhanced imaging and HBP imaging can save overall scanning time without influencing the CIRs, ADCs, and diagnostic capabilities of hepatic lesions at both low and high b-values., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-962/coif). LN and XW are from GE Healthcare China. The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Hepatocellular carcinoma (HCC) is a principal histologic type of liver cancer with high mortality. Long non-coding RNAs (LncRNAs) exert a crucial role in the pathogenesis of human tumors. To date, the functions and mechanisms of lncRNA HAGLROS in HCC are rarely reported. In the current study, HAGLROS exhibited a higher level in HCC tissues and cells. HAGLROS expression was positively correlated with tumor size, TNM stage and poor clinical prognosis. Loss-of-function experiments showed that knockdown of HAGLROS significantly lowered cell proliferation, cell cycle progression, migration, invasion and epithelial to mesenchymal transition (EMT) but induced apoptosis in vitro . Consistently, tumor growth in the nude mice was effectively slowed by the depletion of HAGLROS. Mechanistically, HAGLROS could competitively bind to miR-26b-5p to prevent the suppression of miR-26b-5p on its downstream target gene Karyopherin α2 (KPNA2). Moreover, the inhibitory effects of HAGLROS knockdown on cell malignant behaviors were reversed due to the miR-26b-5p down-regulation or KPNA2 overexpression. It was interesting to note that HAGLROS inactivated p53 signaling through targeting miR-26b-5p/KPNA2. In conclusion, our results demonstrated that HAGLROS contributed to the malignant progression of HCC via serving as a sponge for miR-26b-5p to facilitate KPNA2 expression and inactivate p53 signaling. Targeting HAGLROS/miR-26b-5p/KPNA2 axis might be an alternative therapeutic strategy for HCC patients.

Objectives: Orthotopic liver transplant remains technically challenging., Materials and Methods: We performed whole graft orthotopic liver transplants with different anhepatic times (≤20 min, n = 19; vs 30 min, n = 9) and partial orthotopic liver transplants in rats including a male-to-male Sprague-Dawley group (n = 15), a male-to-male Lewis-to-Brown Norway group (n = 20), and a male-to-male Sprague-Dawley-to-Lewis group (n = 20); there was also a female-to-male SpragueDawley group (n = 19)., Results: For the groups with ≤20-minute or 30-minute anhepatic time, 14-day and 30-day survival rates were 94.7%, 89.5%, 88.9%, and 88.9%, respectively, and there was no difference in survival (P = .716). For 50% orthotopic liver transplants from the male-tomale Sprague-Dawley group, 14-day and 30-day survival rates were 93.3% and 86.7%, respectively, with no difference between whole and 50% graft orthotopic liver transplant. The 14-day and 30-day survival rates were, respectively, 30% and 10% for the Lewis-to-Brown Norway group and 30% and 6.6% for the Sprague-Dawley-to-Lewis group, with no differences between the 2 groups (P = .564). Most of the recipient rats died within 72 hours. Acute rejections and wound dehiscence were the causes of death. Recipients from the female-to-male SpragueDawley orthotopic liver transplant group died shortly after surgery., Conclusions: Orthotopic liver transplants can be performed to achieve high success rates in the extended anhepatic time; however, orthotopic liver transplants from female Sprague-Dawley donor rats have a high risk of failure.

The aim of this study was to investigate the values of computed tomography (CT) imaging technology based on image segmentation algorithm (ISA). It was applied in the radial shock wave therapy (RSWT) to treat knee osteoarthritis (KOA), so its curative effect and rehabilitation effect on nerve function were mainly analyzed in this study. 84 patients with KOA were selected and grouped into an ultrasonic treatment group (group A) and a RSW group (group B). All the patients received the ISA-based CT examination and high-quality nursing intervention. There were comparisons on the effects of pain improvement, knee joint function, and nerve function rehabilitation of patients in groups A and B. Results showed that visual analogue scale (VAS) scores before and after treatment were markedly different among all patients, and the pain degree of patients in group B was lower than the degree of group A ( P < 0.05). The knee joint function of group B after treatment was greatly better than group A ( P < 0.05). Scandinavian stroke scale (SSS) scores of nerve function rehabilitation after nursing in patients from group B were sharply lower than the scores of group A ( P < 0.05). Results indicated that ISA-based CT images could be applied in analysis of curative effect on KOA, and there was more obvious effect of RSWT in the treatment of KOA., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Jinghai Tian et al.)

Background: The tumor-promoting roles of ST8SIA6-AS1 and miR-145-5p have been found in several cancers, but their function in cholangiocarcinoma (CHOL) remains speculative. The purpose of this study was to examine the regulatory functions of the ST8SIA6-AS1/MAL2/miR-145-5p pathway in CHOL progression., Methods: RT-qPCR assay was used to detect ST8SIA6-AS1 expression in CHOL tissues and cell lines. Cell migration, apoptosis, invasion, and proliferation abilities were assessed by RIP, RNA pull-down, and luciferase assays. CCK-8, BrdU, transwell, and FITC assays to investigate the regulatory functions of ST8SIA6-AS1, miR-145-5p, and MAL2 function in CHOL cells., Results: Findings revealed the enrichment of ST8SIA6-AS1 in CHOL tissues and cell lines. It was also found that ST8SIA6-AS1 facilitated cell growth and migration, but it reduced the apoptosis level of the CHOL cells. The results of experiments showed that ST8SIA6-AS1 sponged miR-145-5p, thereby allowing MAL2 to exert its biological function on CHOL cells., Conclusion: This research suggested that the ST8SIA6-AS1/miR-145-5p/MAL2 axis could enhance CHOL progression, which might be useful to improve the clinical outcomes of CHOL patients., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2021 He et al.)

Although there is some progress in immunosuppressive therapy of acute rejection, there is still a lack of standardized diagnosis and treatment. For the acute rejection after liver transplantation, there is still a lack of an exact treatment at this stage. Tacrolimus (TAC) side effects will also affect the survival rate and quality of life of recipients after transplantation to a large extent. Rat orthotopic liver transplantation model was established and divided into three groups. In the tolerance group, Brown Norway (BN) to Lewis liver transplantation was used; in the rejection group, Lewis to BN liver transplantation was used; in the TAC group, TAC was injected after operation on the basis of establishing rejection model. The expression of GITRL in Kupffer cells and the change of cytokines were detected 7 days after operation. In this study, the animal model of acute rejection of rat liver transplantation was established to simulate the clinical allogeneic liver transplantation, and the important role of TAC in the acute rejection of rat liver transplantation was evaluated.

Hepatocellular carcinoma (HCC) has a high mortality rate, which imposes a huge burden on patients and society. Glypican-1 (GPC1) is considered to be an ideal diagnostic marker. The present study aimed to investigate GPC1 expression in HCC, its association with clinicopathological factors and its prognostic significance in HCC progression. Reverse transcription-quantitative PCR, western blotting and immunohistochemical staining were used to investigate GPC1 expression in 175 HCC and paired normal tissues, and in HCC and normal cells. Serolo2gical levels of GPC1 were examined via enzyme-linked immunosorbent assay in patients with HCC. Kaplan-Meier survival analysis and Cox regression analysis were used to assess the prognostic significance of GPC1. The present results suggested that GPC1 expression was upregulated in HCC tissues, especially in metastatic HCC. Similar results were observed in HCC cell lines. Serum GPC1 was higher in patients with HCC than in healthy controls (HCs). Patients with high GPC1 expression had shorter recurrence-free survival (RFS) and disease-specific survival (DSS) times compared with those with low GPC1 expression. In addition, high GPC1 expression was significantly associated with tumor size and Tumor-Node-Metastasis (TNM) stage (P<0.05). Furthermore, tumor size, TNM stage and GPC1 expression were independent predictive factors for RFS and DSS in patients with HCC. In conclusion, the present results revealed that high GPC1 expression was closely associated with a poor prognosis in patients with HCC and that it may therefore be used as a potential target for accurate diagnosis and treatment of HCC., (Copyright: © Chen et al.)

Terminal differentiation induced ncRNA (TINCR), a newly identified lncRNA, has been found to be associated with different human cancers including hepatocellular carcinoma (HCC). However, little is known regarding the pathological mechanisms of TINCR in HCC progression. In this study, we confirmed that TINCR expression was upregulated in HCC tumors and cell lines, and high TINCR expression was associated with larger tumor size, advanced tumor node metastasis stage, and poor prognosis. Functionally, knockdown of TINCR facilitated apoptosis and suppressed viability, colony formation and invasion in Huh7 and Hep3B cells. Mechanically, TINCR functioned as competing endogenous RNA (ceRNA) to regulate DEAD-box helicase 5 (DDX5) expression through sponging miR-218-5p. Moreover, the miR-218-5p expression was downregulated and DDX5 expression was upregulated in HCC tumors. The silencing of miR-218-5p or ectopic expression of DDX5 abated the tumor-suppressive effect of TINCR knockdown in vitro. Furthermore, si-TINCR-induced inactivation of AKT signaling was rescued by suppression of miR-218-5p or overexpression of DDX5. Also, the silencing of TINCR resulted in tumor growth inhibition in vivo. In summary, knockdown of TINCR suppressed HCC progression presumably by inactivation of AKT signaling through targeting the miR-218-5p/DDX5 axis, suggesting a novel TINCR/miR-218-5p/DDX5 pathway and therapy target for HCC., (© 2020 Wiley Periodicals, Inc.)

Background: In clinical practice arterial anatomy evaluation is often determined using computed tomographic angiography (CTA); the effect of enhanced MRI has been neglected., Purpose: To evaluate whether multiple arterial phase (MAP) images from patients who underwent differential subsampling with Cartesian ordering (DISCO) acquisition would improve the hepatic arterial display compared with single arterial phase (SAP) and CTA., Study Type: A prospective, randomized trial., Subjects: In all, 130 patients (mean age, 55.81 ± 9.43 years; range, 35-78 years) including 89 men and 41 women., Field Strength/sequence: 3.0T, DISCO, liver acquisition with volume acceleration-flexible (LAVA-Flex), CTA., Assessment: A simple randomization was conducted and the study was subdivided into study part I (DISCO vs. SAP) and study part II (DISCO vs. CTA). Ten hepatic arterial segments were independently evaluated by three readers in the axial plane and the quality of hepatic arterial display was assessed using a four-point scale., Statistical Tests: Kendall's W-test, χ 2 test, Mann-Whitney U-test, and Kruskal-Wallis one-way analysis of variance (ANOVA) test., Results: Excellent interobserver agreement was obtained for hepatic arterial display (all Kendall's W values >0.80). For study part I, the mean arterial display scores for the common hepatic artery (CHA), proper hepatic artery (PHA), left hepatic artery (LHA), right hepatic artery (RHA), left gastric artery (LGA), and gastroduodenal artery (GDA) obtained with DISCO were higher than that obtained with SAP imaging (all P < 0.01). For study part II, comparable image quality for CHA (P = 0.798), PHA (P = 0.440), LHA (P = 0.211), RHA (P = 0.775) LGA (P = 0.468), and GDA (P = 0.801) was obtained with DISCO and CTA., Data Conclusion: The use of MAP acquisition with DISCO is superior to the use of SAP in hepatic arterial display and compares favorably with CTA; in the future, DISCO possibly can replace the latter ionization-related method to provide a more comprehensive evaluation of the liver arterial vessels., Level of Evidence: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1766-1776., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: Pancreatic duct decompression relieves pancreatic duct stone (PDS)-associated abdominal pain, though a consensus indication for the drainage procedure of the main pancreatic duct (MPD) is lacking. Moreover, major prognostic factors for postsurgical long-term pain relief and recurrence are largely unknown., Methods: The clinical outcomes of 65 consecutive PDS patients undergoing surgery from 2008-2012 with 3+ years of follow-up were assessed., Results: At postsurgical follow-up (median, 4.5 years; range, 3-7 years; procedure: Partington, n = 32; Frey, n = 27; pancreatoduodenectomy, n = 3; distal pancreatectomy, n = 3), the early complication and complete stone clearance rates were 29.2% and 97%, respectively. Long-term, complete and partial pain relief were 93.9%, 83.1%, and 10.8%, respectively. The risk of pancreatic fistula was higher in the <8 mm group than in the >8 mm group (P < 0.05), and 80% of the pancreatic fistula cases occurred in the <8 mm group. A shorter pain duration (P = 0.007), smaller MPD diameter (P = 0.04), and lower Izbicki pain score (P < 0.001) predicted long-term pain relief. Pain recurrence after initial remission occurred in 5 patients and was only related to pain duration (P = 0.02). Stone recurrence and pancreatic exocrine functional and endocrine functional deterioration occurred in 2, 5, and 11 patients, respectively., Conclusion: Surgery provides excellent stone clearance, long-term pain relief, and acceptable postoperative morbidity. Using 8 mm as the criterion for drainage surgery can minimize the postoperative pancreatic fistula risk. Individualized and timely surgical treatment may improve the effect of surgery., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2020, the Korean Surgical Society.)

Objectives: T-cell immunoglobulin domain and mucin domain-4 (TIM-4) is selectively expressed on antigen-presenting cells (APCs) and modulates various immune responses. However, the role of TIM-4 expressed by Kupffer cells (KCs) in liver fibrosis remains unclear. The present study aimed to explore whether and how TIM-4 expressed by KCs is involved in liver fibrosis., Materials and Methods: Mice chronic liver fibrosis models were established and divided into the olive-induced control group, CCL4-induced control group, olive-induced TIM-4 interference group and CCL4-induced TIM-4 interference group. Different techniques were used to monitor the fibrotic effects of TIM-4, including histopathological assays, Western blotting, ELISA and transmission electron microscopy. Additionally, mice liver transplant models were established to determine the fibrotic effects of TIM-4 on fibrosis after liver transplantation (LT)., Results: We found that the induction of liver fibrosis by CCL4 was associated with TIM-4 expression in KCs. TIM-4 interference essentially contributed to liver fibrosis resolution. KCs from the TIM-4 interference group had decreased levels of pro-fibrotic markers, reduced TGF-β1 secretion and inhibited hepatic stellate cell (HSC) differentiation into myofibroblast-like cells. In addition, we used GdCl3 to verify that KCs are the primary source of TGF-β1 during fibrosis progression. Moreover, KCs from CCL4-induced mice showed increased ROS production, mitophagy activation and TGF-β1 secretion. However, TIM-4 interference in the KCs inhibited Akt1-mediated ROS production, resulting in the suppression of PINK1, Parkin and LC3-II/I activation and the reduction of TGF-β1 secretion during liver fibrosis. Additionally, TIM-4 interference potentially attenuated development of fibrosis after LT., Conclusions: Our findings revealed the underlying mechanisms of TIM-4 interference in KCs to mitigate liver fibrosis., (© 2019 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.)

Background: Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer associated with a high mortality. Long non-coding RNAs (lncRNAs) have recently emerged as regulators in the development and progression of several cancers, and therefore represent an opportunity to uncover new targets for therapy. In the present study, we aimed to investigate the potential effect of lncRNA BZRAP1-AS1 on the angiogenesis of HCC., Methods: Microarray-based data analysis was initially employed to screen genes and lncRNAs that are differentially expressed in HCC and the candidate BZRAP1-AS1 was identified as a hit. The expression of BZRAP1-AS1 and thrombospondin-1 (THBS1) in HCC tissues and cells were then determined using RT-qPCR. The gene methylation level was measured by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) assays. Next, the interactions between BZRAP1-AS1, DNA methyltransferase 3B (DNMT3b), and THBS1 were assessed by RIP, RNA pull-down and ChIP assays. Finally, the roles of BZRAP1-AS1, DNMT3b and THBS1 in angiogenesis in vitro as well as tumorigenesis in vivo were evaluated by a battery of the gain- and loss-of function experiments., Results: BZRAP1-AS1 was identified as a highly expressed lncRNA in HCC tissues and cells. Down-regulation of BZRAP1-AS1 in HCC cells inhibited HUVEC proliferation, migration and angiogenesis. By interacting with DNMT3b, BZRAP1-AS1 induced methylation of the THBS1 promoter and inhibited the transcription of THBS1, resulting in promoted angiogenesis of HUVECs. Moreover, silencing of BZRAP1-AS1 repressed the angiogenesis as well as the tumor growth of HCC in vivo via up-regulating THBS1., Conclusion: This study provides evidence that angiogenesis in HCC is hindered by silencing of BZRAP1-AS1. Thus, BZRAP1-AS1 may be a promising marker for the treatment of HCC.

Hepatectomy of large hepatocellular carcinomas (>10 cm) in over 70 year-old patients is presumed futile. We retrospectively reviewed 5970 patients with liver tumors Jan 2010 through Dec 2016 in our institute, of them, 37 older patients with large hepatocellular carcinomas staged I-III and Child-Pugh A liver functions receiving conservative treatments (conservative group, n = 37) and 16 older patients with large hepatocellular carcinomas staged I- III who underwent partial hepatectomy (resection group, n = 16) were included, the risk factors for poor survival were analyzed by univariate and multivariate analyses. Compared with the conservative treatments, Partial hepatectomy achieved better median survival time (25.5 months versus 11 months, log-rank = 0.0001) and better median performance status (1 versus 3, p = 0.023), there was different in Charlson comorbidity index (p = 0.019). For the conservative group, the 3-month, 1, 2, 3-year survival rate was 78.4%, 43.2%, 5.4%, 0%; for the resection group, The 3-month, 1, 2, 3-year survival rate was 100%, 93.7.2%, 56.3%, 12.5%; Multivariate Cox regression analysis showed the Charlson comorbidity index and the performance status associated with poor outcomes of those patients (p = 0.001, 0.018, respectively). Resections of large hepatocellular carcinomas in older patients can be performed safely to prolong life expectancy and improve life quality with or without cancer recurrence.

ABO-incompatible (ABO-i) living-donor liver transplantation (LDLT) is performed if an ABO-compatible graft cannot be obtained. However, a perfect desensitization protocol has not been established worldwide, especially for simultaneous ABO-i LDLT and splenectomy. We herein report two cases of ABO-i LDLT. To the best of our knowledge, this is the first case report of ABO-i LDLT in an adult patient in China. Splenectomy and T-cell-targeted immunosuppression (basiliximab) was used to overcome the blood group barrier in these recipients. The patients had good graft function without signs of antibody-mediated rejection throughout the 12-month follow-up. Thus, ABO-i LDLT with splenectomy is undoubtedly life-saving when an ABO-compatible graft cannot be obtained for patients in critical condition.

Background: Liver transplantation (LT) accompanied by jejunectomy to treat patients with acute or chronic hepatic cirrhosis with thrombosis in the portal system is extremely rare., Case Presentation: A 47-year-old man presented with hematemesis and melena, and a diagnosis of decompensated cirrhosis, chronic portal vein thrombosis (PVT) and secondary gastro-esophageal variceal hemorrhage was made. Coagulants were administered, but portal vein thrombi occurred rapidly, and gastrointestinal bleeding recurred shortly thereafter. The patient underwent LT, phlebothrombectomy and a partial jejunectomy. His recovery from a fistula was uneventful, and follow-up visits over 70 months were unremarkable., Conclusion: Liver transplantation and partial jejunectomy is a feasible and effective surgical option for select patients with end-stage liver disease accompanied by acute portal venous thrombosis.

Qi arrival is the meridian qi response to acupuncture stimulation. Through analyzing the relevant concepts of qi arrival and summarizing the general understanding of it in clinic and on the basis of the collection of the relevant literature at home and abroad on the determination of qi arrival and its strength, the characteristics are analyzed on the present method and the method for the determination of qi arrival and its strength is discussed in terms of the results in the needling sensation scale. It is believed that the needling sensation and its strength can be used to determine whether the qi is arrived or not and its strength. The components of different types of needling sensation are much better applicable for the analysis on the characteristics and rules on the influence on qi arrival. This method is in compliance not only with the theoretic connotation of qi arrival, but also with the clinical general understanding, which lays the foundation for the analysis on the scale results.

Background: Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome. They have important regulatory functions in chromatin remodeling and gene expression. Dysregulated lncRNAs have been studied in cancers, but their role in esophageal squamous cell carcinoma (ESCC) remains largely unknown. We have conducted lncRNA expression screening and a genome-wide analysis of lncRNA and coding gene expression on primary tumor and adjacent normal tissue from four ESCC patients, tend to understand the functionality of lncRNAs in carcinogenesis of esopheagus in combination with experimental and bioinformatics approach., Methods: LncRNA array was used for coding and non-coding RNA expression. R program and Bioconductor packages (limma and RedeR) were used for differential expression and co-expression network analysis, followed by independent confirmation and functional studies of inferred onco-lncRNA ESCCAL-1 using quantitative real time polymerase chain reaction, small interfering RNA-mediated knockdown, apoptosis and invasion assays in vitro., Results: The global coding and lncRNA gene expression pattern is able to distinguish ESCC from adjacent normal tissue. The co-expression network from differentially expressed coding and lncRNA genes in ESCC was constructed, and the lncRNA function may be inferred from the co-expression network. LncRNA ESCCAL-1 is such an example as a predicted novel onco-lncRNA, and it is overexpressed in 65% of an independent ESCC patient cohort (n = 26). More over, knockdown of ESCCAL-1 expression increases esophageal cancer cell apoptosis and reduces the invasion in vitro., Conclusion: Our study uncovered the landscape of ESCC-associated lncRNAs. The systematic analysis of coding and lncRNAs co-expression network increases our understanding of lncRNAs in biological network. ESCCAL-1 is a novel putative onco-lncRNA in esophageal cancer development.

Objective: To screen for esophageal squamous cell carcinoma (ESCC)-associated long non-coding RNAs (lncRNA) and identify oncogenic lncRNA contributing to ESCC pathogenesis., Methods: A lncRNA array containing 7419 lncRNA was used to detect the transcriptional profiles of lncRNA of four pairs of ESCC and matched normal esophageal tissue. Bioinformatic analysis was employed to identify differentially expressed ESCC associated lncRNA (ESCCAL). Quantitative real-time PCR was used to verify selected dysregulated lncRNA on independent ESCC samples., Results: Genome-wide transcriptome profiling (coding and or noncoding RNA transcripts) was able to distinguish ESCC from normal tissue. Among these, bioinformatic analysis has identified 154 differentially expressed ESCC associated lncRNA (ESCCALs), which included 111 downregulated and 43 upregulated lncRNA in ESCC relative to the normal tissue (P< 0.01). The highest upregulated lncRNA (ESCCAL&#95;1) and known onco-lncRNA HOTAIR was further verified in 26 paired ESCC samples. ESCCAL&#95;1 and HOTAIR were found to be highly expressed in 17 ESCC and 18 ESCC compared with normal esophageal tissues., Conclusion: This investigation has revealed large scale aberrant expression of lncRNA in ESCC. About 70% of novel lncRNA-ESCCAL&#95;1, together with a known lncRNA-HOTAIR, are highly expressed in ESSC, suggesting that ESCCAL&#95;1 and HOTAIR may participate in the pathological process of ESCC. Furthermore, lncRNA could be potential diagnostic and prognostic biomarkers for ESCC.

Background and Objectives: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. The regulator of G-protein signaling 5 (RGS5) has been reported to be highly expressed in some malignant tumors. However, its expression and role in HCC has not been reported., Methods: The expression of RGS5 was examined in liver cancer tissues and cell lines by real-time quantitative PCR. The cell migration and invasion was investigated by wound healing and transwell invasion assay. The epithelial-mesenchymal transition markers were detected by Western blotting or immunofluorescence., Results: We observed that RGS5 is over-expressed in most of liver cancer tissue samples and cell lines compared with matched normal samples. Further analysis showed that the over-expression of RGS5 is associated with liver cancer recurrence, venous infiltration, and patients' poor survival. Next, we found that knockdown of RGS5 significantly inhibits liver cancer cell migration and invasion in highly invasive liver cancer cells. Furthermore, we found that over-expression of RGS5 induces epithelial-mesenchymal transition in epithelial liver cancer cells., Conclusions: These results indicate that over-expression of RGS5 promotes tumor metastasis by inducing epithelial-mesenchymal transition in HCC., (Copyright © 2013 Wiley Periodicals, Inc.)

BTG3 is identified as a tumor suppressor gene in some malignancies. Btg3-deficient mice display a higher incidence of lung cancer. These results suggest that BTG3 plays an important role in lung tumorigenesis, although the underlying mechanisms are unknown. The BTG3 expression was detected using immunohistochemical staining and our results showed that the expression of BTG3 was reduced in lung cancer compared to benign lung tissues. We identified two BTG3 isoforms present in lung cancer: Full-length BTG3 and BTG3b lacking the 44 amino acids. BTG3 was predominantly expressed in benign lung tissues, whereas its expression was generally undetectable in lung cancer and cancer cell lines. Functional analysis revealed that BTG3 but not BTG3b inhibited lung cancer growth. Our results disclosed an important role of BTG3 in lung tumorigenesis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the "cancer initiatome." Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC). We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.

Objective: To explore the effect of phosphorus, nitrogen on the production of microcystin under specific laboratory condition., Methods: The microcystis were ampliatively cultured for three times in N and P free culture. Then the microcysitis were inoculated in the culture at the concentrations of 0, 0.5, 1.0, 5.0 and 10.0 mg/L P for 20 days. The microcystis were inoculated in the BG-11 cultures at the concentrations of 0.05 mg/L and 5.0 mg/L P, NaNO3 were added in the culture according to the mol ratios of N/P were 5:1, 10:1, 20:1, 50:1, 100:1 and were cultured for 20 days. The changes of the count of the microcystis were observed. The microcystis cell were breaked at the 8th, 12th, 16th and 20th days after the beginning of culturing, the the microcystin were extracted and detected by HPLC., Results: When the concentrations of phosphorus were lower than 5.0 mg/L, The productions of microcystin increased with the phosphorus concentrations. But when the concentrations of phosphorus were 10.0 mg/L, the productions of microcystin significantly decreased. In the culture at the concentrations of 0.05 mg/L P, the microcystin concentration per cell (MCYST fg/cell) and the microcystin concentrations per milliliter (MCYST microg/ml culture) presented the greatest value when the N/P ratio was 50:1. But, In the culture at the concentrations of 5.0 mg/L P, the microcystin concentrations per cell (MCYST fg/cell) and the microcystin concentrations per milliliter (MCYST microg/ml culture) presented the greatest value when the N/P ratio was 20:1., Conclusion: P concentrations significantly incluence the production of microcystin. The P concentrations in water should be controlled through different way to control the production of microcystins.